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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 | |
Category Variants Paths |
JAK3 mutant JAK3 act mut JAK3 V722I |
Transcript | NM_000215.4 |
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 |
---|---|---|---|---|---|
XM_047438786.1 | 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 |
NM_000215 | chr19:g.17834887C>T | c.2164G>A | p.V722I | RefSeq | GRCh38/hg38 |
NM_000215.4 | chr19:g.17834887C>T | c.2164G>A | p.V722I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 | decreased response | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vonjo (pacritinib) 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 | 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 | 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 |
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 |