Protein / target
GTPase KRas
Protein at a glance
Biological role
Protein-containing complex binding
Primary system
Immune system
Strongest disease association
Noonan syndrome 3
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
2 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival (PubMed:22711838, PubMed:23698361). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Activates MAPK1/MAPK3 resulting in phosphorylation and ultimately degradation of GJA1 (By similarity). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (PubMed:24623306). Recognized by LZTR1 that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex (PubMed:40934300)
Subcellular location
Domains and Gene Ontology detail (33)Hide
Gene Ontology
- Ccytoplasm
- Ccytoplasmic side of plasma membrane
- Ccytosol
- Cendoplasmic reticulum membrane
- Cfocal adhesion
- CGolgi membrane
- Cmembrane
- Cmitochondrial outer membrane
- Cplasma membrane
- FG protein activity
- FGDP binding
- FGMP binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·cytokine-mediated signaling pathway
- ·Activation of RAS in B cells
Transcriptional regulation
- ·Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation an…
- ·positive regulation of gene expression
Kinase signalling
- ·Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation an…
View underlying pathways (25)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
GTPase KRas inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm, non-small cell lung carcinoma
GTPase KRas inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, neoplasm, non-small cell lung carcinoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 2,404 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 3 total
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
lung cancer · non-small cell lung carcinoma · malignant pancreatic neoplasm
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- New publicationEfficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer.
- Regulatory approval
Approval: Krazati (EMA)
- New publicationAdagrasib in Advanced Solid Tumors Harboring a <i>KRAS</i><sup><i>G12C</i></sup> Mutation.
- New publicationAdagrasib with or without Cetuximab in Colorectal Cancer with Mutated <i>KRAS</i> G12C.
- New publicationSotorasib in <i>KRAS</i> p.G12C-Mutated Advanced Pancreatic Cancer.
- New publicationAdagrasib in Non-Small-Cell Lung Cancer Harboring a <i>KRAS<sup>G12C</sup></i> Mutation.
- Regulatory approval
Approval: Lumykras (EMA)
- New publicationEGFR Blockade Reverts Resistance to KRAS<sup>G12C</sup> Inhibition in Colorectal Cancer.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.