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Gene Symbol JAK3
Synonyms JAK-3 | JAK3_HUMAN | JAKL | L-JAK | LJAK
Gene Description JAK3, tyrosine-protein kinase JAK3, 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). JAK3 gain of function mutations are commonly observed in T-cell leukemias and lymphomas (PMID: 30079384, PMID: 30250904, PMID: 28284718).

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1090T missense unknown JAK3 A1090T lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). A1090T has been identified in sequencing studies (PMID: 27923066), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Mar 2019).
A572T missense gain of function JAK3 A572T lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). A572T results in constitutive phosphorylation of Jak3, activation of Stat5 and Erk signaling, and is transforming in cell culture (PMID: 25193870).
A572V missense gain of function JAK3 A572V lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). A572V confers a gain of function to the Jak3 protein, as demonstrated by increased Jak3 autophosphorylation (PMID: 29046866), constitutive phosphorylation of Jak3 and activation of downstream Stat5 (PMID: 22705984), and leads to cytokine-independent proliferation of cultured cells (PMID: 22705984, PMID: 28284718).
A573V missense gain of function JAK3 A573V lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). A573V results in constitutive phosphorylation of Jak3, activation of downstream Stat5 and Erk, is transforming in cultured cells (PMID: 18755984, PMID: 29046866, PMID: 28284718), and induces T-cell acute lymphoblastic leukemia in mouse models (PMID: 25193870).
A58del deletion loss of function JAK3 A58del results in the deletion of one amino acid in the FERM domain of the Jak3 protein at amino acid 58 (UniProt.org). A58del confers a loss of function as demonstrated by the loss of Jak3 autophosphorylation and loss of binding to the IL-2R alpha receptor in cell culture (PMID: 14615376).
A593T missense no effect - predicted JAK3 A593T lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). A593T has not been biochemically characterized, but is not transforming in cell culture (PMID: 29046866), and therefore, is predicted to have no effect on Jak3 protein function.
A728fs frameshift loss of function - predicted JAK3 A728fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 728 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (PMID: 12351625), A728fs is predicted to lead to a loss of Jak3 protein function.
act mut unknown gain of function JAK3 act mut indicates that this variant results in a gain of function in the Jak3 protein. However, the specific amino acid change has not been identified.
C1077F missense unknown JAK3 C1077F lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). C1077F has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
C162Y missense unknown JAK3 C162Y lies within the FERM domain of the Jak3 protein (UniProt.org). C162Y has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
C759R missense loss of function JAK3 C759R lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). C759R confers a loss of function to the Jak3 protein, as demonstrated by loss of phosphorylase activity (PMID: 11741532) and the lack of IL-2-dependent Stat5 activation in cell culture (PMID: 10629052).
D169E missense loss of function JAK3 D169E lies within the FERM domain of the Jak3 protein (UniProt.org). D169E confers a loss of function to the Jak3 protein, as demonstrated by loss of binding to the IL-2R alpha receptor (PMID: 11741532), and the inability to autophosphorylate Jak3 (PMID: 11741532, PMID: 14615376).
D294G missense unknown JAK3 D294G lies within the FERM domain of the Jak3 protein (UniProt.org). D294G has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
D863E missense unknown JAK3 D863E lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). D863E has been identified in sequencing studies (PMID: 27245685), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
D949N missense no effect - predicted JAK3 D949N lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). D949N demonstrates subcellular localization similar to wild-type Jak3, and promotes expression of cytokine receptor common gamma chain membrane in cell culture (PMID: 15143194), and therefore, is predicted to have no effect on Jak3 protein function.
E1106G missense no effect JAK3 E1106G lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). E1106G demonstrates phosphorylation of Jak3 similar to wild-type protein and is not transforming in cell culture (PMID: 25193870).
E183G missense gain of function JAK3 E183G lies within the FERM domain of the Jak3 protein (UniProt.org). E183G confers a gain of function to the Jak3 protein as demonstrated by increased protein stability compared to wild-type, increased Stat5a phosphorylation, and transformation in cultured cells (PMID: 21821710).
E552Q missense unknown JAK3 E552Q lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). E552Q has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
E639K missense loss of function JAK3 E639K lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). E639K confers a loss of function to the Jak3 protein, as demonstrated by failure to mediate IL-2-dependent Stat5 activation in cell culture (PMID: 10629052), and the inability to properly localize to the cell membrane (PMID: 15143194).
E694fs frameshift loss of function - predicted JAK3 E694fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 694 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a significant portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), E694fs is predicted to lead to a loss of function.
E717K missense unknown JAK3 E717K lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). E717K has been identified in sequencing studies (PMID: 27245685), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
E958K missense gain of function JAK3 E958K lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). E958K confers a gain of function to the Jak3 protein, as demonstrated by increased cytokine receptor complex-dependent activation of Jak3 in cell culture (PMID: 26446793), activation of Stat5, and is transforming in cell culture (PMID: 26206799).
F569Y missense unknown JAK3 F569Y lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). F569Y has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
F666L missense gain of function - predicted JAK3 F666L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). F666L (corresponding to F662L in mouse) results in cytokine-independent proliferation in cell culture (PMID: 25855603), and therefore, is predicted to lead to a gain of Jak3 protein function.
F711fs frameshift loss of function - predicted JAK3 F711fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 711 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), F711fs is predicted to lead to a loss of Jak3 protein function.
G1057N missense unknown JAK3 G1057N lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). G1057N has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
G538D missense unknown JAK3 G538D lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). G538D has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
G589D missense gain of function - predicted JAK3 G589D lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). G589D has not been biochemically characterized, but demonstrates transformation of cells in culture (PMID: 28284718), and therefore, is predicted to lead to a gain of Jak3 protein function.
G589S missense loss of function - predicted JAK3 G589S lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). G589S demonstrates loss of Jak3 autophosphorylation, but results in normal binding to the cytokine receptor, IL2R-alpha gamma chain in cell culture (PMID: 14615376), and therefore, is predicted to lead to a loss of Jak3 protein function.
G62S missense gain of function JAK3 G62S lies within the FERM domain of the Jak3 protein (UniProt.org). G62S confers a gain of function to the Jak3 protein, as demonstrated by increased autophosphorylation of Jak3, Stat5 activation (PMID: 29046866), and is weakly transforming in cell culture (PMID: 20400977).
G969V missense unknown JAK3 G969V lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). G969V has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
H1118R missense unknown JAK3 H1118R does not lie within any known functional domains of the Jak3 protein (UniProt.org). H1118R has been identified in the scientific literature (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
H583N missense unknown JAK3 H583N lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). H583N has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
H583Y missense gain of function - predicted JAK3 H583Y lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). H538Y has not been biochemically characterized, but demonstrates transformation of cells in culture (PMID: 28284718), and therefore, is predicted to lead to a gain of function Jak3 protein function.
I535M missense unknown JAK3 I535M lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). I535M has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
I688F missense unknown JAK3 I688F lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). I688F has been identified in the scientific literature (PMID: 29437595, PMID: 29880898, PMID: 17344846), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
I688L missense unknown JAK3 I688L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). I688L has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
I726fs frameshift loss of function - predicted JAK3 I726fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 726 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), I726fs is predicted to lead to a loss of Jak3 protein function.
I87T missense gain of function JAK3 I87T lies within the FERM domain of the Jak3 protein (UniProt.org). I87T confers a gain of function to Jak3, as demonstrated by increased Jak3 autophosphorylation (PMID: 29046866), constitutive phosphorylation of downstream Stat5, and is transforming in cell culture (PMID: 18397343).
K556A missense unknown JAK3 K556A lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). K556A demonstrates activation of Stat5 signaling similar to wild-type Jak3, but attenuates Stat5 activation by activating Jak3 mutations (PMID: 30560087), and fails to localize to membrane in cell culture (PMID: 15143194), and therefore, its effect on Jak3 protein function is unknown.
K855A missense loss of function JAK3 K855A lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). K855A confers a loss of function to the Jak3 protein, as demonstrated by loss of phosphorylase activity (PMID: 29046866, PMID: 11741532, PMID: 14615376), and the lack of IL-2-dependent Stat5 activation in cell culture (PMID: 10629052).
L1017M missense gain of function - predicted JAK3 L1017M lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). L1017M has not been biochemically characterized, but demonstrates transformation of cells in culture (PMID: 20400977), and therefore, is predicted to lead to a gain of Jak3 protein function.
L1091R missense unknown JAK3 L1091R lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). L1091R has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
L156P missense gain of function JAK3 L156P lies within the FERM domain of the Jak3 protein (UniProt.org). L156P results in a gain of function of the Jak3 protein as demonstrated by increased protein stability and transformation in cell culture (PMID: 21821710).
L527P missense unknown JAK3 L527P lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). L527P is predicted to be activating based on structural modeling (PMID: 24817905), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown.
L527R missense unknown JAK3 L527R lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). L527R has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
L586_M592del deletion loss of function - predicted JAK3 L586_M592del results in the deletion of seven amino acids in the protein kinase domain 1 of the Jak3 protein from amino acids 586 to 592 (PMID: 10629052). L586_M592del results in constitutive hyperphosphorylation in cell culture but demonstrates failure to mediate IL-2-dependent Stat5 activation (PMID: 10629052), and therefore, is predicted to lead to a loss of Jak3 protein function.
L679V missense unknown JAK3 L679V lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). L679V has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
L857H missense gain of function - predicted JAK3 L857H lies within the protein kinase domain 2 of the Jak3 proteim (UniProt.org). L857H results in cytokine receptor complex-independent activation of Jak3 in cell culture (PMID: 26446793), and therefore, is predicted to lead to a gain of Jak3 protein function.
L857P missense gain of function JAK3 L857P lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). L857P results in cytokine receptor complex-independent activation of Jak3 and increased cell proliferation in culture (PMID: 26446793).
L857Q missense gain of function JAK3 L857Q lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). L857Q results in constitutive phosphorylation of Jak3, activation of Stat5 and Erk signaling, hyperplasia in animal models, and is transforming in cell culture (PMID: 25193870, PMID: 28852199).
M511I missense gain of function JAK3 M511I does not lie within any known functional domains of the Jak3 protein (UniProt.org). M511I results in increased phosphorylation of Jak3, activation of Stat5 and Erk signaling, enhanced tumor growth in animal models, and is transforming in cell culture (PMID: 25193870, PMID: 28852199, PMID: 20400977, PMID: 29046866).
M576fs frameshift loss of function - predicted JAK3 M576fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 576 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a significant portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), M576fs is predicted to lead to a loss of Jak3 protein function.
M576L missense gain of function - predicted JAK3 M576L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). M576L results in increased Jak3 autophosphorylation and is capable of phosphorylating Stat5 (PMID: 29046866) and therefore, is predicted to lead to a gain of Jak3 protein function.
M937T missense unknown JAK3 M937T lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). M937T has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
P1086Q missense unknown JAK3 P1086Q lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). P1086Q has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
P132A missense unknown JAK3 P132A lies within the FERM domain of the Jak3 protein (UniProt.org). P132A demonstrates phosphorylation of Jak3, Stat5 and Erk to similar levels of wild-type Jak3, and is not transforming in culture, however, promotes tumor formation in mouse models (PMID: 21599579), and therefore, its effect on Jak3 protein function is unknown.
P132T missense gain of function JAK3 P132T lies within the FERM domain of the Jak3 protein (UniProt.org). P132T confers a gain of function to the Jak3 protein, as demonstrated by increased Jak3 autophosphorylation, Stat5 activation (PMID: 29046866), and increased cell proliferation in culture (PMID: 16843266).
P151R missense unknown JAK3 P151R lies within the FERM domain of the Jak3 protein (UniProt.org). P151R has been identified in the scientific literature (PMID: 17456055, PMID: 29681454, PMID: 27151993), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
P396L missense unknown JAK3 P396L lies within the SH2 domain of the Jak3 protein (UniProt.org). P396L has been identified in sequencing studies (PMID: 24728327), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
P420S missense unknown JAK3 P420S lies within the SH2 domain of the Jak3 protein (UniProt.org). P420S has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
P725fs frameshift loss of function - predicted JAK3 P725fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 725 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), P725fs is predicted to lead to a loss of Jak3 protein function.
P84fs frameshift loss of function - predicted JAK3 P84fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 84 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (PMID: 12351625), P84fs is predicted to lead to a loss of Jak3 protein function.
P906S missense gain of function - predicted JAK3 P906S lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). P906S results in increased cytokine receptor complex-dependent activation of Jak3 in cell culture (PMID: 26446793), and therefore, is predicted to lead to a gain of Jak3 protein function.
P975L missense unknown JAK3 P975L lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). P975L has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
Q283H missense no effect - predicted JAK3 Q283H lies within the FERM domain of the Jak3 protein (UniProt.org). Q283H is not transforming in cell culture (PMID: 26206799), and therefore, is predicted to have no effect on Jak3 protein function.
Q39fs frameshift loss of function - predicted JAK3 Q39fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 39 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), Q39fs is predicted to lead to a loss of Jak3 protein function.
Q501H missense gain of function JAK3 Q501H does not lie within any known functional domains of the Jak3 protein (UniProt.org). Q501H confers a gain of function to Jak3, as indicated by phosphorylation of downstream Stat5, and is transforming in cell culture (PMID: 18397343, PMID: 20400977).
Q507L missense unknown JAK3 Q507L does not lie within any known functional domains of the Jak3 protein (UniProt.org). Q507L has been identified in sequencing studies (PMID: 26806015, PMID: 23619167), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
Q507P missense gain of function JAK3 Q507P does not lie within any known functional domains of the Jak3 protein (UniProt.org). Q507P results in increased Stat5b phosphorylation in culture and increased transcriptional activity in a reporter assay (PMID: 24825865).
Q507R missense unknown JAK3 Q507R does not lie within any known functional domains of the Jak3 protein (UniProt.org). Q507R has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
Q743L missense unknown JAK3 Q743L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). Q743L has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R1085Q missense unknown JAK3 R1085Q lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R1085Q has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R172Q missense gain of function JAK3 R172Q lies within the FERM domain of the Jak3 protein (UniProt.org). R172Q confers a gain of function to the Jak3 protein as demonstrated by constitutive autophosphorylation of Jak3 and increased phosphorylation of Stat5a, and is transforming in cultured cells (PMID: 21821710).
R172W missense unknown JAK3 R172W lies within the FERM domain of the Jak3 protein (UniProt.org). R172W has been identified in sequencing studies (PMID: 25822088), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R223H missense unknown JAK3 R223H lies within the FERM domain of the Jak3 protein (UniProt.org). R223H has been identified in sequencing studies (PMID: 26444865), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R272H missense no effect JAK3 R272H lies within the FERM domain of the Jak3 protein (UniProt.org). R272H demonstrates phosphorylation of Jak3 similar to wild-type protein and is not transforming in cell culture (PMID: 25193870).
R402H missense loss of function - predicted JAK3 R402H lies within the SH2 domain of the Jak3 protein (UniProt.org). R402H demonstrates altered subcellular localization and failure to properly localize the common gamma chain to the cell membrane in culture (PMID: 15143194), and therefore, is predicted to lead to a loss of Jak3 protein function.
R403H missense no effect JAK3 R403H lies within the SH2 domain of the Jak3 protein (UniProt.org). R403H demonstrates phosphorylation of Jak3 similar to wild-type protein and is not transforming in cell culture (PMID: 25193870).
R40H missense unknown JAK3 R40H lies within the FERM domain of the Jak3 protein (UniProt.org). R40H has been identified in sequencing studies (PMID: 22037554), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R540H missense unknown JAK3 R540H lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). R540H has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R657Q missense gain of function JAK3 R657Q lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). R657Q confers a gain of function to Jak3, as indicated by phosphorylation of downstream Stat5, and is transforming in cell culture (PMID: 18397343, PMID: 20400977).
R657W missense gain of function - predicted JAK3 R657W lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). R657W has not been biochemically characterized, but demonstrates transformation of cells in culture (PMID: 25193870), and therefore, is predicted to lead to a gain of Jak3 protein function.
R887C missense unknown JAK3 R887C lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R887C has been identified in sequencing studies (PMID: 30404791, PMID: 28671688, PMID: 22610119), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R918C missense gain of function - predicted JAK3 R918C lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R918C has not been biochemically characterized, but demonstrates transformation of cells in culture (PMID: 20400977), and therefore, is predicted to lead to a gain of Jak3 protein function.
R925S missense no effect JAK3 R925S lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R925S demonstrates phosphorylation of Jak3 similar to wild-type protein and is not transforming in cell culture (PMID: 25193870).
R943C missense unknown JAK3 R943C lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R943C has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R944H missense unknown JAK3 R944H lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R944H has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R948C missense unknown JAK3 R948C lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). R948C has been identified in the scientific literature (PMID: 23619167, PMID: 27284958, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
R953* nonsense unknown JAK3 R953* results in a premature truncation of the Jak3 protein at amino acid 953 of 1124 (UniProt.org). R953* has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
S1124L missense unknown JAK3 S1124L does not lie within any known functional domains of the Jak3 protein (UniProt.org). S1124L has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
S577fs frameshift loss of function - predicted JAK3 S577fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 577 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a significant portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), S577fs is predicted to lead to a loss of Jak3 protein function.
S703fs frameshift loss of function - predicted JAK3 S703fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 703 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), S703fs is predicted to lead to a loss of Jak3 protein function.
S720N missense unknown JAK3 S720N lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). S720N has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
S727fs frameshift loss of function - predicted JAK3 S727fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 727 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), S727fs is predicted to lead to a loss of Jak3 protein function.
S989I missense unknown JAK3 S989I lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). S989I has been identified in the scientific literature (PMID: 26415585), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
T848A missense gain of function - predicted JAK3 T848A lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). T848A results in cytokine receptor complex-dependent activation of Jak3 in cell culture (PMID: 26446793), and therefore, is predicted to lead to a gain of Jak3 protein function.
T8M missense unknown JAK3 T8M lies within the cytokine/interferon/growth hormone receptor-interacting region of the Jak3 protein (UniProt.org). T8M has been identified in sequencing studies (PMID: 24728327, PMID: 23153540), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
V579fs frameshift loss of function - predicted JAK3 V579fs results in a change in the amino acid sequence of the Jak3 protein beginning at aa 579 of 1124, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a significant portion of the protein kinase 1 domain and the entire functional protein kinase 2 domain (PMID: 12351625), V579fs is predicted to lead to a loss of Jak3 protein function.
V674A missense gain of function JAK3 V674A lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V674A confers a gain of function on the Jak3 protein as demonstrated by increased kinase activity and the ability to transform cells in culture (PMID: 16790275, PMID: 20400977).
V674F missense unknown JAK3 V674F lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V674F has been identified in the scientific literature (PMID: 24446122, PMID: 27389054), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
V678L missense gain of function JAK3 V678L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V678L confers a gain of function to the Jak3 protein, as demonstrated by Stat5 activation and transformation of cells in culture (PMID: 26206799).
V678M missense gain of function JAK3 V678M lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V678M results in constitutive phosphorylation of Jak3, activation of Stat5 and Erk signaling, and is transforming in cell culture (PMID: 25193870).
V715A missense unknown JAK3 V715A lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V715A has not been characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
V715I missense unknown JAK3 V715I lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V715I has been identified in the scientific literature (PMID: 18559588), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
V718L missense unknown JAK3 V718L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V718L has been identified in sequencing studies (PMID: 29844865, PMID: 27282351, PMID: 25017477), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown ((PubMed, Oct 2019).
V722I missense gain of function JAK3 V722I lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). V722I results in constitutive phosphorylation of Jak3, and activation of downstream signaling in cell culture and in patient samples, and is transforming in cell culture (PMID: 23689514, PMID: 16843266).
W709C missense unknown JAK3 W709C lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). W709C has been identified in sequencing studies (PMID: 26806015), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
W709L missense unknown JAK3 W709L lies within the protein kinase domain 1 of the Jak3 protein (UniProt.org). W709L has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
W716* nonsense loss of function - predicted JAK3 W716* results in a premature truncation of the Jak3 protein at amino acid 716 of 1124 (UniProt.org). Due to the loss of most protein kinase domains (UniProt.org), W716* is predicted to lead to a loss of Jak3 protein function.
wild-type none no effect Wild-type JAK3 indicates that no mutation has been detected within the JAK3 gene.
Y100A missense loss of function JAK3 Y100A lies within the FERM domain of the Jak3 protein (UniProt.org). Y100A confers a loss of function to the Jak3 protein, as demonstrated by a loss of Jak3 kinase activity in cell culture (PMID: 11741532), and the inability to bind the cytokine receptor common gamma-c chains (PMID: 10075926).
Y100C missense loss of function JAK3 Y100C lies within the FERM domain of the Jak3 protein (UniProt.org). Y100C confers a loss of function to the Jak3 protein, as demonstrated by loss of phosphorylase activity (PMID: 11741532), and also results in a loss of gamma c binding and blocks IL-2-dependent Jak3 activation in cell culture (PMID: 10075926).
Y1023H missense unknown JAK3 Y1023H lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). Y1023H has been identified in sequencing studies (PMID: 26415585), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Oct 2019).
Y980F missense loss of function JAK3 Y980F lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). Y980F results in impaired Jak3 kinase activity, decreased Stat5 phosphorylation and DNA-binding activity in cell culture (PMID: 9391116).
ETV6 - JAK3 fusion gain of function ETV6-JAK3 results from the fusion of ETV6 and JAK3, which leads to constitutive activation of Stat1 and Stat3, increased expression of Stat5 target genes, and is transforming in cell culture (PMID: 10706877).