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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CTLA4 Gene

protein-coding GIFtS: 66
GCID: GC02P204696

cytotoxic T-lymphocyte-associated protein 4

(Previous name: celiac disease 3 )
(Previous symbol: CELIAC3)

Explore 196 diseases affiliated with
CTLA4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Cytotoxic T-Lymphocyte-Associated Protein 4¹ ²		CD28¹
CD152¹ ² ³		ICOS¹
CELIAC3¹ ² ⁵		CD152 Isoform²
CD¹ ²		Cytotoxic T Lymphocyte Associated Antigen 4 Short Spliced Form²
GSE¹ ²		Cytotoxic T-Lymphocyte Antigen 4²
Celiac Disease 3¹ ²		Cytotoxic T-Lymphocyte Protein 4²
Cytotoxic T-Lymphocyte-Associated Antigen 4² 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
IDDM12² ⁵

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CTLA4:

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)

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)

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_005403.17

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for CTLA4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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

Subcellular location: 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;

6/7 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 Q0PP65 Q52MC1 Q53TD5 Q5S005 Q8WXJ1 Q96P43 Q9UKN9

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

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

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

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P16410

CTLA4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001032720.1 NP_005205.2

ENSEMBL proteins:

ENSP00000303939 ENSP00000295854 ENSP00000417779 ENSP00000409707

Reactome Protein details: P16410
Human Recombinant Protein Products for CTLA4:

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	Uscn Proteins for CTLA4

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): 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 to plasma membrane	TAS	3220103
GO:0009897	external side of plasma membrane	IDA	18641304
GO:0016020	membrane	--	--

CTLA4 for ontologies About GeneDecksing

CTLA4 Antibody Products:

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	Uscn ELISAs and CLIAs for CTLA4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

CTLA4 for domains About GeneDecksing

4 InterPro domains/families:

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 families:

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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

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 (GO ID links to tree view): About this table

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

CTLA4 for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for CTLA4:

Increased cell number in G1, a

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

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

CTLA4 for phenotypes About GeneDecksing

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

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for CTLA4

miRNA Products:		miRTarBase miRNAs that target CTLA4: hsa-mir-155 (MIRT004436)

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		8/14 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CTLA4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/10 super-pathways (see all 10) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Immune System

Immune System

1.00

Adaptive Immune System

0.59

CD28 co-stimulation

Costimulation by the CD28 family

0.41

CTLA4 Signaling

0.15

Rheumatoid arthritis

Rheumatoid arthritis

1.00

Cell adhesion molecules (CAMs)

Cell adhesion molecules (CAMs)

1.00

PKC-Theta Pathway

TCR Signaling

0.68

Pathway sources
See GeneCards unified pathways
Show all pathways

3 Downloadable PowerPoint Slides of QIAGEN 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

4 Reactome Pathways for CTLA4

	Costimulation by the CD28 family
	Adaptive Immune System
	CTLA4 inhibitory signaling
	Immune System

4 Kegg Pathways (Kegg details for CTLA4):

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

CTLA4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for CTLA4

STRING Interaction Network Preview (showing 5 interactants - click image to see 22)

5/24 Interacting proteins for CTLA4 (P16410^{1, 2, 3} ENSP00000303939⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 24)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986²^,³, ENSP00000274335⁴	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

About this table

Gene Ontology (GO): 5/7 biological process terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006955	immune response	IEA	--
GO:0006974	response to DNA damage stimulus	IMP	17875758
GO:0030889	negative regulation of B cell proliferation	IMP	17875758
GO:0031295	T cell costimulation	TAS	--
GO:0043065	positive regulation of apoptotic process	IMP	17875758

CTLA4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

CTLA4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

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

10/50 Novoseek 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)

Search CenterWatch for drugs/clinical trials and news about CTLA4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 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,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

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

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		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

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Additional cDNA 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:

U90273 BC074842 AF414120 NM_005214 AF486806 AI819438 AW207094 AW515943

BC074893 BG058720 BG236211 BV183431 BM997840 BC069566 AY209009 L15006

CD639535 BC070162 BE837454 AA210929 BG536887 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

CTLA4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TATAATATTT

About this image
See CTLA4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for CTLA4

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

SABiosciences Expression via Pathway-Focused 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

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		QIAGEN 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)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for CTLA4 gene from 3/9 species (see all 9) 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_009843.3¹ 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	-- --	--	34(a) 31(a)	many → 1 many → 1	AAWZ02040505(1945-5793) GL343208.1(2684025-2687950)

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)
About This Section

Paralogs for CTLA4 gene

CD28²

1 SIMAP similar gene for CTLA4 using alignment to 8 protein entries: CTLA4_HUMAN (see all proteins):

CTLA-4

CTLA4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Polymorphism: 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	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs231775^1,2	C,F,O,A,H	other	196580012(+)	`TGGCTA/GCCAGG`	4	T A	mis¹ ese³		39	EA NA MN NS CSA WA EU	11608
rs35832561^1,2	F	--	196577998(+)	`TGCTCA/GTCCCC`	2	--	us2k¹		5	MN	404
rs13410149^1,2	C,H	--	196578058(+)	`CTTTAG/ACCCAT`	2	--	us2k¹		9	NS EA MN	824
rs733619^1,2	C,F,H	--	196578103(-)	`ATTGAG/CAACAG`	2	--	us2k¹		16	NS EA NA MN CSA WA	1585
rs36021810^1,2	F	--	196578126(+)	`CTTTTC/TGTCTT`	2	--	us2k¹		5	MN	404
rs3087241^1,2	C,H	--	196578189(+)	`TACATA/GATACT`	2	--	us2k¹		9	MN NS EA	824
rs4553808^1,2	C,F,A,H	--	196578303(+)	`TTTTTA/GAAAAA`	2	--	us2k¹		14	MN NS EA NA WA	1014
rs62182595^1,2	C,F	--	196578486(+)	`AATCTG/ACATGT`	2	--	us2k¹		6	NA WA EA	248
rs16840252^1,2	C,F,H	--	196578817(+)	`ATGGAC/TGGACT`	2	--	us2k¹		32	NA NS EA WA	3332
rs11571317^1,2	C,F,H	--	196579306(+)	`TTTTCC/TGCCTA`	2	--	us2k¹ trp³		21	MN NS EA NA	2374

HapMap Linkage Disequilibrium report for CTLA4 (204732509 - 204738683 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for CTLA4: --
Human Gene Mutation Database (HGMD): CTLA4

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat 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.)
About This Section

CTLA4 for disorders           About GeneDecksing

OMIM gene information: 123890
OMIM disorders: 140300  601388  609755
UniProtKB/Swiss-Prot: CTLA4_HUMAN, P16410

Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE

is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the

skin, joints, kidneys and serosal membranes. SLE is thought to represent a failure of the regulatory mechanisms of the

autoimmune system

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

associated with overactivity of the thyroid gland and hyperthyroidism

Genetic variation in CTLA4 is the cause of susceptibility to diabetes mellitus insulin-dependent type 12

(IDDM12) [MIM:601388]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to

ketoacidosis in the absence of insulin therapy. Clinical fetaures 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

Genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3 (CELIAC3) [MIM:609755]. It

is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It

is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the

ingestion of wheat gluten or related rye and barley proteins. In its classic form, celiac disease is characterized in

children by malabsorption and failure to thrive

20/196 diseases for CTLA4 (see all 196): About MalaCards

celiac disease systemic lupus erythematosus diabetes mellitus lupus erythematosus

graves' disease graft versus host disease thyroiditis b-cell non-hodgkin lymphoma

diffuse large b-cell lymphoma hypersensitivity reaction type ii disease thrombotic thrombocytopenic purpura non-hodgkin lymphoma

chronic inflammatory demyelinating polyneuropathy wegener's granulomatosis demyelinating polyneuropathy microscopic polyangiitis

sclerosing cholangitis myasthenia gravis b-cell lymphomas common variable immunodeficiency

9 diseases from the University of Copenhagen DISEASES database for CTLA4:

Hypersensitivity reaction type II disease Melanoma Hyperthyroidism Thyroiditis

Diabetes mellitus Rheumatoid arthritis Connective tissue disease Multiple sclerosis

Asthma

10/93 Novoseek 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 9 sources (see all 1455):
(articles sorted by number of sources associating them with CTLA4)

Utopia: connect your pdf to the dynamic
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. (2005)
Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. (PubMed id 15138458)^{1, 2, 4, 9} Barreto M.... Vicente A.M. (2004)
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. (1997)
A common CTLA4 haplotype associated with coeliac disease. (PubMed id 15657618)^{1, 2, 4} Hunt K.A.... van Heel D.A. (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. (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. (1999)
CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. (PubMed id 10189842)^{1, 2, 4} Djilali-Saiah I.... Caillat-Zucman S. (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. (1988)
CTLA4 is differentially associated with autoimmune diseases in the Dutch population. (PubMed id 16025348)^{1, 4, 9} Zhernakova A....Koeleman B.P. (2005)
Polymorphsims of CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 in spondyloarthropathies. (PubMed id 11771526)^{1, 4, 9} Lee Y.H....Song G.G. (2001)

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

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

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, and/or UniProtKB/TrEMBL,
Wikipedia and/or 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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CTLA4 (Gene Symbol)
Cytotoxic T-Lymphocyte-Associated Protein 4
CD152
CELIAC3
CD
GSE
Celiac Disease 3
Cytotoxic T-Lymphocyte-Associated Antigen 4
CTLA-4
GRD4
IDDM12
CD28
ICOS
CD152 Isoform
Cytotoxic T Lymphocyte Associated Antigen 4 Short Spliced Form
Cytotoxic T-Lymphocyte Antigen 4
Cytotoxic T-Lymphocyte Protein 4
Cytotoxic T-Lymphocyte-Associated Serine Esterase-4
Ligand And Transmembrane Spliced Cytotoxic T Lymphocyte Associated Antigen 4
CD152 Antigen

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
Shock
Hepatitis B Chronic
Multiple Sclerosis
HEMATOLOGIC DISORDERS
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Hypoparathyroidism
Psoriasis
Rheumatoid Arthritis
Hepatitis Autoimmune
prostate cancer
Tumors
Metastasis
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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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