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

HAVCR2 Gene

protein-coding   GIFtS: 54
GCID: GC05M156512

hepatitis A virus cellular receptor 2

 Explore 43 diseases affiliated with
HAVCR2 via our new
 Human Malady Compendium 
Biological research products
for HAVCR2
    

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

Aliases
Hepatitis A Virus Cellular Receptor 21 2     T-Cell Membrane Protein 32 3
TIM31 2 3 5     FLJ144281
TIMD31 2 3     KIM-32
Tim-31 2     Kidney Injury Molecule-32
HAVcr-22 3     T Cell Immunoglobulin Mucin 32
TIMD-32 3     T Cell Immunoglobulin Mucin-32
T-Cell Immunoglobulin And Mucin Domain-Containing Protein 32 3     TIM-33

External Ids:    HGNC: 184371   Entrez Gene: 848682   Ensembl: ENSG000001350777   OMIM: 6066525   UniProtKB: Q8TDQ03   

Export aliases for HAVCR2 gene to outside databases

Previous GC identifers: GC05M157063 GC05M156448 GC05M156493 GC05M156445 GC05M151601


(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 HAVCR2:
The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T
helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns.
Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity
reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of
atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage
activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. (provided
by RefSeq, Sep 2011)

UniProtKB/Swiss-Prot: HAVR2_HUMAN, Q8TDQ0
Function: Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune
responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9

Gene Wiki entry for HAVCR2


(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_000005.9  NC_018916.1  NT_023133.13  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the HAVCR2 gene promoter:
         HFH-3   AP-2rep   C/EBPbeta   XBP-1   Roaz   GATA-2   FOXI1   FOXJ2 (long isoform)   HFH-1   FOXJ2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHAVCR2 promoter sequence
   Search SABiosciences Chromatin IP Primers for HAVCR2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HAVCR2


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

Entrez Gene cytogenetic band: 5q33.3   Ensembl cytogenetic band:  5q33.3   HGNC cytogenetic band: 5q34

HAVCR2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HAVCR2 gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05M156512:  view genomic region     (about GC identifiers)

Start:
156,512,843 bp from pter      End:
156,569,880 bp from pter
Size:
57,038 bases      Orientation:
minus 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: HAVR2_HUMAN, Q8TDQ0 (See protein sequence)
Recommended Name: Hepatitis A virus cellular receptor 2 precursor  
Size: 301 amino acids; 33394 Da
Subcellular location: Membrane; Single-pass type I membrane protein (Potential)
Secondary accessions: B2RAY2 Q8WW60 Q96K94
Alternative splicing: 2 isoforms:  Q8TDQ0-1   Q8TDQ0-2   

Explore the universe of human proteins at neXtProt for HAVCR2: NX_Q8TDQ0

Post-translational modifications:

  • O-glycosylated with core 1 or possibly core 8 glycans1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q8TDQ0

  • HAVCR2 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_116171.3  
    ENSEMBL proteins: 
     ENSP00000312002   ENSP00000430873   ENSP00000430328  

    Human Recombinant Protein Products: 
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    Uscn Proteins for HAVCR2

    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0016021integral to membrane IEA--


    HAVCR2 for ontologies           About GeneDecksing



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    Uscn ELISAs and CLIAs for HAVCR2


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

    HAVCR2 for domains           About GeneDecksing

    4 InterPro domains/families:
     IPR013783 Ig-like_fold
     IPR013106 Ig_V-set
     IPR007110 Ig-like_dom
     IPR003599 Ig_sub

    Graphical View of Domain Structure for InterPro Entry Q8TDQ0

    ProtoNet protein and cluster: Q8TDQ0

    1 Blocks protein family: IPB003599 Immunoglobulin subtype

    UniProtKB/Swiss-Prot: HAVR2_HUMAN, Q8TDQ0
    Similarity: Belongs to the immunoglobulin superfamily. TIM family
    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,
    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, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: HAVR2_HUMAN, Q8TDQ0
    Function: Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune
    responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9

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    hsa-miR-593 hsa-miR-330-5p hsa-miR-326 hsa-miR-3182 hsa-miR-103a-2* hsa-miR-3657
    SwitchGear 3'UTR luciferase reporter plasmidHAVCR2 3' UTR sequence
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    2 GenomeRNAi human phenotypes for HAVCR2:
     Decreased G3BP1 protein expres  Increased cilium length after  

    Animal Models:
         Mouse knock-out Havcr2tm1Tbs for HAVCR2
         5 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Havcr2):
     cellular  growth/size  hematopoietic system  immune system  mortality/aging 

    HAVCR2 for phenotypes           About GeneDecksing


    (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



    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for HAVCR2

    (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
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for HAVCR2
    Search CenterWatch for drugs/clinical trials and news about HAVCR2 / HAVR2 

    (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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    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 HAVCR2 gene: 
    NM_032782.4  

    Unigene Cluster for HAVCR2:

    Hepatitis A virus cellular receptor 2
    Hs.710500  [show with all ESTs]
    Unigene Representative Sequence: NM_032782
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000307851(uc003lwk.2) ENST00000522593 ENST00000524219 ENST00000521665
    ENST00000522902(uc003lwl.3) ENST00000517358

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    hsa-miR-593 hsa-miR-330-5p hsa-miR-326 hsa-miR-3182 hsa-miR-103a-2* hsa-miR-3657
    SwitchGear 3'UTR luciferase reporter plasmidHAVCR2 3' UTR sequence
    Inhib. RNA
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    Additional cDNA sequence: 

    AF251707.1 AF450242.1 AF450243.1 AK027334.1 AK130144.1 AK314406.1 AY069944.1 BC020843.1 
    BC063431.1 JX049979.1 

    6 DOTS entries:

    DT.431150  DT.97839520  DT.99928688  DT.120827768  DT.95084108  DT.40291503 

    24/51 AceView cDNA sequences (see all 51):

    BI906710 BM923617 CA307836 BP340002 AA664217 AI202037 AF450242 BX417090 
    AF450243 BQ581620 CD710266 BX431364 NM_032782 BP373569 AJ705624 CD640560 
    AW025572 AK130144 CD522575 BC020843 BP345570 BP344854 AI636449 CD520418 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for HAVCR2    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7
    SP1:        -     -                                             
    SP2:        -     -                 -                           
    SP3:                                                            
    SP4:                                                            


    ECgene alternative splicing isoforms for HAVCR2

    (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

    HAVCR2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: ATTTGCCTGC

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image
    See HAVCR2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for HAVCR2

    SOURCE GeneReport for Unigene cluster: Hs.710500

    UniProtKB/Swiss-Prot: HAVR2_HUMAN, Q8TDQ0
    Tissue specificity: T-helper type 1 lymphocyte (Th1)-specific

        SABiosciences Expression via Pathway-Focused PCR Arrays including HAVCR2: 
              Th1/Th2 Response in human mouse rat
              T Helper Cell Differentiation in human mouse rat

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    In Situ
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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 HAVCR2 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 Havcr21 , 5 hepatitis A virus cellular receptor 21, 5 74.64(n)1
    66.79(a)1
      11 (27.90 cM)5
    1712851  NM_134250.21  NP_599011.21 
     464549355 
    chicken
    (Gallus gallus)
    Aves Q5ZKI8_CHICK6
    hepatitis A virus cellular receptor 1
    43(a)
    1 → many
    13(11525677-11573991)
    zebrafish
    (Danio rerio)
    Actinopterygii timd46
    T-cell immunoglobulin and mucin domain containing ...
    25(a)
    1 → many
    21(28485046-28494504)


    ENSEMBL Gene Tree for HAVCR2 (if available)
    TreeFam Gene Tree for HAVCR2 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for HAVCR2 gene
    HAVCR12  TIMD42  
    1 SIMAP similar gene for HAVCR2 using alignment to 3 protein entries:     HAVR2_HUMAN (see all proteins):
    HAVCR1

    HAVCR2 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)
    About This Section

    10/525 NCBI SNPs in HAVCR2 are shown (see all 525    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs65558431,2
    C,F,A,H--156512349(+) AATAAC/TGCCGC 1 -- ds50013Minor allele frequency- T:0.50NA 6
    rs65558441,2
    C,A,H--156512420(+) CCCTAC/TTTAAT 1 -- ds50011Minor allele frequency- T:0.50NA 2
    rs1810047861,2
    --156512546(+) AAACCA/CTAAAA 1 -- ds50010--------
    rs1854945101,2
    --156512552(+) TAAAAA/GCCCTA 1 -- ds50010--------
    rs1906956121,2
    --156512573(+) TAGACA/TTTACC 1 -- ds50010--------
    rs361713021,2
    C--156512640(+) CACAAC/AAGCCA 1 -- ds50011Minor allele frequency- A:0.50NA 2
    rs715910971,2
    C,F--156512746(+) ATTTTC/TGCAAC 1 -- ds50012Minor allele frequency- T:0.50NA 4
    rs674676101,2
    C,--156512771(+) AAGGGC/TTAATA 1 -- ds50011Minor allele frequency- T:0.50NA 2
    rs1814340281,2
    --156512803(+) AGACAC/GAGCGA 1 -- ds50010--------
    rs1396516151,2
    --156512922(+) CAAGAC/TAGATC 1 -- ut310--------

    HapMap Linkage Disequilibrium report for HAVCR2 (156512843 - 156569880 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for HAVCR2: --

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    (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

    HAVCR2 for disorders           About GeneDecksing

    OMIM gene information: 606652    OMIM disorders: --

    20/43 diseases for HAVCR2 (see all 43):    About MalaCards
    hepatitis a    hepatitis    dendritic cell thymoma    allergic rhinitis
    systemic lupus erythematosus    aplastic anemia    lupus erythematosus    atopic dermatitis
    rhinitis    chronic lymphocytic leukemia    multiple sclerosis    allergic asthma
    lymphocytic leukemia    encephalomyelitis    bronchiolitis    hodgkin's lymphoma
    eczema    rheumatoid arthritis    asthma    pulmonary tuberculosis

    2 diseases from the University of Copenhagen DISEASES database for HAVCR2:
    Epithelial malignant thymoma     Prostatic adenoma

    8 Novoseek disease relationships for HAVCR2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    autoimmune diseases 52.4 12 11823861 (3), 19768575 (2), 15272240 (1), 19332093 (1) (see all 7)
    asthma 34.8 11 15867855 (4), 19494522 (3), 18785518 (2), 15603868 (2)
    encephalomyelitis 31.5 2 15153541 (1), 11823861 (1)
    allergic rhinitis 30.9 2 15603868 (2)
    allergy 23.8 3 17517968 (1), 17665973 (1)
    multiple sclerosis 22.7 3 15153541 (1), 17665973 (1), 19768575 (1)
    inflammation 3.35 2 17513715 (2)
    tumors 0 3 17096021 (3)

    Genetic Association Database (GAD): HAVCR2
    Human Genome Epidemiology (HuGE) Navigator: HAVCR2 (23 documents)

    Export disorders for HAVCR2 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 HAVCR2 gene, integrated from 9 sources (see all 109):
    (articles sorted by number of sources associating them with HAVCR2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. (PubMed id 11823861)1, 2, 3, 9 Monney L....Kuchroo V.K. (2002)
    2. The association of TIM-3 gene polymorphism with atopic disease in Korean population. (PubMed id 15603868)1, 4, 9 Chae S.C....Chung H.T. (2004)
    3. Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American population. (PubMed id 15867855)1, 4, 9 Gao P.S....Huang S.K. (2005)
    4. Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33. (PubMed id 16159638)1, 4, 9 Graves P.E....Martinez F.D. (2005)
    5. The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis. (PubMed id 15325803)1, 4, 9 Chae S.-C.... Chung H.-T. (2004)
    6. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. (PubMed id 16286920)1, 2 Zhu C.... Kuchroo V.K. (2005)
    7. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (2004)
    8. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    9. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. (PubMed id 14556005)1, 2 Sanchez-Fueyo A.... Strom T.B. (2003)
    10. T cell immunoglobulin- and mucin-domain-containing mo lecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B. (PubMed id 20133006)1, 9 Ju Y....Ma C. (2010)

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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 84868 HGNC: 18437 AceView: HAVCR2 Ensembl:ENSG00000135077 euGenes: HUgn84868
    ECgene: HAVCR2 H-InvDB: HAVCR2

    (According to HUGE)
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    NameDescription
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