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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CTLA4 Gene

protein-coding   GIFtS: 64
GCID: GC02P204696

Cytotoxic T-Lymphocyte-Associated Protein 4

(Previous name: celiac disease 3)
(Previous symbol: CELIAC3)
Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Cytotoxic T-Lymphocyte-Associated Protein 41 2     GSE2
CELIAC31 2 5     CD152 Isoform2
Celiac Disease 31 2     Cytotoxic T Lymphocyte Associated Antigen 4 Short Spliced Form2
Cytotoxic T-Lymphocyte-Associated Antigen 42 3     Cytotoxic T-Lymphocyte Antigen 42
CD1522 3     Cytotoxic T-Lymphocyte Protein 42
CTLA-42 3     Cytotoxic T-Lymphocyte-Associated Serine Esterase-42
GRD42 5     Ligand And Transmembrane Spliced Cytotoxic T Lymphocyte Associated Antigen
42
IDDM122 5     CD152 Antigen3
CD2     

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 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 graves' disease, and celiac disease 3, and among its related super-pathways are Costimulation by the CD28 family and Immune System. GO annotations related to this gene include protein binding. 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000002.11  NT_005403.17  NC_018913.2  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the CTLA4 gene promoter:
         AML1a   AP-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCTLA4 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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 Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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 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:

  • UniProtKB: N-glycosylation is important for dimerization
  • UniProtKB: Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to
    retention of CTLA4 on the cell surface
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P16410

  • CTLA4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    CTLA4 Protein Expression
    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: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for CTLA4 (CTLA-4)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for CTLA4
    OriGene Custom MassSpec 
    OriGene Custom Protein Services for CTLA4
    GenScript Custom Purified and Recombinant Proteins Services for CTLA4
    Novus Biologicals CTLA4 Proteins
    Novus Biologicals CTLA4 Lysate
    Sino Biological Recombinant Protein for CTLA4
    Sino Biological Cell Lysate for CTLA4 
    ProSpec Recombinant Protein for CTLA4
    Cloud-Clone Corp. Proteins for CTLA4 

    Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005794Golgi apparatus IDA15814706
    GO:0005886plasma membrane TAS--
    GO:0005887integral to plasma membrane TAS3220103
    GO:0009897external side of plasma membrane IDA18641304
    GO:0045334clathrin-coated endocytic vesicle IDA15814706

    CTLA4 for ontologies           About GeneDecksing



    CTLA4 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of CTLA4
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    Novus Biologicals CTLA4 Antibodies
    Abcam antibodies for CTLA4
    Cloud-Clone Corp. Antibodies for CTLA4 
    ThermoFisher Antibodies for CTLA4
    LSBio Antibodies in human, mouse, rat for CTLA4 

    Assay Products for CTLA4: 
    Browse Kits and Assays available from EMD Millipore
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    Cloud-Clone Corp. ELISAs for CTLA4 
    Cloud-Clone Corp. CLIAs for CTLA4


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


    CTLA4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, 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, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 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 IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI11279501
         
    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:
         MGI mouse knock-outs for CTLA4: Ctla4tm1All Ctla4tm1Mak Ctla4tm1Shr

       inGenious Targeting Laboratory - Custom generated mouse model solutions for CTLA4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for CTLA4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CTLA4 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CTLA4 

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

    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CTLA4
    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 plasmidCTLA4 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for CTLA4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CTLA4

    Gene Editing
    Products:
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    Sirion Biotech Customized adenovirus for overexpression of CTLA4

    Clone
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    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for CTLA4 (see all 9)
    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
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CTLA4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CTLA4
    Sirion Biotech Customized lentivirus for stable overexpression of CTLA4 
                         Customized lentivirus expression plasmids for stable overexpression of CTLA4 

    Cell Line
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    Search LifeMap BioReagents cell lines for CTLA4
    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, Sino Biological, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for CTLA4 About   (see all 10)                                                                                              See pathways by source

    SuperPathContained pathways About
    1CD28 co-stimulation
    Costimulation by the CD28 family0.41
    CTLA4 Signaling0.31
    2Immune System
    Immune System0.56
    Adaptive Immune System0.56
    3PKC-Theta Pathway
    TCR Signaling0.68
    4ICos-ICosL Pathway in T-Helper Cell
    CD28 Signaling in T-Helper Cell0.66
    5Allograft rejection
    Autoimmune thyroid disease0.62

    Pathways by source                                                                                                                                                                 See SuperPaths
    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 CentralTM 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 (P164101, 2, 3 ENSP000003039394) via UniProtKB, MINT, STRING, and/or I2D (see all 24)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PIK3R1P279862, 3, ENSP000002743354MINT-8035246 MINT-8035216 MINT-8035201 I2D: score=2 STRING: ENSP00000274335
    CD86P420811, 3, ENSP000003320494EBI-1030991,EBI-1030956 I2D: score=3 STRING: ENSP00000332049
    CD80P336811, 3, ENSP000002642464EBI-1030991,EBI-1031024 I2D: score=4 STRING: ENSP00000264246
    FYNP062413, ENSP000003576564I2D: score=4 STRING: ENSP00000357656
    LCKP062393, ENSP000003378254I2D: 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 IDQualified GO termEvidencePubMed IDs
    GO:0006955immune response IEA--
    GO:0006974response to DNA damage stimulus IMP17875758
    GO:0030889negative regulation of B cell proliferation IMP17875758
    GO:0031295T cell costimulation TAS--
    GO:0043065positive regulation of apoptotic process IMP17875758

    CTLA4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, 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
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Alpha-D-Mannose-- 3458-28-4target--17139284 17016423

    10/50 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), 19412189 (1), 19252247 (1), 17642247 (1), 17787038 (1), 17404488 (1), 18538830 (1), 19280938 (1), 19786766 (1), 17642237 (1) (see top 4)
    ctla4-ig 74.7 17 8228824 (2), 17924973 (2), 7678111 (1), 7504299 (1), 1385153 (1), 12665422 (1), 7504294 (1), 7964482 (1), 10497065 (1), 11685115 (1), 12518898 (1), 18816483 (1), 19262560 (1) (see top 4)
    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), 17938902 (1) (see top 4)
    ionomycin 38.2 12 12444128 (3), 10600000 (2), 10777098 (1), 9857283 (1)
    tyrosine 27.9 60 9712716 (6), 9973379 (4), 10604992 (3), 10842319 (3), 9856951 (3), 19405949 (2), 7559643 (2), 11676481 (1), 17334650 (1), 17052659 (1), 11994459 (1), 16483921 (1), 18988535 (1), 19500759 (1), 19209622 (1), 19180256 (1), 16403820 (1), 9353155 (1), 18324481 (1), 17509159 (1), 16257508 (1), 9638368 (1), 16442659 (1), 16229750 (1), 9813138 (1), 19961590 (1), 9203414 (1), 12972512 (1), 18776148 (1) (see top 4)
    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 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,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    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
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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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
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CTLA4
    Sirion Biotech Customized lentivirus for stable overexpression of CTLA4 
                         Customized lentivirus expression plasmids for stable overexpression of CTLA4 
    Primer
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    OriGene qPCR primer pairs and template standards for CTLA4
    OriGene qSTAR qPCR primer pairs in human, mouse for CTLA4
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat CTLA4
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat 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 BC074893 U90273 AF486806 AW207094 NM_005214 BG236211 AF414120 
    AI819438 BC074842 BG058720 AY209009 BC070162 CD639535 BC069566 L15006 
    BV183431 BM997840 BE837454 BG536887 AA210929 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)      CTLA4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TATAATATTT
    CTLA4 Expression
    About this image


    CTLA4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/4 selected tissues (see all 4) fully expand
     
     Blood (Cardiovascular System)    fully expand to see all 6 entries
             T Helper Cells Thymus
             Regulatory T cells
             Peripheral blood Pan-T Cells   
             cd4+ t cells   
     
     Thymus (Hematopoietic System)
             T Helper Cells Thymus
     
     Lymph (Hematopoietic System)
             lymph node   
     
     Tonsil (Hematopoietic System)

    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

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              T-Cell Anergy & Immune Tolerance in human mouse rat
              Diabetes in human mouse rat

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    (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 4/10 species (see all 10)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Ctla41 , 5 cytotoxic T-lymphocyte-associated protein 41, 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 --
    --
    Uncharacterized protein
    34(a)
    31(a)
    many → 1
    many → 1
    AAWZ02040505(955-5793)
    GL343208.1(2684025-2687950)
    zebrafish
    (Danio rerio)
    Actinopterygii cd286
    CD28 molecule
    24(a)
    1 → many
    9(14262659-14265291)


    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  

    CTLA4 for paralogs           About GeneDecksing



    (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) 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)
    About This Section

    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]


    10/179 SNPs in CTLA4 are shown (see all 179)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2317751,2,4
    C,F,O,A,Hother1204122578(+) TGGCTA/GCCAGG 4 T A mis1 ese339Minor allele frequency- G:0.44EA NA MN NS CSA WA EU 11608
    rs358325611,2
    F--204120564(+) TGCTCA/GTCCCC 2 -- us2k15Minor allele frequency- G:0.01MN 404
    rs134101491,2
    C,H--204120624(+) CTTTAG/ACCCAT 2 -- us2k19Minor allele frequency- A:0.00NS EA MN 824
    rs1472677151,2
    --204120657(+) CCACCC/TTTTTC 2 -- us2k10--------
    rs7336191,2
    C,F,H--204120669(-) ATTGAG/CAACAG 2 -- us2k116Minor allele frequency- C:0.03NS EA NA MN CSA WA 1585
    rs360218101,2
    F--204120692(+) CTTTTC/TGTCTT 2 -- us2k15Minor allele frequency- T:0.01MN 404
    rs30872411,2
    C,H--204120755(+) TACATA/GATACT 2 -- us2k19Minor allele frequency- G:0.00MN NS EA 824
    rs115713151,2
    C,F,H--204120765(-) ctggaG/Attgaa 2 -- us2k130Minor allele frequency- A:0.48NS EA NA MN WA CSA 2732
    rs7336181,2
    C,F,A,H--204120808(-) GACAGA/GCAGCT 2 -- us2k121Minor allele frequency- G:0.17NS EA NA MN WA 2742
    rs45538081,2
    C,F,A,H--204120869(+) TTTTTA/GAAAAA 2 -- us2k114Minor allele frequency- G:0.15MN NS EA NA WA 1014

    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
    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    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

  • 20/186 diseases for CTLA4 (see all 186):    About MalaCards
    graves' disease    celiac disease 3    paracoccidioidomycosis    celiac disease
    autoimmune hepatitis    wegener's granulomatosis    allergic encephalomyelitis    cd40 ligand deficiency
    diabetic ketoacidosis    autoimmune thyroiditis    diabetes mellitus    primary biliary cirrhosis
    myxedema    autoimmune myocarditis    type 1 diabetes mellitus    addison's disease
    blood disorders    hypothyroidism, autoimmune    type 1 diabetes    myasthenia gravis

    9 diseases 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

    CTLA4 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014

    10/93 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)
    About This Section

    PubMed articles for CTLA4 gene, integrated from 9 sources (see all 1496):
    (articles sorted by number of sources associating them with CTLA4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. 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)
    2. Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. (PubMed id 15138458)1, 2, 4, 9 Barreto M.... Vicente A.M. (2004)
    3. 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)
    4. A common CTLA4 haplotype associated with coeliac disease. (PubMed id 15657618)1, 2, 4 Hunt K.A.... van Heel D.A. (2005)
    5. 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)
    6. 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)
    7. CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. (PubMed id 10189842)1, 2, 4 Djilali-Saiah I.... Caillat-Zucman S. (1998)
    8. 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)
    9. Expression of CD152 (CTLA-4) in children with autoimm une 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. (2009)
    10. CTLA4 is differentially associated with autoimmune diseases in the Dutch population. (PubMed id 16025348)1, 4, 9 Zhernakova A....Koeleman B.P. (2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    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)
    About This Section
    Entrez Gene: 1493 HGNC: 2505 AceView: CTLA4 Ensembl:ENSG00000163599 euGenes: HUgn1493
    ECgene: CTLA4 Kegg: 1493 H-InvDB: CTLA4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for CTLA4 Pharmacogenomics, SNPs, Pathways
    Wikipedia http://en.wikipedia.org/wiki/CTLA-4

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for CTLA4 gene:
    Search GeneIP for patents involving CTLA4

    GeneCards and IP:
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