Gene

HRAS

HRas proto-oncogene, GTPase

Explore in graph →CI-GENE-00005011HGNC:5173 ENSG00000174775 NCBI 3265 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (24)

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

civicCuratedShowing 1–24 of 24 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
BRAF V600E + HRAS Mutation + KRAS Mutation + NF1 Inactivating Mutation + NRAS MutationHRAS NF1 BRAF KRAS NRAS1

Cohorts

Alteration frequency by cohort (67)

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

cbioportalObserved67 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
Bladder Urothelial Carcinoma (BGI, Nat Genet 2013) blca_bgi	Bladder Urothelial Carcinoma	Ssm

Literature

Linked publications (7)

25 per page, newest first.

pubmedPublishedShowing 1–7 of 7 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial.
· J Clin Oncol · 2022 · PMID 35363510 · validated civic_curation pubmed
Telomerase in differentiated thyroid cancer: promoter mutations, expression and localization.
· Mol Cell Endocrinol · 2015 · PMID 25448848 · validated civic_curation pubmed
A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations.
· Clin Cancer Res · 2020 · PMID 32636318 · validated civic_curation pubmed
Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations.
· J Clin Oncol · 2021 · PMID 33750196 · validated

BRAF V600E + HRAS Mutation + KRAS Mutation + NF1 Mutation + NRAS MutationHRAS BRAF NF1 KRAS NRAS1
Selumetinib	Malignant NeoplasmALIAS	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID11681 In this phase II study of the arm E of the NCI-COG pediatric MATCH trial, 20 patients (median age: 14) were treated with Selumetinib. High-grade glioma (n=7) and rhabdomyosarcoma (n=7) were the most c… (full text at CIViC) PMID 35363510 · Eckstein et al., 2022 · Open in CIViC	civic

BRAF V600E + HRAS Mutation + KRAS Mutation + NF1 Mutation + NRAS MutationHRAS BRAF NF1 KRAS NRAS1

Selumetinib

Malignant NeoplasmALIAS

Predictive

Does Not Support Sensitivity Response

accepted

EID11681

In this phase II study of the arm E of the NCI-COG pediatric MATCH trial, 20 patients (median age: 14) were treated with Selumetinib. High-grade glioma (n=7) and rhabdomyosarcoma (n=7) were the most c… (full text at CIViC)

PMID 35363510 · Eckstein et al., 2022 · Open in CIViC

HRAS G12D2
Erlotinib	Malignant Head and Neck NeoplasmALIAS	Predictive	D	Supports Resistance	—	submitted	EID3697 In an in vitro study, a H31 cell line expressing HRAS G12D mutation demonstrated decreased sensitivity to erlotinib treatment (GI50s >3.50 uM vs. 0.067�0.184 uM) compared to UM-SCC-19 or MSK-922 or M… (full text at CIViC) PMID 24123531 · Hah et al., 2014 · Open in CIViC	civic
Vemurafenib	Skin Squamous Cell Carcinoma	Predictive	C	Supports Resistance	—	submitted	EID3698 In a retrospective study of 23 patients with BRAF V600 mutation (a known vemurafenib sensitizing mutation) that developed cutaneous squamous-cell carcinoma upon treatment with vemurafenib monotherapy,… (full text at CIViC) PMID 22256804 · Su et al., 2012 · Open in CIViC	civic

HRAS G12V3
Alpelisib	Head and Neck Squamous Cell Carcinoma	Predictive	D	Supports Resistance	1	submitted	EID9087 In this preclinical study, cell lines with constitutively-active G12V mutant found that forced overexpression of HRAS G12V caused a reduced susceptibility to PI3K inhibitor BYL719 in comparison to wil… (full text at CIViC) PMID 30115483 · Ruicci et al., 2018 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	—	submitted	EID3855 In an in vitro study, DiFi colorectal cancer cell lines stably expressing HRAS G12V mutation demonstrated resistance to cetuximab treatment compared to DiFi cells expressing wild-type HRAS. Resistance… (full text at CIViC) PMID 22797062 · Kasper et al., 2013 · Open in CIViC	civic
Erlotinib	Malignant Head and Neck NeoplasmALIAS	Predictive	D	Supports Resistance	—	submitted	EID3854 In an in vitro study, UM-SCC-10B, UM-SCC-22A and HN5 cell lines expressing HRAS G12V mutation demonstrated decreased sensitivity to erlotinib treatment compared to the respective sensitive parental ce… (full text at CIViC) PMID 24123531 · Hah et al., 2014 · Open in CIViC	civic

HRAS G13R3
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12905 HRAS p.Gly13Arg (NM_005343.4:c.37G>C) causes increased pERK/ERK ratio, and increased GTP-bound HRAS PMID 22683711 · Groesser et al., 2012 · Open in CIViC	civic
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	5	submitted	EID12906 HRAS p.Gly13Arg (NM_005343.4:c.37G>C) causes increased proliferation, experiments were done in triplicates. PMID 22683711 · Groesser et al., 2012 · Open in CIViC	civic
Vemurafenib	Thyroid Gland Carcinoma	Predictive	D	Supports Resistance	—	submitted	EID3853 In an in vitro study, a C643 cell line expressing HRAS G13R demonstrated reduced sensitivity to vemurafenib treatment, compared to BRAF V600E expressing cells (8505C, SWI1736, BHT101 and BCPAP). Sensi… (full text at CIViC) PMID 19880792 · Salerno et al., 2010 · Open in CIViC	civic

HRAS Mutation2
Tipifarnib	Bladder Urothelial Carcinoma	Predictive	B	Supports Sensitivity Response	2	accepted	EID9632 4 of 16 patients with urothelial carcinoma harboring HRAS hotspot point mutations and 1 patient with an HRAS frameshift insertion had a partial response to the farnesyltransferase inhibitor tipifarnib… (full text at CIViC) PMID 32636318 · Lee et al., 2020 · Open in CIViC	civic
〃	Head and Neck Squamous Cell Carcinoma	Predictive	B	Supports Sensitivity Response	2	accepted	EID9633 In a phase II HNSCC trial, an objective response rate of 55% was seen in HRAS-mutant patients (11 of 20) treated with the farnesyltransferase inhibitor tipifarnib with a PFS of 5.6 months and an OS of… (full text at CIViC) PMID 33750196 · Ho et al., 2021 · Open in CIViC	civic

HRAS Q61L2
Everolimus + SelumetinibCombination	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID1955 Inhibition of mTOR or combined inhibition of MEK and mTOR reduced cell growth in a synergistic manner. Cells transformed with mutant HRAS isoforms Q61L, Q61R and G12V demonstrated equal sensitivity to… (full text at CIViC) PMID 26544513 · Kiessling et al., 2015 · Open in CIViC	civic
Vemurafenib	Skin Squamous Cell Carcinoma	Predictive	C	Supports Resistance	—	submitted	EID3848 In a retrospective study of 23 patients with BRAF V600 mutation (a known vemurafenib sensitizing mutation) that developed cutaneous squamous-cell carcinoma upon treatment with vemurafenib monotherapy,… (full text at CIViC) PMID 22256804 · Su et al., 2012 · Open in CIViC	civic