Gene Detail

Gene Symbol JAK2
Synonyms JTK10 | THCYT3
Gene Description JAK2, tyrosine-protein kinase JAK2, is a non-receptor protein tyrosine kinase that binds cytokine receptors to activate the interferon-alpha/beta/gamma pathway and is a member of the JAK/STAT signaling pathway (PMID: 15575979, PMID: 30092288). JAK2 mutations are observed in a variety of tumor types, including myeloproliferative neoplasms (PMID: 30074114), lymphoma (PMID: 29984752), leukemia (PMID: 29979407), and cervical cancer (PMID: 30003068).
Entrez Id 3717
Chromosome 9
Map Location 9p24.1
Canonical Transcript NM_004972

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
E1080* nonsense unknown JAK2 E1080* results in a premature truncation of the Jak2 protein at amino acid 1080 of 1132 (UniProt.org). E1080* has been identified in sequencing studies (PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
E985K missense unknown JAK2 E985K lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). E985K has been described as a secondary drug resistance mutation (PMID: 21926964), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
E543_D544del deletion unknown JAK2 E543_D544del results in the deletion of two amino acids of the Jak2 protein from amino acids 543 to 544 (UniProt.org). E543_D544del has been identified in the scientific literature (PMID: 27410038, PMID: 26361084, PMID: 17984312), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
I682G missense gain of function - predicted JAK2 I682G lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). I682G is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased enzyme kinetics and decreased structural stability (PMID: 25940527).
Y44C missense gain of function - predicted JAK2 Y44C lies within the FERM domain of the Jak2 protein (PMID: 26419724). Y44C is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
E274* nonsense loss of function - predicted JAK2 E274* results in a premature truncation of the Jak2 protein at amino acid 274 of 1132 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), E274* is predicted to lead to a loss of Jak2 function.
I540T missense unknown JAK2 I540T does not lie within any known functional domains of the Jak2 protein (UniProt.org). I540T has been identified in sequencing studies (PMID: 21497288), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
L113V missense unknown JAK2 L113V lies within the FERM domain of the Jak2 protein (UniProt.org). L113V has been identified in sequencing studies (PMID: 30811597, PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
I682S missense gain of function - predicted JAK2 I682S lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). I682S is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased enzyme kinetics and decreased structural stability (PMID: 25940527).
H608Y missense unknown JAK2 H608Y lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). H608Y has been identified in sequencing studies (PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
K912T missense unknown JAK2 K912T lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). K912T has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
I404N missense unknown JAK2 I404N lies within the SH2 domain of the Jak2 protein (UniProt.org). I404N has been identified in sequencing studies (PMID: 271475990), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
I645V missense unknown JAK2 I645V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I645V has been identified in sequencing studies (PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R426* nonsense loss of function - predicted JAK2 R426* results in a premature truncation of the Jak2 protein at amino acid 426 of 1132 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), R426* is predicted to lead to a loss of Jak2 function.
D894G missense unknown JAK2 D894G lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). D894G has been identified in sequencing studies (PMID: 22675565), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
E177V missense unknown JAK2 E177V lies within the FERM domain of the Jak2 protein (UniProt.org). E61K has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
G276A missense unknown JAK2 G276A lies within the FERM domain of the Jak2 protein (UniProt.org). G276A has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
Y813D missense unknown JAK2 Y813D lies within a linker region of the Jak2 protein (PMID: 29685781). Y813D has been identified in sequencing studies (PMID: 19643476), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
inact mut unknown loss of function JAK2 inact mut indicates that this variant results in a loss of function of the Jak2 protein. However, the specific amino acid change has not been identified.
G127D missense unknown JAK2 G127D lies within the FERM domain and cytokine/interferon/growth hormone receptors-interacting region of the Jak2 protein (UniProt.org). G127D is predicted to result in decreased protein stability in computational models (PMID: 28775167), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jul 2019).
R975G missense gain of function - predicted JAK2 R975G lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). R975G is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased Jak2, Stat5, Akt and Erk phosphorylation, and has also been described as a secondary drug resistance mutation in the context of ETV6-JAK2 (PMID: 22916261). Y
G614fs frameshift loss of function - predicted JAK2 G614fs results in a change in the amino acid sequence of the Jak2 protein beginning at aa 614 of 1132, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most of protein kinase domain 1 and all of protein kinase domain 2 (UniProt.org, PMID: 16879967), G614fs is predicted to lead to a loss of Jak2 protein function.
G834S missense unknown JAK2 G834S does not lie within any known functional domains of the Jak2 protein (UniProt.org). G834S has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
P933R missense gain of function - predicted JAK2 P933R lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). D873N is predicted to confer a gain of function to the Jak2 protein based on mouse Jak2 D873N increased Jak2 and Stat5 phoshorylation and transformation of cells in culture (PMID: 19470474).
C618R missense gain of function JAK2 C618R lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). C618R confers a gain of function to the Jak2 protein as demonstrated by increased Jak2 kinase activity in an in-vitro assay and is transforming in cell culture (PMID: 22960131).
M483R missense gain of function - predicted JAK2 M483R lies within the SH2 domain of the Jak2 protein (PMID: 26419724). M483R is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
I540N missense unknown JAK2 I540N does not lie within any known functional domains of the Jak2 protein (UniProt.org). I540N has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
T875N missense gain of function JAK2 T875N lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). T875N confers a gain of function to the Jak2 protein as demonstrated by increased Jak2 and Stat1, Stat3, and Stat5 phosphorylation (PMID: 19543316) and is transforming in cell culture (PMID: 21362419).
I682T missense no effect - predicted JAK2 I682T lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). I682T induces activation of Stat5 similar to wild-type in a reporter assay and therefore, is predicted to have no effect on Jak2 protein function (PMID: 26216197).
V567A missense unknown JAK2 V567A lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). V567A has been identified in sequencing studies (PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
Y62C missense unknown JAK2 Y62C lies within the FERM domain of the Jak2 protein (UniProt.org). Y62C has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R938Q missense gain of function JAK2 R938Q lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). R938Q confers a gain of function to the Jak2 protein, as demonstrated by constitutive Stat5 signaling (PMID: 29025600), transformation of cultured cells (PMID: 24398328), and also displays resistance to Jak1/2 ATP-competitive inhibitors (PMID: 29025600). Y
Y918H missense unknown JAK2 Y918H lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y918H has been demonstrated to occur as a secondary drug resistance mutation (PMID: 22916261), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
D569Y missense unknown JAK2 D569Y lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). D569Y has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
E987D missense unknown JAK2 E987D lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). E987D has been described as a secondary resistance mutation (PMID: 26419724), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
Y613_G614insTSY insertion unknown JAK2 Y613_G614insTSY results in the insertion of three amino acids in the protein kinase domain 1 of the Jak2 protein between amino acids 613 and 614 (UniProt.org). Y613_G614insTSY has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
S15F missense unknown JAK2 S15F lies within the cytokine/interferon/growth hormone receptors-interacting region of the Jak2 protein (UniProt.org). S15F has been identified in the scientific literature (PMID: 30811597, PMID: 28561041), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
I540_E543delinsMK indel unknown JAK2 I540_E543delinsMK results in a deletion of four amino acids from amino acids 540 to 543 of the Jak2 protein, combined with the insertion of a methionine (M) and a lysine (K) at the same site (UniProt.org). I540_E543delinsMK has been identified in sequencing studies (PMID: 22642932), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R683T missense gain of function - predicted JAK2 R683T lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (PMID: 26419724). R683E is predicted to confer a gain of function to the Jak2 protein, as demonstrated by the ability to transform cells in culture (PMID: 26419724).
M929I missense gain of function - predicted JAK2 M929I is a gatekeeper mutation that lies within the protein kinase 2 domain of the Jak2 protein (PMID: 22916261, PMID: 23823659). M929I is predicted to confer a gain of function to the Jak2 protein as demonstrated by increased Jak2 and Stat5 phosphorylation (PMID: 22916261), and has also been described as a secondary drug resistance mutation in the context of other Jak2 activating mutations (PMID: 22916261, PMID: 23823659, PMID: 21926964). Y
E283del deletion unknown JAK2 E283del results in the deletion of one amino acid within the FERM domain of the Jak2 protein at amino acid 283 (UniProt.org). E283del has been identified in the scientific literature (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
I324T missense unknown JAK2 I324T lies within the FERM domain of the Jak2 protein (UniProt.org). I324T has been identified in sequencing studies (PMID: 30811597, PMID: 29338072), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
I682F missense gain of function - predicted JAK2 I682F lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). I682F is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased enzyme kinetics and decreased structural stability (PMID: 25940527).
E177* nonsense loss of function - predicted JAK2 E177* results in a premature truncation of the Jak2 protein at amino acid 177 of 1132 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), E177* is predicted to lead to a loss of Jak2 function.
H538_K539delinsQL indel gain of function JAK2 H538_K539delinsQL results in a deletion of two amino acids from amino acids 538 to 539 of the Jak2 protein, combined with the insertion of a glutamine (Q) and a leucine (L) at the same site (UniProt.org). H538_K539delinsQL results in Jak2 autophosphorylation, increased Erk phosphorylation and cell proliferation in culture (PMID: 17267906).
N542_E543del deletion gain of function JAK2 N542_E543del is an exon 12 deletion that results in the deletion of two amino acids in the kinase domain of the Jak2 protein from amino acids 542 to 543 (PMID: 17267906). N542_E543del confers a gain of function to the Jak2 protein as demonstrated by increased proliferation, Jak2 phosphorylation, and downstream Stat5 phosphorylation (PMID: 17267906).
S593C missense unknown JAK2 S593C lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). S593C has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
S797C missense unknown JAK2 S797C lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). S797C has been identified in sequencing studies (PMID: 30811597, PMID: 30337359), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
H110R missense gain of function - predicted JAK2 H110R lies within the FERM domain of the Jak2 protein (PMID: 26419724). H110R is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
R541_E543delinsK indel unknown JAK2 R541_E543delinsK results in a deletion of three amino acids from amino acids 541 to 543 of the Jak2 protein, combined with the insertion of a lysine (K) at the same site (UniProt.org). R541_E543delinsK has been identified in the scientific literature (PMID: 26361084), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R564L missense unknown JAK2 R564L lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R564L is predicted to disrupt the Jak2 kinase domain conformation by structural simulation (PMID: 19744331), but has not been biochemically characterized and therefore its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
E10K missense unknown JAK2 E10K lies within the cytokine/interferon/growth hormone receptors-interacting region of the Jak2 protein (UniProt.org). E10K has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
V392M missense unknown JAK2 V392M does not lie within any known functional domains of the Jak2 protein (UniProt.org). V392M has been identified in sequencing studies (PMID: 30811597, PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
N1108S missense unknown JAK2 N1108S lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). N1108S has been identified in the scientific literature (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
wild-type none no effect Wild-type JAK2 indicates that no mutation has been detected within the JAK2 gene.
L579I missense unknown JAK2 L579I lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L579I has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R588M missense unknown JAK2 R588M lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). The functional effect of R588M is conflicting, as R588M demonstrates autophosphorylation and activation of Stat5, Erk, and Akt to similar levels of wild-type Jak2, but has increased kinase activity in an in vitro kinase assay and is transforming in cell culture (PMID: 19638629).
H538Q missense unknown JAK2 H538Q does not lie within any known functional domains of the Jak2 protein (UniProt.org). H538Q leads to increased proliferation, Jak2 phosphorylation, and downstream Stat5 phosphorylation when co-mutated with K539L in culture (PMID: 17267906, PMID: 22584586), but has not been individually characterized and therefore, its effect on Jak2 protein function is unknown.
D319N missense unknown JAK2 D319N lies within the FERM domain of the Jak2 protein (UniProt.org). D319N has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R1063H missense gain of function JAK2 R1063H lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). R1063H results increased EPO-induced growth, STAT5 phosphorylation and transcriptional activity, and EPO-dependent and independent hematopoietic colony formation in-vitro relative to wild-type Jak2 (PMID: 27389715).
G571S missense no effect - predicted JAK2 G571S lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). G571S lies next to a critical phosphorylation site and thus was predicted to result in constitutive JAK2 kinase activity in a manner similar to mutations at codon 570 (PMID: 19074595, PMID: 27924280), however, G571S does not demonstrate ligand-independent JAK2-STAT5 signaling and regulates cell viability similar to wild-type Jak2 (PMID: 26423830) and therefore, is predicted to have no effect on the Jak2 protein.
F694S missense gain of function - predicted JAK2 F694S lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). F694S is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased kinase activity, activation of Stat5, Erk, and Akt (PMID: 19638629).
G831R missense unknown JAK2 G831R does not lie within any known functional domains of the Jak2 protein (UniProt.org). G831R has been demonstrated to occur as a secondary drug resistance mutation (PMID: 22916261), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
L393V missense gain of function JAK2 L393V lies within a linker region of the Jak2 protein (PMID: 29685781). L393V confers a gain of function to the Jak2 protein, as demonstrated by increased transcriptional activity of Stat1, 3, and 5, and ligand-dependent increased cell viability as compared to wild-type (PMID: 27647865).
E61K missense unknown JAK2 E61K lies within the FERM domain of the Jak2 protein (UniProt.org). E61K has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R1127K missense unknown JAK2 R1127K does not lie within any known functional domains of the Jak2 protein (UniProt.org). R1127K has been demonstrated to occur as a secondary drug resistance mutation (PMID: 22916261), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
H538_K539delinsL indel unknown JAK2 H538_K539delinsL results in a deletion of two amino acids from amino acids 538 to 539 of the Jak2 protein, combined with the insertion of a leucine (L) at the same site (UniProt.org). H538_K539delinsL has been identified in the scientific literature (PMID: 27410038), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
T514M missense unknown JAK2 T514M lies within a linker region of the Jak2 protein (PMID: 29685781). T514M has been identified in sequencing studies (PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
F537_K539delinsL indel gain of function JAK2 F537_K539delinsL results in a deletion of three amino acids from 537 to 539 within the protein kinase domain of the Jak2 protein, combined with the insertion of a leucine (L) (UniProt.org, PMID: 17267906). JAK2 F537_K539delinsL confers a gain of function to the Jak2 protein as demonstrated by increased proliferation, Jak2 phosphorylation, and downstream Stat5 phosphorylation (PMID: 17267906).
G48E missense unknown JAK2 G48E lies within the FERM domain and cytokine/interferon/growth hormone receptors-interacting region of the Jak2 protein (UniProt.org). G48E has been identified in sequencing studies (PMID: 30811597, PMID: 25801821), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
L1047I missense unknown JAK2 L1047I lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). L1047I has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R683G missense gain of function JAK2 R683G lies within the protein kinase 1 (JH2, pseudokinase) of the Jak2 protein (UniProt.org). R683G results in constitutive activation of the Jak2 protein, as demonstrated by increased transcription of Stat5 (PMID: 26216197, PMID: 23748007) and is transforming in cell culture, independent of cytokines (PMID: 26216197, PMID: 18805579).
G417S missense unknown JAK2 G417S lies within the atypical SH2 domain of the Jak2 protein (UniProt.org). G417S has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
over exp none no effect JAK2 over exp indicates an over expression of the Jak2 protein. However, the mechanism causing the over expression is unspecified.
Y931F missense gain of function - predicted JAK2 Y931F lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). Y931F is predicted to confer a gain of function to the Jak2 protein as demonstrated by the ability to transform cells in culture (PMID: 26419724).
D544G missense unknown JAK2 D544G does not lie within any known functional domains of the Jak2 protein (UniProt.org). D544G has been identified in sequencing studies (PMID: 19491085), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R443* nonsense loss of function - predicted JAK2 R443* results in a premature truncation of the Jak2 protein at amino acid 443 of 1132 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), R443* is predicted to lead to a loss of Jak2 function.
N99S missense gain of function - predicted JAK2 N99S lies within the FERM domain of the Jak2 protein (PMID: 26419724). N99S is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
A676V missense unknown JAK2 A676V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). A676V has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
A660S missense unknown JAK2 A660S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). A660S has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
V881fs frameshift loss of function - predicted JAK2 V881fs results in a change in the amino acid sequence of the Jak2 protein beginning at aa 881 of 1132, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the protein kinase 2 domain (UniProt.org), V881fs is predicted to lead to a loss of Jak2 protein function.
G417P missense gain of function - predicted JAK2 G417P lies within the SH2 domain of the Jak2 protein (PMID: 26419724). G417P is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
mutant unknown unknown JAK2 mutant indicates and unspecified mutation in the JAK2 gene.
act mut unknown gain of function JAK2 act mut indicates that this variant results in a gain of function in the Jak2 protein. However, the specific amino acid change has not been identified.
L545S missense unknown JAK2 L545S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). D544G has been identified in sequencing studies (PMID: 19491085), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
W737L missense unknown JAK2 W737L lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). W737L has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
P870L missense unknown JAK2 P870L lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). P870L has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
N533Y missense unknown JAK2 N533Y lies within a linker region of the Jak2 protein (PMID: 29685781). N533Y has been identified in sequencing studies (PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R564G missense unknown JAK2 R564G lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R564G has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
L624P missense unknown JAK2 L624P lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L624P may cause a conformational change in the Jak2 protein (PMID: 19744331), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R133Q missense unknown JAK2 R133Q lies within the FERM domain of the Jak2 protein (UniProt.org). R133Q has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
L611S missense gain of function JAK2 L611S lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). L611S confers a gain of function to the Jak2 protein, as demonstrated by increased kinase activity, activation of Stat5, Erk, and Akt, and is transforming in cell culture (PMID: 19638629).
E386* nonsense loss of function - predicted JAK2 E386* results in a premature truncation of the Jak2 protein at amino acid 386 of 1132 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), E386* is predicted to lead to a loss of Jak2 function.
fusion fusion unknown JAK2 fusion indicates a fusion of the JAK2 gene, but the fusion partner is unknown.
V625F missense gain of function JAK2 V625F lies within the protein kinase 1 (JH2, pseudokinase) of the Jak2 protein (UniProt.org). V625F confers a gain of function to the Jak2 protein, as demonstrated by cytokine-independent JAK2-STAT5 signaling and hypersensitivity to TPO and IL3 as indicated by increased cell viability (PMID: 26423830).
R683E missense gain of function JAK2 R683E lies within the protein kinase 1 (JH2, pseudokinase) of the Jak2 protein (UniProt.org). R683E confers a gain of function to the Jak2 protein, as demonstrated by increased Stat5 activation and enhanced enzyme kinetics as compared to wild-type (PMID: 23748007).
V881A missense gain of function - predicted JAK2 V881A lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). V881A is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased Jak2, Stat5, Akt and Erk phosphorylation, and has also been described as a secondary drug resistance mutation in the context of ETV6-JAK2 (PMID: 22916261). Y
R215Q missense unknown JAK2 R215Q lies within the FERM domain of the Jak2 protein (UniProt.org). R215Q has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R938L missense unknown JAK2 R938L lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). R938L has been demonstrated to occur as a secondary drug resistance mutation (PMID: 21926964), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
G295E missense unknown JAK2 G295E lies within the FERM domain of the Jak2 protein (UniProt.org). G295E has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
L579V missense unknown JAK2 L579V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L579V has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
R683S missense gain of function JAK2 R683S lies within the protein kinase 1 (JH2, pseudokinase) of the Jak2 protein (UniProt.org). R683S confers a gain of function to the Jak2 protein as demonstrated by constitutive Jak2 phosphorylation (PMID: 18805579), Stat5 activation (PMID: 23748007), and increased cytokine-independent growth and proliferation (PMID: 18805579, PMID: 19638629).
N533I missense unknown JAK2 N533I lies within a linker region of the Jak2 protein (PMID: 29685781). N533I has not been characterized and therefore, its effect on Jak2 function is unknown (PubMed, Apr 2019).
R683K missense unknown JAK2 R683K lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R683K demonstrates kinase kinetics and Stat5 binding similar to wuld-type Jak2 in one study (PMID: 23748007), but results in constitutive Jak2 phosphorylation and supports cytokine-independent growth in another study (PMID: 18805579), therefore, its effect on Jak2 protein function is unknown.
K167Q missense unknown JAK2 K167Q lies within the FERM domain of the Jak2 protein (UniProt.org). K167Q has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R683* nonsense loss of function - predicted JAK2 R683* results in a premature truncation of the Jak2 protein at amino acid 683 of 1182 (UniProt.org). Due to the loss of a portion of protein kinase domain 1 and all of protein kinase domain 2 (UniProt.org), R683* is predicted to lead to a loss of Jak2 protein function.
I682L missense no effect - predicted JAK2 I682L lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). I682L has enzyme kinetics and structural stability similar to wild-type and therefore, is predicted to have no effect on Jak2 protein function (PMID: 25940527).
N909K missense gain of function - predicted JAK2 N909K lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). N909K is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased Jak2, Stat5, Akt and Erk phosphorylation, and has also been described as a secondary drug resistance mutation in the context of ETV6-JAK2 (PMID: 22916261). Y
T246I missense unknown JAK2 T246I lies within the FERM domain of the Jak2 protein (UniProt.org). T246I has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
R340Q missense no effect - predicted JAK2 R340Q lies in the FERM domain of the Jak2 protein (UniProt.org). R340Q is not transforming in cell culture as demonstrated by similar proliferation levels as wild-type and therefore, is predicted to have no effect on Jak2 protein function (PMID: 28473624).
E818* nonsense loss of function - predicted JAK2 E818* results in a premature truncation of the Jak2 protein at amino acid 818 of 1132 (UniProt.org). Due to the loss of the protein kinase 2 domain (UniProt.org), E818* is predicted to lead to a loss of Jak2 protein function.
L805V missense unknown JAK2 L805V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L805V has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
I136L missense unknown JAK2 I136L lies within the FERM domain and cytokine/interferon/growth hormone receptors-interacting region of the Jak2 protein (UniProt.org). I136L has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
K607N missense gain of function JAK2 K607N lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). K607N results in constitutive activation of Jak2 and enhanced proliferation and transformation in cell cultrue (PMID: 30521925).
L359I missense unknown JAK2 L359I lies within the FERM domain of the Jak2 protein (UniProt.org). L359I has been identified in sequencing studies (PMID: 30811597, PMID: 30259120), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
S126N missense unknown JAK2 S126N lies within the FERM domain of the Jak2 protein (UniProt.org). S126N has not been characterized in the scientific literature and therefore, its effect on Jak2 function is unknown (PubMed, Apr 2019).
F439S missense unknown JAK2 F439S lies within the SH2 domain of the Jak2 protein (UniProt.org). F439S has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
P58A missense gain of function - predicted JAK2 P58A lies within the FERM domain of the Jak2 protein (PMID: 26419724). P58A is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
R588I missense unknown JAK2 R588I lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R588I has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
Y317H missense gain of function JAK2 Y317H lies in the FERM domain of the Jak2 protein (UniProt.org). Y317H confers a gain of function to the Jak2 protein as demonstrated by increased cytokine-dependent activation of Stat3, Stat5, and Akt and is transforming in cell culture (PMID: 28473624).
E846D missense gain of function JAK2 E846D lies within a linker region of the Jak2 protein (PMID: 29685781). E846D confers a gain of function to the Jak2 protein as demonstrated by prolonged Epo-induced Stat5 activation in an in-vitro assay and is transforming in cell culture (PMID: 27389715).
L634P missense no effect - predicted JAK2 L634P lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). L634P induces activation of Stat5 similar to wild-type in a reporter assay and therefore, is predicted to have no effect on Jak2 protein function (PMID: 26216197).
R683H missense no effect - predicted JAK2 R683H lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). R683H is predicted to have no effect on Jak2 protein function, as demonstrated by Stat5 activation and enzyme kinetics similar to wild-type (PMID: 23748007)
F694L missense gain of function JAK2 F694L lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). F694L confers a gain of function to the Jak2 protein, as demonstrated by increased kinase activity, activation of Stat5, Erk, and Akt, and is transforming in cell culture (PMID: 19638629).
H574R missense gain of function JAK2 H574R lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). H574R confers a gain of function to the Jak2 protein, as demonstrated by cytokine-independent phosphorylation of Jak2 and Stat5 and enhanced cell proliferation (PMID: 26216197).
H606Q missense unknown JAK2 H606Q lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). H606Q is predicted to disrupt Jak2 protein function by structural modeling (PMID: 19744331), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
G935R missense gain of function - predicted JAK2 G935R lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). G935R is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased Jak2 and Stat5 phosphorylation and also prevents apoptosis in the presence of a Jak inhibitor (PMID: 22916261) and therefore, has been described as a secondary drug resistance mutation in the context of other Jak2 activating mutations (PMID: 22271575, PMID: 22916261). Y
R487C missense unknown JAK2 R487C does not lie within any known functional domains of the Jak2 protein (UniProt.org). R487C has been identified in sequencing studies (PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
M535I missense unknown JAK2 M535I does not lie within any known functional domains of the Jak2 protein (UniProt.org). The functional effect of M535I is conflicting, as M535I demonstrates signaling activity and ligand-independent growth similar to wild-type Jak2 in one study (PMID: 18755984), but has increased Jak2 kinase activity and is transforming in cell culture in another study (PMID: 19638629).
I960V missense unknown JAK2 I960V lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). I960V has been described as a secondary drug resistance mutation in the context of JAK2 V617F (PMID: 23009939, PMID: 21926964), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
Y613fs frameshift loss of function - predicted JAK2 Y613fs results in a change in the amino acid sequence of the Jak2 protein beginning at aa 613 of 1132, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most of protein kinase domain 1 and all of protein kinase domain 2 (PMID: 16879967), Y613fs is predicted to lead to a loss of Jak2 protein function.
S887I missense unknown JAK2 S887I lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). S887I has not been characterized and therefore, its effect on Jak2 function is unknown (PubMed, Apr 2019).
I899T missense unknown JAK2 I899T lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). I899T has been identified in sequencing studies (PMID: 30811597, PMID: 30259120), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
E864K missense gain of function - predicted JAK2 E864K lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). E864K is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased Jak2 and Stat5 phosphorylation and also prevents apoptosis in the presence of a Jak inhibitor (PMID: 22916261) and therefore, has been described as a secondary drug resistance mutation in the context of other Jak2 activating mutations (PMID: 22916261, PMID: 22271575). Y
N337D missense unknown JAK2 N337D lies within the FERM domain of the Jak2 protein (UniProt.org). N337D has been identified in sequencing studies (PMID: 30259120, PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
R277K missense gain of function - predicted JAK2 R277K lies within the FERM domain of the Jak2 protein (PMID: 26419724). R277K is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
F556V missense gain of function - predicted JAK2 F556V lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). F556V is predicted to confer a gain of function to the Jak2 protein, as demonstrated by cytokine-independent phosphorylation of Stat5 and hypersensitivity to the TPO ligand (PMID: 26423830).
V563I missense unknown JAK2 V563I lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). V563I has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
E890* nonsense loss of function - predicted JAK2 E890* results in a premature truncation of the Jak2 protein at amino acid 890 of 1132 (UniProt.org). Due to the disruption of the protein kinase 2 domain (UniProt.org), E890* is predicted to lead to a loss of Jak2 protein function.
P870S missense unknown JAK2 P870S lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). P870S has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
Y254H missense unknown JAK2 Y254H lies within the FERM domain of the Jak2 protein (UniProt.org). Y254H has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
S591L missense unknown JAK2 S591L lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). S591L demonstrates autophosphorylation and activation of Stat5, Erk, and Akt to similar levels of wild-type Jak2, but also has increased kinase activity in an in vitro kinase assay and is transforming in cell culture (PMID: 19638629), therefore, its effect on Jak2 protein function is unknown.
T108A missense gain of function JAK2 T108A lies within the FERM domain of the Jak2 protein (UniProt.org). T108A is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transcriptional activity of Stat1, 3, and 5, and ligand-dependent increased cell viability as compared to wild-type (PMID: 27647865).
S358* nonsense loss of function - predicted JAK2 S358* results in a premature truncation of the Jak2 protein at amino acid 358 of 1132 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), S358* is predicted to lead to a loss of Jak2 function.
G301R missense unknown JAK2 G301R lies within the FERM domain of the Jak2 protein (UniProt.org). G301R has been identified in sequencing studies (PMID: 30811597, PMID: 30259120), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
amp none no effect JAK2 amp indicates an increased number of copies of the JAK2 gene. However, the mechanism causing the increase is unspecified.
I682D missense gain of function - predicted JAK2 I682D lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). I682D is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased enzyme kinetics and decreased structural stability (PMID: 25940527).
K539I missense gain of function JAK2 K539I does not lie within any known functional domains of the Jak2 protein (Uniprot.org). K539I confers a gain of function to the Jak2 protein, as demonstrated by increased kinase activity, activation of Stat5, Erk, and Akt, and is transforming in cell culture (PMID: 19638629).
F556L missense unknown JAK2 F556L lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). F556L has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
P1057S missense unknown JAK2 P1057S lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). P1057S has been demonstrated to occur as a secondary drug resistance mutation (PMID: 23670175), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019). Y
F560S missense unknown JAK2 F560S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). F560S has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
Y931C missense gain of function JAK2 Y931C lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org, PMID: 21393331). Y931C results in increased Jak2 kinase activity (PMID: 21393331) and is transforming in cell culture (PMID: 21393331, PMID: 26419724).
I1126V missense unknown JAK2 I1126V does not lie within any known functional domains of the Jak2 protein (UniProt.org). I1126V has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
L611fs frameshift loss of function - predicted JAK2 L611fs results in a change in the amino acid sequence of the Jak2 protein beginning at aa 611 of 1132, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most of protein kinase domain 1 and all of protein kinase domain 2 (UniProt.org, PMID: 16879967), L611fs is predicted to lead to a loss of Jak2 protein function.
Y637C missense unknown JAK2 Y637C lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y637C has been identified in sequencing studies (PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
K244R missense unknown JAK2 K244R lies within the FERM domain of the Jak2 protein (UniProt.org). K244R demonstrates sumoylation similar to wild-type Jak2 in culture (PMID: 29020972), but has not been fully biochemically characterized and therefore, its effect on Jak2 protein function is unknown.
D620E missense unknown JAK2 D620E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). D620E has been identified in sequencing studies (PMID: 17008888), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
L609fs frameshift loss of function - predicted JAK2 L609fs results in a change in the amino acid sequence of the Jak2 protein beginning at aa 609 of 1132, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most of protein kinase domain 1 and all of protein kinase domain 2 (UniProt.org, PMID: 16879967), L609fs is predicted to lead to a loss of Jak2 protein function.
V366G missense gain of function - predicted JAK2 V366G lies within the FERM domain of the Jak2 protein (PMID: 26419724). V366G is predicted to confer a gain of function to the Jak2 protein, as demonstrated by increased transformation ability in cell culture (PMID: 26419724).
N622I missense gain of function JAK2 N622I lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). N622I confers a gain of function to the Jak2 protein, as demonstrated by increased kinase activity, activation of Stat5, Erk, and Akt, and is transforming in cell culture (PMID: 19638629).
H538L missense gain of function JAK2 H538L does not lie within any known functional domains of the Jak2 protein (UniProt.org). H538L confers a gain of function to the Jak2 protein as demonstrated by increased Jak2 autophosphorylation and transformation of cells in culture (PMID: 19638629).
C480F missense unknown JAK2 C480F lies within the SH2 domain of the Jak2 protein (UniProt.org). C480F has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R867Q missense gain of function JAK2 R867Q lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). R867Q results in constitutive activation of STAT3/5, AKT and ERK signaling, and increased proliferation in thrombopoietin receptor-expressing cells in culture (PMID: 24398328).
K607E missense gain of function JAK2 K607E lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). K607E confers a gain of function to the Jak2 protein as demonstrated by increased Jak2 autophosphorylation and transformation of cells in culture (PMID: 19638629).
S602I missense unknown JAK2 S602I lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). S602I has not been characterized in the scientific literature and therefore, its effect on Jak2 function is unknown (PubMed, Apr 2019).
N612fs frameshift loss of function - predicted JAK2 N612fs results in a change in the amino acid sequence of the Jak2 protein beginning at aa 612 of 1132, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most of protein kinase domain 1 and all of protein kinase domain 2 (UniProt.org, PMID: 16879967), N612fs is predicted to lead to a loss of Jak2 protein function.
S755R missense gain of function - predicted JAK2 S755R lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). S755R demonstrates basal activity similar to wild-type Jak2 but increased Akt phosphorylation and cell growth when stimulated with high level thrombopoietin (PMID: 24398328), and therefore, is predicted to lead to a gain of Jak2 protein function.
K539L missense gain of function JAK2 K539L lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (PMID: 30092288). K539L confers a gain of function to the Jak2 protein as demonstrated by increased cell proliferation (PMID: 17267906, PMID: 21362419) and cytokine-independent phosphorylation of Jak2, Stat5, and Stat1 (PMID: 17267906, PMID: 30092288).
E484K missense unknown JAK2 E484K does not lie within any known functional domains of the Jak2 protein (UniProt.org). E484K has been identified in sequencing studies (PMID: 28028924), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
D873N missense gain of function - predicted JAK2 D873N lies within the JH1 protein kinase domain 2 of the Jak2 protein (UniProt.org). D873N is predicted to confer a gain of function to the Jak2 protein based on mouse Jak2 D873N increased Jak2 and Stat5 phoshorylation and transformation of cells in culture (PMID: 19470474).
D319G missense unknown JAK2 D319G lies within the FERM domain of the Jak2 protein (UniProt.org). D319G has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
R564Q missense gain of function JAK2 R564Q lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). R564Q confers a gain of function to the Jak2 protein, as demonstrated by increased kinase activity, activation of Stat1, 3, 5, Erk, and Akt, and is transforming in cell culture (PMID: 24381227).
E1012* nonsense unknown JAK2 E1012* results in a premature truncation of the Jak2 protein at amino acid 1012 of 1132 (UniProt.org). E1012* has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
V617F missense gain of function JAK2 V617F lies within the protein kinase 1 (JH2, pseudokinase) of the Jak2 protein (UniProt.org). V617F results in constitutive activation of Jak2 and downstream Stat5 and Erk, is transforming in cell culture, and leads to development of erythrocytosis in mouse models (PMID: 15858187, PMID: 15837627, PMID: 15793561, PMID: 28473624).
L941F missense unknown JAK2 L941F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). L941F has been identified in sequencing studies (PMID: 30811597, PMID: 27997549), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jun 2019).
V617I missense gain of function - predicted JAK2 V617I lies within the protein kinase 1 (JH2, pseudokinase) of the Jak2 protein (UniProt.org). V617I is predicted to confer a gain of function to the Jak2 protein as demonstrated by increased kinase activity through Jak2 autophosphorylation (PMID: 19638629).
V911A missense unknown JAK2 V911A lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). V911A has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
rearrange unknown unknown JAK2 rearrange indicates an unspecified rearrangement of the JAK2 gene.
H587N missense unknown JAK2 H587N lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). H587N is predicted to disrupt Jak2 protein function by structural modeling (PMID: 19744331), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Apr 2019).
L611V missense no effect - predicted JAK2 L611V lies within the protein kinase 1 (JH2, pseudokinase) domain of the Jak2 protein (UniProt.org). L611V results in Jak2, Stat5, and Akt phosphorylation levels comparable to wild-type Jak2, and therefore, is predicted to have no effect on the Jak2 protein function, however, the L611V does result in constitutive activation of Jak2 when co-mutated with V617F (PMID: 20182460).
ETV6 - JAK2 fusion gain of function ETV6-JAK2 results from the fusion of ETV6 (also referred to as TEL) and JAK2 (PMID: 9736611). ETV6-JAK2 results in growth factor independence, constitutive kinase activity and increased downstream signaling (PMID: 9736611).
Molecular Profile Protein Effect Treatment Approaches
JAK2 E1080* unknown
JAK2 V617F JAK2 E985K
JAK2 E985K unknown
JAK2 E543_D544del unknown
JAK2 I682G gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 Y44C gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E274* loss of function - predicted
JAK2 I540T unknown
JAK2 L113V unknown
JAK2 I682S gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 H608Y unknown
JAK2 K912T unknown
JAK2 I404N unknown
JAK2 I645V unknown
JAK2 R426* loss of function - predicted
JAK2 D894G unknown
JAK2 E177V unknown
JAK2 G276A unknown
JAK2 Y813D unknown
JAK2 inact mut loss of function
JAK2 G127D unknown
ETV6-JAK2 JAK2 R975G
JAK2 R975G gain of function - predicted JAK Inhibitor (Pan) JAK2 Inhibitor
JAK2 G614fs loss of function - predicted
JAK2 G834S unknown
JAK2 P933R gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 C618R gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 M483R gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 I540N unknown
JAK2 T875N gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 I682T no effect - predicted
JAK2 V567A unknown
JAK2 Y62C unknown
JAK2 R938Q gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
ETV6 - JAK2 JAK2 Y918H
JAK2 Y918H unknown
JAK2 D569Y unknown
JAK2 E987D unknown
JAK2 Y613_G614insTSY unknown
JAK2 S15F unknown
JAK2 I540_E543delinsMK unknown
JAK2 R683T gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
ETV6-JAK2 JAK2 M929I
JAK2 M929I gain of function - predicted JAK Inhibitor (Pan) JAK2 Inhibitor
ETV6 - JAK2 JAK2 M929I
JAK2 V617F JAK2 M929I
JAK2 E283del unknown
JAK2 I324T unknown
JAK2 I682F gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E177* loss of function - predicted
JAK2 H538_K539delinsQL gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 N542_E543del gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 S593C unknown
JAK2 S797C unknown
JAK2 H110R gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 R541_E543delinsK unknown
JAK2 R564L unknown
JAK2 E10K unknown
JAK2 V392M unknown
JAK2 N1108S unknown
JAK2 wild-type no effect
CALR wild-type JAK2 wild-type MPL wild-type
JAK2 L579I unknown
JAK2 R588M unknown
JAK2 H538Q unknown
JAK2 D319N unknown
JAK2 R1063H gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 G571S no effect - predicted
JAK2 F694S gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
ETV6 - JAK2 JAK2 G831R
JAK2 G831R unknown
JAK2 L393V gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E61K unknown
JAK2 R1127K unknown
ETV6 - JAK2 JAK2 R1127K
JAK2 H538_K539delinsL unknown
JAK2 T514M unknown
JAK2 F537_K539delinsL gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 G48E unknown
JAK2 L1047I unknown
JAK2 R683G JAK2 G935R
JAK2 R683G JAK2 E864K
JAK2 R683G gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 G417S unknown
JAK2 over exp no effect
JAK2 over exp MPL over exp
JAK2 Y931F gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 D544G unknown
JAK2 R443* loss of function - predicted
JAK2 N99S gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 A676V unknown
JAK2 A660S unknown
JAK2 V881fs loss of function - predicted
JAK2 G417P gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 mutant unknown
JAK2 act mut gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 L545S unknown
JAK2 W737L unknown
JAK2 P870L unknown
JAK2 N533Y unknown
JAK2 R564G unknown
JAK2 L624P unknown
JAK2 R133Q unknown
JAK2 L611S gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E386* loss of function - predicted
JAK2 fusion unknown
JAK2 V625F gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 R683E gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 V881A gain of function - predicted JAK Inhibitor (Pan) JAK2 Inhibitor
ETV6-JAK2 JAK2 V881A
JAK2 R215Q unknown
JAK2 R938L unknown
JAK2 V617F JAK2 R938L
JAK2 G295E unknown
JAK2 L579V unknown
JAK2 R683S gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 N533I unknown
JAK2 R683K unknown
JAK2 K167Q unknown
JAK2 R683* loss of function - predicted
JAK2 I682L no effect - predicted
JAK2 N909K gain of function - predicted JAK Inhibitor (Pan) JAK2 Inhibitor
ETV6-JAK2 JAK2 N909K
JAK2 T246I unknown
JAK2 R340Q no effect - predicted
JAK2 E818* loss of function - predicted
JAK2 L805V unknown
JAK2 I136L unknown
JAK2 K607N gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 L359I unknown
JAK2 S126N unknown
JAK2 F439S unknown
JAK2 P58A gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 R588I unknown
JAK2 Y317H gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E846D gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 L634P no effect - predicted
JAK2 R683H no effect - predicted
JAK2 F694L gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 H574R gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 H606Q unknown
JAK2 G935R gain of function - predicted JAK Inhibitor (Pan) JAK2 Inhibitor
ETV6-JAK2 JAK2 G935R
ETV6 - JAK2 JAK2 G935R
JAK2 V617F JAK2 G935R
JAK2 R487C unknown
JAK2 M535I unknown
JAK2 I960V unknown
JAK2 V617F JAK2 I960V
JAK2 Y613fs loss of function - predicted
JAK2 S887I unknown
JAK2 I899T unknown
ETV6 - JAK2 JAK2 E864K
JAK2 E864K gain of function - predicted JAK Inhibitor (Pan) JAK2 Inhibitor
JAK2 V617F JAK2 E864K
ETV6-JAK2 JAK2 E864K
JAK2 N337D unknown
JAK2 R277K gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 F556V gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 V563I unknown
JAK2 E890* loss of function - predicted
JAK2 P870S unknown
JAK2 Y254H unknown
JAK2 S591L unknown
JAK2 T108A gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 S358* loss of function - predicted
JAK2 G301R unknown
JAK2 amp no effect
JAK2 I682D gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 K539I gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 F556L unknown
ETV6 - JAK2 JAK2 P1057S
JAK2 P1057S unknown
JAK2 F560S unknown
JAK2 Y931C gain of function JAK Inhibitor (Pan) JAK2 Inhibitor
JAK2 V617F JAK2 Y931C
JAK2 I1126V unknown
JAK2 L611fs loss of function - predicted
JAK2 Y637C unknown
JAK2 K244R unknown
JAK2 D620E unknown
JAK2 L609fs loss of function - predicted
JAK2 V366G gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 N622I gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 H538L gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 C480F unknown
JAK2 R867Q gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 K607E gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 S602I unknown
JAK2 N612fs loss of function - predicted
JAK2 S755R gain of function - predicted
JAK2 K539L gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E484K unknown
JAK2 D873N gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 D319G unknown
JAK2 R564Q gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 E1012* unknown
JAK2 V617F MPL wild-type
JAK2 V617F gain of function JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 L941F unknown
JAK2 V617I gain of function - predicted JAK Inhibitor (Pan) JAK Inhibitor (Pan) - ATP competitive JAK2 Inhibitor JAK2 Inhibitor - ATP competitive
JAK2 V911A unknown
JAK2 rearrange unknown
JAK2 H587N unknown
JAK2 L611V no effect - predicted
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK2 V617F JAK2 E985K hematologic cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 E985K double mutation demonstrated resistance to Jakafi (Ruxolitinib) in culture (PMID: 21926964). 21926964
JAK2 inact mut melanoma predicted - resistant Pembrolizumab Case Reports/Case Series Actionable In a clinical study, a melanoma patient treated with Keytruda (pembrolizumab) initially demonstrated a partial response, however, post 734 days developed disease progression due to a splice site mutation in JAK2, which resulted in an intron inclusion and an early stop codon, leading to a loss of protein expression (PMID: 27433843). 27433843
ETV6-JAK2 JAK2 R975G hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the R975G mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 R938Q B-cell childhood acute lymphoblastic leukemia resistant Ruxolitinib Preclinical - Patient cell culture Actionable In a preclinical study, bone marrow mononuclear cells from a pediatric B-cell acute lymphoblastic leukemia with an acquired Jak2 R938Q mutation were resistant to Jakafi (ruxolitinib) (PMID: 29025600). 29025600
ETV6 - JAK2 JAK2 Y918H hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the Y918H mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
ETV6 - JAK2 JAK2 M929I hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the M929I mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 V617F JAK2 M929I hematologic cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 M929I double mutation demonstrated resistance to Jakafi (Ruxolitinib) in culture (PMID: 21926964). 21926964
CALR wild-type JAK2 wild-type MPL wild-type myelofibrosis not applicable N/A Guideline Prognostic The presence of concurrent wild-type JAK2, MPL, and CALR in myelofibrosis patients is associated with inferior leukemia-free survival compared to patients with JAK2 and/or CALR mutations, and is associated with inferior overall survival when compared to patients with CALR mutations (NCCN.org). detail...
ETV6 - JAK2 JAK2 G831R hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the G831R mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
ETV6 - JAK2 JAK2 R1127K hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the R1127K mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 R683G JAK2 G935R cancer resistant NVP-BSK805 Preclinical - Cell culture Actionable In a preclinical study, cells expressing the JAK2 R683G/G935R double mutation demonstrated resistance to NVP-BSK805 in culture (PMID: 22271575). 22271575
JAK2 R683G JAK2 G935R cancer resistant NVP-BVB808 Preclinical Actionable In a preclinical study, cells expressing the JAK2 R683G/G935R double mutation demonstrated resistance to NVP-BVB808 in culture (PMID: 22271575). 22271575
JAK2 R683G JAK2 G935R cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, cells expressing the JAK2 R683G/G935R double mutation demonstrated resistance to Jakafi (Ruxolitinib) in culture (PMID: 22271575). 22271575
JAK2 R683G JAK2 E864K cancer resistant NVP-BSK805 Preclinical - Cell culture Actionable In a preclinical study, cells expressing the JAK2 R683G/E864K double mutation demonstrated resistance to NVP-BSK805 in culture (PMID: 22271575). 22271575
JAK2 R683G JAK2 E864K cancer resistant NVP-BVB808 Preclinical Actionable In a preclinical study, cells expressing the JAK2 R683G/E864K double mutation demonstrated resistance to NVP-BVB808 in culture (PMID: 22271575). 22271575
JAK2 over exp triple-receptor negative breast cancer sensitive NVP-BSK805 + Paclitaxel Preclinical - Pdx Actionable In a preclinical study, NVP-BSK805 with Abraxane (paclitaxel) inhibited tumor growth in patient-derived xenograft models of triple-negative breast cancer with JAK2 overexpression (PMID: 27075627). 27075627
JAK2 over exp Advanced Solid Tumor sensitive Ruxolitinib + TGX-221 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and TGX-221 synergistically inhibited growth of transformed cell lines over expressing wild-type Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp Advanced Solid Tumor sensitive Ruxolitinib + ZSTK474 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and ZSTK474 synergistically inhibited growth of transformed cell lines over expressing wild-type Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp Advanced Solid Tumor sensitive BEZ235 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and BEZ235 synergistically inhibited growth of transformed cell lines over expressing wild-type Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp Advanced Solid Tumor sensitive Pictilisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Pictilisib (GDC-0941) synergistically inhibited growth of transformed cell lines over expressing wild-type Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp Advanced Solid Tumor sensitive Ruxolitinib + ZSTK474 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and ZSTK474 synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp Advanced Solid Tumor sensitive Pictilisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Pictilisib (GDC-0941) synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp Advanced Solid Tumor sensitive Ruxolitinib + TGX-221 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and TGX-221 synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
JAK2 over exp MPL over exp Advanced Solid Tumor sensitive BEZ235 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and BEZ235 synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and Jak2 in cell culture (PMID: 24251790). 24251790
ETV6-JAK2 JAK2 V881A hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the V881A mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 V617F JAK2 R938L hematologic cancer resistant Lestaurtinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 R938L double mutation demonstrated resistance to lestauranib in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 R938L hematologic cancer resistant AZD1480 Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 R938L double mutation demonstrated resistance to AZD1480 in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 R938L hematologic cancer resistant SAR302503 Preclinical - Cell culture Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 R938L double mutation demonstrated resistance to fedratinib (SAR302503) in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 R938L hematologic cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 R938L double mutation demonstrated resistance to Jakafi (Ruxolitinib) in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 R938L hematologic cancer resistant Momelotinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 R938L double mutation demonstrated resistance to Momelotinib (CYT387) in culture (PMID: 21926964). 21926964
ETV6-JAK2 JAK2 N909K hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the N909K mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
ETV6 - JAK2 JAK2 G935R hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the G935R mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 V617F JAK2 G935R hematologic cancer resistant NVP-BSK805 Preclinical - Cell culture Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 G935R double mutation demonstrated resistance to NVP-BSK805 in culture (PMID: 22271575). 22271575
JAK2 V617F JAK2 G935R hematologic cancer resistant NVP-BVB808 Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 G935R double mutation demonstrated resistance to NVP-BVB808 in culture (PMID: 22271575). 22271575
JAK2 V617F JAK2 G935R hematologic cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 G935R double mutation demonstrated resistance to Jakafi (Ruxolitinib) in culture (PMID: 22271575). 22271575
JAK2 V617F JAK2 I960V hematologic cancer resistant Momelotinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 I960V double mutation demonstrated resistance to Momelotinib in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 I960V hematologic cancer resistant SAR302503 Preclinical - Cell culture Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 I960V double mutation demonstrated resistance to Fedratinib (SAR302503) in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 I960V hematologic cancer resistant AZD1480 Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 I960V double mutation demonstrated resistance to AZD1480 in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 I960V hematologic cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 I960V double mutation demonstrated resistance to Jakafi (Ruxolitinib) in culture (PMID: 21926964). 21926964
JAK2 V617F JAK2 I960V hematologic cancer resistant Lestaurtinib Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 I960V double mutation demonstrated resistance to Lestauranib in culture (PMID: 21926964). 21926964
ETV6 - JAK2 JAK2 E864K hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the E864K mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 V617F JAK2 E864K hematologic cancer resistant NVP-BVB808 Preclinical Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 E864K double mutation demonstrated resistance to NVP-BVB808 in culture (PMID: 22271575). 22271575
JAK2 V617F JAK2 E864K hematologic cancer resistant NVP-BSK805 Preclinical - Cell culture Actionable In a preclinical study, immune cells expressing the JAK2 V617F and JAK2 E864K double mutation demonstrated resistance to NVP-BSK805 in culture (PMID: 22271575). 22271575
JAK2 amp triple-receptor negative breast cancer sensitive NVP-BSK805 + Paclitaxel Preclinical - Pdx Actionable In a preclinical study, NVP-BSK805 with Abraxane (paclitaxel) inhibited tumor growth in triple-negative breast cancer patient-derived xenograft models with JAK2 amplification (PMID: 27075627). 27075627
JAK2 amp triple-receptor negative breast cancer sensitive NVP-BSK805 Preclinical - Pdx Actionable In a preclinical study, NVP-BSK805 inhibited tumor growth in triple-negative breast cancer patient-derived xenograft models harboring JAK2 amplification (PMID: 27075627). 27075627
ETV6 - JAK2 JAK2 P1057S hematologic cancer resistant Pyridone 6 Preclinical Actionable In a preclinical study, immune cells expressing ETV6-JAK2 with the P1057S mutation demonstrated resistance to Pyridone 6 (CMP6) in culture (PMID: 22916261). 22916261
JAK2 Y931C cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, cells harboring JAK2 Y931C displayed resistance to ATP-competetive JAK inhibitors, such as Jakafi (Ruxolitinib) (PMID: 21393331). 21393331
JAK2 V617F JAK2 Y931C cancer resistant Ruxolitinib Preclinical Actionable In a preclinical study, cells harboring the JAK2 V617F/Y931C double mutation displayed resistance to ATP-competetive JAK inhibitors, such as Jakafi (Ruxolitinib) (PMID: 21393331). 21393331
JAK2 R867Q hematologic cancer decreased response Luminespib Preclinical Actionable In a preclinical study, immune cells expressing JAK2 R867Q demonstrated decreased response to Luminespib (AUY922) in culture (PMID: 24398328). 24398328
JAK2 R867Q hematologic cancer decreased response AZ960 Preclinical Actionable In a preclinical study, immune cells expressing JAK2 R867Q demonstrated decreased response to AZ960 in culture (PMID: 24398328). 24398328
JAK2 R867Q hematologic cancer decreased response Momelotinib Preclinical Actionable In a preclinical study, immune cells expressing JAK2 R867Q demonstrated decreased response to Momelotinib (CYT387) in culture (PMID: 24398328). 24398328
JAK2 R867Q hematologic cancer decreased response SAR302503 Preclinical - Cell culture Actionable In a preclinical study, immune cells expressing JAK2 R867Q demonstrated decreased response to Fedratinib (SAR302503) in culture (PMID: 24398328). 24398328
JAK2 R867Q hematologic cancer decreased response Ruxolitinib Preclinical Actionable In a preclinical study, immune cells expressing JAK2 R867Q demonstrated decreased response to Jakafi (ruxolitinib) in culture (PMID: 24398328). 24398328
JAK2 V617F MPL wild-type Advanced Solid Tumor sensitive Pictilisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Pictilisib (GDC-0941) synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F MPL wild-type Advanced Solid Tumor sensitive Ruxolitinib + ZSTK474 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and ZSTK474 synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F MPL wild-type Advanced Solid Tumor sensitive BEZ235 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and BEZ235 synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F MPL wild-type Advanced Solid Tumor sensitive Ruxolitinib + TGX-221 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and TGX-221 synergistically inhibited growth of transformed cell lines over expressing wild-type Mpl and JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F myeloid leukemia resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed mouse myeloid cells over expressing JAK2 V617F were resistant to Gleevec (imatinib) in culture (PMID: 21224473). 21224473
JAK2 V617F Advanced Solid Tumor sensitive Pictilisib + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and Pictilisib (GDC-0941) synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F essential thrombocythemia sensitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited proliferation and induced apoptosis in an essential thrombocythemia cell line harboring JAK2 V617F in culture (PMID: 22015772). 22015772
JAK2 V617F bone marrow cancer sensitive Ruxolitinib + SGI-1776 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) worked synergistically with SGI-1776 to inhibit proliferation of myeloproliferative cancer cell lines harboring JAK2 V617F in culture (PMID: 26472029). 26472029
JAK2 V617F bone marrow cancer decreased response SGI-1776 Preclinical Actionable In a preclinical study, myeloproliferative cancer cell lines harboring JAK2 V617F demonstrated reduced sensitivity to SGI-1776 induced growth inhibition in culture (PMID: 26472029). 26472029
JAK2 V617F myeloproliferative neoplasm predicted - sensitive LY2784544 Phase I Actionable In a Phase I trial, treatment with Gandotinib (LY2784544) demonstrated safety in myeloproliferative neoplasm patients harboring JAK2 V617F and resulted in clinical improvement as best response in 29% (9/31) patients with myelofibrosis (PMID: 28934680). 28934680
JAK2 V617F acute myeloid leukemia sensitive Go6976 Preclinical Actionable In a preclinical study, Go 6976 inhibited proliferation of cultured acute myeloid leukemia cells expressing the JAK2 V617F mutation (PMID: 16956345). 16956345
JAK2 V617F bone marrow cancer sensitive AZD1208 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) worked synergistically with AZD1208 to inhibit proliferation of myeloproliferative cancer cell lines harboring JAK2 V617F in culture (PMID: 26472029). 26472029
JAK2 V617F hematologic cancer sensitive SHP099 Preclinical - Cell culture Actionable In a preclinical study, SHP099 inhibited proliferation of a hematopoietic cancer cell line harboring JAK2 V617F in culture (PMID: 27362227). 27362227
JAK2 V617F Advanced Solid Tumor sensitive Ruxolitinib + ZSTK474 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and ZSTK474 synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F acute myeloid leukemia sensitive RP6530 + Ruxolitinib Preclinical Actionable In a preclinical study, RP6530 worked synergistically with Jakafi (ruxolitinib) to inhibit proliferation of Jakafi (ruxolitinib)-resistant erythroleukemia cell lines carrying JAK2 V617F mutation ( Cancer Res August 1, 2015 75; 2704 ). detail...
JAK2 V617F myelofibrosis not applicable N/A Guideline Prognostic JAK2 V617F is associated with intermediate prognosis and higher risk of thrombosis when compared to the presence of CALR mutations in patients with primary myelofibrosis (NCCN.org). detail...
JAK2 V617F myeloproliferative neoplasm sensitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited colony growth in myeloproliferative neoplasm patient-derived hematopoetic progenitor cells harboring JAK2 V617F in culture (PMID: 22015772). 22015772
JAK2 V617F Advanced Solid Tumor sensitive BEZ235 + Ruxolitinib Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and BEZ235 synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F bone marrow cancer sensitive CHZ868 Preclinical Actionable In a preclinical study, CHZ868 inhibited proliferation of myeloproliferative neoplasm cells harboring JAK2 V617F , including cells with decreased response to Type I JAK inhibitors following chronic exposure, and decreased mutant allele burden in a mouse polycythemia vera model expressing JAK2 V617F (PMID: 26175413). 26175413
JAK2 V617F bone marrow cancer decreased response AZD1208 Preclinical Actionable In a preclinical study, myeloproliferative cancer cell lines harboring JAK2 V617F demonstrated reduced sensitivity to AZD1208 induced growth inhibition in culture (PMID: 26472029). 26472029
JAK2 V617F hematologic cancer sensitive BMS-911543 Preclinical - Cell culture Actionable In a preclinical study, BMS-911543 inhibited proliferation of transformed cells expressing JAK2 V617F in culture (PMID: 22015772). 22015772
JAK2 V617F hematologic cancer sensitive NS-018 Preclinical Actionable In a preclinical study, cells expressing JAK2 V617F were sensitive to treatment with NS-108, demonstrating cell growth inhibition and increased apoptotic activity in culture and improved survival in transgenic mouse models (PMID: 22829185). 22829185
JAK2 V617F Advanced Solid Tumor sensitive Ruxolitinib + TGX-221 Preclinical Actionable In a preclinical study, Jakafi (ruxolitinib) and TGX-221 synergistically inhibited growth of transformed cell lines over expressing JAK2 V617F in cell culture (PMID: 24251790). 24251790
JAK2 V617F acute myeloid leukemia sensitive A-1155463 Preclinical Actionable In a preclinical study, acute myeloid leukemia cells harboring JAK2 V617F demonstrated sensitivity to A-1155463 in culture (PMID: 25787766). 25787766