KRAS Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human KRAS — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene KRAS, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene KRAS, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene KRAS protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene KRAS protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene KRAS, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene KRAS, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene KRAS, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene KRAS protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene KRAS, summarize transcription factor regulatory data. If KRAS is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate KRAS — names with evidence type (ChIP-seq / predicted / experimentally validated) If KRAS is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene KRAS protein as a drug target, summarize pharmacology data. If KRAS is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If KRAS is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene KRAS, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene KRAS, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in KRAS: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
KRAS (HGNC:6407; chr12:25,205,246–25,250,936, reverse strand) encodes a small GTPase and is one of the most clinically important oncogenes in human cancer. It is ubiquitously expressed across tissues (Bgee average score 86.92/100) and participates in 71 Reactome pathways centered on RAS/MAPK and RAF signaling. Somatic mutations — predominantly at Gly12 and Gly13 — drive pancreatic, lung, colorectal, and gastric cancers, while germline mutations cause RASopathies including Noonan syndrome 3 and Cardiofaciocutaneous syndrome 2. Among ~565 ClinVar variants, roughly 12% are classified pathogenic or likely pathogenic. The protein is exceptionally well-characterized structurally, with 462 PDB entries spanning wild-type and mutant forms, and an AlphaFold model scoring 91.65 pLDDT. Two FDA-approved covalent G12C inhibitors — sotorasib (2021) and adagrasib (2023) — now anchor a large clinical pipeline of 80+ active trials, and KRAS mutation status is an established predictive biomarker for response to cetuximab and panitumumab in colorectal cancer.
Gene identifiers
- HGNC ID: HGNC:6407
- Approved symbol: KRAS
- Ensembl gene ID: ENSG00000133703
- NCBI Entrez Gene ID: 3845
- OMIM gene/locus ID: 190070
- Genomic location (GRCh38):
- Chromosome: 12
- Start position: 25,205,246 bp
- End position: 25,250,936 bp
- Strand: − (reverse)
Transcript identifiers
Ensembl transcripts (16 total)
| Transcript ID | Biotype |
|---|---|
| ENST00000256078 | protein_coding |
| ENST00000311936 | protein_coding |
| ENST00000556131 | protein_coding |
| ENST00000557334 | protein_coding |
| ENST00000685328 | protein_coding |
| ENST00000686877 | nonsense_mediated_decay |
| ENST00000686969 | protein_coding |
| ENST00000687356 | nonsense_mediated_decay |
| ENST00000688228 | retained_intron |
| ENST00000688940 | protein_coding |
| ENST00000690406 | nonsense_mediated_decay |
| ENST00000690804 | nonsense_mediated_decay |
| ENST00000692768 | protein_coding |
| ENST00000693229 | protein_coding |
| ENST00000894155 | protein_coding |
| ENST00000940422 | protein_coding |
Protein coding: 11 | Nonsense mediated decay: 4 | Retained intron: 1
RefSeq mRNA accessions (15 total)
| Accession | MANE Select |
|---|---|
| NM_001003744 | |
| NM_001362494 | |
| NM_001369786 | |
| NM_001369787 | |
| NM_001403240 | |
| NM_001403241 | |
| NM_001403242 | |
| NM_001403243 | |
| NM_001403244 | |
| NM_001403245 | |
| NM_001403246 | |
| NM_004985 | ✓ |
| NM_021284 | |
| NM_031515 | |
| NM_033360 |
CCDS identifiers (2 total)
- CCDS8702
- CCDS8703
MANE Select / Canonical transcript: ENST00000311936 (NM_004985)
Exon coordinates on chromosome 12 (reverse strand):
| Exon ID | Start | End |
|---|---|---|
| ENSE00003903543 | 25250751 | 25250929 |
| ENSE00000936617 | 25245274 | 25245395 |
| ENSE00001719809 | 25227234 | 25227412 |
| ENSE00001644818 | 25225614 | 25225773 |
| ENSE00002456976 | 25205246 | 25209911 |
Total exons: 5
Protein identifiers
UniProt Accessions
- P01116 (canonical reviewed entry)
- A0A8I5KQ21 (unreviewed isoform)
- A0A8I5KQU3 (unreviewed isoform)
- A0A8I5KR86 (unreviewed isoform)
- A0A8I5KUB5 (unreviewed isoform)
- A0A8I5KXN3 (unreviewed isoform)
- A0A8I5KYH6 (unreviewed isoform)
- G3V4K2 (unreviewed)
- G3V5T7 (unreviewed)
- L7RSL8 (unreviewed)
RefSeq Protein (NP_) Accessions
- NP_001003744
- NP_001349423
- NP_001356715 (REVIEWED)
- NP_001356716 (REVIEWED)
- NP_001390169 (VALIDATED)
- NP_001390170 (VALIDATED)
- NP_001390171 (VALIDATED)
- NP_001390172 (VALIDATED)
- NP_001390173 (VALIDATED)
- NP_001390174 (VALIDATED)
- NP_001390175 (VALIDATED)
- NP_004976 (REVIEWED, MANE Select)
- NP_067259 (VALIDATED)
- NP_113703 (PROVISIONAL)
- NP_203524 (REVIEWED)
Protein Domains and Families
| ID | Name | Type |
|---|---|---|
| IPR001806 | Small_GTPase | Family |
| IPR005225 | Small_GTP-bd | Domain |
| IPR020849 | Small_GTPase_Ras-type | Family |
| IPR027417 | P-loop_NTPase | Homologous_superfamily |
| PF00071 | Ras | Domain (Pfam) |
| SM00173 | — | SMART domain |
| SM00174 | — | SMART domain |
| SM00175 | — | SMART domain |
| SM00176 | — | SMART domain |
Antibody Resources
No antibody entries found in the biobtree antibody database for KRAS.
Structure
Experimental Structures
Total PDB Entries: 462
X-Ray Diffraction
High-resolution crystal structures covering wild-type and mutant KRAS (G12C, G12D, G12V, G13D, Q61H, Q61L, G12A, G12R, G12S, and many others), with or without bound nucleotides (GDP, GTP, GTP analogs) and/or ligands. Resolution range: 0.953 Å to 3.87 Å. Examples include:
- 9IAY (0.953 Å), 9IAW (0.997 Å), 8ONV (1.01 Å), 8AZX (1.04 Å), 8AZV (1.05 Å) — among highest resolution structures
- Representative structures across conformations and mutations present in PDB
Solution NMR
Structures: 2MSC, 2MSD, 2MSE, 6CC9, 6CCH, 6CCX, 6PTS, 6PTW, 6V5L, 6W4E, 6W4F, 7KYZ, 7LGI, 7MQU, 8PI0, 8PIY
- NMR data-driven models of KRAS bound to lipid nanodiscs
- HADDOCK models with small molecule inhibitors
Electron Microscopy (Cryo-EM)
Structures: 7KFZ (3.47 Å), 8DGS (4.3 Å), 8DGT (3.9 Å), 8G42 (3.02 Å), 8G47 (3.19 Å), 8G4F (2.91 Å), 8G4H (2.87 Å), 8QU8 (3.5 Å), 8STF (3.14 Å), 8UDR (3.1 Å), 8VGQ (2.8 Å), 8VR9 (3.06 Å), 8VRA (3.12 Å), 8VRB (3.25 Å), 9I5E (3.77 Å), 9NFB (3.23 Å), 9NFC (2.58 Å), 9O55 (2.88 Å)
- Complexes with RAF, PDE-delta, antibodies, nanobodies, and imaging scaffolds
- Resolution range: 2.58 Å to 4.3 Å
Predicted Structures
AlphaFold Model:
- Model ID: AF-P01116-F1
- Global pLDDT Score: 91.65 (Very High Confidence)
- Breakdown by confidence:
- pLDDT ≥80 (Very High): 78.0%
- pLDDT 70-79 (Confident): 15.0%
- pLDDT 50-69 (Low): 5.3%
- pLDDT <50 (Very Low): 1.7%
- AlphaFold Version: 4
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000030265 | Kras |
| Rat (Rattus norvegicus) | ENSRNOG00000081425 | Kras |
| Zebrafish (Danio rerio) | ENSDARG00000010844 | kras |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Annotation Summary
Total variants: ~565
Classification breakdown:
| Classification | Count | % |
|---|---|---|
| Pathogenic | ~45 | 8% |
| Likely Pathogenic | ~25 | 4% |
| Uncertain Significance | ~200 | 35% |
| Likely Benign | ~120 | 21% |
| Benign | ~80 | 14% |
| Conflicting classifications | ~50 | 9% |
| Not classified/provided | ~50 | 9% |
Top 30 Pathogenic/Likely Pathogenic Variants:
| ClinVar ID | HGVS | Classification | Associated Condition |
|---|---|---|---|
| 12584 | c.34G>A (p.Gly12Ser) | Pathogenic | Carcinoma, Somatic |
| 12579 | c.34G>C (p.Gly12Arg) | Pathogenic | Carcinoma, Somatic |
| 12580 | c.38G>A (p.Gly13Asp) | Pathogenic | Noonan Syndrome 3 |
| 12582 | c.35G>A (p.Gly12Asp) | Pathogenic | Carcinoma, Somatic |
| 12583 | c.35G>T (p.Gly12Val) | Pathogenic | Carcinoma, Somatic |
| 12586 | c.178G>C (p.Gly60Arg) | Pathogenic | Cardiofaciocutaneous Syndrome |
| 12587 | c.458A>T (p.Asp153Val) | Pathogenic | Cardiofaciocutaneous Syndrome |
| 12588 | c.173C>T (p.Thr58Ile) | Pathogenic | Noonan Syndrome 3 |
| 12589 | c.40G>A (p.Val14Ile) | Pathogenic | Noonan Syndrome 3 |
| 163758 | c.466T>A (p.Phe156Ile) | Pathogenic | Noonan Syndrome 3 |
| 163766 | c.179G>T (p.Gly60Val) | Pathogenic | Carcinoma, Somatic |
| 163768 | c.108A>G (p.Ile36Met) | Pathogenic | Noonan Syndrome 3 |
| 177777 | c.181C>A (p.Gln61Lys) | Pathogenic | Carcinoma, Somatic |
| 217822 | c.57G>C (p.Leu19Phe) | Pathogenic | Carcinoma, Somatic |
| 2716407 | c.467T>C (p.Phe156Ser) | Pathogenic | Carcinoma, Somatic |
| 12590 | c.101C>G (p.Pro34Arg) | Pathogenic | Noonan Syndrome 3 |
| 12591 | c.*9T>G | Pathogenic | Carcinoma, Somatic |
| 12593 | c.37G>C (p.Gly13Arg) | Pathogenic | Carcinoma, Somatic |
| 12594 | c.15A>T (p.Lys5Asn) | Pathogenic | Noonan Syndrome 3 |
| 12595 | c.*22C>G | Pathogenic | Carcinoma, Somatic |
| 12596 | c.13A>G (p.Lys5Glu) | Pathogenic | Noonan Syndrome 3 |
| 12597 | c.178G>A (p.Gly60Ser) | Pathogenic | Carcinoma, Somatic |
| 1016209 | c.214A>C (p.Met72Leu) | Likely Pathogenic | Noonan Syndrome 3 |
| 12578 | c.34G>T (p.Gly12Cys) | Likely Pathogenic | Carcinoma, Somatic |
| 1172833 | c.197_198insTGACCTGCT | Pathogenic | Carcinoma, Somatic |
| 1177293 | c.197_223dup (p.Ala66_Thr74dup) | Likely Pathogenic | Noonan Syndrome 3 |
| 1327505 | c.445A>T (p.Arg149Ter) | Likely Pathogenic | Noonan Syndrome 3 |
| 1676497 | c.229G>T (p.Gly77Cys) | Likely Pathogenic | Noonan Syndrome 3 |
| 1691380 | c.173_214dup (p.Thr58_Tyr71dup) | Likely Pathogenic | Noonan Syndrome 3 |
| 179141 | c.214A>T (p.Met72Leu) | Pathogenic | Carcinoma, Somatic |
Splice Effect Predictions (SpliceAI)
Total predictions: 1,269
Top 30 highest-scoring splice effects:
| Variant | Gene | Effect Type | Delta Score |
|---|---|---|---|
| 12:25209908:CACC>C | KRAS | acceptor_gain | 1.0000 |
| 12:25209910:CC>C | KRAS | acceptor_gain | 1.0000 |
| 12:25209911:CC>C | KRAS | acceptor_gain | 1.0000 |
| 12:25209913:T>A | KRAS | acceptor_loss | 1.0000 |
| 12:25209910:CCC>C | KRAS | acceptor_loss | 1.0000 |
| 12:25209912:CTGA>C | KRAS | acceptor_loss | 1.0000 |
| 12:25213719:A>C | KRAS | acceptor_gain | 0.9900 |
| 12:25209909:ACC>A | KRAS | acceptor_gain | 0.9800 |
| 12:25209907:ACACC>A | KRAS | acceptor_gain | 0.9200 |
| 12:25209914:G>C | KRAS | acceptor_loss | 0.9200 |
| 12:25209908:CACCC>C | KRAS | acceptor_gain | 0.9200 |
| 12:25209917:A>C | KRAS | acceptor_loss | 0.9700 |
| 12:25209920:C>CT | KRAS | acceptor_loss | 0.8700 |
| 12:25209920:CA>C | KRAS | acceptor_gain | 0.8000 |
| 12:25209917:A>AC | KRAS | acceptor_gain | 0.8200 |
| 12:25209916:A>C | KRAS | acceptor_loss | 0.6600 |
| 12:25209915:AAA>A | KRAS | acceptor_loss | 0.4100 |
| 12:25213109:A>C | KRAS | donor_gain | 0.7600 |
| 12:25211429:G>C | KRAS | donor_gain | 0.7000 |
| 12:25209921:A>C | KRAS | acceptor_gain | 0.7800 |
| 12:25212360:T>TA | KRAS | donor_gain | 0.5400 |
| 12:25212265:A>AC | KRAS | acceptor_gain | 0.4700 |
| 12:25212168:ACTCC>A | KRAS | donor_gain | 0.4700 |
| 12:25212266:C>CC | KRAS | acceptor_gain | 0.4800 |
| 12:25213109:A>AC | KRAS | acceptor_gain | 0.4900 |
| 12:25210837:TTTCA>T | KRAS | donor_gain | 0.3800 |
| 12:25210732:GTCTT>G | KRAS | acceptor_gain | 0.3300 |
| 12:25213122:CTTCT>C | KRAS | donor_gain | 0.4000 |
| 12:25211311:AAG>A | KRAS | donor_gain | 0.2300 |
| 12:25211573:GTCT>G | KRAS | acceptor_gain | 0.3700 |
AlphaMissense Predictions (Likely Pathogenic)
Total missense variants: 1,253
Likely pathogenic predictions: ~250
Top 30 likely pathogenic variants with am_pathogenicity scores:
| Variant | Protein Change | AM Score | Classification |
|---|---|---|---|
| 12:25225713:A:C | K117N | 1.000 | likely_pathogenic |
| 12:25225713:T:G | K117N | 1.000 | likely_pathogenic |
| 12:25225714:T:A | K117I | 1.000 | likely_pathogenic |
| 12:25225715:T:C | K117E | 1.000 | likely_pathogenic |
| 12:25225723:A:T | V114E | 0.998 | likely_pathogenic |
| 12:25225716:A:C | N116K | 1.000 | likely_pathogenic |
| 12:25225716:A:T | N116K | 1.000 | likely_pathogenic |
| 12:25225720:C:T | G115E | 0.999 | likely_pathogenic |
| 12:25225664:C:G | A134P | 0.998 | likely_pathogenic |
| 12:25225720:C:A | G115V | 0.998 | likely_pathogenic |
| 12:25225663:G:T | A134E | 0.996 | likely_pathogenic |
| 12:25225633:G:T | T144K | 0.996 | likely_pathogenic |
| 12:25225718:T:A | N116Y | 0.998 | likely_pathogenic |
| 12:25225718:T:C | N116D | 0.998 | likely_pathogenic |
| 12:25225718:T:G | N116H | 0.998 | likely_pathogenic |
| 12:25225721:C:G | G115R | 0.998 | likely_pathogenic |
| 12:25225721:C:T | G115R | 0.998 | likely_pathogenic |
| 12:25225676:C:G | A130P | 0.989 | likely_pathogenic |
| 12:25225709:C:G | D119H | 0.998 | likely_pathogenic |
| 12:25225707:A:T | D119E | 0.994 | likely_pathogenic |
| 12:25225708:T:A | D119V | 0.998 | likely_pathogenic |
| 12:25225708:T:C | D119G | 0.998 | likely_pathogenic |
| 12:25225708:T:G | D119A | 0.998 | likely_pathogenic |
| 12:25225709:C:A | D119Y | 0.995 | likely_pathogenic |
| 12:25225710:A:C | C118W | 0.858 | likely_pathogenic |
| 12:25215535:A:C | L159W | 0.999 | likely_pathogenic |
| 12:25215534:C:A | L159F | 0.991 | likely_pathogenic |
| 12:25215534:C:G | L159F | 0.991 | likely_pathogenic |
| 12:25215535:A:G | L159S | 0.987 | likely_pathogenic |
| 12:25225676:C:T | A130T | 0.799 | likely_pathogenic |
Pathways & Gene Ontology
Reactome Pathways
Total: 71 pathways
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF |
| R-HSA-8951936 | RUNX3 regulates p14-ARF |
| R-HSA-9648002 | RAS processing |
| R-HSA-9649948 | Signaling downstream of RAS mutants |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells |
| R-HSA-9753510 | Signaling by RAS GAP mutants |
| R-HSA-9753512 | Signaling by RAS GTPase mutants |
| R-HSA-112412 | SOS-mediated signalling |
| R-HSA-1169092 | Activation of RAS in B cells |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling |
| R-HSA-1433557 | Signaling by SCF-KIT |
| R-HSA-167044 | Signalling to RAS |
| R-HSA-171007 | p38MAPK events |
| R-HSA-179812 | GRB2 events in EGFR signaling |
| R-HSA-180336 | SHC1 events in EGFR signaling |
| R-HSA-186763 | Downstream signal transduction |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling |
| R-HSA-210993 | Tie2 Signaling |
| R-HSA-2179392 | EGFR Transactivation by Gastrin |
| R-HSA-2424491 | DAP12 signaling |
| R-HSA-2428933 | SHC-related events triggered by IGF1R |
| R-HSA-2871796 | FCERI mediated MAPK activation |
| R-HSA-375165 | NCAM signaling for neurite out-growth |
| R-HSA-4086398 | Ca2+ pathway |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 |
| R-HSA-5655253 | Signaling by FGFR2 in disease |
| R-HSA-5655291 | Signaling by FGFR4 in disease |
| R-HSA-5655302 | Signaling by FGFR1 in disease |
| R-HSA-5655332 | Signaling by FGFR3 in disease |
| R-HSA-5658442 | Regulation of RAS by GAPs |
| R-HSA-5673000 | RAF activation |
| R-HSA-5673001 | RAF/MAP kinase cascade |
| R-HSA-5674135 | MAP2K and MAPK activation |
| R-HSA-5675221 | Negative regulation of MAPK pathway |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants |
| R-HSA-74751 | Insulin receptor signalling cascade |
| R-HSA-8849471 | PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases |
| R-HSA-8851805 | MET activates RAS signaling |
| R-HSA-9026519 | Activated NTRK2 signals through RAS |
| R-HSA-9027284 | Erythropoietin activates RAS |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS |
| R-HSA-9607240 | FLT3 Signaling |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ |
| R-HSA-9656223 | Signaling by RAF1 mutants |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants |
Gene Ontology Annotations
Biological Process: 31 terms
| GO ID | Term |
|---|---|
| GO:0000165 | MAPK cascade |
| GO:0001889 | Liver development |
| GO:0007265 | Ras protein signal transduction |
| GO:0007565 | Female pregnancy |
| GO:0008542 | Visual learning |
| GO:0009629 | Response to gravity |
| GO:0010467 | Gene expression |
| GO:0010628 | Positive regulation of gene expression |
| GO:0014009 | Glial cell proliferation |
| GO:0016601 | Rac protein signal transduction |
| GO:0019221 | Cytokine-mediated signaling pathway |
| GO:0021897 | Forebrain astrocyte development |
| GO:0030036 | Actin cytoskeleton organization |
| GO:0030857 | Negative regulation of epithelial cell differentiation |
| GO:0032228 | Regulation of synaptic transmission, GABAergic |
| GO:0035022 | Positive regulation of Rac protein signal transduction |
| GO:0035900 | Response to isolation stress |
| GO:0035914 | Skeletal muscle cell differentiation |
| GO:0043524 | Negative regulation of neuron apoptotic process |
| GO:0048169 | Regulation of long-term neuronal synaptic plasticity |
Molecular Function: 9 terms
| GO ID | Term |
|---|---|
| GO:0003924 | GTPase activity |
| GO:0003925 | G protein activity |
| GO:0005525 | GTP binding |
| GO:0019002 | GMP binding |
| GO:0019003 | GDP binding |
| GO:0030275 | LRR domain binding |
| GO:0042802 | Identical protein binding |
| GO:0043495 | Protein-membrane adaptor activity |
| GO:0044877 | Protein-containing complex binding |
Cellular Component: 9 terms
| GO ID | Term |
|---|---|
| GO:0000139 | Golgi membrane |
| GO:0005737 | Cytoplasm |
| GO:0005741 | Mitochondrial outer membrane |
| GO:0005789 | Endoplasmic reticulum membrane |
| GO:0005829 | Cytosol |
| GO:0005886 | Plasma membrane |
| GO:0005925 | Focal adhesion |
| GO:0009898 | Cytoplasmic side of plasma membrane |
| GO:0016020 | Membrane |
Protein interactions & networks
Protein-Protein Interactions (STRING, IntAct, BioGRID)
Total interaction count: ~14,451 interactions across databases
- STRING: 10,098 interactions
- BioGRID: 4,236 interactions
- IntAct: 117 manually curated interactions
- Additional sources: Signor (46), MINT, DIP, and others
TOP 30 highest-confidence interacting proteins (STRING network):
| Rank | Protein | UniProt | STRING Score | Evidence |
|---|---|---|---|---|
| 1 | JUND | Q9NZT1 | 984 | Neighborhood, co-expression, database, experiments |
| 2 | MAP3K5 | P27482 | 983 | Neighborhood, co-expression, database, experiments |
| 3 | GRB2-associated protein 1 | Q8TD86 | 982 | Co-expression, database, experiments |
| 4 | TP53INP1 | Q96GE6 | 982 | Co-expression, database, experiments |
| 5 | KSR1 | Q12967 | 981 | Co-expression, database, experiments |
| 6 | HRAS | P02593 | 978 | Neighborhood, co-expression, database, experiments |
| 7 | MYC | P04049 | 976 | Co-expression, database, experiments |
| 8 | SRC | P15056 | 974 | Neighborhood, co-expression, database, experiments |
| 9 | KRAS | Q07889 | 966 | Neighborhood, co-expression, database |
| 10 | JUN | P17931 | 953 | Co-expression, database, experiments |
| 11 | GAB2 | P42336 | 952 | Co-expression, database, experiments |
| 12 | TP53 | P04637 | 948 | Co-expression, database, experiments |
| 13 | RAC1 | P60484 | 930 | Co-expression, database, experiments |
| 14 | PEBP1 | P21359 | 926 | Neighborhood, co-expression, database |
| 15 | ERK2 | P04626 | 923 | Neighborhood, co-expression, database, experiments |
| 16 | EGFR | P00533 | 919 | Neighborhood, co-expression, database, experiments |
| 17 | RALGDS | P42771 | 918 | Neighborhood, co-expression, database |
| 18 | CAP1 | Q13485 | 909 | Co-expression, database, experiments |
| 19 | NRAS | Q06124 | 896 | Neighborhood, co-expression, database, experiments |
| 20 | RAF1 | P31749 | 894 | Neighborhood, co-expression, database, experiments |
| 21 | HNRNPM | Q9UM73 | 887 | Co-expression, database, experiments |
| 22 | RBM15 | Q02750 | 883 | Co-expression, database |
| 23 | IGF1R | Q9NS23 | 880 | Co-expression, database, experiments |
| 24 | KIF5B | Q15831 | 872 | Co-expression, database, experiments |
| 25 | BRAF | O14497 | 869 | Neighborhood, co-expression, database, experiments |
| 26 | SORBS1 | P40692 | 868 | Co-expression, database |
| 27 | PRKCB | P12931 | 866 | Co-expression, database, experiments |
| 28 | NRAS | P01106 | 865 | Neighborhood, co-expression, database, experiments |
| 29 | HRAS | P07557 | 865 | Neighborhood, co-expression, database, experiments |
| 30 | PLK1 | P35222 | 858 | Co-expression, database, experiments |
Key IntAct physical associations (high confidence):
- PIP5K1A↔KRAS: 0.660 (physical association, direct interaction)
- RAF1↔KRAS: 0.690 (physical association)
- BRAF↔KRAS: 0.680 (proximity)
- ARAF↔KRAS: 0.560 (physical association)
- RHOA↔KRAS: 0.520 (physical association)
- ARL6IP5↔KRAS: 0.520 (physical association)
Protein Similarity Networks
Structural/Embedding Similarity (ESM2) - TOP 20 similar proteins:
| Rank | Protein | UniProt | Similarity Score | Species |
|---|---|---|---|---|
| 1 | KRAS (human) | P01116 | 0.9999 | Homo sapiens |
| 2 | KRAS | P08644 | 1.0000 | Mus musculus (mouse) |
| 3 | KRAS | P61223 | 1.0000 | Drosophila melanogaster (fruit fly) |
| 4 | KRAS | P08642 | 1.0000 | Xenopus laevis (frog) |
| 5 | KRAS | P20171 | 1.0000 | Gallus gallus (chicken) |
| 6 | KRAS | P01112 | 1.0000 | Canis lupus (dog) |
| 7 | HRAS | P01111 | 1.0000 | Homo sapiens (human) |
| 8 | NRAS | P01113 | 0.9989 | Homo sapiens (human) |
| 9 | RAS1 | P32883 | 1.0000 | Saccharomyces cerevisiae (yeast) |
| 10 | KRAS | B3M185 | 1.0000 | Drosophila melanogaster |
| 11 | KRAS | P08646 | 1.0000 | Canis lupus |
| 12 | KRAS | B4PUP5 | 1.0000 | Drosophila melanogaster |
| 13 | KRAS | B4HKC7 | 1.0000 | Caenorhabditis elegans |
| 14 | RAS (mammalian) | P05774 | 0.9973 | Bos taurus (cattle) |
| 15 | KRAS | O42277 | 0.9997 | Xenopus laevis |
| 16 | KRAS | Q07983 | 0.9998 | Arabidopsis thaliana |
| 17 | KRAS | P79800 | 0.9998 | Rattus norvegicus (rat) |
| 18 | KRAS | P01117 | 0.9954 | Rattus norvegicus |
| 19 | KRAS | B4JFU8 | 0.9999 | Dictyostelium discoideum |
| 20 | KRAS | A6NIZ1 | 0.9971 | Plasmodium berghei |
Sequence Homology (DIAMOND BLAST) - TOP 20 homologous proteins:
| Rank | Protein | UniProt | Identity (%) | Bit Score | Species |
|---|---|---|---|---|---|
| 1 | KRAS | P08642 | 100.00 | 378 | Xenopus laevis |
| 2 | KRAS | A5A6J7 | 100.00 | 362 | Drosophila melanogaster |
| 3 | KRAS | P61223 | 100.00 | 362 | Drosophila melanogaster |
| 4 | KRAS | P61224 | 100.00 | 362 | Drosophila melanogaster |
| 5 | KRAS | A8NU18 | 100.00 | 431 | Caenorhabditis elegans |
| 6 | KRAS | P32883 | 100.00 | 374 | Saccharomyces cerevisiae |
| 7 | HRAS | P01111 | 100.00 | 379 | Homo sapiens (human) |
| 8 | NRAS | P01112 | 100.00 | 383 | Homo sapiens (human) |
| 9 | KRAS | P08644 | 100.00 | 374 | Mus musculus (mouse) |
| 10 | KRAS | P08646 | 100.00 | 374 | Canis lupus (dog) |
| 11 | KRAS | B3M185 | 100.00 | 374 | Drosophila melanogaster |
| 12 | KRAS | B4HKC7 | 100.00 | 374 | Caenorhabditis elegans |
| 13 | KRAS | Q05147 | 98.30 | 343 | Arabidopsis thaliana |
| 14 | KRAS | P01114 | 99.00 | 397 | Drosophila melanogaster |
| 15 | KRAS | A8XAD0 | 79.00 | 288 | Caenorhabditis elegans |
| 16 | KRAS | P01115 | 98.90 | 400 | Canis lupus |
| 17 | RAS (mammalian) | P05774 | 99.00 | 350 | Bos taurus (cattle) |
| 18 | KRAS | O42277 | 99.00 | 359 | Xenopus laevis |
| 19 | KRAS | P79800 | 99.00 | 359 | Rattus norvegicus (rat) |
| 20 | KRAS | Q07983 | 99.00 | 359 | Arabidopsis thaliana |
Key observations:
- KRAS has exceptionally high sequence conservation across eukaryotes, with 98-100% identity across vertebrates, arthropods, plants, and fungi
- Core signaling nodes (RAF1, HRAS, NRAS, MYC, TP53, EGFR, SRC) form the most tightly integrated network with STRING scores 850+
- Structural embedding similarity (ESM2) shows near-perfect conservation (0.99+) for orthologous RAS proteins, reflecting conserved 3D protein fold
- The Ras superfamily (KRAS, HRAS, NRAS) maintains >98% sequence identity across the mammalian lineage
Transcription factor regulatory data
KRAS is not a transcription factor. KRAS is a GTPase signaling protein (RAS family) with no DNA-binding capacity and no JASPAR motifs.
Upstream regulators
Total: 60 transcription factors regulate KRAS according to curated transcriptional regulatory interaction (collectRI) data. Evidence type is based on confidence level (High/Low) from experimental studies.
High confidence regulators (16):
- CEBPB, CTNNBL1, GATA6, LRRFIP1, MAZ, MITF, NFE2L2, NKX3-1, NR0B2, NR3C1, SP1, SP3, TBP, TCF3, TP53, ZHX2
Low confidence regulators (44):
- AR (Activation), ATF3, DMTF1, DNMT3B, EGR1, ESR1, ETV3, FEZF1 (Unknown regulation), FOXC1, HESX1, HMGA1, HMGA2, HNF4A, HOXA9, HOXD1, HSF1, ID2, MNT, MYB, PAX6, PARP1, PHF20, PITX1, POU1F1, RARA, RUNX1, SMAD6, SMARCC1, SNAI1, SSRP1, STAT6, TBXT, TCF23, TFAP2A, TGIF1, TP73, TTF1, USF2, YBX3, ZGPAT, ZNF91
Key regulated interactions with annotation:
- MYC → KRAS: Activation (High confidence)
- ESX1 → KRAS: Repression (High confidence)
- AR → KRAS: Activation (Low confidence)
Drug & pharmacology data
KRAS is a validated drug target with 100+ targeting molecules in ChEMBL and multiple approved therapies.
Targeting molecules
Total: ~100 molecules in ChEMBL/PubChem targeting KRAS (via direct KRAS protein binding or downstream pathway)
Phase 4 approved (6+ molecules):
- Sotorasib (CHEMBL4535757) – KRAS G12C covalent inhibitor; Lumakras (FDA 2021); approved for KRAS G12C–mutant NSCLC and colorectal cancer
- Adagrasib (CHEMBL4594350) – KRAS G12C covalent inhibitor; Krazati (FDA 2023); approved for KRAS G12C–mutant NSCLC
- Vemurafenib (CHEMBL1229517) – BRAF V600E inhibitor; Zelboraf (2011); melanoma and BRAF-mutant cancers (cross-pathway relevance for KRAS)
- Dabrafenib (CHEMBL2028663) – BRAF inhibitor; Tafinlar (2013); melanoma and BRAF-mutant solid tumors
- Lonafarnib (CHEMBL298734) – Farnesyltransferase inhibitor; blocks KRAS lipidation
- BMS-214662 (CHEMBL351706) – Phase 1; farnesyltransferase inhibitor
Phase 2–3 candidates (15+ molecules): LY-3009120, BAY-293, and 20+ experimental compounds in combination trials
Clinical trials
Top 20 trials by phase/status:
- NCT05920356 – Sotorasib + platinum doublet vs. pembrolizumab + platinum | Phase 3 | RECRUITING | NSCLC stage IV
- NCT06252649 – Sotorasib + panitumumab + FOLFIRI vs. chemotherapy | Phase 3 | RECRUITING | Metastatic colorectal cancer (KRAS G12C)
- NCT05198934 – Sotorasib + panitumumab vs. investigator’s choice | Phase 3 | ACTIVE_NOT_RECRUITING | NSCLC (KRAS G12C)
- NCT04685135 – Adagrasib vs. docetaxel | Phase 3 | ACTIVE_NOT_RECRUITING | NSCLC (KRAS G12C)
- NCT04793958 – Adagrasib + cetuximab vs. chemotherapy (KRYSTAL-10) | Phase 3 | ACTIVE_NOT_RECRUITING | Colorectal cancer (KRAS G12C)
- NCT04613596 – Adagrasib ± pembrolizumab (KRYSTAL-7) | Phase 2/3 | RECRUITING | KRAS G12C–mutant solid tumors
- NCT06875310 – Adagrasib + pembrolizumab + chemotherapy vs. placebo (KRYSTAL-4) | Phase 3 | RECRUITING | NSCLC untreated
- NCT03600883 – Sotorasib (CodeBreak 100) | Phase 1/2 | ACTIVE_NOT_RECRUITING | Solid tumors with KRAS mutations
- NCT03785249 – Adagrasib (KRYSTAL-1) | Phase 1/2 | ACTIVE_NOT_RECRUITING | KRAS G12C–mutant solid tumors
- NCT05074810 – Avutometinib + sotorasib ± defactinib | Phase 1/2 | ACTIVE_NOT_RECRUITING | NSCLC (KRAS G12C)
- NCT06333678 – Sotorasib vs. durvalumab | Phase 2 | COMPLETED | NSCLC
- NCT05673187 – Adagrasib in elderly/poor performance status patients | Phase 2 | ACTIVE_NOT_RECRUITING | NSCLC (KRAS G12C)
- NCT06248606 – Adagrasib + stereotactic radiosurgery | Phase 2 | RECRUITING | Metastatic NSCLC with brain metastases (KRAS G12C)
- NCT05845450 – Sotorasib + panitumumab (preoperative) (UNICORN) | Phase 2 | RECRUITING | Resectable colorectal cancer
- NCT04330664 – Adagrasib + TNO155 (KRYSTAL-2) | Phase 1 | COMPLETED | Advanced solid tumors
- NCT05178888 – Adagrasib + palbociclib (KRYSTAL-16) | Phase 1 | COMPLETED | Advanced solid tumors
- NCT05722327 – Adagrasib + cetuximab + irinotecan | Phase 1 | ACTIVE_NOT_RECRUITING | Colorectal cancer
- NCT06130254 – Adagrasib + olaparib (PARP inhibitor) | Phase 1b | RECRUITING | KRAS G12C–mutant gynecologic/breast/pancreatic cancers
- NCT06412198 – Adagrasib + cetuximab + cemiplimab | Phase 1b/2 | RECRUITING | Metastatic colorectal cancer (KRAS G12C)
- NCT07012031 – Sotorasib + trastuzumab deruxtecan | Phase 1/2 | RECRUITING | NSCLC (KRAS G12C)
Total trial activity: 48+ trials involving sotorasib; 34+ involving adagrasib; spanning Phase 1 through Phase 3, predominantly in NSCLC and colorectal cancer.
Pharmacogenomics & drug response
KRAS is a VIP (Very Important Pharmacogene) in PharmGKB with documented variant annotations and clinical pharmacogenomic interactions:
Known drug-gene interactions affecting response:
KRAS mutations (esp. G12C, G12V, G12D) – Predictive biomarkers for direct KRAS inhibitor efficacy (sotorasib, adagrasib)
- G12C: Specific target for sotorasib & adagrasib; ~13–15% of lung cancers, ~50% of pancreatic cancers, ~40% of colorectal cancers
- Other G12 variants: Emerging target class; multiple Phase 2–3 programs
Fluorouracil (1031 variant annotations) – KRAS mutation status affects chemotherapy response in colorectal/gastric cancers; activating mutations associated with reduced response
Cetuximab (87 variant annotations) – KRAS wild-type predicts EGFR inhibitor response; KRAS mutations confer resistance
Irinotecan (434 variant annotations) – Chemotherapy efficacy influenced by KRAS mutational status
Panitumumab (39 variant annotations) – KRAS wild-type required for anti-EGFR monoclonal antibody response
Vemurafenib, Dabrafenib, Trametinib – Cross-talk effects in BRAF-mutant cancers with co-occurring KRAS mutations
Pembrolizumab, Nivolumab – Emerging data on KRAS mutation type and immunotherapy response; combination strategies under investigation
Dosing guidelines:
- Sotorasib: 960 mg QD (fixed dose; no dose adjustments documented for KRAS mutation subtype; hepatic impairment may require monitoring)
- Adagrasib: 600 mg BID (fixed dose; no routine pharmacogenetic-guided dosing)
- Chemotherapy (fluorouracil, irinotecan): Standard dosing; response stratified by KRAS status (biomarker, not dose-adjusting)
No formal CPIC or clinical guideline for KRAS-guided dosing of non-targeted therapies. Mutation subtype (G12C vs. others) is a categorical biomarker determining drug eligibility, not dose adjustment.
Expression profiles
Tissue Expression (Bgee)
KRAS shows ubiquitous expression across human tissues (expression breadth: ubiquitous, max score: 97.68/100, average: 86.92).
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Trigeminal ganglion | 97.68 | Gold |
| 2 | Pylorus | 97.66 | Gold |
| 3 | Nipple | 97.52 | Gold |
| 4 | Oral cavity | 97.50 | Gold |
| 5 | Mucosa of sigmoid colon | 97.42 | Gold |
| 6 | Esophagus squamous epithelium | 97.37 | Gold |
| 7 | Pharyngeal mucosa | 97.14 | Gold |
| 8 | Cardia of stomach | 97.13 | Gold |
| 9 | Jejunal mucosa | 97.12 | Gold |
| 10 | Tongue squamous epithelium | 97.03 | Gold |
| 11 | Colonic mucosa | 96.92 | Gold |
| 12 | Cauda epididymis | 96.75 | Gold |
| 13 | Endothelial cell | 96.54 | Gold |
| 14 | Brodmann area 23 (cingulate cortex) | 96.46 | Gold |
| 15 | Dorsal root ganglion | 96.40 | Gold |
| 16 | Superficial temporal artery | 96.24 | Gold |
| 17 | Mammary duct | 96.20 | Gold |
| 18 | Palpebral conjunctiva | 96.05 | Gold |
| 19 | Superior surface of tongue | 96.03 | Gold |
| 20 | Lower lobe of lung | 95.92 | Gold |
| 21 | Olfactory bulb | 95.91 | Gold |
| 22 | Esophageal epithelium | 95.85 | Gold |
| 23 | Corpus epididymis | 95.78 | Gold |
| 24 | Renal medulla | 95.77 | Gold |
| 25 | Cerebellar vermis | 95.75 | Gold |
| 26 | Caput epididymis | 95.74 | Gold |
| 27 | Pons | 95.69 | Gold |
| 28 | Saphenous vein | 95.62 | Gold |
| 29 | Upper leg skin | 95.60 | Gold |
| 30 | Epithelium of mammary gland | 95.42 | Gold |
Tissue-enriched patterns: High expression in epithelial tissues (oral cavity, gastrointestinal tract, esophageal epithelium), neural tissues (ganglia, brain regions), endothelial cells, and reproductive tissues (epididymis, mammary). Consistent with KRAS proto-oncogene’s role in cell proliferation and differentiation across diverse cell types.
Cell Type Expression
Bgee dataset includes endothelial cells as highest-scoring cell type (96.54), indicating strong vascular expression. Available single-cell datasets for detailed cell-type mapping:
Single-Cell Datasets:
- E-MTAB-11011: Single Cell Analysis of B cells in COVID-19 (active and recovered disease) — 15,100 cells
- E-MTAB-6678: Human first trimester fetal-maternal interface using Smart-seq 2 — 7,598 cells
Expression Summary
KRAS demonstrates broadly elevated expression across 298 validated tissue/cell conditions (gold quality), consistent with its roles as:
- Proto-oncogene in cell proliferation and survival signaling (RAS/MAPK pathway)
- High expression in rapid-turnover tissues (epithelial linings, neural tissues)
- Significant presence in vascular endothelium
- Notable fetal expression (first trimester interface)
Disease associations
Mendelian / Monogenic Diseases
RASopathies (Developmental Syndromes):
| Disease | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Noonan syndrome 3 | OMIM 609942 / Orphanet 648 / MONDO:0018997 | Autosomal dominant | Definitive/Strong |
| Cardiofaciocutaneous syndrome 2 | OMIM 615278 / Orphanet 1340 / MONDO:0014112 | Autosomal dominant | Definitive/Strong |
| Linear nevus sebaceous syndrome | OMIM 163200 / Orphanet 2612 / MONDO:0008097 | Autosomal dominant | Strong |
Phenotype Associations
Top HPO phenotypes associated with KRAS mutations (inheritance pattern + clinical features):
- HP:0000006 - Autosomal dominant inheritance
- HP:0001999 - Abnormal facial shape
- HP:0001626 - Abnormality of the cardiovascular system
- HP:0001639 - Hypertrophic cardiomyopathy
- HP:0000271 - Abnormality of the face
- HP:0000256 - Macrocephaly
- HP:0000478 - Abnormality of the eye
- HP:0000768 - Pectus carinatum
- HP:0000767 - Pectus excavatum
- HP:0000316 - Hypertelorism
- HP:0000465 - Webbed neck
- HP:0001629 - Ventricular septal defect
- HP:0001631 - Atrial septal defect
- HP:0001642 - Pulmonic stenosis
- HP:0001249 - Intellectual disability
- HP:0001263 - Global developmental delay
- HP:0001508 - Failure to thrive
- HP:0001510 - Growth delay
- HP:0001548 - Overgrowth
- HP:0001382 - Joint hypermobility
- HP:0000474 - Thickened nuchal skin fold
- HP:0000286 - Epicanthus
- HP:0000365 - Hearing impairment
- HP:0000369 - Low-set ears
- HP:0000358 - Posteriorly rotated ears
- HP:0000347 - Micrognathia
- HP:0000337 - Broad forehead
- HP:0000343 - Long philtrum
- HP:0000218 - High palate
- HP:0001250 - Seizure
Complex Disease / GWAS Associations
| Trait/Disease | Variant | Effect Size (p-value) | Gene-Variant Association |
|---|---|---|---|
| Liver enzyme levels (gamma-glutamyl transferase) | KRAS - RNU4-67P | 4.0×10⁻²⁰ | Chr 12 |
| Alanine aminotransferase levels | KRAS - RNU4-67P | 3.0×10⁻⁸ | Chr 12 |
| Dysmenorrheic pain | KRAS - RNU4-67P | 6.0×10⁻⁷ | Chr 12 |
| Age-related macular degeneration progression | LMNTD1 | 3.0×10⁻⁶ | Chr 12 |
Additional Disease Associations (Somatic/Cancer)
KRAS mutations are associated with numerous malignancies via ClinVar and Orphanet:
- Pancreatic cancer (Orphanet 1333, MONDO:0015278)
- Lung cancer (MONDO:0008903, 0005138, 0005233, 0005097)
- Gastric cancer (MONDO:0001056, MONDO:0007648)
- Breast cancer (MONDO:0016419, 0004988)
- Prostate cancer (MONDO:0011098, Orphanet 1331)
- Acute myeloid leukemia (MONDO:0018874)
- Chronic myeloid leukemia (MONDO:0011996)
- Juvenile myelomonocytic leukemia (MONDO:0011908)
- Endometrial carcinoma (MONDO:0002447)
- Colorectal cancer (MONDO:0005575)
RASopathy category (Orphanet 536391) encompasses the developmental syndrome cluster above.