CTLA4 cytotoxic T-lymphocyte associated protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CTLA4provided by HGNC
Official Full Name: cytotoxic T-lymphocyte associated protein 4provided by HGNC
Primary source: HGNC:HGNC:2505
See related: Ensembl:ENSG00000163599 MIM:123890; AllianceGenome:HGNC:2505
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD; GSE; GRD4; ALPS5; CD152; CTLA-4; IDDM12; CELIAC3
Summary: 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]
Expression: Biased expression in lymph node (RPKM 10.3), appendix (RPKM 9.7) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q33.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (203867771..203873965)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (204349656..204355847)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (204732494..204738688)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

High PD-1 and CTLA-4 expression correlates with host immune suppression in patients and a mouse model infected with Echinococcus multilocularis.
Title: High PD-1 and CTLA-4 expression correlates with host immune suppression in patients and a mouse model infected with Echinococcus multilocularis.
Association between Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4) Locus and Early-Onset Anti-acetylcholine Receptor-Positive Myasthenia Gravis in Serbian Patients.
Title: Association between Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4) Locus and Early-Onset Anti-acetylcholine Receptor-Positive Myasthenia Gravis in Serbian Patients.
Association of four CTLA-4 gene polymorphisms with pemphigus risk: a systematic review, meta-analysis, and meta-regression.
Title: Association of four CTLA-4 gene polymorphisms with pemphigus risk: a systematic review, meta-analysis, and meta-regression.
Decoding the genetic influence of CT60 non-coding polymorphism in CTLA-4 gene and sCTLA-4 biomarker with rheumatoid arthritis in the Indian population.
Title: Decoding the genetic influence of CT60 non-coding polymorphism in CTLA-4 gene and sCTLA-4 biomarker with rheumatoid arthritis in the Indian population.
Cytotoxic T-lymphocyte associated protein 4 (CTLA4) polymorphisms are linked to systemic lupus erythematosus: an updated meta-analysis.
Title: Cytotoxic T-lymphocyte associated protein 4 (CTLA4) polymorphisms are linked to systemic lupus erythematosus: an updated meta-analysis.
Effect of DNA methylation at the CTLA4 gene on the clinical status of autoimmune thyroid diseases.
Title: Effect of DNA methylation at the CTLA4 gene on the clinical status of autoimmune thyroid diseases.
Prognostic effect of CTLA4/LAG3 Expression by T-Cells Subsets on Acute Myeloid Leukemia Patients.
Title: Prognostic effect of CTLA4/LAG3 Expression by T-Cells Subsets on Acute Myeloid Leukemia Patients.
Relationship Between Cytotoxic T-Lymphocyte-associated Antigen-4: Programmed Death-1 Genes Polymorphisms and Susceptibility to Pediatric B-Cell Acute Lymphoblastic Leukemia.
Title: Relationship Between Cytotoxic T-Lymphocyte-associated Antigen-4: Programmed Death-1 Genes Polymorphisms and Susceptibility to Pediatric B-Cell Acute Lymphoblastic Leukemia.
[Association of CTLA-4 gene polymorphisms with the genetic susceptibility and prognosis of patients with Bladder urothelial carcinoma].
Title: [Association of CTLA-4 gene polymorphisms with the genetic susceptibility and prognosis of patients with Bladder urothelial carcinoma].
CTLA-4 silencing could promote anti-tumor effects in hepatocellular.
Title: CTLA-4 silencing could promote anti-tumor effects in hepatocellular.

Submit: New GeneRIF Correction See all GeneRIFs (1044)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency MedGen: C4015214 OMIM: 616100 GeneReviews: Not available	Compare labs
Celiac disease, susceptibility to, 3 MedGen: C1857845 OMIM: 609755 GeneReviews: Not available	Compare labs
Hashimoto thyroiditis MedGen: C0677607 OMIM: 140300 GeneReviews: Not available	Compare labs
Systemic lupus erythematosus MedGen: C0024141 OMIM: 152700 GeneReviews: Not available	Compare labs
Type 1 diabetes mellitus 12 MedGen: C1832392 OMIM: 601388 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies two new risk loci for Graves' disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel associations for hypothyroidism include known autoimmune risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 Env co-localizes with CTLA4 in HIV-1 infected CD4+ T cells	PubMed
	env	The envelope glycoprotein (gp160)) of HIV-1 is directed to intracellular CTLA-4-containing granules rather than trafficking constitutively from the Golgi to the cell surface	PubMed
Nef	nef	HIV-1 Nef-mediated CTLA-4 downregulation is associated with upregulation of IL-2 production in infected primary CD4+ T-cells	PubMed
	nef	HIV-1 Nef downregulates CTLA-4 in 293T cells and infected primary CD4+ T-cells. The Nef-induced downregulation of CTLA-4 requires the EE155, LL165, and DD175 motifs in Nef	PubMed
	nef	HIV-1 Nef co-localizes with CTLA-4 in early and recycling endosomes with transferrin marker protein in HeLa cells	PubMed
	nef	HIV-1 Nef expression in Jurkat cells upregulates the level of CTLA4 production in the absence of CD3 and CD28 stimulation	PubMed
Vpr	vpr	HIV-1 Vpr increases the levels of CTLA4 expression in infected T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:482061

GDB:180415 (e-PCR)
- UniSTS:48500

NoName (e-PCR)
- UniSTS:481662

STS-M37245 (e-PCR)
- UniSTS:21475

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in B cell receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in T cell receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of regulatory T cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of regulatory T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated endocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein complex involved in cell adhesion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cytotoxic T-lymphocyte protein 4

Names: celiac disease 3; cytotoxic T lymphocyte associated antigen 4 short spliced form; cytotoxic T-lymphocyte-associated serine esterase-4; gluten-sensitive enteropathy; insulin-dependent diabetes mellitus 12; ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011502.1 RefSeqGene

Range

4986..11180

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1220

mRNA and Protein(s)

NM_001037631.3 → NP_001032720.1 cytotoxic T-lymphocyte protein 4 isoform CTLA-4delTM precursor

See identical proteins and their annotated locations for NP_001032720.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform CTLA-4delTM (also known as sCTLA4) is soluble and lacks the transmembrane domain, compared to isoform a. The exon skip represented in this variant is is based on human U90273.1, and is consistent with mouse U90270.1 and the data published in PMID:10831323 and PMID:10556814.

Source sequence(s)

AC010138, AF414120, AI733018

Consensus CDS

CCDS42803.1

UniProtKB/TrEMBL

Q8TDA6

Related

ENSP00000295854.6, ENST00000295854.10

Conserved Domains (1) summary

cd05721
Location:39 → 152

IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
NM_005214.5 → NP_005205.2 cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor

See identical proteins and their annotated locations for NP_005205.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer membrane-bound isoform CTLA4-TM.

Source sequence(s)

AC010138, AF414120, AI733018

Consensus CDS

CCDS2362.1

UniProtKB/Swiss-Prot

A0N1S0, E9PDH0, O95653, P16410, Q0PP65, Q52MC1, Q53TD5, Q5S005, Q8WXJ1, Q96P43, Q9UKN9

UniProtKB/TrEMBL

Q6GR94

Related

ENSP00000497102.1, ENST00000648405.2

Conserved Domains (1) summary

cd05721
Location:39 → 152

IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)