Protein / target
GTPase KRas
Protein at a glance
Biological role
Protein-containing complex binding
Strongest disease association
Noonan syndrome 3
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival.
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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.
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Oncogenic signalling
- ·Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation an…
- ·Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
Receptor tyrosine kinase signalling
- ·SHC1 events in ERBB2 signaling
- ·SHC1 events in ERBB4 signaling
- ·GRB2 events in ERBB2 signaling
Growth-factor signalling
- ·Constitutive Signaling by EGFRvIII
Cell proliferation & survival
- ·positive regulation of cell population proliferation
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
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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
GTPase KRas inhibitor
Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms
GTPase KRas inhibitor
Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene KRAS
Gene-level evidence surfaced through the gene KRASthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
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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 per-type scores above show the calculation.
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Drug development
3 compounds recorded · 2 approved · 1 in clinical development
View all recorded compounds (3)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (10)Hide
Raw Open Targets tractability assessment buckets, by modality.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- New publicationEfficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer.
- Regulatory approval
Approval: Krazati (EMA)
- 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)
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.