CTLA4
Chr 2ADcytotoxic T-lymphocyte associated protein 4
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)
Definitive — sufficient evidence for diagnostic panels
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
References
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CTLA4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
PHOENIX: QL1706 Plus Chemotherapy and Bevacizumab in AGA-Resistant, PD-L1 ≥50% Non-Squamous NSCLC
NOT YET RECRUITINGIpilimumab and Nivolumab in Combination With Radiation Therapy in Treating Patients With Stage 2-3 Non-small Lung Cancer
ACTIVE NOT RECRUITINGOlaparib With or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy
RECRUITINGDurvalumab and Tremelimumab After Radioembolization for the Treatment of Unresectable, Locally Advanced Liver Cancer
ACTIVE NOT RECRUITINGDabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
ACTIVE NOT RECRUITINGNeoadjuvant and Adjuvant Anti-PD1 or Combinations for Locoregionally Advanced Melanoma
RECRUITINGNovel Genetic Disorders of the Immune System
RECRUITINGRC48 in Combination With AK104 and Bevacizumab in OCCC
RECRUITINGGenetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study
RECRUITINGProspective Exploration of Vascular Complications Associated With the Use of Immune Checkpoint Inhibitors
NOT YET RECRUITINGAn Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
ACTIVE NOT RECRUITINGLung-MAP: Nivolumab With or Without Ipilimumab as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools