Gene Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Gene Symbol JAK3
Synonyms JAK-3 | JAK3_HUMAN | JAKL | L-JAK | LJAK
Gene Description JAK3, Janus kinase 3, 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).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
3718 19 19p13.11 NM_000215 Oncogene (PMID: 30606230)

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1090T missense unknown JAK3 A1090T lies within 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, May 2024).
A572T missense gain of function JAK3 A572T lies within 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 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, PMID: 35622134), 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 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.
A699V missense unknown JAK3 A699V lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). A699V has been identified in the scientific literature (PMID: 27369867), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Jan 2024).
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 a portion of protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), 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 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, May 2024).
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, May 2024).
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, May 2024).
D863E missense unknown JAK3 D863E lies within 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, May 2024).
D949N missense no effect - predicted JAK3 D949N lies within 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 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, May 2024).
E567R missense unknown JAK3 E567R lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). E567R has no effect on Stat5 activity in combination with R657Q and is unable to reduce Jak1 V658K-driven activation of Stat5 in in vitro assays (PMID: 31892268), but has not been characterized individually and therefore, its effect on Jak3 protein function is unknown.
E639K missense loss of function JAK3 E639K lies within 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 portion of protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), E694fs is predicted to lead to a loss of Jak3 protein function.
E717K missense unknown JAK3 E717K lies within 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, May 2024).
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 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, May 2024).
F666L missense gain of function - predicted JAK3 F666L lies within 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 protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), F711fs is predicted to lead to a loss of Jak3 protein function.
fusion fusion unknown JAK3 fusion indicates a fusion of the JAK3 gene, but the fusion partner is unknown.
G1057N missense unknown JAK3 G1057N lies within 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, May 2024).
G538D missense unknown JAK3 G538D lies within 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, May 2024).
G589D missense gain of function - predicted JAK3 G589D lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). G589D has not been biochemically characterized, but results in 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 protein kinase domain 1 of the Jak3 protein (UniProt.org). G589S results in normal binding to IL2R-alpha gamma chain but demonstrates loss of Jak3 autophosphorylation 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).
G888A missense unknown JAK3 G888A lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). G888A results in increased mRNA levels of JAK3, PIM1, PIM2, and PIM3 in a patient sample, but does not support cytokine-independent growth in culture (PMID: 32639993), and therefore, its effect on Jak3 protein function is unknown.
G969V missense unknown JAK3 G969V lies within 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, May 2024).
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, May 2024).
H583N missense unknown JAK3 H583N lies within 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, May 2024).
H583Y missense gain of function - predicted JAK3 H583Y lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). H583Y has not been biochemically characterized, but results in transformation of cells in culture (PMID: 28284718), and therefore, is predicted to lead to a gain of Jak3 protein function.
I535F missense loss of function - predicted JAK3 I535F lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). I535F results in the disruption of ATP binding, and in the context of L857Q leads to reduced Stat5 activation (PMID: 30560087), and therefore, is predicted to lead to a loss of Jak3 protein function.
I535M missense unknown JAK3 I535M lies within 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, May 2024).
I688F missense unknown JAK3 I688F lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). I688F has been identified in the scientific literature (PMID: 29437595, PMID: 29880898, PMID: 35082828), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, May 2024).
I688L missense unknown JAK3 I688L lies within 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, May 2024).
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 protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), 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).
inact mut unknown loss of function JAK3 inact mut indicates that this variant results in a loss of function of the Jak3 protein. However, the specific amino acid change has not been identified.
K550N missense unknown JAK3 K550N lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). K550N has been identified in the scientific literature (PMID: 32639993), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Mar 2024).
K556A missense unknown JAK3 K556A lies within 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.
K733N missense unknown JAK3 K733N lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). K733N has been identified in the scientific literature (PMID: 32639993), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Mar 2024).
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 unknown JAK3 L1017M lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L1017M results in transformation of cells in one study (PMID: 20400977) but does not transform cells in another study (PMID: 29046866) and therefore, its effect on Jak3 protein function is unknown.
L1091P missense no effect - predicted JAK3 L1091P lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L1091P does not support cytokine-independent growth in culture (PMID: 32639993), and therefore, is predicted to have no effect on Jak3 protein function.
L1091R missense unknown JAK3 L1091R lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L1091R 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, May 2024).
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).
L168* nonsense loss of function - predicted JAK3 L168* results in a premature truncation of the Jak3 protein at amino acid 168 of 1124 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), L168* is predicted to lead to a loss of Jak3 protein function.
L527P missense unknown JAK3 L527P lies within 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 (PubMed, Mar 2024).
L527R missense unknown JAK3 L527R lies within 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, May 2024).
L570F missense no effect - predicted JAK3 L570F lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). L570F results in basal and IL-2 induced Stat5 activation similar to wild-type Jak3 in culture (PMID: 31892268), and therefore, is predicted to have no effect on Jak3 protein function.
L586_M592del deletion loss of function - predicted JAK3 L586_M592del results in the deletion of seven amino acids in protein kinase domain 1 of the Jak3 protein from amino acids 586 to 592 (PMID: 10629052). L586_M592del results in constitutive hyperphosphorylation but demonstrates failure to mediate IL-2-dependent Stat5 activation in culture (PMID: 10629052), and therefore, is predicted to lead to a loss of Jak3 protein function.
L679V missense unknown JAK3 L679V lies within 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, May 2024).
L857H missense unknown JAK3 L857H lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L857H has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, Jan 2024).
L857P missense gain of function JAK3 L857P lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L857P results in cytokine receptor complex-independent activation of Jak3, increased cell proliferation (PMID: 26446793), and cytokine-independent growth in culture (PMID: 35411095).
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).
L875H missense gain of function JAK3 L875H lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). L875H results in transforming activity (PMID: 29187379), receptor-independent Jak3 activation (PMID: 26446793), and demonstrates resistance to some JAK inhibitors in culture (PMID: 31976485). Y
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 portion of protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), M576fs is predicted to lead to a loss of Jak3 protein function.
M576L missense gain of function - predicted JAK3 M576L lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). M576L results in increased Jak3 autophosphorylation and is capable of phosphorylating Stat5 in culture (PMID: 29046866), and therefore, is predicted to lead to a gain of Jak3 protein function.
M592F missense gain of function - predicted JAK3 M592F lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). M592F does not lead to cytokine-independent growth (PMID: 16239216), but results in increased Stat5 activity in cell culture (PMID: 31892268), and therefore, is predicted to lead to a gain of Jak3 protein function.
M937T missense unknown JAK3 M937T lies within 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, May 2024).
mutant unknown unknown JAK3 mutant indicates an unspecified mutation in the JAK3 gene.
P1086Q missense unknown JAK3 P1086Q lies within 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, May 2024).
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: 29681454, PMID: 27151993, PMID: 32639993), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Mar 2024).
P307S missense unknown JAK3 P307S lies within the FERM domain of the Jak3 protein (UniProt.org). P307S has been identified in the scientific literature (PMID: 32639993), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, May 2024).
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, May 2024).
P420S missense unknown JAK3 P420S lies within the SH2 domain of the Jak3 protein (UniProt.org). P420S has been identified in sequencing studies (PMID: 28467829), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, May 2024).
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 protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), 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 (UniProt.org), P84fs is predicted to lead to a loss of Jak3 protein function.
P906S missense gain of function - predicted JAK3 P906S lies within 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 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, May 2024).
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, May 2024).
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, May 2024).
Q743L missense unknown JAK3 Q743L lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). Q743L has been identified in sequencing studies (PMID: 30224629), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, May 2024).
Q988P missense gain of function JAK3 Q988P lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). Q988P confers a gain of function to the Jak3 protein as demonstrated by constitutive JAK/STAT pathway activation (PMID: 37712558, PMID: 39033228), increased c-Myc and S6 phosphorylation and Pim1 expression (PMID: 39033228), and cytokine-independent growth in culture (PMID: 37712558).
R1085Q missense unknown JAK3 R1085Q lies within 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, May 2024).
R142C missense unknown JAK3 R142C lies within the FERM domain of the Jak3 protein (UniProt.org). R142C has been identified in the scientific literature (PMID: 32639993), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Mar 2024).
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, Jun 2024).
R175Q missense unknown JAK3 R175Q lies within the FERM domain of the Jak3 protein (UniProt.org). R175Q has not been characterized in the scientific literature and therefore, its effect on Jak3 protein function is unknown (PubMed, May 2024).
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, Jun 2024).
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, PMID: 35708139), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Jun 2024).
R540H missense unknown JAK3 R540H lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). R540H has been identified in sequencing studies (PMID: 27149842, PMID: 38024597), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Jun 2024).
R549Q missense gain of function - predicted JAK3 R549Q lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). R549Q results in cytokine-independent growth in culture (PMID: 35411095), and therefore, is predicted to lead to a gain of Jak3 protein function.
R657Q missense gain of function JAK3 R657Q lies within 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 protein kinase domain 1 of the Jak3 protein (UniProt.org). R657W has not been biochemically characterized, but results in transformation of cells in culture (PMID: 25193870), and therefore, is predicted to lead to a gain of Jak3 protein function.
R887C missense gain of function - predicted JAK3 R887C lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). R887C results in cytokine-independent growth in cell culture (PMID: 35411095), and therefore, is predicted to lead to a gain of Jak3 protein function.
R918C missense unknown JAK3 R918C lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). R918C results in transformation of cells in one study (PMID: 20400977) but does not transform cells in another study (PMID: 29046866) and therefore, its effect on Jak3 protein function is unknown.
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 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, Jun 2024).
R944H missense unknown JAK3 R944H lies within 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, Jun 2024).
R948C missense unknown JAK3 R948C lies within protein kinase domain 2 of the Jak3 protein (UniProt.org). R948C has been identified in the scientific literature (PMID: 37569332, PMID: 27284958, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Jun 2024).
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, Jun 2024).
rearrange unknown unknown JAK3 rearrangement indicates an unspecified rearrangement of the JAK3 gene.
S1124L missense unknown JAK3 S1124L does not lie within any known functional domains of the Jak3 protein (UniProt.org). S1124L has been identified in sequencing studies (Annals of Oncology (2019) 30 (Supplement 7) vii6-vii7), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Mar 2024).
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 portion of protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), 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 protein kinase domain 1 and the entire protein kinase domain 2 (PMID: 12351625), S703fs is predicted to lead to a loss of Jak3 protein function.
S720N missense unknown JAK3 S720N lies within 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, Jun 2024).
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 protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), S727fs is predicted to lead to a loss of Jak3 protein function.
S989I missense unknown JAK3 S989I lies within 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, Jun 2024).
T1022I missense gain of function JAK3 T1022I lies within the protein kinase domain 2 of the Jak3 protein (UniProt.org). T1022I confers a gain of function on Jak3 as demonstrated by increased phosphorylation of Stat5 and Erk, and cytokine-independent growth in culture (PMID: 32639993).
T848A missense gain of function - predicted JAK3 T848A lies within 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, Jun 2024).
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 portion of protein kinase domain 1 and the entire protein kinase domain 2 (UniProt.org), V579fs is predicted to lead to a loss of Jak3 protein function.
V674A missense gain of function JAK3 V674A lies within 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 (PMID: 16790275, PMID: 20400977) and the ability to transform cells in culture (PMID: 16790275, PMID: 20400977, PMID: 35411095).
V674F missense unknown JAK3 V674F lies within 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, Jun 2024).
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 protein kinase domain 1 of the Jak3 protein (UniProt.org). V678M results in constitutive phosphorylation of Jak3, activation of Stat5 and Erk signaling (PMID: 25193870), and is transforming in cell culture (PMID: 25193870, PMID: 35411095).
V715A missense unknown JAK3 V715A lies within 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, Jun 2024).
V715I missense unknown JAK3 V715I lies within 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, Jun 2024).
V718L missense unknown JAK3 V718L lies within 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, Jun 2024).
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 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, Jun 2024).
W709L missense unknown JAK3 W709L lies within protein kinase domain 1 of the Jak3 protein (UniProt.org). W709L has been identified in sequencing studies (PMID: 22980975, PMID: 35116055), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Jun 2024).
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 a portion of protein kinase domain 1 and the entire protein kinase domain 2 (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 protein kinase domain 2 of the Jak3 protein (UniProt.org). Y1023H has been identified in sequencing studies (PMID: 26415585, PMID: 25801821), but has not been biochemically characterized and therefore, its effect on Jak3 protein function is unknown (PubMed, Jun 2024).
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).