Protein / target
Cytotoxic T-lymphocyte protein 4
Protein at a glance
Biological role
Receptor decoy activity
Primary system
Immune system
Strongest disease association
hypothyroidism
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
2 approved · 4 in clinical development
Research activity
Actively researched
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Inhibitory receptor acting as a major negative regulator of T-cell responses (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:18641304, PubMed:28484017). Acts as a decoy receptor: the affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28 (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:28484017)
Subcellular location
Domains and Gene Ontology detail (19)Hide
Domains & features
Gene Ontology
- Cclathrin-coated endocytic vesicle
- Cexternal side of plasma membrane
- CGolgi apparatus
- Cperinuclear region of cytoplasm
- Cplasma membrane
- Cprotein complex involved in cell adhesion
- Freceptor decoy activity
- Padaptive immune response
- PB cell receptor signaling pathway
- PDNA damage response
- Pimmune response
- Pnegative regulation of B cell proliferation
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
- ·adaptive immune response
- ·B cell receptor signaling pathway
- ·immune response
- ·negative regulation of B cell proliferation
Cell adhesion
- ·protein complex involved in cell adhesion
Apoptosis & cell death
- ·positive regulation of apoptotic process
View underlying pathways (3)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.
Cytotoxic T-lymphocyte protein 4 inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, hepatocellular carcinoma, non-small cell lung carcinoma, hepatocellular 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 1,709 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 · 6 total
clear cell renal carcinoma · non-small cell lung carcinoma · hepatocellular carcinoma
non-small cell lung carcinoma · cervical cancer · soft tissue sarcoma
cervical cancer · gastroesophageal junction adenocarcinoma · gastric adenocarcinoma
non-small cell lung carcinoma · non-small cell lung carcinoma · pancreatic ductal adenocarcinoma
metastatic melanoma · melanoma · colorectal neoplasm
non-small cell lung carcinoma · hepatocellular carcinoma · non-small cell lung carcinoma
Tractability
Safety liabilities
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.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
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 a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- Industry developmentAnother AstraZeneca Emerald glimmers as Imfinzi, Imjudo delay liver cancer progression
- New publicationPlasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial.
- Regulatory approval
Approval: Imjudo (EMA)
- New publicationDurvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.
- New publicationTremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma.
- New publicationEffect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study.
- New publicationDurvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial.
- New publicationDurvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study.
- New publicationTremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer.
- New publicationTremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma.
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.