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CTLA4 Gene

protein-coding GIFtS: 65
GCID: GC02P204696

Cytotoxic T-Lymphocyte-Associated Protein 4

(Previous names: celiac disease 3, insulin-dependent diabetes mellitus 12)
(Previous symbols: CELIAC3, IDDM12)

See CTLA4-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Cytotoxic T-Lymphocyte-Associated Protein 4¹ ²		CD²
CELIAC3¹ ² ⁵		GSE²
IDDM12¹ ² ⁵		CD152 Isoform²
Celiac Disease 3¹ ²		Cytotoxic T Lymphocyte Associated Antigen 4 Short Spliced Form²
Insulin-Dependent Diabetes Mellitus 12¹ ²		Cytotoxic T-Lymphocyte Antigen 4²
Cytotoxic T-Lymphocyte-Associated Antigen 4² ³		Cytotoxic T-Lymphocyte Protein 4²
CD152² ³		Cytotoxic T-Lymphocyte-Associated Serine Esterase-4²
CTLA-4² ³		Ligand And Transmembrane Spliced Cytotoxic T Lymphocyte Associated Antigen 4²
GRD4² ⁵		CD152 Antigen³

External Ids:	HGNC: 2505¹	Entrez Gene: 1493²	Ensembl: ENSG00000163599⁷	OMIM: 123890⁵	UniProtKB: P16410³

Export aliases for CTLA4 gene to outside databases

Previous GC identifers: GC02P202949 GC02P203457 GC02P204935 GC02P204558 GC02P204440 GC02P196580

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CTLA4 Gene:

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)

GeneCards Summary for CTLA4 Gene:

CTLA4 (cytotoxic T-lymphocyte-associated protein 4) is a protein-coding gene. Diseases associated with CTLA4 include celiac disease 3, and paracoccidioidomycosis. An important paralog of this gene is CD28.

UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Function: Inhibitory receptor acting as a major negative regulator of T-cell responses. 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

Gene Wiki entry for CTLA4 (CTLA-4) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000002.11 NT_005403.18 NC_018913.2

Regulatory elements:

Regulatory transcription factor binding sites in the CTLA4 gene promoter:
AML1a AP-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: CTLA4 promoter sequence

Search Chromatin IP Primers for CTLA4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CTLA4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q33 Ensembl cytogenetic band: 2q33.2 HGNC cytogenetic band: 2q33

CTLA4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CTLA4 gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02P204696: view genomic region (about GC identifiers)

Start:	204,732,509 bp from pter	End:	204,738,683 bp from pter
Size:	6,175 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410 (See protein sequence)

Recommended Name: Cytotoxic T-lymphocyte protein 4 precursor

Size: 223 amino acids; 24656 Da

Subunit: Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2

Selected PDB 3D structures from and Proteopedia for CTLA4 (see all 7):

1AH1 (3D)

1H6E (3D)

1I85 (3D)

1I8L (3D)

2X44 (3D)

3BX7 (3D)

Secondary accessions: A0N1S0 E9PDH0 O95653 Q0PP65 Q52MC1 Q53TD5 Q5S005 Q8WXJ1 Q96P43 Q9UKN9

Alternative splicing: 5 isoforms: P16410-1 P16410-2 P16410-3 P16410-4 P16410-5

Explore the universe of human proteins at neXtProt for CTLA4: NX_P16410

Explore proteomics data for CTLA4 at MOPED

Post-translational modifications:

N-glycosylation is important for dimerization¹

Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to

retention of CTLA4 on the cell surface¹

Glycosylation² at Asn113, Asn145

Modification sites at PhosphoSitePlus

See CTLA4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (2 alternative transcripts):

NP_001032720.1 NP_005205.2

ENSEMBL proteins:

ENSP00000303939 ENSP00000295854 ENSP00000417779 ENSP00000409707

Reactome Protein details: P16410

CTLA4 Human Recombinant Protein Products:

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	antibodies-online proteins for CTLA4 (24 products)
	antibodies-online peptides for CTLA4

CTLA4 Antibody Products:

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	eBioscience ELISAs for CTLA4: Human sCD152/CTLA-4 Platinum ELISA 10 x 96 tests
	antibodies-online kits for CTLA4 (37 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

CD: CD molecules

VSET: Immunoglobulin superfamily / V-set domain containing

4 InterPro protein domains:

IPR003596 Ig_V-set_subgr

IPR013783 Ig-like_fold

IPR013106 Ig_V-set

IPR008096 CTLA4

Graphical View of Domain Structure for InterPro Entry P16410

ProtoNet protein and cluster: P16410

3 Blocks protein domains:

IPB003596 Immunoglobulin V-type

IPB003599 Immunoglobulin subtype

IPB008096 Cytotoxic T-lymphocyte antigen 4 signature

UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Similarity: Contains 1 Ig-like V-type (immunoglobulin-like) domain

Find genes that share domains with CTLA4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: CTLA4_HUMAN, P16410

Function: Inhibitory receptor acting as a major negative regulator of T-cell responses. 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

Genatlas biochemistry entry for CTLA4:

cytotoxic T-lymphocyte-associated granule serine protease 4,B7 costimulatory protein receptor for

CD80,CD86,negative regulatory T cell presenting costimulatory molecule,member of the immunoglobulin

superfamily,with an association of the exon 3 microsatellite,106bp allele with autoimmune disorders (conferring

susceptibility to Graves disease and to thyroid associated orbitopathy but not to systemic lupus

erythematosus),susceptibility gene for the celiac disease and for multiple sclerosis

Gene Ontology (GO): 1 molecular function term: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	11279501

Find genes that share ontologies with CTLA4 About GenesLikeMe

Phenotypes:
1 GenomeRNAi human phenotype for CTLA4:

Increased cell number in G1, a

13 MGI mutant phenotypes (inferred from 5 alleles) (MGI details for Ctla4):

cardiovascular system	digestive/alimentary	endocrine/exocrine gland	hematopoietic system	homeostasis/metabolism
immune system	integument	liver/biliary system	mortality/aging	normal
pigmentation	respiratory system	skeleton

Find genes that share phenotypes with CTLA4 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for CTLA4: Ctla4^tm1All Ctla4^tm1Mak Ctla4^tm1Shr

genOway: Develop your customized and physiologically relevant rodent model for CTLA4

miRNA Products:		miRTarBase miRNAs that target CTLA4: hsa-mir-155-5p (MIRT004436), hsa-mir-92a-3p (MIRT049319)

		Block miRNA regulation of human, mouse, rat CTLA4 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate CTLA4 (see all 14):
		hsa-miR-4324 hsa-miR-502-5p hsa-miR-4311 hsa-miR-3688-3p hsa-miR-4255 hsa-miR-496 hsa-miR-656 hsa-miR-544b

		SwitchGear 3'UTR luciferase reporter plasmid: CTLA4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for CTLA4
		Predesigned siRNA for gene silencing in human, mouse, rat CTLA4

Gene Editing
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DNA2.0 Custom Protein Engineering Service for CTLA4

Clone Products:		OriGene clones in human, mouse for CTLA4 (see all 10) OriGene ORF clones in mouse, rat for CTLA4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): CTLA4 (NM_005214)
		Sino Biological Human cDNA Clone for CTLA4
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CTLA4

Flow Cytometry
Products:

eBioscience FlowRNA Probe Sets ( VA1-14135) for CTLA4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

CTLA4_HUMAN, P16410: Cell membrane; Single-pass type I membrane protein. Note=Exists primarily an intracellular

antigen whose surface expression is tightly regulated by restricted trafficking to the cell surface and rapid

internalisation;

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
plasma membrane	5
golgi apparatus	4
extracellular	2
nucleus	2

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Gene Ontology (GO): Selected cellular component terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005794	Golgi apparatus	IDA	15814706
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	TAS	3220103
GO:0009897	external side of plasma membrane	IDA	18641304
GO:0045334	clathrin-coated endocytic vesicle	IDA	15814706

Find genes that share ontologies with CTLA4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for CTLA4 About (see all 9)

See pathways by source

Powered
by

SuperPath

Contained pathways About

CD28 co-stimulation

	Costimulation by the CD28 family	0.44			CTLA4 Signaling	0.30
	CTLA4 inhibitory signaling	0.32

TCR Signaling (Qiagen)

TCR Signaling

0.68

ICos-ICosL Pathway in T-Helper Cell

CD28 Signaling in T-Helper Cell

0.66

Allograft rejection

Autoimmune thyroid disease

0.61

Class I MHC mediated antigen processing and presentation

Adaptive Immune System

0.41

Find genes that share SuperPaths with CTLA4 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CTLA4

	CTLA4 Signaling
	TCR Signaling
	CD28 Signaling in T-Helper Cell

1 BioSystems Pathway for CTLA4

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

1 Reactome Pathway for CTLA4

CTLA4 inhibitory signaling

4 Kegg Pathways (Kegg details for CTLA4):

	Cell adhesion molecules (CAMs)
	T cell receptor signaling pathway
	Autoimmune thyroid disease
	Rheumatoid arthritis

Pathway & Disease-focused RT² Profiler PCR Arrays including CTLA4:

Cell Surface Markers in human mouse rat

Th1/Th2 Response in human mouse rat

T-cell & B-cell Activation in human mouse rat

T-Cell Anergy & Immune Tolerance in human mouse rat

Diabetes in human mouse rat

Interactions:

GeneGlobe Interaction Network for CTLA4

STRING Interaction Network Preview (showing 5 interactants - click image to see 23)

Selected Interacting proteins for CTLA4 (P16410^{1, 2, 3} ENSP00000303939⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 25)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986¹^,²^,³, ENSP00000274335⁴	EBI-1030991,EBI-79464 MINT-8035246 MINT-8035216 MINT-8035201 I2D: score=2 STRING: ENSP00000274335
CD86	P42081¹^,³, ENSP00000332049⁴	EBI-1030991,EBI-1030956 I2D: score=3 STRING: ENSP00000332049
CD80	P33681¹^,³, ENSP00000264246⁴	EBI-1030991,EBI-1031024 I2D: score=4 STRING: ENSP00000264246
FYN	P06241³, ENSP00000357656⁴	I2D: score=4 STRING: ENSP00000357656
LCK	P06239³, ENSP00000337825⁴	I2D: score=2 STRING: ENSP00000337825

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Gene Ontology (GO): Selected biological process terms (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006955	immune response	IEA	--
GO:0006974	cellular response to DNA damage stimulus	IMP	17875758
GO:0030889	negative regulation of B cell proliferation	IMP	17875758
GO:0031295	T cell costimulation	TAS	--
GO:0042130	negative regulation of T cell proliferation	IEA	--

Find genes that share ontologies with CTLA4 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for CTLA4

UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Pharmaceutical: Engineered fusion proteins consisting of the extracellular domain of CTLA4 and the IgG Fc region

(Ctla4-Ig), inhibit T-cell-dependent antibody responses, and are used as immunosuppressive agents. They are

soluble, have an enhanced affinity for B7 ligands and act as a competitive inhibitor of CD28

1 DrugBank Compound for CTLA4 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Alpha-D-Mannose	--	3458-28-4	target	--	17139284 17016423

Selected Novoseek inferred chemical compound relationships for CTLA4 gene (see all 50) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
mh-30	81.1	3	15841095 (1), 15316504 (1)
abatacept	77.4	32	18050376 (2), 18718877 (1), 19243211 (1), 19259798 (1) (see all 13)
ctla4-ig	74.7	17	8228824 (2), 17924973 (2), 7678111 (1), 7504299 (1) (see all 13)
belatacept	63	3	16121705 (1), 20502720 (1)
indoleamine	45.9	4	17981708 (1), 17715231 (1), 18816483 (1), 16493086 (1)
il 10	42.3	7	15607008 (2), 15708894 (1), 18261221 (1), 18337305 (1) (see all 5)
ionomycin	38.2	12	12444128 (3), 10600000 (2), 10777098 (1), 9857283 (1)
tyrosine	27.9	60	9712716 (6), 9973379 (4), 10604992 (3), 10842319 (3) (see all 29)
tgf beta1	21.3	6	19269255 (4), 19597336 (1), 16872485 (1)
infliximab	18.8	1	19104936 (1)

4 PharmGKB related drug/compound annotations for CTLA4 gene About this table

Drug/compound	PharmGKB Annotation
bortezomib	CA
dexamethasone	CA
melphalan	CA
prednisone	CA

Find genes that share compounds with CTLA4 About GenesLikeMe

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for CTLA4 gene (2 alternative transcripts):

NM_001037631.2 NM_005214.4

Unigene Cluster for CTLA4:

Cytotoxic T-lymphocyte-associated protein 4

Hs.247824 [show with all ESTs]

Unigene Representative Sequence: NM_005214

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000302823(uc002vak.2 uc002val.2 uc010fty.2 uc010ftz.2)

ENST00000295854 ENST00000487393 ENST00000472206 ENST00000427473

miRNA Products:		Block miRNA regulation of human, mouse, rat CTLA4 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate CTLA4 (see all 14):
		hsa-miR-4324 hsa-miR-502-5p hsa-miR-4311 hsa-miR-3688-3p hsa-miR-4255 hsa-miR-496 hsa-miR-656 hsa-miR-544b

		SwitchGear 3'UTR luciferase reporter plasmid: CTLA4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for CTLA4
		Predesigned siRNA for gene silencing in human, mouse, rat CTLA4

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		GenScript: all cDNA clones in your preferred vector (see all 2): CTLA4 (NM_005214)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CTLA4
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Primer Products:		OriGene qPCR primer pairs and template standards for CTLA4 OriGene qSTAR qPCR primer pairs in human, mouse for CTLA4
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat CTLA4
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		QuantiFast Probe-based Assays in human, mouse, rat CTLA4

Flow Cytometry
Products:

eBioscience FlowRNA Probe Sets ( VA1-14135) for CTLA4

Additional mRNA sequence:

AF414120.1 AF486806.1 AJ298052.1 AK313732.1 AY209009.1 AY792514.1 AY999702.1 BC069566.1

BC070162.1 BC074842.2 BC074893.2 DQ785106.1 L15006.1 U90273.1

5 DOTS entries:

DT.40126443 DT.91756479 DT.95146339 DT.95133126 DT.99980295

22 AceView cDNA sequences:

AW515943 BG058720 AI819438 U90273 BG236211 AF486806 AF414120 NM_005214

BC074842 AW207094 BC074893 BM997840 BV183431 L15006 CD639535 AY209009

BC070162 BC069566 AA210929 BG536887 BE837454 AI860199

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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CTLA4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: TATAATATTT

About this image

CTLA4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 3) fully expand


Blood (Cardiovascular System) fully expand to see all 7 entries
T Helper Cells Peripheral Blood
Regulatory T cells
CD19+ B Cells
cd4+ t cells

Thymus (Hematopoietic System)
T Helper Cells Thymus

Tonsil (Hematopoietic System)

CTLA4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

CTLA4 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.247824

UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Tissue specificity: Widely expressed with highest levels in lymphoid tissues. Detected in activated T-cells where

expression levels are 30- to 50-fold less than CD28, the stimulatory coreceptor, on the cell surface following

activation

Pathway & Disease-focused RT² Profiler PCR Arrays including CTLA4:

Cell Surface Markers in human mouse rat

Th1/Th2 Response in human mouse rat

T-cell & B-cell Activation in human mouse rat

T-Cell Anergy & Immune Tolerance in human mouse rat

Diabetes in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for CTLA4 OriGene qSTAR qPCR primer pairs in human, mouse for CTLA4
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat CTLA4
		QuantiTect SYBR Green Assays in human, mouse, rat CTLA4
		QuantiFast Probe-based Assays in human, mouse, rat CTLA4

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CTLA4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for CTLA4 gene from Selected species (see all 11) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Ctla4^{1 , 5}	cytotoxic T-lymphocyte-associated protein 4^{1, 5}	79.97(n)¹ 74.89(a)¹		1 (30.58 cM)⁵ 12477¹ NM_009843.4¹ NP_033973.2¹ 60887000⁵
chicken (Gallus gallus)	Aves	CTLA4¹	cytotoxic T-lymphocyte-associated protein 4	60.85(n) 49.23(a)		424106 NM_001040091.1 NP_001035180.1
lizard (Anolis carolinensis)	Reptilia	-- --	Uncharacterized protein	34(a) 31(a)	many → 1 many → 1	AAWZ02040505(955-5793) GL343208.1(2684025-2687950)
tropical clawed frog (Xenopus tropicalis)	Amphibia	ctla4¹	cytotoxic T-lymphocyte-associated protein 4	51.87(n) 42.25(a)		100493714 XM_002936530.2 XP_002936576.1
zebrafish (Danio rerio)	Actinopterygii	cd28⁶	CD28 molecule	21(a)	1 ↔ 1	9(14262659-14265291) ENSDARG00000095070

ENSEMBL Gene Tree for CTLA4 (if available)
TreeFam Gene Tree for CTLA4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for CTLA4 gene

CD28²

Find genes that share paralogs with CTLA4 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Polymorphic Variants from UniProtKB/Swiss-Prot

CTLA4_HUMAN, P16410: Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders. They

influence responsiveness to hepatitis B virus (HBV) infection [MIM:610424]

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs231775^1,2,,4	C,F,O,A,H	other¹	204122578(+)	`TGGCTA/GCCAGG`	4	T A	mis¹ ese³		39		EA NA MN NS CSA WA EU	11608
rs35832561^1,2	F	--	204120564(+)	`TGCTCA/GTCCCC`	2	--	us2k¹		5		MN	404
rs13410149^1,2	C,H	--	204120624(+)	`CTTTAG/ACCCAT`	2	--	us2k¹		9		NS EA MN	824
rs147267715^1,2		--	204120657(+)	`CCACCC/TTTTTC`	2	--	us2k¹		0	--	--	--	--
rs733619^1,2	C,F,H	--	204120669(-)	`ATTGAG/CAACAG`	2	--	us2k¹		16		NS EA NA MN CSA WA	1585
rs36021810^1,2	F	--	204120692(+)	`CTTTTC/TGTCTT`	2	--	us2k¹		5		MN	404
rs3087241^1,2	C,H	--	204120755(+)	`TACATA/GATACT`	2	--	us2k¹		9		MN NS EA	824
rs11571315^1,2	C,F,H	--	204120765(-)	`ctggaG/Attgaa`	2	--	us2k¹		30		NS EA NA MN WA CSA	2732
rs733618^1,2	C,F,A,H	--	204120808(-)	`GACAGA/GCAGCT`	2	--	us2k¹		21		NS EA NA MN WA	2742
rs4553808^1,2	C,F,A,H	--	204120869(+)	`TTTTTA/GAAAAA`	2	--	us2k¹		14		MN NS EA NA WA	1014
rs188607442^1,2		--	204120933(+)	`TTGGCC/GCTTGA`	2	--	us2k¹		0	--	--	--	--
rs11571316^1,2	C,F,H	--	204120953(-)	`AGAAAC/TCTTCA`	2	--	us2k¹		25		NA NS EA MN CSA WA	2437
rs115552468^1,2	F	--	204120992(+)	`GCAGGT/ACAGAA`	2	--	us2k¹		1		WA	118
rs181481382^1,2		--	204121039(+)	`TACATA/GTGTAA`	2	--	us2k¹		0	--	--	--	--
rs62182595^1,2	C,F	--	204121052(+)	`AATCTG/ACATGT`	2	--	us2k¹		6		NA WA EA	248
rs231771^1,2	C	--	204121104(+)	`AATTTA/TAAAAA`	2	--	us2k¹ tfbs³		6		NA WA EA	246
rs16840252^1,2	C,F,H	--	204121383(+)	`ATGGAC/TGGACT`	2	--	us2k¹		32		NA NS EA WA	3332
rs231772^1,2	C,F,H	--	204121417(+)	`CTGTTG/ACAACT`	2	--	us2k¹		23		NS EA NA WA CSA	1888
rs185971650^1,2		--	204121477(+)	`TTTTTG/TTTTTG`	2	--	us2k¹		0	--	--	--	--
rs231773^1,2	C,F,O,H	--	204121536(+)	`CCCATA/GAATGT`	2	--	us2k¹ tfbs³		20		NS EA NA WA CSA	1602
rs190364914^1,2		--	204121643(+)	`CTGTCA/TCAAAT`	2	--	us2k¹		0	--	--	--	--
rs11571317^1,2	C,F,H	--	204121872(+)	`TTTTCC/TGCCTA`	2	--	us2k¹ trp³		21		MN NS EA NA	2374
rs231774^1,2	C,F,O,A,H	--	204122087(+)	`TGGAGA/TTGTCA`	2	--	us2k¹ tfbs³		32		NA MN NS EA WA CSA	2291
rs5742909^1,2	C,F,H	--	204122211(+)	`ATCCTC/TAAAGT`	2	--	us2k¹		30		NS NA MN EA	4106
rs201778935^1,2	C	--	204122551(+)	`TTCAGC/TGGCAC`	4	R W	mis¹		0	--	--	--	--
rs138279736^1,2	C	--	204122552(+)	`TCAGCG/AGCACA`	4	/Q /R	mis¹		1		NA	4548
rs16840275^1,2	C,F	--	204122604(+)	`CTCCTG/CTTTTT`	4	/L	syn¹ ese³		6		NA WA	4814
rs231776^1,2	C,F,H	--	204122714(+)	`GTCAAG/AGGCAG`	2	--	int¹		31		EA NA NS WA CSA	2149
rs182554438^1,2		--	204122734(+)	`GCAAAA/GCCAGA`	2	--	int¹		0	--	--	--	--
rs187201888^1,2		--	204122862(+)	`TAGTAA/GGGGCT`	2	--	int¹		0	--	--	--	--
rs140842959^1,2		--	204122928(+)	`CTATGA/GGACTG`	2	--	int¹		0	--	--	--	--
rs117492436^1,2	F	--	204122962(+)	`TAGCCA/TTAGTC`	2	--	int¹		1		EA	120
rs144795106^1,2		--	204123084(+)	`GTCCTC/TGGATT`	2	--	int¹		0	--	--	--	--
rs190838764^1,2		--	204123198(+)	`ATTCTA/CCTAGC`	2	--	int¹		0	--	--	--	--
rs149392730^1,2	C	--	204123243(+)	`TTGCC-/AAAAAA`	2	--	int¹		0	--	--	--	--
rs182356877^1,2		--	204123356(+)	`GTTTTC/TAGCTC`	2	--	int¹		0	--	--	--	--
rs147514192^1,2		--	204123396(+)	`GGCTTA/CAAATG`	2	--	int¹		0	--	--	--	--
rs185654189^1,2	C	--	204123411(+)	`GTATAA/TCCATT`	2	--	int¹		0	--	--	--	--
rs231777^1,2	C,F,O,A,H	--	204123452(+)	`CTTGGC/TTAAGA`	2	--	int¹		25		NA NS EA WA CSA	2270
rs190363127^1,2		--	204123590(+)	`CTCTTA/TGAAGT`	2	--	int¹		0	--	--	--	--
rs231778^1,2	C,F,O,H	--	204123685(+)	`GTGATA/GAGTGT`	2	--	int¹		20		NA NS EA WA CSA	938
rs35219727^1,2	C,F	--	204123913(+)	`AGGATG/ACTCAG`	2	--	int¹		6		MN EA	524
rs3087242^1,2	C	--	204123949(+)	`AGGGTA/C/G/T AGGGA`	2	--	int¹		5		MN	404
rs183036274^1,2		--	204124081(+)	`TCTCTA/TATATA`	2	--	int¹		0	--	--	--	--
rs115832527^1,2	F	--	204124179(+)	`TATTTA/GTTGTA`	2	--	int¹		1		WA	118
rs231779^1,2	C,F,O,A,H	--	204124351(+)	`GCAAGC/TCTCTC`	2	--	int¹		22		NS EA NA WA	2552
rs75339524^1,2	F	--	204124465(+)	`TCAGGG/AGAAGC`	2	--	int¹		1		WA	118
rs148575091^1,2		--	204124528(+)	`GCCCTC/TGGCTC`	2	--	int¹		0	--	--	--	--
rs142975926^1,2		--	204124588(+)	`GAAGGC/TGGAGG`	2	--	int¹		0	--	--	--	--
rs188823513^1,2	C	--	204124610(+)	`CATCAA/GGACAC`	2	--	int¹		0	--	--	--	--
rs151127713^1,2		--	204124628(+)	`CCTGGA/GTGACA`	2	--	int¹		0	--	--	--	--
rs145606860^1,2	C	--	204124751(+)	`TCCGG-/AGC TATATAGCTC`	2	--	int¹		0	--	--	--	--
rs140690384^1,2		--	204124810(+)	`ATCTCA/CTCTAA`	2	--	int¹		0	--	--	--	--
rs145746390^1,2	C	--	204124952(+)	`GAATC-/TTATTT`	2	--	int¹		0	--	--	--	--
rs192924632^1,2		--	204124963(+)	`CTCAGC/TAAGAA`	2	--	int¹		0	--	--	--	--
rs183868708^1,2		--	204125005(+)	`TTGAGA/GGATGG`	2	--	int¹		0	--	--	--	--
rs149674062^1,2		--	204125041(+)	`GGAAGA/GGGTAA`	2	--	int¹		0	--	--	--	--
rs55657178^1,2	C	--	204125065(+)	`TGAAGC/GGGGGA`	2	--	int¹		0	--	--	--	--
rs140298725^1,2		--	204125069(+)	`GGGGGC/GAGAAA`	2	--	int¹		0	--	--	--	--
rs56387603^1,2	C,F	--	204125080(+)	`AGGCCG/ATGGGG`	2	--	int¹		1		EA	120
rs200180357^1,2		--	204125166(+)	`TTTCCA/GTGCTA`	2	--	int¹		0	--	--	--	--
rs199943943^1,2	C	--	204125279(+)	`GTGACA/GTGCTT`	4	T	syn¹		1		EU	1323
rs1065442^1,2	C,H	--	204125335(+)	`CATGAT/CGGGGA`	4	/T /M	mis¹		10		MN NS EA	990
rs144988077^1,2	C	--	204125389(+)	`CAGTGG/AAAATC`	4	/E /G	mis¹		1		NA	4552
rs188862082^1,2	C	--	204125474(+)	`CCACCA/GCCATA`	4	P	syn¹		0	--	--	--	--
rs41265959^1,2	C	--	204125544(+)	`CTGAGC/TTGACA`	2	--	int¹		0	--	--	--	--
rs202187877^1,2		--	204125558(+)	`GTTGCA/GTTGCA`	2	--	int¹		0	--	--	--	--
rs73993040^1,2	C,F	--	204125674(+)	`ATTGTG/TGGTGG`	2	--	int¹		3		WA CSA	122
rs41265961^1,2	C,F	--	204125725(+)	`GGGAAG/ATTGGG`	2	--	int¹		1		NA	120
rs113505692^1,2	C	--	204125785(+)	`ATATGT/ATATGA`	2	--	int¹		1		CSA	1
rs138029887^1,2		--	204125818(+)	`AATAGC/TCAAAC`	2	--	int¹		0	--	--	--	--
rs201300281^1,2		--	204125921(+)	`TAGAGC/TTTAAA`	2	--	int¹		0	--	--	--	--
rs200271600^1,2	C	--	204125941(+)	`GGGAGG/TCTCTG`	2	--	int¹		0	--	--	--	--
rs200657280^1,2	C	--	204125975(+)	`GAACCG/ATGCCC`	3	/P	syn¹ int¹		1		EU	1323
rs199659316^1,2		--	204126056(+)	`ACAGCC/TGTTTC`	3	A	syn¹ int¹		0	--	--	--	--
rs55806747^1,2	C	--	204126214(+)	`AGAACA/GCACTA`	2	--	int¹		0	--	--	--	--
rs79971295^1,2		--	204126224(+)	`AGAACC/TGTAGG`	2	--	int¹		0	--	--	--	--
rs138160778^1,2	C	--	204126360(+)	`TGCTC-/TTTGTCT`	2	--	int¹		0	--	--	--	--
rs188456452^1,2		--	204126451(+)	`GATGGC/TCTTTA`	2	--	int¹		0	--	--	--	--
rs231780^1,2	C,H	--	204126561(+)	`TCCCTA/GTTATC`	2	--	int¹		21		EA NA NS WA CSA	815
rs11571324^1,2	C,F,H	--	204126724(-)	`CAGAGG/TTGTCT`	2	--	int¹		4		NS EA	414
rs231781^1,2	C,A,H	--	204126751(+)	`CCATTG/ACAAAC`	2	--	int¹		17		EA NA WA CSA	428
rs184294545^1,2		--	204126804(+)	`TTCTCA/GCTCTT`	2	--	int¹		0	--	--	--	--
rs114352937^1,2	F	--	204126851(+)	`ACATAC/TACAAA`	2	--	int¹		1		NA	120
rs190067755^1,2		--	204126865(+)	`ATACTC/TTATTC`	2	--	int¹		0	--	--	--	--
rs181723616^1,2	C	--	204126868(+)	`CTCTAC/TTCCAA`	2	--	int¹		0	--	--	--	--
rs115395872^1,2	F	--	204126880(+)	`ATCCTC/GTACCC`	2	--	int¹		1		NA	120
rs143179855^1,2		--	204127006(+)	`TTGATC/TAATTA`	2	--	int¹		0	--	--	--	--
rs148281316^1,2		--	204127077(+)	`ATTCAA/GGGCAA`	2	--	int¹		0	--	--	--	--
rs11571318^1,2	C,F,H	--	204127185(-)	`GAATGT/CTCACA`	2	--	int¹		4		NS EA	414
rs74808460^1,2	C	--	204127342(+)	`ATGCCC/GCCAAC`	4	P A	syn¹ mis¹		0	--	--	--	--
rs34162447^1,2	C,F	--	204127433(+)	`TTTCAA/GTTTCC`	2	--	ut3¹		5		MN	400
rs56102377^1,2	C,F	--	204127499(+)	`CATTTG/AGGGGG`	2	--	ut3¹		1		EA	120
rs56083753^1,2	C	--	204127667(+)	`TTATGA/GTGTGG`	2	--	ut3¹		0	--	--	--	--
rs13384548^1,2	C,F,H	--	204127774(+)	`GAGACG/ATTTAT`	2	--	ut3¹ ese³		4		NS EA	396
rs35411154^1,2	C,F	--	204127850(+)	`TCAAGG/CCTTCA`	2	--	ut3¹		5		MN	400
rs180789983^1,2		--	204127941(+)	`TGATAA/GTATTG`	2	--	ut3¹		0	--	--	--	--
rs139105990^1,2	C	--	204128006(+)	`TATATA/GGCAGT`	2	--	ut3¹		0	--	--	--	--
rs55696217^1,2	C	--	204128399(+)	`TGAAGA/GTTTCT`	2	--	ut3¹		0	--	--	--	--
rs190211458^1,2		--	204128412(+)	`AAATTA/TACACT`	2	--	ut3¹		0	--	--	--	--
rs231721^1,2	C,F,H	--	204128547(+)	`GTGTTT/CAAATT`	2	--	ds500¹		30		NS EA MN NA WA CSA	2382
rs35482731^1,2	C,F	--	204128691(+)	`GGAAGG/CTATCC`	2	--	ds500¹		5		MN	396
rs182533364^1,2		--	204128700(+)	`CCATCC/TTCTTT`	2	--	ds500¹		0	--	--	--	--
rs139354616^1,2		--	204128706(+)	`TCTTTC/GCTTTT`	2	--	ds500¹		0	--	--	--	--
rs34031880^1,2	C,F	--	204128710(+)	`TCCTTT/CTGATT`	2	--	ds500¹		6		MN WA	514
rs3087243^1,2	C,F,O,H	--	204128741(+)	`ATAACG/ATGGGT`	2	--	ds500¹		30		NS EA NA MN CSA WA	4045
rs11571319^1,2	C,F,H	--	204128760(-)	`GACTGC/TTATGT`	2	--	ds500¹		17		MN NS EA NA WA	1152
rs142863133^1,2	C	--	204738051(+)	`TATAC-/ATATATATATATATATATAT ATATATATATATATATATATATATATA`	2	--	cds¹		0	--	--	--	--
rs59665421^1,2	C	--	204738092(+)	`ATATAC/TATATA`	2	--	ut3¹		1		NA	2
rs67181450^1,2	C	--	204738106(+)	`TATAT-/ATATATATATATATATATAT ATATATATATATATATATATATTTTAA`	2	--	cds¹		1		NA	2
rs376571886^1,2	--	--	204125134(+)	`AGGAGC/TATGAG`	2	--	int¹		0	--	--	--	--
rs66857345^1,2	--	--	204738043(+)	`ATTGC-/ATAT ATACATATATA`	2	--	ut3¹		0	--	--	--	--
rs113528941^1,2	--	--	204124321(+)	`TTGGCA/GTGCAG`	2	--	int¹		0	--	--	--	--
rs372230996^1,2	--	--	204122670(+)	`ATGGAG/TGAGGT`	2	--	int¹		0	--	--	--	--
rs372940614^1,2	--	--	204124742(+)	`CATTAC/TAGTTC`	2	--	int¹		0	--	--	--	--
rs111771307^1,2	--	--	204124505(+)	`CCTAGA/-AGAGG`	2	--	int¹		1		CSA	2
rs147679342^1,2	--	--	204125453(+)	`TGCAAG/AGTGGA`	4	/K	syn¹		1		NA	4552
rs367760388^1,2	--	--	204127391(+)	`TTCCCA/GTCAAT`	3	I V	mis¹ ut3¹		0	--	--	--	--
rs370224520^1,2	--	--	204127741(+)	`AGACTA/GTATTG`	2	--	ut3¹		0	--	--	--	--
rs372830774^1,2	--	--	204125046(+)	`GGGTAA/GTGATA`	2	--	int¹		0	--	--	--	--
rs370517673^1,2	--	--	204127393(+)	`CCCATC/TATTGA`	3	I	syn¹ ut3¹		0	--	--	--	--
rs112640013^1,2	--	--	204126101(+)	`CACCAC/TGTCTG`	2	--	int¹		0	--	--	--	--
rs373219319^1,2	--	--	204127425(+)	`AGTCCA/GTATTT`	2	--	ut3¹		0	--	--	--	--
rs146571801^1,2	--	--	204126053(+)	`CTCACA/TGCTGT`	3	T	syn¹ int¹		1		NA	4550
rs139154557^1,2	--	--	204125309(+)	`GTGACT/CGAAGT`	4	/T	syn¹		1		NA	4552
rs112593251^1,2	--	--	204124529(+)	`CCCTCA/GGCTCT`	2	--	int¹		0	--	--	--	--
rs199912925^1,2	--	--	204126072(+)	`GCAAAA/GTGGTG`	3	M V	mis¹ int¹		0	--	--	--	--
rs367910852^1,2	--	--	204123116(+)	`AGCCAC/GTTGTT`	2	--	int¹		0	--	--	--	--
rs59387738^1,2	--	--	204128717(+)	`GATTTC/TTTCAC`	2	--	ds500¹		0	--	--	--	--
rs376591332^1,2	--	--	204122571(+)	`CTGAAC/TCTGGC`	4	N	syn¹		0	--	--	--	--
rs370681295^1,2	--	--	204127728(+)	`GGAGCA/GGGGAG`	2	--	ut3¹		0	--	--	--	--
rs376537840^1,2	--	--	204122687(+)	`CCTACC/TGGGTT`	2	--	int¹		0	--	--	--	--
rs368427057^1,2	--	--	204125532(+)	`AAAGCC/TATTTC`	2	--	int¹		0	--	--	--	--
rs370443546^1,2	--	--	204125331(+)	`CCTACA/GTGATG`	4	M V	mis¹		0	--	--	--	--
rs374743192^1,2	--	--	204733184(+)	`TTTTT-/TGCTAT`	2	--	int¹		0	--	--	--	--
rs375949600^1,2	--	--	204126023(+)	`AGTTCA/GGGGTT`	3	S	syn¹ int¹		0	--	--	--	--
rs376644587^1,2	--	--	204124880(+)	`ATCACA/GATTTC`	2	--	int¹		0	--	--	--	--
rs201801137^1,2	--	--	204738051(+)	`TATAC-/ATATATATATA TATATATATATATATATA`	2	--	cds¹		0	--	--	--	--
rs373393185^1,2	--	--	204125234(+)	`TTTGTA/GTGTGA`	4	V	syn¹		0	--	--	--	--
rs60872763^1,2	--	--	204738101(+)	`TATAT-/ATATAT TTTAA`	2	--	cds¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for CTLA4 (204732509 - 204738683 bp)

Structural Variations
Database of Genomic Variants (DGV) variations for CTLA4: --
Human Gene Mutation Database (HGMD): CTLA4

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing CTLA4

DNA2.0 Custom Variant and Variant Library Synthesis for CTLA4

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 123890
OMIM disorders: 140300 601388 609755
UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile

multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints,

kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory

mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated

erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease

susceptibility is associated with variations affecting the gene represented in this entry

Note=Genetic variations in CTLA4 may influence susceptibility to Graves disease, an autoimmune disorder

associated with overactivity of the thyroid gland and hyperthyroidism

Diabetes mellitus, insulin-dependent, 12 (IDDM12) [MIM:601388]: A multifactorial disorder of glucose

homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical

features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and

secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and

blood vessels. Note=Disease susceptibility is associated with variations affecting the gene represented in this

entry

Celiac disease 3 (CELIAC3) [MIM:609755]: A multifactorial, chronic disorder of the small intestine caused

by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal

absorption, and malnutrition. In predisposed individuals, the ingestion of gluten-containing food such as wheat

and rye induces a flat jejunal mucosa with infiltration of lymphocytes. Note=Disease susceptibility is associated

with variations affecting the gene represented in this entry

Selected diseases for CTLA4 (see all 30):
About MalaCards

celiac disease 3 paracoccidioidomycosis thyroiditis graves' disease

hypothyroidism, autoimmune severe hemophilia a type 1 diabetes mellitus diabetes mellitus

celiac disease wegener's granulomatosis lupus erythematosus autoimmune hepatitis

allergic encephalomyelitis primary biliary cirrhosis urinary schistosomiasis systemic lupus erythematosus

addison's disease behcet's disease diabetic ketoacidosis meniere's disease

9 inferred disease relationships from the University of Copenhagen DISEASES database for CTLA4:

Hypersensitivity reaction type II disease Melanoma Hyperthyroidism Thyroiditis

Rheumatoid arthritis Diabetes mellitus Connective tissue disease Multiple sclerosis

Asthma

Find genes that share disorders with CTLA4 About GenesLikeMe

Selected Novoseek inferred disease relationships for CTLA4 gene (see all 93) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
autoimmune thyroid disease	84.6	60	9861324 (2), 12202150 (2), 17504905 (2), 19559744 (2) (see all 38)
autoimmune diseases	84.2	258	18613834 (3), 10215771 (3), 15649153 (3), 9861324 (2) (see all 99)
graves disease	82.3	122	19524188 (4), 15182328 (4), 10404810 (4), 9231050 (3) (see all 63)
autoimmunity	80.1	83	19595177 (4), 15790353 (3), 16046318 (2), 19412189 (2) (see all 56)
hashimotos thyroiditis	75.3	38	9398726 (4), 17020648 (3), 16611252 (2), 12225635 (2) (see all 16)
genetic susceptibility	70.3	54	11752507 (2), 8989248 (2), 16405845 (2), 10619986 (1) (see all 35)
metastatic melanoma	68.3	31	16283570 (2), 18528295 (2), 16490844 (2), 16615096 (2) (see all 22)
cancer regression	64	5	12826605 (2), 16283570 (1), 18528295 (1)
addisons disease	58.8	22	9398726 (4), 10197076 (3), 15240634 (2), 15621571 (1) (see all 9)
diabetes mellitus insulin-dependent	55.4	37	10619986 (3), 15961581 (2), 15237707 (2), 19136037 (2) (see all 19)

Genetic Association Database (GAD): CTLA4
Human Genome Epidemiology (HuGE) Navigator: CTLA4 (525 documents)

Export disorders for CTLA4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for CTLA4 gene, integrated from 10 sources (see all 1527):
(articles sorted by number of sources associating them with CTLA4)

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world of online information

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta- analysis. (PubMed id 15688186)^{1, 2, 4, 9} Lee Y.H.... Nath S.K. (Hum. Genet. 2005)
Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. (PubMed id 15138458)^{1, 2, 4, 9} Barreto M.... Vicente A.M. (Eur. J. Hum. Genet. 2004)
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry. (PubMed id 8817351)^{1, 3, 4, 9} NisticA^ L....Todd J.A. (Hum. Mol. Genet. 1996)
Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. (PubMed id 9259273)^{1, 2, 4, 9} Marron M.P.... She J.-X. (Hum. Mol. Genet. 1997)
A common CTLA4 haplotype associated with coeliac disease. (PubMed id 15657618)^{1, 2, 4} Hunt K.A.... van Heel D.A. (Eur. J. Hum. Genet. 2005)
Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. (PubMed id 12724780)^{1, 2, 4} Ueda H.... Gough S.C. (Nature 2003)
Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy. (PubMed id 10475192)^{1, 2, 4} Vaidya B.... Pearce S.H.S. (Lancet 1999)
CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. (PubMed id 10189842)^{1, 2, 4} Djilali-Saiah I.... Caillat-Zucman S. (Gut 1998)
Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. (PubMed id 3220103)^{1, 2, 3} Dariavach P.... Lefranc M.-P. (Eur. J. Immunol. 1988)
Expression of CD152 (CTLA-4) in children with autoimmune thyroiditis and +49 A/G polymorphism of exon 1 of the CTLA-4 gene. (PubMed id 20134044)^{1, 4, 9} Kucharska A.M....Demkow U. (J. Physiol. Pharmacol. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 1493	HGNC: 2505	AceView: CTLA4	Ensembl:ENSG00000163599	euGenes: HUgn1493
ECgene: CTLA4	Kegg: 1493	H-InvDB: CTLA4

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for CTLA4	Pharmacogenomics, SNPs, Pathways
Wikipedia	http://en.wikipedia.org/wiki/CTLA-4

Intellectual Property for CTLA4 gene
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Patent Information for CTLA4 gene:
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CTLA4 Gene

Cytotoxic T-Lymphocyte-Associated Protein 4

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Diabetic Ketoacidosis
stable disease
Genetic Susceptibility
Dermatitis Atopic
Thymoma
Colitis Ulcerative
allergy
Liver diseases
Breast Cancer
Hyperthyroidism
primary tumor
Rheumatic Diseases
Asthma
BILIARY CIRRHOSIS PRIMARY
Allergic rhinitis
Cancer
Diabetes Mellitus Insulin-Dependent
Uveitis
Lymphoma
Periodontal Diseases
Miscarriage
cancer regression
RENAL DISEASE
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Hepatitis B Chronic
Multiple Sclerosis
HEMATOLOGIC DISORDERS
Inflammation
Hepatitis
Hypoparathyroidism
Psoriasis
Rheumatoid Arthritis
Hepatitis Autoimmune
prostate cancer
Tumors
Metastasis
Necrosis
Celiac Disease
Autoimmunity
mimicry
Asthma allergic
Melanoma B16
virus infection
ENDOCRINE DISORDER
Preeclampsia
Colitis
Thyroiditis
Autoimmune Diseases
Melanoma
Encephalomyelitis
Dermatitis
arthropathy
Leukemia Lymphocytic Chronic
Vasculitis
atopy
Hyperplasia
Goiter Nodular
Demyelination
Carcinoma
Osteoarthritis
Hypothyroidism
Myeloid Leukemia Chronic
Addisons Disease
Diabetes Mellitus
Myasthenia Gravis
HEPATOCELLULAR CARCINOMA
metastatic melanoma
Carcinoma Renal Cell
Cancer Lung
Inflammatory Bowel Diseases
Mastocytoma
KIDNEY TRANSPLANT REJECTION
Adenoma
Liver Diseases Alcoholic
BEHCET DISEASE
Enterocolitis
Lymphocytic Leukemia Chronic B-Cell
autoimmune thyroid disease
Carcinoma Squamous Cell
Paracoccidioidomycosis
Hepatitis C Chronic
Autoimmune Response
Wegeners Granulomatosis
Graves Disease
Infection chronic
Graft-Versus-Host Disease
Hashimotos Thyroiditis
Sclerosis Systemic
Diabetes Autoimmune
Vitiligo
Polymyositis
Arthritis
Lupus Erythematosus Systemic

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CTLA4 Gene

Cytotoxic T-Lymphocyte-Associated Protein 4

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