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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).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
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, Oct 2019).
A676V missense unknown JAK2 A676V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). A676V has been identified in sequencing studies (PMID: 28292439), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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.
amp none no effect JAK2 amp indicates an increased number of copies of the JAK2 gene. However, the mechanism causing the increase is unspecified.
C480F missense unknown JAK2 C480F lies within the atypical SH2 domain of the Jak2 protein (UniProt.org). C480F 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, Oct 2019).
C618R missense gain of function JAK2 C618R lies within the protein kinase domain 1 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).
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, Oct 2019).
D319N missense unknown JAK2 D319N lies within the FERM domain of the Jak2 protein (UniProt.org). D319N has been identified in sequencing studies (PMID: 26674132, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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, Oct 2019).
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, Oct 2019).
D620E missense unknown JAK2 D620E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). D620E has been identified in the scientific literature (PMID: 16871281, PMID: 17008888), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
D873N missense gain of function - predicted JAK2 D873N lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). D873N results in increased Jak2 and Stat5 phoshorylation, and transformation of cells based on mouse Jak2 D873N in culture (PMID: 19470474), and therefore, is predicted to lead a gain of Jak2 protein 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: 27561722, PMID: 22675565), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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 and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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, Oct 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, Oct 2019).
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.
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, Oct 2019).
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.
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: 31742675, PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020).
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.
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, Oct 2019).
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, Oct 2019).
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, Oct 2019).
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.
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).
E864K missense gain of function - predicted JAK2 E864K lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). E864K results in increased Jak2 and Stat5 phosphorylation and prevents apoptosis in the presence of a Jak inhibitor (PMID: 22916261), and has been described as a secondary drug resistance mutation in the context of other Jak2 activating mutations (PMID: 22916261, PMID: 22271575), and therefore, is predicted to lead to a gain of Jak2 protein function. Y
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.
E985K missense unknown JAK2 E985K lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). E985K has been demonstrated to confer resistance to Jak inhibitors in the context of complex JAK2 mutations (PMID: 21926964), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020). Y
E987D missense unknown JAK2 E987D lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). E987D has been demonstrated to confer resistance to Jak inhibitors in the context of complex JAK2 mutations (PMID: 26419724), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020). Y
F1061W missense unknown JAK2 F1061W lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). F1061W has been demonstrated to confer Jak2 inhibitor resistance in combination with V617F and Y931C in culture (PMID: 26419724), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020).
F439S missense unknown JAK2 F439S lies within the atypical SH2 domain of the Jak2 protein (UniProt.org). F439S has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
F537_K539delinsL indel gain of function JAK2 F537_K539delinsL results in a deletion of three amino acids from 537 to 539 of the Jak2 protein, combined with the insertion of a leucine (L) (UniProt.org). F537_K539delinsL confers a gain of function to the Jak2 protein as demonstrated by increased proliferation, Jak2 phosphorylation, and downstream Stat5 phosphorylation in cell culture (PMID: 17267906).
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, Oct 2019).
F556V missense gain of function - predicted JAK2 F556V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). F556V results in cytokine-independent phosphorylation of Stat5 and hypersensitivity to the Tpo in culture (PMID: 26423830), and therefore, is predicted to lead to a gain of Jak2 protein function.
F560S missense unknown JAK2 F560S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). F560S has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
F694L missense gain of function JAK2 F694L lies within the protein kinase domain 1 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).
F694S missense gain of function JAK2 F694S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). F694S results in increased kinase activity, and activation of Stat5, Erk, and Akt in cell culture (PMID: 19638629).
fusion fusion unknown JAK2 fusion indicates a fusion of the JAK2 gene, but the fusion partner is unknown.
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, Feb 2020).
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, Oct 2019).
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, Oct 2019).
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, Feb 2020).
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).
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, Feb 2020).
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, Feb 2020).
G571S missense no effect - predicted JAK2 G571S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). G571S does not demonstrate ligand-independent JAK2-STAT5 signaling and results in cell viability similar to wild-type Jak2 in culture (PMID: 26423830), and therefore, is predicted to have no effect on Jak2 protein function.
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.
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, Oct 2019). Y
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, Feb 2020).
G935R missense gain of function - predicted JAK2 G935R lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). G935R results in increased Jak2 and Stat5 phosphorylation, and prevents apoptosis in the presence of a Jak inhibitor (PMID: 22916261), and has been described as a secondary drug resistance mutation in the context of other Jak2 activating mutations (PMID: 22271575, PMID: 22916261), and therefore, is predicted to lead to a gain of Jak2 protein function. Y
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).
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).
H538Q missense unknown JAK2 H538Q does not lie within any known functional domains of the Jak2 protein (UniProt.org). H538Q results in increased proliferation, Jak2 phosphorylation, and downstream Stat5 phosphorylation in combination with K539L in culture (PMID: 22584586, PMID: 17267906), but has not been individually characterized and therefore, its effect on Jak2 protein function is unknown.
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, PMID: 22642932), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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).
H574R missense gain of function JAK2 H574R lies within the protein kinase domain 1 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 in culture (PMID: 26216197).
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, Oct 2019).
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, Oct 2019).
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, Oct 2019).
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, Feb 2020).
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, Feb 2020).
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, Feb 2020).
I404N missense unknown JAK2 I404N lies within the atypical SH2 domain of the Jak2 protein (UniProt.org). I404N has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020).
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, Oct 2019).
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, Oct 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, PMID: 17984312, PMID: 17914411), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 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, Oct 2019).
I682D missense gain of function - predicted JAK2 I682D lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I682D demonstrates increased enzyme activity and decreased structural stability in an in vitro assay (PMID: 25940527), and therefore, is predicted to lead to a gain of Jak2 protein function.
I682F missense gain of function - predicted JAK2 I682F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I682F demonstrates increased enzyme activity and decreased structural stability in an in vitro assay (PMID: 25940527), and therefore, is predicted to lead to a gain of Jak2 protein function.
I682G missense gain of function - predicted JAK2 I682G lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I682G demonstrates increased enzyme activity and decreased structural stability in an in vitro assay (PMID: 25940527), and therefore, is predicted to lead to a gain of Jak2 protein function.
I682L missense no effect - predicted JAK2 I682L lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I682L demonstrates enzyme kinetics and structural stability similar to wild-type Jak2 in in vitro assays (PMID: 25940527), and therefore, is predicted to have no effect on Jak2 protein function.
I682S missense gain of function - predicted JAK2 I682S lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I682S demonstrates increased enzyme activity and decreased structural stability in in vitro assays (PMID: 25940527), and therefore, is predicted to lead to a gain of Jak2 protein function.
I682T missense no effect - predicted JAK2 I682T lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). I682T results in the activation of Stat5 similar to wild-type Jak2 in a reporter assay (PMID: 26216197), and therefore, is predicted to have no effect on Jak2 protein function.
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, Feb 2020).
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, Oct 2019). Y
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.
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, Oct 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.
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).
K539L missense gain of function JAK2 K539L does not lie within any known functional domains of the Jak2 protein (UniProt.org). 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).
K607E missense gain of function JAK2 K607E lies within the protein kinase domain 1 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).
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).
K882R missense loss of function JAK2 K882R lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). K882R demonstrates increased protein stability, and loss of kinase activity, Epo-induced activation of Jak2, and reduced cytokine-induced colony formation compared to wild-type Jak2 in culture (PMID: 17024180, PMID: 18160720).
K912T missense unknown JAK2 K912T lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). K912T 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, Oct 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, Oct 2019).
L113V missense unknown JAK2 L113V lies within the FERM domain and cytokine/interferon/growth hormone receptors-interacting region 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, Feb 2020).
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, Feb 2020).
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 increased ligand-dependent cell viability as compared to wild-type Jak2 in culture (PMID: 27647865).
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, Oct 2019).
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, Oct 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, Feb 2020).
L583_A586delinsP indel unknown JAK2 L583_A586delinsP results in a deletion of four amino acids from amino acids 583 to 586 of the Jak2 protein, combined with the insertion of a proline (P) at the same site (UniProt.org). L583_A586delinsP has been identified in the scientific literature (PMID: 31697804), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jan 2020).
L583_A586delinsQ indel unknown JAK2 L583_A586delinsQ results in a deletion of four amino acids from amino acids 583 to 586 of the Jak2 protein, combined with the insertion of a glutamine (Q) at the same site (UniProt.org). L583_A586delinsQ has been identified in the scientific literature (PMID: 31697804), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Jan 2020).
L583_A586delinsS indel gain of function JAK2 L583_A586delinsS results in a deletion of four amino acids from amino acids 583 to 586 of the Jak2 protein, combined with the insertion of a serine (S) at the same site (UniProt.org). L583_A586delinsS confers a gain of function to the Jak2 protein as indicated by ligand-independent cell growth and activation of Stat5, Erk1/2, and common beta chain-associated cytokine receptors, and has been demonstrated to confer resistance to Jak2 inhibitors in cultured cells (PMID: 31697804). Y
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.
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.
L611S missense gain of function JAK2 L611S lies within the protein kinase domain 1 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).
L611V missense no effect - predicted JAK2 L611V lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L611V results in Jak2, Stat5, and Akt phosphorylation levels comparable to wild-type Jak2 in culture, however, L611V demonstrates constitutive activation of Jak2 when co-mutated with V617F (PMID: 20182460), and therefore, is predicted to have no effect on Jak2 protein function.
L624P missense unknown JAK2 L624P lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L624P is predicted to result in a conformational change in the Jak2 protein by computational modeling (PMID: 19744331), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
L634P missense no effect - predicted JAK2 L634P lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). L634P results in activation of Stat5 similar to wild-type in a reporter assay (PMID: 26216197), and therefore, is predicted to have no effect on 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, Feb 2020).
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: 31742675, PMID: 30811597, PMID: 27997549), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020).
L983F missense unknown JAK2 L983F lies within the active site of the Jak2 protein (PMID: 26419724). L983F confers resistance to a Jak inhibitor, and demonstrates decreased cell proliferation in combination with JAK2 V617F in culture (PMID: 26419724), but has not been individually characterized and therefore, its effect on Jak2 protein function is unknown. Y
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).
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), and therefore, its effect on Jak2 protein function is unknown.
M929I missense gain of function - predicted JAK2 M929I is a gatekeeper mutation that lies within the protein kinase domain 2 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
mutant unknown unknown JAK2 mutant indicates an unspecified mutation in the JAK2 gene.
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, Dec 2019).
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, Feb 2020).
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 protein function is unknown (PubMed, Oct 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, Oct 2019).
N542_E543del deletion gain of function JAK2 N542_E543del is an exon 12 deletion that results in the deletion of two amino acids 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).
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.
N622I missense gain of function JAK2 N622I lies within the protein kinase domain 1 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).
N909K missense gain of function - predicted JAK2 N909K lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). N909K results in 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), and therefore, is predicted to lead to a gain of Jak2 protein function. Y
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).
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.
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: 22916261), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019). Y
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).
P870L missense unknown JAK2 P870L lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). P870L has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
P870S missense unknown JAK2 P870S lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). P870S has been identified in sequencing studies (PMID: 23890154), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
P933R missense gain of function - predicted JAK2 P933R lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). D873N results in increased Jak2 and Stat5 phoshorylation, and transformation of cells based on mouse Jak2 D873N in culture (PMID: 19470474), and therefore, is predicted to lead to a gain of Jak2 protein function.
R1063H missense gain of function JAK2 R1063H lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). R1063H results in increased Epo-induced growth, Stat5 phosphorylation and transcriptional activity, and Epo-dependent and independent hematopoietic colony formation in-vitro as compared to wild-type Jak2 in culture (PMID: 27389715).
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, Oct 2019). Y
R133Q missense unknown JAK2 R133Q lies within the FERM domain of the Jak2 protein (UniProt.org). R133Q 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, Oct 2019).
R215Q missense unknown JAK2 R215Q lies within the FERM domain of the Jak2 protein (UniProt.org). R215Q has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 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).
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).
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.
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.
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: 29420467, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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, PMID: 23810504, PMID: 17920755), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
R564G missense unknown JAK2 R564G lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R564G has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 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, Oct 2019).
R564Q missense gain of function JAK2 R564Q lies within the protein kinase domain 1 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).
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, Oct 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 it 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), and therefore, its effect on Jak2 protein function is unknown.
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.
R683E missense gain of function - predicted JAK2 R683E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R683E results in increased Stat5 binding and enhanced enzyme kinetics as compared to wild-type Jak2 in in vitro assays (PMID: 23748007), and therefore, is predicted to lead to a gain of Jak2 protein function.
R683G missense gain of function JAK2 R683G lies within the protein kinase domain 1 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 results in cytokine-independent transformation in cell culture (PMID: 26216197, PMID: 18805579).
R683H missense no effect - predicted JAK2 R683H lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R683H results in enzyme kinetics and binding to Stat5 similar to wild-type Jak2 in in vitro assays (PMID: 23748007), and therefore, is predicted to have no effect on Jak2 protein function.
R683K missense unknown JAK2 R683K lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R683K demonstrates enzyme activity and Stat5 binding similar to wild-type Jak2 in one study (PMID: 23748007), but results in constitutive Jak2 and Stat5 phosphorylation, and supports cytokine-independent cell growth in another study (PMID: 18805579), and therefore, its effect on Jak2 protein function is unknown.
R683S missense gain of function JAK2 R683S lies within the protein kinase domain 1 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 in culture (PMID: 18805579, PMID: 19638629).
R683T missense gain of function - predicted JAK2 R683T lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). R683E has not been biochemically characterized, but results in transformation of cells in culture (PMID: 26419724), and therefore, is predicted to lead to a gain of Jak2 protein function.
R867Q missense gain of function JAK2 R867Q lies within the 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).
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, Oct 2019). Y
R938Q missense gain of function JAK2 R938Q lies within the 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
R971G missense unknown JAK2 R971G lies within the activation-loop of the Jak2 protein (PMID: 26419724). R971G confers resistance to a Jak inhibitor, and demonstrates reduced cell proliferation in combination with JAK2 V617F in culture (PMID: 26419724), but has not been individually characterized and therefore, its effect on Jak2 protein function is unknown. Y
R975G missense gain of function - predicted JAK2 R975G lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). R975G results in 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), and therefore, is predicted to lead to a gain of Jak2 protein function. Y
rearrange unknown unknown JAK2 rearrange indicates an unspecified rearrangement of the JAK2 gene.
S1025C missense unknown JAK2 S1025C lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). S1025C has been demonstrated to confer Jak2 inhibitor resistance in combination with V617F and Y931C in culture (PMID: 26419724), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020). Y
S126N missense unknown JAK2 S126N lies within the FERM domain of the Jak2 protein (UniProt.org). S126N has not been characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 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, Feb 2020).
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.
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 assay and is transforming in cell culture (PMID: 19638629), and therefore, its effect on Jak2 protein function is unknown.
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, Feb 2020).
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 protein function is unknown (PubMed, Oct 2019).
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.
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, Feb 2020).
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 protein function is unknown (PubMed, Oct 2019).
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).
T246I missense unknown JAK2 T246I lies within the FERM domain of the Jak2 protein (UniProt.org). T246I has been identified in sequencing studies (PMID: 31742675, PMID: 30811597), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020).
T514M missense unknown JAK2 T514M lies within a linker region of the Jak2 protein (PMID: 29685781). T514M has been identified in sequencing studies (PMID: 30239046, PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
T875N missense gain of function JAK2 T875N lies within the 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, PMID: 31299252).
V1075F missense unknown JAK2 V1075F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). V1075F has been demonstrated to confer Jak2 inhibitor resistance in combination with V617F and Y931C in culture (PMID: 26419724), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020). Y
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).
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, Feb 2020).
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, Oct 2019).
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: 24728327, PMID: 19074595), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
V617F missense gain of function JAK2 V617F lies within the protein kinase domain 1 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).
V617I missense gain of function - predicted JAK2 V617I lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). V617I results in increased kinase activity through Jak2 autophosphorylation (PMID: 19638629), and therefore, is predicted to lead to a gain of Jak2 protein function.
V625F missense gain of function JAK2 V625F lies within the protein kinase domain 1 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 Interleukin-3 as indicated by increased cell viability in culture (PMID: 26423830).
V881A missense gain of function - predicted JAK2 V881A lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). V881A results in 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), and therefore, is predicted to lead to a gain of Jak2 protein function. Y
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.
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, Oct 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, Oct 2019).
wild-type none no effect Wild-type JAK2 indicates that no mutation has been detected within the JAK2 gene.
Y1007F missense loss of function JAK2 Y1007F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1007F demonstrates increased protein stability, and loss of kinase activity, Epo-induced activation of Jak2 and reduced cytokine-induced colony formation compared to wild-type Jak2 in culture (PMID: 17024180, PMID: 18160720).
Y1008F missense no effect JAK2 Y1008F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1008F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y1021F missense no effect JAK2 Y1021F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1021F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y1045F missense no effect JAK2 Y1045F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1045F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y1045W missense unknown JAK2 Y1045W lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1045W has been demonstrated to confer Jak2 inhibitor resistance in combination with V617F and Y931C in culture (PMID: 26419724), but has not been biochemically characterized and therefore, its effect on Jak2 protein function is unknown (PubMed, Feb 2020). Y
Y1050F missense no effect JAK2 Y1050F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1050F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y1099F missense no effect JAK2 Y1099F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y1099F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
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, Oct 2019).
Y317H missense gain of function JAK2 Y317H lies within 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).
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).
Y570E missense no effect JAK2 Y570E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y570E results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y570F missense no effect JAK2 Y570F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y570F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y590E missense no effect JAK2 Y590E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y590E results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y590F missense no effect JAK2 Y590F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y590F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y613E missense gain of function JAK2 Y613E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y613E results in constitutive activation of Jak2 and restores colony formation in cells lacking Jak2 in the absence of Epo, but does not restore colony formation in the absence of Epo/IL3 in culture (PMID: 18160720).
Y613F missense no effect JAK2 Y613F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y613F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
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.
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, Oct 2019).
Y62C missense unknown JAK2 Y62C lies within the FERM domain of the Jak2 protein (UniProt.org). Y62C has not been characterized in the scientific literature and therefore, its effect on Jak2 protein function is unknown (PubMed, Oct 2019).
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, Feb 2020).
Y637E missense no effect JAK2 Y637E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y637E results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y637F missense no effect JAK2 Y637F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y637F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y766E missense loss of function - predicted JAK2 Y766E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y766E results in Epo-induced activation of Jak2, but reduced cytokine-induced colony formation compared to wild-type Jak2 in culture (PMID: 18160720), and therefore, is predicted to lead to a loss of Jak2 protein function.
Y766F missense no effect JAK2 Y766F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y766F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y790E missense no effect JAK2 Y790E lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y790E results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y790F missense no effect JAK2 Y790F lies within the protein kinase domain 1 of the Jak2 protein (UniProt.org). Y790F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
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, Oct 2019).
Y813F missense no effect JAK2 Y813F lies within the kinase domain of the Jak2 protein (PMID: 18160720). Y813F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y868F missense no effect JAK2 Y868F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y868F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y913F missense no effect JAK2 Y913F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y913F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y918F missense no effect JAK2 Y918F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y918F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
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, Oct 2019). Y
Y931C missense gain of function JAK2 Y931C lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y931C results in increased phosphorylation of Jak2 and Stat5, is transforming in cell culture, and confers resistance to Jak inhibitors (PMID: 21393331, PMID: 26419724). Y
Y931F missense unknown JAK2 Y931F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y931F results in Epo-induced activation of Jak2 and colony formation similar to wild-type Jak2 in culture (PMID: 18160720), but is transforming in culture (PMID: 26419724), and therefore, its effect on Jak2 protein function is unknown.
Y934F missense no effect JAK2 Y934F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y934F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y940F missense no effect JAK2 Y940F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y940F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y956F missense no effect JAK2 Y956F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y956F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y966F missense no effect JAK2 Y966F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y966F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
Y972F missense no effect JAK2 Y972F lies within the protein kinase domain 2 of the Jak2 protein (UniProt.org). Y972F results in Epo-induced activation of Jak2 and cytokine-induced colony formation similar to wild-type Jak2 in culture (PMID: 18160720).
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).