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Gene Symbol JAK1
Synonyms AIIDE | JAK1A | JAK1B | JTK3
Gene Description JAK1, Janus kinase 1, is a non-receptor protein tyrosine kinase involved in the interferon-alpha/beta/gamma pathway and is a member of the JAK/STAT signaling pathway (PMID: 15575979) and plays a role in the immune response (PMID: 31892268). JAK1 gain of function mutations have been identified in T-cell neoplasms (PMID: 30079384) and loss of function mutations are associated with high mutational burden and microsatellite instability (PMID: 29121062).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1086S missense no effect JAK1 A1086S lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). A1086S results in phosphorylation of Jak1, Stat3, and Stat5 to similar levels of wild-type Jak1, and is not transforming in cell culture (PMID: 26701727).
A283V missense unknown JAK1 A283V lies within the FERM domain of the Jak1 protein (UniProt.org). A283V has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
A634D missense gain of function JAK1 A634D lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). A634D results in constitutive activation of Stat3 and Stat5 signaling, and is transforming in cell culture (PMID: 18362173, PMID: 19139102, PMID: 21551237).
A723D missense gain of function JAK1 A723D lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). A723D results in constitutive phosphorylation of Jak1 and Stat5 in cell culture (PMID: 21393331, PMID: 24735922).
act mut unknown gain of function JAK1 act mut indicates that this variant results in a gain of function in the Jak1 protein. However, the specific amino acid change has not been identified.
amp none no effect JAK1 amplification indicates an increased number of copies of the JAK1 gene. However, the mechanism causing the increase is unspecified.
C1131Y missense unknown JAK1 C1131Y lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). C1131Y has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
C657R missense unknown JAK1 C657R lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). C657R has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
D604Y missense gain of function - predicted JAK1 D604Y lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). D604Y (corresponds to D603Y in mouse) results in cytokine-independent proliferation in cell culture (PMID: 25855603), and therefore, is predicted to lead to a gain of Jak1 protein function.
D775N missense loss of function JAK1 D775N lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). D775N results in failure to activate Jak1 and Stat signaling and upregulate PD-L1 expression in response to interferon alpha, beta, and gamma in cell culture (PMID: 27903500).
D82A missense unknown JAK1 D82A lies within the FERM domain of the Jak1 protein (UniProt.org). D82A in combination with Y81A impairs binding to gp130 (PMID: 11468294), but has not been individually characterized, and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
D831E missense unknown JAK1 D831E lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). D831E has been identified in the scientific literature (PMID: 27369867), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022)
D895H missense gain of function JAK1 D895H lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). D895H results in constitutive Jak1 phosphorylation, increased phosphorylation of Stat5 and Erk in culture, and tumor formation in mouse models (PMID: 21393331).
dec exp none no effect JAK1 dec exp indicates decreased expression of the Jak1 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
del deletion loss of function JAK1 del indicates a deletion of the JAK1 gene.
E1051Q missense unknown JAK1 E1051Q lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). E1051Q has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
E275D missense unknown JAK1 E275D lies within the FERM domain of the Jak1 protein (UniProt.org). E275D has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
E483D missense no effect JAK1 E483D lies within the SH2 domain of the Jak1 protein (UniProt.org). E483D results in phosphorylation of Jak1, Stat3, and Stat5 to similar levels of wild-type Jak1, and is not transforming in cell culture (PMID: 26701727).
E637K missense unknown JAK1 E637K lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). E637K has been identified in sequencing studies (PMID: 20668451), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, Aug 2022).
E668* nonsense loss of function - predicted JAK1 E668* results in a premature truncation of the Jak1 protein at amino acid 668 of 1154 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), E668* is predicted to lead to a loss of Jak1 protein function.
E668Q missense unknown JAK1 E668Q lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). E668Q has been identified in the scientific literature (PMID: 26819051), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, Aug 2022).
E897K missense gain of function - predicted JAK1 E897K lies within the protein kinase domain 2 of the Jak1 protein (UniProt). E897K results in constitutive Jak1 phosphorylation, and increased phosphorylation of Stat5 and Erk in culture (PMID: 21393331), and therefore, is predicted to lead a gain of Jak1 protein function.
E966V missense loss of function JAK1 E966V lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). E966V results in reduced Jak1 phosphorylation and is not transforming in culture (PMID: 19176360).
E966_K989del deletion no effect - predicted JAK1 E966_K989del results in the deletion of 24 amino acids in the protein kinase domain 2 of the Jak1 protein from amino acids 966 to 989 (UniProt.org). E966_K989del results in similar Jak1 phosphorylation to wild-type Jak1 and is not transforming in culture (PMID: 19176360), and therefore, is predicted to have no effect on Jak1 protein function.
F635V missense gain of function JAK1 F635V lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). F635V results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331).
F636del deletion unknown JAK1 F636del results in the deletion of on amino acid in the protein kinase domain 1 of the Jak1 protein at amino acids 636 (UniProt.org). F636del retains catalytic activity, but results in decreased Jak1 autophosphorylation and Stat3 phosphorylation compared to wild-type Jak1 and is not transforming in cell culture (PMID: 32094462), and therefore, its effect on Jak1 protein function is unknown.
F734L missense gain of function - predicted JAK1 F734L lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). F734L results in constitutive Jak1 phosphorylation, and increased phosphorylation of Stat5 and Erk in culture (PMID: 21393331), and therefore, is predicted to lead a gain of Jak1 protein function.
F779L missense unknown JAK1 F779L lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). F779L is predicted to be activating based on structural modeling (PMID: 27082517), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
F837Lfs*25 frameshift unknown JAK1 F837Lfs*25 indicates a shift in the reading frame starting at amino acid 837 and terminating 25 residues downstream causing a premature truncation of the 1154 amino acid Jak1 protein (UniProt.org). F837Lfs*25 has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
F958C missense gain of function JAK1 F958C lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). F958C results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, transformation of cultured cells, and confers resistance to Jak inhibitors in culture (PMID: 21393331). Y
F958L missense gain of function - predicted JAK1 F958L lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). F958L results in constitutive Jak1 phosphorylation, increased phosphorylation of Stat5 and Erk in culture, and confers resistance to Jak inhibitors in culture (PMID: 21393331), and therefore, is predicted to lead to a gain of Jak1 protein function. Y
F958S missense gain of function JAK1 F958S lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). F958S results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, transformation of cultured cells, and confers resistance to Jak inhibitors in culture (PMID: 21393331, PMID: 20868368). Y
F958V missense gain of function JAK1 F958V lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). F958V results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, transformation of cultured cells, and tumor formation in mouse models, and confers resistance to Jak inhibitors in culture (PMID: 21393331). Y
G1097C missense unknown JAK1 G1097C lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). G1097C has been identified in the scientific literature (PMID: 32188095), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, Jul 2022).
G1097D missense gain of function - predicted JAK1 G1097D lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). G1097D results in increased Jak1 and Stat3 phosphorylation in culture (PMID: 25873174), and therefore, is predicted to lead to a gain of Jak1 protein function.
G1097N missense unknown JAK1 G1097N lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). G1097N has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, Aug 2022).
G511D missense unknown JAK1 G511D lies within the SH2 domain of the Jak1 protein (UniProt.org). G511D has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
G600W missense loss of function JAK1 G600W lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). G600W results in a loss of Stat1 phosphorylation, failure to upregulate Stat1 and Irf1 protein expression, and inability to induce mRNA expression of genes involved in antigen presentation in response to interferon gamma stimulation in patient-derived cells (PMID: 28561041).
G741D missense unknown JAK1 G741D lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). G741D has been identified in sequencing studies (PMID: 27586204), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
G780R missense unknown JAK1 G780R lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). G780R has been identified in sequencing studies (PMID: 28561041), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
G990R missense unknown JAK1 G990R lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). G990R has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
H647Y missense unknown JAK1 H647Y lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). H647Y has been identified in sequencing studies (PMID: 18559588), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
I293F missense unknown JAK1 I293F lies within the FERM domain of the Jak1 protein (UniProt.org). I293F has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
I359M missense unknown JAK1 I359M lies within the FERM domain of the Jak1 protein (UniProt.org). I359M has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
I377K missense unknown JAK1 I377K lies within the FERM domain of the Jak1 protein (UniProt.org). I377K has been identified in sequencing studies (PMID: 23603912), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
I444V missense unknown JAK1 I444V lies within the SH2 domain of the Jak1 protein (UniProt.org). I444V has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
I597F missense unknown JAK1 I597F lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). I597F results in increased basal Stat5 phosphorylation and Stat5 activation in a reporter assay, but demonstrates attenuated response to Il-2 stimulation in culture, and reduced thermal stability (PMID: 31892268), and therefore, its effect on Jak1 protein function is unknown.
I62V missense unknown JAK1 I62V lies within the FERM domain of the Jak1 protein (UniProt.org). I62V has been identified in the scientific literature (PMID: 18362173), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
I631R missense unknown JAK1 I631R lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). I631R has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
inact mut unknown loss of function JAK1 inact mut indicates that this variant results in a loss of function of the Jak1 protein. However, the specific amino acid change has not been identified.
K1026E missense gain of function - predicted JAK1 K1026E lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). K1026E is transforming in culture and promotes tumor formation in mouse models, but results in variable phosphorylation levels of Jak1 and downstream signaling proteins in culture (PMID: 21393331, PMID: 20868368), and therefore, is predicted to lead to a gain of Jak1 protein function.
K142fs frameshift loss of function - predicted JAK1 K142fs results in a change in the amino acid sequence of the Jak1 protein beginning at aa 142 of 1154, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), K142fs is predicted to lead to a loss of Jak1 protein function.
K142Rfs*26 frameshift loss of function - predicted JAK1 K142Rfs*26 indicates a shift in the reading frame starting at amino acid 142and terminating 22 residues downstream causing a premature truncation of the 1154 amino acid Jak1 protein (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), K142Rfs*26 is predicted to lead to a loss of Jak1 protein function.
K204M missense unknown JAK1 K204M lies within the FERM domain of the Jak1 protein (UniProt.org). K204M has been identified in sequencing studies (PMID: 18362173), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
K527N missense unknown JAK1 K527N lies within the SH2 domain of the Jak1 protein (UniProt.org). K527N has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
K616T missense unknown JAK1 K616T lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). K616T has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
K622A missense loss of function JAK1 K622A lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). K622A results in a loss of Jak1 phosphorylation (PMID: 25825724) and decreased basal Stat5 activation in cell culture (PMID: 31892268).
K648N missense gain of function JAK1 K648N lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). K648N results in constitutive Jak1 and Stat3 phosphorylation, and is transforming in cell culture (PMID: 21551237).
K736E missense unknown JAK1 K736E lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). K736E has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
K860fs frameshift loss of function JAK1 K860fs results in a change in the amino acid sequence of the Jak1 protein beginning at aa 860 of 1154, likely resulting in premature truncation of the functional protein (UniProt.org). K860fs results in a loss of Stat1 phosphorylation and failure to upregulate the expression of Irf1, Lmp2, and Tap1 in response to interferon gamma stimulation in culture (PMID: 24154688).
K860N missense unknown JAK1 K860N does not lie within any known functional domains of the Jak1 protein (UniProt.org). K860N has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, Jun 2022).
K860Nfs*16 frameshift loss of function - predicted JAK1 K860Nfs*16 indicates a shift in the reading frame starting at amino acid 860 and terminating 16 residues downstream causing a premature truncation of the 1154 amino acid Jak1 protein (UniProt.org). K860Nfs*16 has not been biochemically characterized, however, due to the effects of a frameshift mutation occurring at K860 (PMID: 24154688), is predicted to lead to a loss of Jak1 protein function.
K908T missense unknown JAK1 K908T lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). K908T has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
K924fs frameshift unknown JAK1 K924fs results in a change in the amino acid sequence of the Jak1 protein beginning at aa 924 of 1154, likely resulting in premature truncation of the functional protein (UniProt.org). K924fs has not been identified in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
L431Vfs*22 frameshift loss of function - predicted JAK1 L431Vfs*22 indicates a shift in the reading frame starting at amino acid 431 and terminating 22 residues downstream causing a premature truncation of the 1154 amino acid Jak1 protein (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), L431Vfs*22 is predicted to lead to a loss of Jak1 protein function.
L633K missense loss of function JAK1 L633K lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). L633K results in reduced activation of Jak1 signaling in response to IL-2 and INFalpha in reporter assays and decreased basal Stat5 phosphorylation in cell culture (PMID: 31892268).
L653F missense gain of function - predicted JAK1 L653F lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). L653F (corresponding to L652F in mouse) results in cytokine-independent proliferation in cell culture (PMID: 25855603), and therefore, is predicted to lead to a gain of Jak1 protein function.
L710V missense unknown JAK1 L710V lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). L710V results in constitutive activation of JAK-STAT signaling in cell culture when combined with STAT3 I498V (PMID: 26415585), but has not been individually characterized and therefore, its effect on Jak1 protein function is unknown.
L783F missense gain of function JAK1 L783F lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). Y652H results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331).
L799P missense unknown JAK1 L799P lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). L799P has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
L910P missense gain of function JAK1 L910P lies within the JH1 protein kinase domain 2 of the Jak1 protein (UniProt.org). L910P results in constitutive activation of Jak1, increased phosphorylation of Stat1, Stat3, and Stat5, and is transforming culture (PMID: 25873174, PMID: 20868368).
L910Q missense gain of function - predicted JAK1 L910Q lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). L910Q results in constitutive Jak1 phosphorylation and increased phosphorylation of Stat5 in culture (PMID: 21393331), and therefore, is predicted to lead to a gain of Jak1 protein function.
L932R missense unknown JAK1 L932R lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). L932R has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
M828I missense unknown JAK1 M828I lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). M828I has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
mutant unknown unknown JAK1 mutant indicates an unspecified mutation in the JAK1 gene.
N339fs frameshift loss of function - predicted JAK1 N339fs results in a change in the amino acid sequence of the Jak1 protein beginning at aa 339 of 1154, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), N339fs is predicted to lead to a loss of Jak1 protein function.
N435D missense unknown JAK1 N435D does not lie within any known functional domains of the Jak1 protein (UniProt.org). N435D has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
N451S missense no effect JAK1 N451S lies within a linker region of the Jak1 protein (PMID: 29685781). N451S results in phosphorylation of Jak1, Stat3, and Stat5 to similar levels of wild-type Jak1, and is not transforming in cell culture (PMID: 26701727).
N973K missense unknown JAK1 N973K lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). N973K has been identified in the scientific literature (PMID: 28410228), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
P370S missense unknown JAK1 P370S lies within the FERM domain of the Jak1 protein (UniProt.org). P370S has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
P429S missense loss of function JAK1 P429S lies within the SH2 domain of the Jak1 protein (UniProt.org). P429S results in short-lived phosphorylation of Stat1 and attenuated induction of PD-L1 expression upon interferon gamma stimulation in patient-derived cells in culture, and is associated with resistance to immunotherapy (PMID: 27903500). Y
P430fs frameshift loss of function JAK1 P430fs results in a change in the amino acid sequence of the Jak1 protein beginning at aa 430 of 1154, likely resulting in premature truncation of the functional protein of (UniProt.org). P430fs results in a loss of Stat1 phosphorylation, failure to upregulate the expression of Irf1, Lmp2, and Tap1, and defects in cell surface expression of the MHC class I molecules in response to interferon gamma stimulation in patient-derived cells in culture (PMID: 24154688).
P430S missense unknown JAK1 P430S does not lie within any known functional domains of the Jak1 protein (UniProt.org). P430S has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
P733L missense unknown JAK1 P733L lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). P773L results in decreased Jak1 phosphorylation, but phosphorylates Stat1 and Stat3 to similar levels as wild-type upon interferon stimulation in culture (PMID: 28008925), and therefore, its effect on Jak1 protein function is unknown (PubMed, Aug 2022).
P761S missense unknown JAK1 P761S lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). P761S has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
P815S missense gain of function JAK1 P815S lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). P815S results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331).
P832S missense no effect - predicted JAK1 P832S lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). P832S results in phosphorylation of Jak1 and Stat1 to similar levels as wild-type Jak1 upon interferon stimulation in culture (PMID: 28008925), and therefore, is predicted to have no effect on Jak1 protein function.
P960S missense gain of function JAK1 P960S lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). P960S results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk (PMID: 21393331), transformation of cultured cells (PMID: 20868368), and confers resistance to Jak inhibitors in culture (PMID: 21393331).. Y
P960T missense gain of function JAK1 P960T lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). P960T results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, transformation of cultured cells, and confers resistance to Jak inhibitors in culture (PMID: 21393331). Y
positive unknown unknown JAK1 positive indicates the presence of the KIT gene, mRNA, and/or protein.
Q503* nonsense loss of function - predicted JAK1 Q503* results in a premature truncation of the Jak1 protein at amino acid 503 of 1154 (UniProt.org). Q503* is associated with resistance to immunotherapy (PMID: 27433843), but due to the loss of the protein kinase domains (UniProt.org), is predicted to result in a loss of Jak1 protein function. Y
Q644H missense unknown JAK1 Q644H lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). Q644H has been identified in sequencing studies (PMID: 23788652), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R1113H missense unknown JAK1 R1113H lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). R1113H has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R1139W missense unknown JAK1 R1139W lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). R1139W has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R128H missense unknown JAK1 R128H lies within the FERM domain of the Jak1 protein (UniProt.org). R128H has been identified in sequencing studies (PMID: 27248819), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R174* nonsense loss of function - predicted JAK1 R174* results in a premature truncation of the Jak1 protein at amino acid 174 of 1154 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), R174* is predicted to lead to a loss of Jak1 protein function.
R360W missense unknown JAK1 R360W lies within the FERM domain of the Jak1 protein (UniProt.org). R360W has been identified in sequencing studies (PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R532C missense unknown JAK1 R532C lies within the SH2 domain of the Jak1 protein (UniProt.org). R532C has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R577Q missense unknown JAK1 R577Q lies within a linker region of the Jak1 protein (PMID: 29685781). R577Q has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R629_D630del deletion gain of function - predicted JAK1 R629_D630del results in the deletion of two amino acids in the protein kinase domain 1 of the Jak1 protein from amino acids 629 to 630 (UniProt.org). R629_D630del is transforming in cell culture (PMID: 20868368), and therefore, is predicted to lead to a gain of Jak1 protein function.
R629_S632delinsSA indel gain of function JAK1 R629_S632delinsSA results in a deletion of four amino acids in the protein kinase domain 1 of the Jak1 protein from amino acids 629 to 632, combined with the insertion of a serine (S) and an alanine (A) at the same site (UniProt.org). R629_S632delinsSA confers a gain of function to the Jak1 protein as demonstrated by increased Stat3 and Stat5 phosphorylation in cultured cells, and is transforming in culture (PMID: 34496019).
R643G missense unknown JAK1 R643G lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). R643G has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R681W missense unknown JAK1 R681W lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). R681W has been identified in sequencing studies (PMID: 29575536), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R724C missense unknown JAK1 R724C lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). R724C has been identified in sequencing studies (PMID: 30079384, PMID: 29279377, PMID: 28581676), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R724H missense gain of function JAK1 R724H lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). R724H results in increased Jak1 and Stat5 phosphorylation, and is transforming in cell culture (PMID: 19176360, PMID: 18362173).
R724S missense gain of function JAK1 R724S lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). R724S results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331).
R755Q missense unknown JAK1 R755Q lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). R755Q has been identified in sequencing studies (PMID: 30610106), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R826S missense unknown JAK1 R826S lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). R826S has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
R879C missense gain of function JAK1 R879C lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). R879C results in increased basal and interferon gamma-induced phosphorylation of Jak1 and Stat1 in culture, is not transforming, and potentiates IL-9 signaling in culture (PMID: 18362173, PMID: 20167706).
R879H missense gain of function JAK1 R879H lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). R879H (corresponds to R878H in mouse) results in constitutive activation of Jak1 and phosphorylation of Stat proteins, leading to hyperproliferation and inflammation in the skin of transgenic mouse models harboring the corresponding mouse variant (PMID: 27111231), and demonstrates cell transformation in culture (PMID: 32296058).
R879S missense unknown JAK1 R879S lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). R879S has been identified in sequencing studies (PMID: 18362173), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
rearrange unknown unknown JAK1 rearrangement indicates an unspecified rearrangement of the JAK1 gene.
S1043I missense gain of function JAK1 S1043I lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). S1043I results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, transformation of cultured cells, and tumor formation in mouse models (PMID: 21393331).
S398F missense unknown JAK1 S398F lies within the FERM domain of the Jak1 protein (UniProt.org). S398F has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
S512L missense unknown JAK1 S512L lies within the SH2 domain of the Jak1 protein (UniProt.org). S512L has been identified in the scientific literature (PMID: 18362173), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
S646F missense gain of function JAK1 S646F lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). S646F results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331, PMID: 21551237).
S646P missense gain of function JAK1 S646P lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). S646P results in autophosphorylation of Jak1, constitutive activation of Stat3 and Erk, and is transforming in culture (PMID: 28410228).
S703I missense gain of function JAK1 S703I lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). S703I results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 24825865, PMID: 21393331).
S71C missense unknown JAK1 S71C lies within the FERM domain of the Jak1 protein (UniProt.org). S71C has been identified in sequencing studies (PMID: 23603912), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
S729C missense gain of function JAK1 S729C lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). S729C results in constitutive phosphorylation of Jak1 and activation of Stat3, is transforming in culture, and induces gene expression signature consistent with Jak1 activation in patient samples (PMID: 23788652).
T478S missense gain of function - predicted JAK1 T478S lies within the SH2 domain of the Jak1 protein (UniProt.org). T478S is not transforming in culture or in animal models but conditionally enhances activation of Stat1, Stat3, Akt, and Erk signaling (PMID: 18160671), and therefore, is predicted to lead to a gain of Jak1 protein function.
T593M missense unknown JAK1 T593M lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). T593M has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
T782M missense unknown JAK1 T782M lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). T782M has been identified in sequencing studies (PMID: 18559588), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
T901G missense unknown JAK1 T901G lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). T901G is predicted to be activating based on structural modeling (PMID: 26819051), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
T901R missense gain of function JAK1 T901R lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). T901R results in constitutive Jak1 phosphorylation, increased phosphorylation of Stat5 and Erk in culture (PMID: 21393331), and therefore, is predicted to lead a gain of Jak1 protein function.
V1037I missense unknown JAK1 V1037I lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). V1037I has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
V268G missense unknown JAK1 V268G lies within the FERM domain of the Jak1 protein (UniProt.org). V268G has not been characterized in the scientific literature and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
V310I missense unknown JAK1 V310I lies within the FERM domain of the Jak1 protein (UniProt.org). V310I has been identified in the scientific literature (PMID: 28241173), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
V427M missense unknown JAK1 V427M lies within a linker region of the Jak1 protein (PMID: 29685781). V427M has been identified in sequencing studies (PMID: 26819051), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
V623A missense gain of function - predicted JAK1 V623A lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). V623A is not transforming in culture and does not induce leukemia in mouse models but conditionally enhances activation of Stat1, Stat3, Akt, and Erk signaling (PMID: 18160671), and therefore, is predicted to lead to a gain of Jak1 protein function.
V645F missense unknown JAK1 V645F lies within protein kinase domain 1 of the Jak1 protein (UniProt.org). V645F has been identified in sequencing studies (PMID: 19239328), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).
V651M missense unknown JAK1 V651M lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). V651M has been identified in the scientific literature (PMID: 24843152), but has not been biochemically characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, Aug 2022).
V658F missense gain of function JAK1 V658F lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). V658F results in constitutive Jak1 activation, increased ligand-independent phosphorylation of Stat1, Stat5, and Erk (PMID: 21393331, PMID: 31892268), transformation of cultured cells, and tumor formation in mouse models (PMID: 21393331).
V658I missense gain of function JAK1 V658I lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). V658I results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331).
V658L missense gain of function JAK1 V658L lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). V658L results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331, PMID: 20868368).
W467* nonsense loss of function - predicted JAK1 W467* results in a premature truncation of the Jak1 protein at amino acid 467 of 1154 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), W467* is predicted to lead to a loss of Jak1 protein function.
W690* nonsense loss of function - predicted JAK1 W690* results in a premature truncation of the Jak1 protein at amino acid 690 of 1154 (UniProt.org). W690* may be associated with resistance to immunotherapy (PMID: 27903500), but due to the loss of the protein kinase domains (UniProt.org), is predicted to result in a loss of Jak1 protein function. Y
wild-type none no effect Wild-type JAK1 indicates that no mutation has been detected within the JAK1 gene.
Y1035C missense gain of function JAK1 Y1035C lies within the protein kinase domain 2 of the Jak1 protein (UniProt.org). Y1035C results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331, PMID: 20868368).
Y107A missense loss of function JAK1 Y107A lies within the FERM domain of the Jak1 protein (UniProt.org). Y107A results in failure to activate Stat3 in the presence of IL-9Ralpha (PMID: 19139102), failure to promote cytokine-independent growth (PMID: 17873904), loss of binding to IL-5R (gp130) and failure to phosphorylate Jak1 upon IL-5 stimulation in cells expressing the corresponding mouse allele (Y107A) in culture (PMID: 11468294).
Y270* nonsense loss of function - predicted JAK1 Y270* results in a premature truncation of the Jak1 protein at amino acid 270 of 1154 (UniProt.org). Due to the loss of the protein kinase domains (UniProt.org), Y270* is predicted to lead to a loss of Jak1 protein function.
Y652H missense gain of function JAK1 Y652H lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). Y652H results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 21393331, PMID: 21551237).
Y654F missense gain of function - predicted JAK1 Y654F lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). Y654F demonstrated constitutive activation of JAK-STAT signaling in primary cells in culture (PMID: 26415585), and therefore, is predicted to lead to a gain of Jak1 protein function.
Y999H missense unknown JAK1 Y999H lies within protein kinase domain 2 of the Jak1 protein (UniProt.org). Y999H has not been characterized and therefore, its effect on Jak1 protein function is unknown (PubMed, May 2022).