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Gene JAK3
Variant V722I
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions 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).
Associated Drug Resistance

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Transcript NM_000215.3
gDNA chr19:g.17834887C>T
cDNA c.2164G>A
Protein p.V722I
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000215 chr19:g.17834887C>T c.2164G>A p.V722I RefSeq GRCh38/hg38
NM_000215.3 chr19:g.17834887C>T c.2164G>A p.V722I 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 )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • 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 V722I Advanced Solid Tumor sensitive Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, Xeljanz (tofacitinib) treatment converted cells expressing JAK3 V722I from factor-independent to factor-dependent growth in cell culture (PMID: 25146434). 25146434
FLT3 exon 14 ins JAK3 V722I hematologic cancer decreased response Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Pacritinib (SB1518) treatment decreased cell proliferation and Akt and Erk phosphorylation, but did not fully inhibit Stat5 phosphorylation in transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I and was less effective compared to treatment with the combination of a FLT3 inhibitor and a JAK inhibitor in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I acute myeloid leukemia predicted - resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation treated with Nexavar (sorafenib) was found to have acquired a JAK3 V722I mutation with a variant allele frequency of 49% upon relapse (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Gilteritinib + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Xospata (gilteritinib) and Jakafi (ruxolitinib) inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I hematologic cancer sensitive Midostaurin + Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Rydapt (midostaurin) and Xeljanz (tofacitinib) inhibited cell growth and downstream signaling of transformed hematologic cells expressing a FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK3 V722I 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 aa FLT3-ITD mutation and JAK3 V722I in culture (PMID: 33149267). 33149267
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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...
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...