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Gene JAK3
Variant A573V
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance

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Transcript NM_000215.3
gDNA chr19:g.17837197G>A
cDNA c.1718C>T
Protein p.A573V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000215 chr19:g.17837197G>A c.1718C>T p.A573V RefSeq GRCh38/hg38
NM_000215.3 chr19:g.17837197G>A c.1718C>T p.A573V RefSeq GRCh38/hg38

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK3 A573V 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 A573V (PMID: 29046866). 29046866
FLT3 exon 14 ins JAK1 R724H JAK3 A573V hematologic cancer resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 R724H JAK3 A573V hematologic cancer resistant Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 R724H JAK3 A573V acute myeloid leukemia resistant Midostaurin Case Reports/Case Series Actionable In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V demonstrated increased allele frequencies for JAK1 R724H (13.5% vs 22%) and JAK3 A573V (13.1% vs 23.1%) after not responding to treatment with Rydapt (midostaurin) and chemotherapy, and in a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 R724H JAK3 A573V hematologic cancer sensitive Midostaurin + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Jakafi (ruxolitinib) inhibited downstream signaling and cell growth in transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 R724H JAK3 A573V hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation, JAK1 R724H, and JAK3 A573V in culture (PMID: 33149267). 33149267
JAK1 Y654F JAK3 A573V Sezary's disease sensitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, Jakafi (ruxolitinib) inhibited growth of a Sezary syndrome cell line harboring JAK1 Y654F and JAK3 A573V in culture (PMID: 26415585). 26415585
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK3 mutant childhood B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic JAK3 mutations are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...
JAK3 mutant B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic JAK3 mutations are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...