Gene

JAK1

Janus kinase 1

Explore in graph →CI-GENE-00006501HGNC:6190 ENSG00000162434 NCBI 3716 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (16)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–16 of 16 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
JAK1 A1086S2
(functional)	—UNRESOLVED	Functional	D	Does Not Support Gain Of Function	3	submitted

Cohorts

Alteration frequency by cohort (130)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved130 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm

Literature

Linked publications (4)

25 per page, newest first.

pubmedPublishedShowing 1–4 of 4 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma.
· N Engl J Med · 2016 · PMID 27433843 · validated civic_curation pubmed
Comparative RNA-Sequencing Analysis Benefits a Pediatric Patient With Relapsed Cancer.
· JCO Precis Oncol · 2018 · PMID 31372595 · validated civic_curation pubmed
Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules.
· Br J Cancer · 2012 · PMID 22333600 · validated civic_curation pubmed
Activating JAK1 mutation may predict the sensitivity of JAK-STAT inhibition in hepatocellular carcinoma.
· Oncotarget · 2016 · PMID 26701727 · validated civic_curation pubmed

JAK1 E483D2
(functional)	—UNRESOLVED	Functional	D	Does Not Support Gain Of Function	3	submitted	EID10054 HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703I, A1086S, S729C) following which phosphorylation of JAK1, STAT3 and STAT5 were measured. Both the known activating mutation … (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic
Ruxolitinib	Hepatocellular Carcinoma	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID10057 JAK1 mutations were identified by sequencing 60 HCC PDX tumour models. There mutations were then functionally characterized. HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703… (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic

JAK1 E483D2

(functional)

—UNRESOLVED

Functional

Does Not Support Gain Of Function

submitted

EID10054

HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703I, A1086S, S729C) following which phosphorylation of JAK1, STAT3 and STAT5 were measured. Both the known activating mutation … (full text at CIViC)

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

Ruxolitinib

Hepatocellular Carcinoma

Predictive

Does Not Support Sensitivity Response

submitted

EID10057

JAK1 mutations were identified by sequencing 60 HCC PDX tumour models. There mutations were then functionally characterized. HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703… (full text at CIViC)

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

JAK1 N451S2
(functional)	—UNRESOLVED	Functional	D	Does Not Support Gain Of Function	3	submitted	EID10053 HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703I, A1086S, S729C) following which phosphorylation of JAK1, STAT3 and STAT5 were measured. Both the known activating mutation … (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic
Ruxolitinib	Hepatocellular Carcinoma	Predictive	D	Does Not Support Sensitivity Response	3	submitted	EID10056 JAK1 mutations were identified by sequencing 60 HCC PDX tumour models. There mutations were then functionally characterized. HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703… (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic

JAK1 N451S2

(functional)

—UNRESOLVED

Functional

Does Not Support Gain Of Function

submitted

EID10053

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

Ruxolitinib

Hepatocellular Carcinoma

Predictive

Does Not Support Sensitivity Response

submitted

EID10056

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

JAK1 OVEREXPRESSION2
Enzastaurin	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	accepted	EID931 Overexpression of JAK1 in 22 lung cancer cell lines was associated with sensitivity to PKC-inhibitor enzastaurin. Silencing of JAK1 (by small molecule JAK 1/2/3 inhibitor) led to resistance. Overexpr… (full text at CIViC) PMID 22333600 · Shimokawa et al., 2012 · Open in CIViC	civic
Ruxolitinib	Sarcoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID7852 Sequencing of an 8-year old patient diagnosed with a left tentorial-based CNS sarcoma discovered an EWSR1-ATF fusion and IL6 and JAK1 overexpression. Patient was treated with ruxolitinib based on over… (full text at CIViC) PMID 31372595 · Newton et al., 2018 · Open in CIViC	civic

JAK1 OVEREXPRESSION2

Enzastaurin

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID931

Overexpression of JAK1 in 22 lung cancer cell lines was associated with sensitivity to PKC-inhibitor enzastaurin. Silencing of JAK1 (by small molecule JAK 1/2/3 inhibitor) led to resistance. Overexpr… (full text at CIViC)

PMID 22333600 · Shimokawa et al., 2012 · Open in CIViC

civic

Ruxolitinib

Sarcoma

Predictive

Supports Sensitivity Response

accepted

EID7852

Sequencing of an 8-year old patient diagnosed with a left tentorial-based CNS sarcoma discovered an EWSR1-ATF fusion and IL6 and JAK1 overexpression. Patient was treated with ruxolitinib based on over… (full text at CIViC)

PMID 31372595 · Newton et al., 2018 · Open in CIViC

civic

JAK1 P429S1
Pembrolizumab	Melanoma	Predictive	C	Supports Resistance	4	submitted	EID2980 This study finds JAK1 and JAK2 mutation as determinants of primary resistance to PD-1 blockade therapy. Baseline tumors from patients with melanoma and colon cancer who did not respond to PD-1 blockad… (full text at CIViC) PMID 27903500 · Shin et al., 2017 · Open in CIViC	civic

JAK1 P429S1

Pembrolizumab

Melanoma

Predictive

Supports Resistance

submitted

EID2980

This study finds JAK1 and JAK2 mutation as determinants of primary resistance to PD-1 blockade therapy. Baseline tumors from patients with melanoma and colon cancer who did not respond to PD-1 blockad… (full text at CIViC)

PMID 27903500 · Shin et al., 2017 · Open in CIViC

civic

JAK1 Q503*1
Pembrolizumab	Cutaneous MelanomaALIAS	Predictive	C	Supports Resistance	4	accepted	EID1567 Paired tumor samples were analyzed from four patients with metastatic melanoma and initial response with a subsequent relapse under pembrolizumab (PD-1 checkpoint inhibitor) therapy. Baseline biopsies… (full text at CIViC) PMID 27433843 · Zaretsky et al., 2016 · Open in CIViC	civic

JAK1 Q503*1

Pembrolizumab

Cutaneous MelanomaALIAS

Predictive

Supports Resistance

accepted

EID1567

Paired tumor samples were analyzed from four patients with metastatic melanoma and initial response with a subsequent relapse under pembrolizumab (PD-1 checkpoint inhibitor) therapy. Baseline biopsies… (full text at CIViC)

PMID 27433843 · Zaretsky et al., 2016 · Open in CIViC

civic

JAK1 S646F1
Ruxolitinib	B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like	Predictive	D	Supports Sensitivity Response	2	submitted	EID7957 A patient derived Ph-like B-ALL Xenograft (V) harboring the JAK1 S646F mutation was treated with ruxolitinib. Compared to vehicle, the ruxolitinib treated Xenograft had lower peripheral and splenic b… (full text at CIViC) PMID 22955920 · Maude et al., 2012 · Open in CIViC	civic

JAK1 S646F1

Ruxolitinib

B Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like

Predictive

Supports Sensitivity Response

submitted

EID7957

A patient derived Ph-like B-ALL Xenograft (V) harboring the JAK1 S646F mutation was treated with ruxolitinib. Compared to vehicle, the ruxolitinib treated Xenograft had lower peripheral and splenic b… (full text at CIViC)

PMID 22955920 · Maude et al., 2012 · Open in CIViC

civic

JAK1 S703I2
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted	EID10051 HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703I, A1086S, S729C) following which phosphorylation of JAK1, STAT3 and STAT5 were measured. Both the known activating mutation … (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic
Ruxolitinib	Hepatocellular Carcinoma	Predictive	D	Supports Sensitivity Response	4	accepted	EID1900 A JAK1 S703I mutation was found to activate the JAK-STAT signaling pathway in vitro and in vivo in hepatocellular carcinoma. Ruxolitinib causes the suppression of JAK-STAT signaling pathway in PDX mod… (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic

JAK1 S703I2

(functional)

—UNRESOLVED

Functional

Supports Gain Of Function

submitted

EID10051

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

Ruxolitinib

Hepatocellular Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID1900

A JAK1 S703I mutation was found to activate the JAK-STAT signaling pathway in vitro and in vivo in hepatocellular carcinoma. Ruxolitinib causes the suppression of JAK-STAT signaling pathway in PDX mod… (full text at CIViC)

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

JAK1 S729C1
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted	EID10052 HEK293FT cells were transfected with JAK1 WT or mutants (N451S, E483D, S703I, A1086S, S729C) following which phosphorylation of JAK1, STAT3 and STAT5 were measured. Both the known activating mutation … (full text at CIViC) PMID 26701727 · Yang et al., 2016 · Open in CIViC	civic

JAK1 S729C1

(functional)

—UNRESOLVED

Functional

Supports Gain Of Function

submitted

EID10052

PMID 26701727 · Yang et al., 2016 · Open in CIViC

civic

JAK1 W690*1
Pembrolizumab	Colon Carcinoma	Predictive	C	Supports Resistance	4	submitted	EID2981 This study finds JAK1 and JAK2 mutation as determinants of primary resistance to PD-1 blockade therapy. Baseline tumors from patients with melanoma and colon cancer who did not respond to PD-1 blockad… (full text at CIViC) PMID 27903500 · Shin et al., 2017 · Open in CIViC	civic

JAK1 W690*1

Pembrolizumab

Colon Carcinoma

Predictive

Supports Resistance

submitted

EID2981

PMID 27903500 · Shin et al., 2017 · Open in CIViC

civic

B2M Mutation + JAK1 Mutation + JAK2 Mutation + HighB2M JAK1 JAK21
Anti-PD1 Monoclonal Antibody	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	submitted	EID12150 Thirty-five MSI-H/dMMR patients were treated with anti-PD-1 therapy. Of the 35 patients, 10 patients harboured B2M mutations, and 8 patients harboured JAK mutations. A low TMB score was noted in patie… (full text at CIViC) PMID 35343934 · Zhang et al., 2022 · Open in CIViC	civic

B2M Mutation + JAK1 Mutation + JAK2 Mutation + HighB2M JAK1 JAK21

Anti-PD1 Monoclonal Antibody

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID12150

Thirty-five MSI-H/dMMR patients were treated with anti-PD-1 therapy. Of the 35 patients, 10 patients harboured B2M mutations, and 8 patients harboured JAK mutations. A low TMB score was noted in patie… (full text at CIViC)

PMID 35343934 · Zhang et al., 2022 · Open in CIViC

civic