KRAS
Chr 12ADKRas proto-oncogene, GTPase
Also known as: 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, K-Ras
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]
Strong evidence — appropriate for clinical testing
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Moderately missense-constrained (top ~2.5%)
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
552 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 38 | 0 | 0 | 38 |
Likely Pathogenic | 1 | 53 | 3 | 1 | 58 |
VUS | 25 | 118 | 44 | 11 | 198 |
Likely Benign | 0 | 5 | 82 | 90 | 177 |
Benign | 0 | 1 | 32 | 3 | 36 |
Conflicting | — | 26 | |||
| Total | 26 | 215 | 161 | 105 | 533 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →38 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap KRAS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
KRAS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
RECRUITINGBiology of Young Lung Cancer Study: The YOUNG LUNG Study
RECRUITINGA Study of Participants in China With Non-Small-Cell Lung Cancer That is Unable to be Treated With Surgery
ACTIVE NOT RECRUITINGA Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy
ACTIVE NOT RECRUITINGPOTENT - Tepotinib in Combination With Pembrolizumab in NSCLC
ACTIVE NOT RECRUITINGPhase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas
ACTIVE NOT RECRUITINGLocal and Systemic Changes in Osteonecrosis of the Jawbone
ENROLLING BY INVITATIONctDNA Assay in Patients With Resectable Pancreatic Cancer
RECRUITINGNeratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation
ACTIVE NOT RECRUITINGDHF-20-1839-2: Clinical Performance Study Protocol for Therascreen® KRAS RGQ PCR Kit
RECRUITINGA Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation
RECRUITINGFirst-line Therapy With Nivolumab Plus Ipilimumab in Combination With Chemotherapy for Metatastatic NSCLC (NICReWo Trial)
RECRUITINGExternal Resources
Links to major genomics databases and tools