CTLA4: Cytotoxic T-Lymphocyte Associated Protein 4
Key Immune Checkpoint Regulator in T-Cell Activation and Cancer Immunotherapy
Gene Information Card
| Symbol | CTLA4 |
|---|---|
| Full Name | Cytotoxic T-Lymphocyte Associated Protein 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q33.2 |
| NCBI Gene ID | 1493 ncbi.nlm.nih.gov/gene/1493 |
| Ensembl ID | ENSG00000163599 |
| UniProt ID | P16410 |
| OMIM ID | 123890 |
| HGNC ID | 2505 |
| Aliases | CD152, CTLA-4, GSE, ALPS5, IDDM12, CELIAC3, GRD4 |
Description
CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) encodes a transmembrane receptor that functions as a key immune checkpoint. It is expressed on activated T cells and regulatory T cells (Tregs) and delivers inhibitory signals to downregulate T-cell activation, thereby maintaining immune homeostasis and preventing autoimmunity. CTLA4 competes with CD28 for binding to CD80/CD86 on antigen-presenting cells, acting as a negative regulator of the immune response. Genetic variants and altered expression of CTLA4 are associated with autoimmune diseases, and the protein is a major target for cancer immunotherapy (e.g., ipilimumab).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune Lymphoproliferative Syndrome Type 5 (ALPS5) | Loss-of-function mutations impair CTLA4-mediated inhibition, leading to uncontrolled T-cell proliferation and autoimmunity. | OMIM #616100; PMID: 25329329 |
| Type 1 Diabetes (IDDM12) | Polymorphisms (e.g., rs231775) reduce CTLA4 expression or function, increasing T-cell autoreactivity. | OMIM #601388; PMID: 12679858 |
| Celiac Disease (CELIAC3) | CTLA4 variants (e.g., CT60) alter splicing and expression, contributing to intestinal inflammation. | OMIM #609753; PMID: 12833157 |
| Graves Disease | CTLA4 polymorphisms (e.g., A49G) are associated with reduced inhibitory function and increased thyroid autoantibodies. | PMID: 10631129 |
| Melanoma (therapeutic target) | CTLA4 blockade with ipilimumab enhances anti-tumor T-cell responses; response correlates with CTLA4 expression. | FDA approval; PMID: 20679247 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Appendix | 8.2 | Medium |
| Bone marrow | 6.1 | Low |
| Thymus | 5.4 | Low |
| Lung | 2.3 | Low |
| Small intestine | 1.9 | Low |
| Colon | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 0.8 | Low baseline; inducible upon activation |
| K562 (leukemia) | 0.2 | Very low expression |
| HEK293 (embryonic kidney) | 0.1 | Not typically expressed |
| Primary CD4+ T cells (activated) | 15.3 | High after anti-CD3/CD28 stimulation |
| Primary Tregs | 22.1 | Constitutively high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.49A>G (p.Thr17Ala) | SNP | ~30% in Caucasians | Reduces CTLA4 surface expression; associated with autoimmune risk |
| c.623G>A (p.Arg208Gln) | Missense | <1% | Loss of ligand binding; causes ALPS5 |
| c.550C>T (p.Arg184Trp) | Missense | <0.5% | Impaired dimerization and function; linked to immune dysregulation |
| c.151_152insC (p.Leu51Profs*13) | Frameshift | Rare | Complete loss of function; severe ALPS5 phenotype |
Mutation functional classification
Loss of Function (LOF)
Most CTLA4 mutations (e.g., p.Arg208Gln, p.Arg184Trp, frameshifts) reduce or abolish inhibitory signaling, leading to T-cell hyperactivation and autoimmunity (ALPS5).
Gain of Function (GOF)
No well-characterized gain-of-function mutations in CTLA4; such variants would theoretically suppress immunity but are not clinically reported.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Arg208Gln) can exert dominant-negative effects by disrupting wild-type CTLA4 dimerization and trafficking, causing haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Immune checkpoint signaling (CTLA4-CD80/CD86)
• T cell receptor signaling pathway (KEGG: hsa04660)
• PD-1/PD-L1 and CTLA4 checkpoint pathway (Reactome: R-HSA-389948)
• Costimulation by the CD28 family (Reactome: R-HSA-388841)
Protein Summary
CTLA4 (CD152) is a 223-amino-acid type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. It consists of an extracellular V-like domain, a transmembrane region, and a short cytoplasmic tail containing a YVKM motif that recruits phosphatases (e.g., SHP-2) to attenuate T-cell receptor signaling. CTLA4 is constitutively expressed on regulatory T cells and induced on activated conventional T cells. It binds CD80 (B7-1) and CD86 (B7-2) with higher affinity than CD28, outcompeting the costimulatory receptor and delivering inhibitory signals. The protein functions as a homodimer and is critical for peripheral tolerance. Therapeutic blockade of CTLA4 with monoclonal antibodies (e.g., ipilimumab) unleashes anti-tumor immunity in melanoma and other cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CTLA4 Knockout HEK293 Cell Line | EDC07546 | Human | 1493 | Details Get a Quote |
| CTLA4 Knockout HeLa Cell Line | EDJ-KQ53023 | Human | 1493 | Details Get a Quote |
| CTLA4 Knockout A-549 Cell Line | EDJ-KQ61487 | Human | 1493 | Details Get a Quote |
| CTLA4 Knockout HCT 116 Cell Line | EDJ-KQ69982 | Human | 1493 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
