CTLA4 Gene

HGNC Family CD molecules (CD), Immunoglobulin superfamily domain containing
Name cytotoxic T-lymphocyte-associated protein 4
Description 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]
Summary
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Moreover, CTLA‑4 undergoes rapid clathrin‑mediated internalization and recycling, processes that fine‑tune its cell surface availability and function during immune activation and tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have demonstrated that polymorphisms and splice‐site variants in the CTLA‑4 gene correlate with altered gene expression, protein processing, and ultimately, immune dysregulation. Variants in CTLA‑4 have been associated with increased susceptibility to a spectrum of autoimmune conditions—including type 1 diabetes, autoimmune thyroid diseases, rheumatoid arthritis, and alopecia areata—by compromising its inhibitory capacity and thus predisposing to excessive T‑cell activation. Moreover, investigations in systemic lupus erythematosus and even in settings of aberrant antibody responses in disorders like hemophilia A further underscore the broad relevance of precise CTLA‑4 regulation for maintaining immune homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTherapeutically, blockade of CTLA‑4 with monoclonal antibodies such as ipilimumab or tremelimumab has been a pioneering strategy to disinhibit effector T‑cell responses against tumors, resulting in durable antitumor effects in melanoma and other cancers. However, such immune checkpoint inhibition must be delicately balanced, as releasing CTLA‑4–mediated inhibition can also enhance immune‐related adverse events and even alter the stability and function of regulatory T cells. Recent work underscores that the clinical efficacy of CTLA‑4 blockade is influenced by additional factors—including tumor mutational burden, metabolic competition within the tumor microenvironment, and the interplay with other immune checkpoints—that may ultimately determine patient outcomes in cancer immunotherapy as well as in contexts like transplant tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "47"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Richard V Parry, Jens M Chemnitz, Kenneth A Frauwirth, et al. 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Synonyms CELIAC3, ALPS5, CTLA-4, CD152, GRD4, IDDM12, GSE
Proteins CTLA4_HUMAN
NCBI Gene ID 1493
API
Download Associations
Predicted Functions View CTLA4's ARCHS4 Predicted Functions.
Co-expressed Genes View CTLA4's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CTLA4's ARCHS4 Predicted Functions.

Functional Associations

CTLA4 has 11,202 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 114 datasets.

Click the + buttons to view associations for CTLA4 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of CTLA4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of CTLA4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of CTLA4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
Biocarta Pathways pathways involving CTLA4 protein from the Biocarta Pathways dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of CTLA4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CTLA4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CTLA4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of CTLA4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of CTLA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CCLE Cell Line Gene Mutation Profiles cell lines with CTLA4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with CTLA4 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CTLA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of CTLA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of CTLA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
ClinVar Gene-Phenotype Associations phenotypes associated with CTLA4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CTLA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing CTLA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing CTLA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with CTLA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with CTLA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with CTLA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with CTLA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with CTLA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
dbGAP Gene-Trait Associations traits associated with CTLA4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by CTLA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Curated Gene-Disease Association Evidence Scores diseases involving CTLA4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving CTLA4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores diseases associated with CTLA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with CTLA4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with CTLA4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CTLA4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with CTLA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with CTLA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
DrugBank Drug Targets interacting drugs for CTLA4 protein from the curated DrugBank Drug Targets dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CTLA4 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CTLA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of CTLA4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing CTLA4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with CTLA4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with CTLA4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of CTLA4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with CTLA4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing CTLA4 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of CTLA4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CTLA4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of CTLA4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CTLA4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of CTLA4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of CTLA4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving CTLA4 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving CTLA4 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving CTLA4 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing CTLA4 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing CTLA4 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing CTLA4 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by CTLA4 gene from the curated GO Molecular Function Annotations 2015 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of CTLA4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CTLA4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CTLA4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
Guide to Pharmacology Chemical Ligands of Receptors ligands (chemical) binding CTLA4 receptor from the curated Guide to Pharmacology Chemical Ligands of Receptors dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with CTLA4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWASdb SNP-Disease Associations diseases associated with CTLA4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with CTLA4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of CTLA4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of CTLA4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CTLA4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPO Gene-Disease Associations phenotypes associated with CTLA4 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for CTLA4 from the curated Hub Proteins Protein-Protein Interactions dataset.
HuBMAP ASCT+B Annotations cell types associated with CTLA4 gene from the HuBMAP ASCT+B dataset.
HuBMAP ASCT+B Augmented with RNA-seq Coexpression cell types associated with CTLA4 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset.
HuBMAP Azimuth Cell Type Annotations cell types associated with CTLA4 gene from the HuBMAP Azimuth Cell Type Annotations dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with CTLA4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for CTLA4 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of CTLA4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEA Substrates of Kinases kinases that phosphorylate CTLA4 protein from the curated KEA Substrates of Kinases dataset.
KEGG Pathways pathways involving CTLA4 protein from the KEGG Pathways dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of CTLA4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of CTLA4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of CTLA4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of CTLA4 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LOCATE Curated Protein Localization Annotations cellular components containing CTLA4 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain CTLA4 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by CTLA4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting CTLA4 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of CTLA4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MoTrPAC Rat Endurance Exercise Training tissue samples with high or low expression of CTLA4 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by CTLA4 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Cancer Gene Co-expression Modules co-expressed genes for CTLA4 from the MSigDB Cancer Gene Co-expression Modules dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of CTLA4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
OMIM Gene-Disease Associations phenotypes associated with CTLA4 gene from the curated OMIM Gene-Disease Associations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for CTLA4 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CTLA4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of CTLA4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving CTLA4 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving CTLA4 protein from the Wikipathways PFOCR 2024 dataset.
Phosphosite Textmining Biological Term Annotations biological terms co-occuring with CTLA4 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.
PhosphoSitePlus Substrates of Kinases kinases that phosphorylate CTLA4 protein from the curated PhosphoSitePlus Substrates of Kinases dataset.
PID Pathways pathways involving CTLA4 protein from the PID Pathways dataset.
Reactome Pathways 2014 pathways involving CTLA4 protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving CTLA4 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CTLA4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CTLA4 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CTLA4 gene from the RummaGEO Gene Perturbation Signatures dataset.
Tabula Sapiens Gene-Cell Associations cell types with high or low expression of CTLA4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of CTLA4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of CTLA4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of CTLA4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of CTLA4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CTLA4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CTLA4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with CTLA4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CTLA4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving CTLA4 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving CTLA4 protein from the WikiPathways Pathways 2024 dataset.