KRAS

Chr 12

KRas proto-oncogene, GTPase

Also known as: 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, K-Ras

NCBI Gene: 3845 ENSG00000133703 UniProt: P01116

The KRAS protein is a small GTPase that regulates cell signaling pathways controlling cell growth and differentiation. Germline mutations cause autosomal dominant neurodevelopmental disorders including Noonan syndrome 3 and cardiofaciocutaneous syndrome 2, while somatic mutations lead to various cancers and RAS-associated autoimmune leukoproliferative disorder. The pathogenic mechanism involves dominant-negative effects from activating mutations, typically single amino acid substitutions that disrupt normal GTPase function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukemia, acute myelogenous

UniProtLeukemia, juvenile myelomonocytic

UniProtNoonan syndrome 3

UniProtGastric cancer

Clinical highlights

Gene-disease validity (ClinGen)

cardiofaciocutaneous syndrome · ADStrongappropriate for clinical testing3 gene-disease associations curated in total

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

4391

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.24

LOEUF

GOF*

Mechanism· G2P

📖

GeneReview available — KRAS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.24LOEUF

pLI 0.001

Z-score 1.06

OE 0.63 (0.34–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

2.32Z-score

OE missense 0.34 (0.26–0.45)

33 obs / 97.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.63 (0.34–1.24)

0≤0.351.4

Missense OE?0.34 (0.26–0.45)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 9.5Missense obs/exp: 33 / 97.4Syn Z: 0.34

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KRAS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

VCEP specificationsRASopathyReleased

Specifications ↗Panel ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — KRAS

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Systemic SclerosisScleroderma

Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)

ACTIVE NOT RECRUITING

NCT05925803Phase PHASE3AstraZenecaStarted 2023-11-08

Anifrolumab (blinded)Placebo (blinded)Anifrolumab (unblinded, open label)

Non Small Cell Lung Cancer

Surufatinib Combined With Toripalimab and Chemotherapy in the Treatment of Non-Small Cell Lung Cancer

ACTIVE NOT RECRUITING

NCT05003037Phase PHASE2Li Zhang, MDStarted 2022-01-06

Surufatinib, Toripalimab, Pemetrexed, Carboplatin/Cisplatin

Carcinoma, Non-Small-Cell Lung

MYLUNG Consortium Study Protocol 2

ACTIVE NOT RECRUITING

NCT05644808US Oncology ResearchStarted 2020-12-29

Carcinoma, Non-Small-Cell LungNeoplasm Metastasis

A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

RECRUITING

NCT06119581Phase PHASE3Eli Lilly and CompanyStarted 2023-12-21

LY3537982PembrolizumabPlacebo

Dysbiosis

Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Dysbiosis

ACTIVE NOT RECRUITING

NCT05836155Phase NAMedical University of GrazStarted 2023-07-10

Intervention

Lung Adenocarcinoma

PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC

NOT YET RECRUITING

NCT07416058Phase PHASE2Guangdong Association of Clinical TrialsStarted 2026-01-31