# KRAS mutation subtypes (G12C, G12D, G12V)

Source: https://onco.cc/terms/kras-mutation-subtypes/  
OnCo record `kras-mutation-subtypes` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change. G12C (common in smokers' lung cancer) was the first to get a drug; G12D dominates pancreatic and colorectal cancer and its inhibitors are arriving now.

## Summary

KRAS is mutated in about 90% of pancreatic, 40% of colorectal and 30% of lung adenocarcinomas. The G12C variant (13% of lung adenocarcinoma) is targeted by sotorasib and adagrasib, approved in 2021-22 with modest durability; G12D (40% of pancreatic cancer) is the target of zoldonrasib and others; daraxonrasib and related RAS(ON) multi-selective inhibitors cover several variants and produced the first positive phase 3 in pancreatic cancer. Variant also predicts behaviour: G12C lung tumours are smoking-related and immunogenic, while colorectal KRAS mutations of any type preclude EGFR antibodies. Co-mutations (STK11, KEAP1, TP53) modify prognosis and immunotherapy benefit.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: G12C; G12D; G12V; G12R; G13D; Q61H; KRAS G12C; KRAS G12D; KRAS-mutant; KRAS-mutated; KRAS mutation; KRAS mutations; RAS-mutant; RAS mutation; RAS-mutated; non-G12C; pan-RAS; pan-KRAS; RAS(ON); RAS(OFF); RAS mutations

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/KRAS
- Wikipedia: https://en.wikipedia.org/wiki/KRAS

## Connected records

- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [KRAS allelic imbalance and mutant KRAS dosage in pancreatic cancer](https://onco.cc/terms/kras-allelic-imbalance/), [Pancreatic cancer trials open today (registry snapshot and UK sites)](https://onco.cc/terms/pancreatic-trials-open-today/), [STK11 / KEAP1 co-mutations](https://onco.cc/terms/stk11-keap1/), [Wild-type (WT)](https://onco.cc/terms/wild-type/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [KRAS & RAS inhibitors](https://onco.cc/technologies/kras-inhibitors/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- drugs: [Adagrasib](https://onco.cc/drugs/adagrasib/), [Fulzerasib](https://onco.cc/drugs/fulzerasib/), [Garsorasib](https://onco.cc/drugs/garsorasib/), [Sotorasib](https://onco.cc/drugs/sotorasib/)
- key papers: [Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018/), [Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities](https://onco.cc/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/), [CodeBreaK 100: sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer](https://onco.cc/key-papers/paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023/), [Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer](https://onco.cc/key-papers/paper-daraxonrasib-pancreatic-n-engl-j-med-2026/), [Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status](https://onco.cc/key-papers/paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022/), [Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer](https://onco.cc/key-papers/paper-arbour-kras-co-mutation-outcomes-ccr-2018/), [KRAS G12D mutation subtype is a prognostic factor for advanced pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016/), [Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes](https://onco.cc/key-papers/paper-almoguera-kras-codon-12-pancreatic-cell-1988/), [Mutational signatures associated with tobacco smoking in human cancer](https://onco.cc/key-papers/paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016/), [Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets](https://onco.cc/key-papers/paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- ideas: [RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression](https://onco.cc/ideas/idea-pdac-ras-inhibitor-combinations-and-sequencing/)
- trials: [CodeBreaK 100 (pancreatic cancer cohort)](https://onco.cc/trials/codebreak-100/), [Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1](https://onco.cc/trials/nct03785249/), [Study of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation](https://onco.cc/trials/nct05737706/), [Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS](https://onco.cc/trials/nct05379985/), [Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mut](https://onco.cc/trials/nct07805954/), [Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta](https://onco.cc/trials/nct07621718/)
- biomarkers: [KRAS G12C](https://onco.cc/biomarkers/kras-g12c/), [KRAS G12D (and other non-G12C KRAS mutations)](https://onco.cc/biomarkers/kras-g12d/), [STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma](https://onco.cc/biomarkers/stk11-keap1-loss/)

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