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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  

(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 thyroiditis, and hypothyroidism, autoimmune. 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 plasmidCTLA4 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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    OriGene Protein Over-expression Lysate for CTLA4
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    Sino Biological Recombinant Protein for CTLA4
    Sino Biological Cell Lysate for CTLA4
    ProSpec Recombinant Protein for CTLA4
    Cloud-Clone Corp. Proteins for CTLA4

     
    Search eBioscience for Proteins for CTLA4 

     
    antibodies-online proteins for CTLA4 (24 products) 

     
    antibodies-online peptides for CTLA4

    CTLA4 Antibody Products:

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    antibodies-online antibodies for CTLA4 (230 products) 

    CTLA4 Assay Products:

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    Cloud-Clone Corp. CLIAs for CTLA4
    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 IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI11279501
         
    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: Ctla4tm1All Ctla4tm1Mak Ctla4tm1Shr

       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 plasmidCTLA4 3' UTR sequence
    Inhib. RNA
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    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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    Clone
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    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

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    In Situ Assay
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    Flow Cytometry
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    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: 

    CompartmentConfidence
    plasma membrane5
    golgi apparatus4
    extracellular2
    nucleus2

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

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

    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

    SuperPathContained pathways About
    1CD28 co-stimulation
    Costimulation by the CD28 family0.44
    CTLA4 Signaling0.30
    CTLA4 inhibitory signaling0.32
    2TCR Signaling (Qiagen)
    TCR Signaling0.68
    3ICos-ICosL Pathway in T-Helper Cell
    CD28 Signaling in T-Helper Cell0.66
    4Allograft rejection
    Autoimmune thyroid disease0.61
    5Class I MHC mediated antigen processing and presentation
    Adaptive Immune System0.41


    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 (P164101, 2, 3 ENSP000003039394) via UniProtKB, MINT, STRING, and/or I2D (see all 25)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PIK3R1P279861, 2, 3, ENSP000002743354EBI-1030991,EBI-79464 MINT-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): Selected biological process terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006955immune response IEA--
    GO:0006974cellular response to DNA damage stimulus IMP17875758
    GO:0030889negative regulation of B cell proliferation IMP17875758
    GO:0031295T cell costimulation TAS--
    GO:0042130negative 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
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Alpha-D-Mannose-- 3458-28-4target--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
    bortezomibCA  
    dexamethasoneCA  
    melphalanCA  
    prednisoneCA  



    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
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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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    GenScript: all cDNA clones in your preferred vector (see all 2): CTLA4 (NM_005214)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CTLA4
    Primer
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    Flow Cytometry
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    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)
    About This Section

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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
    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
     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

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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)
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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 Ctla41 , 5 cytotoxic T-lymphocyte-associated protein 41, 5 79.97(n)1
    74.89(a)1
      1 (30.58 cM)5
    124771  NM_009843.41  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]


    Selected SNPs for CTLA4 (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
    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 31):    
    About MalaCards
    thyroiditis    hypothyroidism, autoimmune    celiac disease 3    graves disease 4
    graves' disease    paracoccidioidomycosis    autoimmune hepatitis    severe hemophilia a
    celiac disease    diabetes mellitus    wegener's granulomatosis    type 1 diabetes mellitus
    allergic encephalomyelitis    addison's disease    diabetic ketoacidosis    urinary schistosomiasis
    lupus erythematosus    autoimmune myocarditis    myxedema    collagen disease

    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

    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)
        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. (Hum. Genet. 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. (Eur. J. Hum. Genet. 2004)
    3. 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)
    4. 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)
    5. 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)
    6. 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)
    7. 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)
    8. 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)
    9. 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)
    10. 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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     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)
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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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    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.)
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    Patent Information for CTLA4 gene:
    Search GeneIP for patents involving CTLA4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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