Gene Variant Detail

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Gene JAK1
Variant S703I
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions JAK1 S703I lies within the protein kinase domain 1 of the Jak1 protein (UniProt.org). S703I results in constitutive Jak1 activation, increased phosphorylation of Stat5 and Erk, and is transforming in cell culture (PMID: 24825865, PMID: 21393331).
Associated Drug Resistance

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Transcript NM_002227.3
gDNA chr1:g.64845520C>A
cDNA c.2108G>T
Protein p.S703I
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001321856 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321854.1 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_002227 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321852 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321852.1 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321853.1 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321853 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001320923 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001320923.1 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321855 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321856.1 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_002227.3 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321855.1 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38
NM_001321854 chr1:g.64845520C>A c.2108G>T p.S703I RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK1 S703I cancer sensitive Ruxolitinib Preclinical Actionable In a preclinical study, transformed cells harboring JAK1 S703I were sensitive to ATP-competetive JAK inhibitors, such as Jakafi (Ruxolitinib) (PMID: 21393331). 21393331
FLT3 exon 14 ins JAK1 S703I 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 JAK1 S703I 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 JAK1 S703I 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 and JAK1 S703I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I hematologic cancer resistant Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Jakafi (ruxolitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I hematologic cancer resistant Tofacitinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Xeljanz (tofacitinib) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I 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 JAK1 S703I in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I acute myeloid leukemia resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation and JAK1 S703I were resistant to treatment with Rydapt (midostaurin) in culture (PMID: 33149267). 33149267
FLT3 exon 14 ins JAK1 S703I 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 and JAK1 S703I in culture (PMID: 33149267). 33149267
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
JAK1 mutant childhood B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic JAK1 mutations are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...
JAK1 mutant B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic JAK1 mutations are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...