CTLA4
Chr 2ADcytotoxic T-lymphocyte associated protein 4
Also known as: ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4, GSE, IDDM12
This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar Variant Classifications
338 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 19 | 6 | 47 | 0 | 72 |
Likely Pathogenic | 5 | 14 | 5 | 0 | 24 |
VUS | 3 | 120 | 17 | 4 | 144 |
Likely Benign | 0 | 8 | 15 | 44 | 67 |
Benign | 0 | 10 | 9 | 2 | 21 |
Conflicting | — | 10 | |||
| Total | 27 | 158 | 93 | 50 | 338 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation
MIM #616100Molecular basis of disorder known
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Novel Genetic Disorders of the Immune System
RECRUITINGA Phase 2 Randomized, Controlled Trial of QL1706 Plus Chemotherapy and Quad Shot for Driver Gene-negative Advanced Non-small Cell Lung Cancer.
NOT YET RECRUITINGNivolumab and Ipilimumab in Treating Patients With Rare Tumors
ACTIVE NOT RECRUITINGGPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
RECRUITINGThe Seven Trial: Exploiting the Unfolded Protein Response
ACTIVE NOT RECRUITINGPhysician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery
ACTIVE NOT RECRUITINGEntinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer
ACTIVE NOT RECRUITINGQL1706 Combined With Chemotherapy in the Treatment of Immune-mediated NSCLC
RECRUITINGRC48 in Combination With AK104 and Bevacizumab in OCCC
RECRUITINGImmun Checkpoint Washout in Patients With Invasive Ductal Breast Cancer
RECRUITINGIpilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery
ACTIVE NOT RECRUITING"Cytotoxic T Lymphocyte-Associated Antigen-4 (CTLA-4) Gene Single-nucleotide Polymorphism in Primary Immune Thrombocytopenic Purpura in Children"
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools