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Gene | JAK3 |
Variant | M511I |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | 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). |
Associated Drug Resistance | |
Category Variants Paths |
JAK3 mutant JAK3 act mut JAK3 M511I |
Transcript | NM_000215.4 |
gDNA | chr19:g.17838299C>G |
cDNA | c.1533G>C |
Protein | p.M511I |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011527991.3 | chr19:g.17838299C>G | c.1533G>C | p.M511I | RefSeq | GRCh38/hg38 |
NM_000215 | chr19:g.17838299C>G | c.1533G>C | p.M511I | RefSeq | GRCh38/hg38 |
NM_000215.4 | chr19:g.17838299C>G | c.1533G>C | p.M511I | RefSeq | GRCh38/hg38 |
NM_000215.3 | chr19:g.17838299C>G | c.1533G>C | p.M511I | RefSeq | GRCh38/hg38 |
XM_047438786.1 | chr19:g.17838299C>G | c.1533G>C | p.M511I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
JAK3 M511I | hematologic cancer | sensitive | Ruxolitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with Jakafi (ruxolitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485). | 31976485 |
JAK3 M511I | T-cell acute lymphoblastic leukemia | sensitive | Selumetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) treatment induced apoptosis and reduced cell viability of patient-derived T-cell acute lymphoblastic leukemia cell lines harboring JAK3 M511I (PMID: 35411095). | 35411095 |
JAK3 M511I | hematologic cancer | sensitive | Tofacitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xeljanz (tofacitinib, CP-690,550) decreased cell viability in transformed mouse Ba/F3 cells expressing Jak3 M511I (PMID: 29046866). | 29046866 |
JAK3 M511I | T-cell acute lymphoblastic leukemia | sensitive | Tofacitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Xeljanz (tofacitinib) treatment inhibited downstream signaling, induced apoptosis, and reduced cell viability of patient-derived T-cell acute lymphoblastic leukemia cell lines harboring JAK3 M511I (PMID: 35411095). | 35411095 |
JAK3 M511I | hematologic cancer | sensitive | Baricitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with Baricitinib (LY3009104) in culture, demonstrating decreased cell proliferation (PMID: 31976485). | 31976485 |
JAK3 M511I | hematologic cancer | sensitive | ASP015K | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with ASP015K (peficitinib) in culture, demonstrating decreased cell proliferation (PMID: 31976485). | 31976485 |
JAK3 M511I | hematologic cancer | sensitive | Decernotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing JAK3 M511I were sensitive to treatment with Decernotinib (VX-509) in culture, demonstrating decreased cell proliferation (PMID: 31976485). | 31976485 |
JAK3 M511I | T-cell acute lymphoblastic leukemia | sensitive | Ritlecitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Ritlecitinib (PF-06651600) treatment inhibited downstream signaling, induced apoptosis, and reduced cell viability of patient-derived T-cell acute lymphoblastic leukemia cell lines harboring JAK3 M511I (PMID: 35411095). | 35411095 |
JAK3 M511I | T-cell acute lymphoblastic leukemia | sensitive | Dexamethasone + Tofacitinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xeljanx (tofacitinib) and Adexone (dexamethasone) combination treatment increased apoptosis and synergistically reduced viability of a patient-derived T-cell acute lymphoblastic leukemia cell line harboring JAK3 M511I in culture and resulted in reduced leukemic burden in a patient-derived xenograft (PDX) model compared to either drug alone (PMID: 35411095). | 35411095 |