Gene

KRAS

KRas proto-oncogene, GTPase

Explore in graph →CI-GENE-00007164HGNC:6407 ENSG00000133703 NCBI 3845 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (525)

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

civicCuratedShowing 1–50 of 525 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
NRG1 Fusion + KRAS WildtypeNRG1 KRAS1
Afatinib	Pancreatic Ductal Adenocarcinoma	Predictive	C	Supports Sensitivity Response

Cohorts

Alteration frequency by cohort (200)

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

cbioportalObserved200 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
Lung Adenocarcinoma (TCGA, Firehose Legacy) luad_tcga	Lung Adenocarcinoma	Ssm	75	230	32.6%

Literature

Linked publications (113)

25 per page, newest first.

pubmedPublishedShowing 1–25 of 113 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
· N Engl J Med · 2008 · PMID 18946061 · validated civic_curation pubmed
Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial.
· JAMA · 2017 · PMID 28492898 · validated civic_curation pubmed
Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.
· J Natl Compr Canc Netw · 2017 · PMID 28275037 · validated civic_curation pubmed
Sotorasib for Lung Cancers with KRAS p.G12C Mutation.
· N Engl J Med · 2021 · PMID 34096690 · validated civic_curation

NRG1 Fusion + KRAS WildtypeNRG1 KRAS1
Afatinib	Pancreatic Ductal Adenocarcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID7492 Whole genome sequencing and transcriptomic analysis were performed on 47 advanced PDAC patients. 3/47 patients were KRAS wildtype and all three of these cases harbored a NRG1 fusion. A 59-year-old met… (full text at CIViC) PMID 31068372 · Jones et al., 2019 · Open in CIViC	civic

NRG1 Fusion + KRAS WildtypeNRG1 KRAS1

Afatinib

Pancreatic Ductal Adenocarcinoma

Predictive

Supports Sensitivity Response

accepted

EID7492

Whole genome sequencing and transcriptomic analysis were performed on 47 advanced PDAC patients. 3/47 patients were KRAS wildtype and all three of these cases harbored a NRG1 fusion. A 59-year-old met… (full text at CIViC)

PMID 31068372 · Jones et al., 2019 · Open in CIViC

EGFR Overexpression + KRAS MutationEGFR KRAS3
Cetuximab	Colorectal Adenocarcinoma	Predictive	B	Supports Adverse Response	3	submitted	EID11059 The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC	civic
(prognostic)	Colorectal Adenocarcinoma	Prognostic	B	Supports Poor Outcome	3	submitted	EID11058 The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC	civic
Cetuximab + ChemotherapyCombination	Colorectal Adenocarcinoma	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID11062 The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC	civic

KRAS A1462
(prognostic)	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Poor Outcome	2	submitted	EID10656 A study of 419 patients with liver metastases of colorectal cancer identified 12 with A146 mutations. Compared to KRAS G12 tumors, patients with A146 positive tumors exhibited higher ctDNA levels. Pat… (full text at CIViC) PMID 34820593 · van 't Erve et al., 2021 · Open in CIViC	civic
Cetuximab + ChemotherapyCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Does Not Support Resistance	3	accepted	EID3939 This was a retrospective study of 605 patients with metastatic, chemotherapy refractory colorectal cancer treated with cetuximab + chemotherapy. Patients harboring KRAS codon 146 mutant tumors (n=11) … (full text at CIViC) PMID 20619739 · De Roock et al., 2010 · Open in CIViC	civic

KRAS A146P11
(oncogenic)	Malignant Colorectal NeoplasmCURATED_BROADER	Oncogenic	B	Supports Oncogenicity	3	submitted	EID13020 In a systematic analysis of KRAS mutations across 2,280 KRAS-mutant colorectal cancer samples from three large clinical sequencing cohorts (DFCI, TCGA, MSKCC), KRAS A146P was confirmed as one of three… (full text at CIViC) PMID 41299036 · Navarro-Jiménez et al., 2025 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Oncogenic	C	Supports Oncogenicity	3	submitted	EID13019 Edkins et al. identified KRAS c.436G>C (p.A146P) in one primary colorectal cancer, PD1978a, during sequencing of two independent colorectal cancer cohorts. Normal DNA from the same individuals was ana… (full text at CIViC) PMID 16969076 · Edkins et al., 2006 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	4	submitted	EID13018 Park et al. evaluated the transforming potential of 169 KRAS variants by introducing sequence-confirmed variant constructs into NIH 3T3 fibroblasts and performing focus-formation assays in triplicate.… (full text at CIViC) PMID 40970755 · Park et al., 2025 · Open in CIViC	civic
〃	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	3	submitted	EID12168 KRAS A146P was tested in Novellus FACT assay to track MAPK pathway activation via foloursent tagged ERK2 translocation to the nucleus in cells transected with different mutant KRAS vectors. The amount… (full text at CIViC) PMID 34117033 · Loree et al., 2021 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3856 In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC	civic
Cetuximab + IrinotecanCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	accepted	EID2225 In a retrospective study of 68 irinotecan-refractory metastatic colorectal cancer patients, one patient's tumor harbored a KRAS codon 146 mutation but was wildtype for BRAF, and KRAS codons 12, 13, an… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	2	submitted	EID13017 In a retrospective study of patients with irinotecan-refractory metastatic colorectal cancer whose tumors were wild type for KRAS codons 12 and 13, one patient whose tumor harbored a KRAS A146 mutatio… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC	civic
Cetuximab + PD98059Substitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID12068 Colorectal cancer cell line HT29 was invected with KRAS lentivirus constructs for wildtype, A146V, A146T, A146P, and empty. Cells were treated with the anti-EGFR monoclonal antibody cetuximab, and MEK… (full text at CIViC) PMID 30448735 · Seol et al., 2019 · Open in CIViC	civic
Cetuximab + PanitumumabSubstitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	2	submitted	EID13023 In a pooled analysis of the CAVE (cetuximab + avelumab) and VELO (panitumumab + trifluridine/tipiracil) anti-EGFR rechallenge trials in tissue RAS-wild-type mCRC, pretreatment plasma ctDNA genotyping … (full text at CIViC) PMID 37046778 · Ciardiello et al., 2023 · Open in CIViC	civic
FOLFIRI-Panitumumab Regimen + PanitumumabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	2	submitted	EID13022 In a prospective-retrospective analysis of the second-line phase III 20050181 trial, patients with metastatic colorectal cancer received panitumumab plus FOLFIRI or FOLFIRI alone. Extended RAS testing… (full text at CIViC) PMID 26341920 · Peeters et al., 2015 · Open in CIViC	civic
FOLFOX-4 Regimen + PanitumumabCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	submitted	EID13021 In the PRIME trial, patients with KRAS exon 3/4 or NRAS mutations beyond exon 2 (n=108) had worse outcomes with panitumumab-FOLFOX4 vs. FOLFOX4 alone (PFS HR 1.28, 95% CI 0.79–2.07; updated OS HR 1.39… (full text at CIViC) PMID 24024839 · Douillard et al., 2013 · Open in CIViC	civic

KRAS A146T12
(predisposing)	Lymphoma	Predisposing	D	Supports Pathogenic	4	submitted	EID7165 A146T variant activates the transforming potential of the c-K-ras gene. DNA from the neutron-induced lymphoma containing the A146T varinat generated three independent nude mouse tumors containing addi… (full text at CIViC) PMID 2403644 · Sloan et al., 1990 · Open in CIViC	civic
(oncogenic)	Malignant NeoplasmALIAS	Oncogenic	D	Supports Oncogenicity	4	accepted	EID12947 This study provides robust preclinical evidence, supported by genomic data from human tumors, demonstrating that exon 4 mutations in KRAS (particularly at codon 146) represent functionally oncogenic v… (full text at CIViC) PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Oncogenic	D	Supports Oncogenicity	1	submitted	EID7167 The variant was found in 6 of 220 primary colorectal cancer patients. Found in 2 Colorectal Cancer cell lines: HCC2998 and LS1034 Found in 1 AML cell line: ML-2 Mutations of this residue presumably al… (full text at CIViC) PMID 16969076 · Edkins et al., 2006 · Open in CIViC	civic
Cetuximab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	submitted	EID2226 In irinotecan-resistant metastatic colorectal cancer patients who had been treated with cetuximab and irinotecan, KRAS mutations in codon 61 or 146 were associated with shorter progression-free surviv… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	—	submitted	EID3857 In a retrospective study of 138 metastatic irinotecan-refractory, colorectal cancer patients, patients with a KRAS codon 61 or 146 mutation (8/68) treated with cetuximab plus chemotherapy were associa… (full text at CIViC) PMID 19603018 · Loupakis et al., 2009 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	3	accepted	EID2943 Preclinical data supporting resistance of Exon 4 mutations, in particular A146T, to cetuximab and sensitivity to PD0325901. This study involved treatment of mice bearing A146T KRAS xenografts treated … (full text at CIViC) PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	3	submitted	EID7176 identified a KRAS(A146T) mutation after four passages in increasing concentrations of cetuximab (20 nM and higher; These cells were indeed resistant to the drug. These mutations that arise are the res… (full text at CIViC) PMID 22722830 · Misale et al., 2012 · Open in CIViC	civic
Cetuximab + FOLFOX-4 RegimenCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID3858 In a retrospective study of 148 treatment naive metastatic colorectal cancer patients, patients with RAS mutations and wildtype BRAF (n=10), including A146T (N=3), G15D (N=1), and V152M/NRAS V160A, tr… (full text at CIViC) PMID 25666295 · Kaczirek et al., 2015 · Open in CIViC	civic
Cetuximab + IrinotecanCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Resistance	3	submitted	EID3859 In a retrospective study of 53, KRAS exon 2 wild-type, metastatic colorectal cancer patients, patients harboring KRAS Q61L (n=2), Q61H (n=1), or A146T (n=2) mutations were reported to be non-responder… (full text at CIViC) PMID 26989027 · Hsu et al., 2016 · Open in CIViC	civic
Cetuximab + PD98059Substitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	3	submitted	EID12070 Colorectal cancer cell line HT29 was invected with KRAS lentivirus constructs for wildtype, A146V, A146T, A146P, and empty. Cells were treated with the anti-EGFR monoclonal antibody cetuximab, and MEK… (full text at CIViC) PMID 30448735 · Seol et al., 2019 · Open in CIViC	civic
Dactolisib + SelumetinibCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID2206 In 28 out of 40 (70%) metastatic colorectal cancer tumors implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabiliza… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic
Mirdametinib	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	submitted	EID2944 Preclinical data supporting resistance of Exon 4 mutations, in particular A146T, to cetuximab and sensitivity to PD0325901. PMID 20570890 · Janakiraman et al., 2010 · Open in CIViC	civic

KRAS A146V3
Abemaciclib	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	accepted	EID794 Case report of a patient with metastatic lung adenocarcinoma. Whole exome sequencing of the metastatic tumor revealed KRAS A146V, STK11 frameshift deletion and ATM alteration. Preclinical evidence led… (full text at CIViC) PMID 24836576 · Van Allen et al., 2014 · Open in CIViC	civic
Cetuximab + PD98059Substitutes	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Resistance	3	submitted	EID12069 Colorectal cancer cell line HT29 was invected with KRAS lentivirus constructs for wildtype, A146V, A146T, A146P, and empty. Cells were treated with the anti-EGFR monoclonal antibody cetuximab, and MEK… (full text at CIViC) PMID 30448735 · Seol et al., 2019 · Open in CIViC	civic
Dactolisib + SelumetinibCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	3	accepted	EID2209 In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring NRAS, KRAS, BRAF or PIK3CA mutations and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/… (full text at CIViC) PMID 22392911 · Migliardi et al., 2012 · Open in CIViC	civic

KRAS Activating Mutation3
Inhibitor	Malignant Pancreatic Neoplasm	Predictive	D	Supports Sensitivity Response	2	submitted	EID7182 Biochemical screening and subsequent structure-based hit optimization yielded inhibitors of the KRAS-PDEδ interaction that inhibit oncogenic RAS signalling and suppress in vitro and in vivo prolifera… (full text at CIViC) PMID 23698361 · Zimmermann et al., 2013 · Open in CIViC	civic
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Malignant Pancreatic Neoplasm	Predictive	D	Supports Sensitivity Response	1	submitted	EID7184 MAP-ERK kinase (MEK) inhibition in a large PDA cell line panel. Combinations of MEK and EGFR inhibitors induced apoptosis. Combinatorial effect was observed in the epithelial but not mesenchymal subt… (full text at CIViC) PMID 23918833 · Mirzoeva et al., 2013 · Open in CIViC	civic
Salirasib	Malignant Pancreatic Neoplasm	Predictive	B	Supports Sensitivity Response	3	submitted	EID7180 Evaluation of the effectiveness of salirasib in preclinical models and patients with metastatic pancreatic adenocarcinoma (PDA). Preclinical study treated with salirasib alone and in combination with … (full text at CIViC) PMID 22547163 · Laheru et al., 2012 · Open in CIViC	civic

KRAS Amplification3
(prognostic)	Malignant Endometrial NeoplasmCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID5836 In this study, KRAS gain (KRAS/CEP12q ratio >1 and <2) or amplification (ratio >2) was detected in 3% (13 of 414) of the primary endometrial carcinomas investigated. Presence of KRAS gain or amplifica… (full text at CIViC) PMID 23099803 · Birkeland et al., 2012 · Open in CIViC	civic
Cetuximab + EncorafenibCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	submitted	EID2928 Paired pre-treatment and post-progression tumor biopsies from BRAF-mutant CRC patients treated with RAF inhibitor combinations were analyzed. Alterations in MAPK pathway genes were found in resistant … (full text at CIViC) PMID 25673644 · Ahronian et al., 2015 · Open in CIViC	civic
Cetuximab + Panitumumab	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	submitted	EID7105 Screening of 1,039 CRC samples to assess the prevalence of KRAS amplification and the role of this genetic alteration on the sensitivity to anti EGFR therapies. KRAS amplification was mutually exclusi… (full text at CIViC) PMID 23404247 · Valtorta et al., 2013 · Open in CIViC	civic