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KLRC3 Gene

protein-coding   GIFtS: 60
GCID: GC12M010564

Killer Cell Lectin-Like Receptor Subfamily C, Member 3

  See related disease
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
Killer Cell Lectin-Like Receptor Subfamily C, Member 31 2
NKG2E2 3 5
NK Cell Receptor E2 3
NKG2-E-Activating NK Receptor2 3
NKG2-E2
NKG2-E Type II Integral Membrane Protein2

External Ids:    HGNC: 63761   Entrez Gene: 38232   Ensembl: ENSG000002058107   OMIM: 6028925   UniProtKB: Q074443   

Export aliases for KLRC3 gene to outside databases

Previous GC identifers: GC12U990043 GC12M010687 GC12M010465 GC12M010456 GC12M010307


(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 KLRC3 Gene:
Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells
without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells
preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation
of NK cell function. KLRC3 is a member of the NKG2 group which are expressed primarily in natural killer (NK)
cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation
(extracellular C terminus) and the presence of a C-type lectin domain. The NKG2 gene family is located within the
NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. Alternative
splicing results in multiple transcript variants encoding different isoforms. (provided by RefSeq, Jul 2008)

GeneCards Summary for KLRC3 Gene:
KLRC3 (killer cell lectin-like receptor subfamily C, member 3) is a protein-coding gene. Diseases associated with KLRC3 include monkeypox. GO annotations related to this gene include transmembrane signaling receptor activity and carbohydrate binding. An important paralog of this gene is KLRC2.

UniProtKB/Swiss-Prot: NKG2E_HUMAN, Q07444
Function: Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some
cytotoxic T-cells




(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:
NC_000012.12  NC_018923.2  NT_009714.18  
Regulatory elements:
   Regulatory transcription factor binding sites in the KLRC3 gene promoter:
         c-Fos   AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidKLRC3 promoter sequence
   Search Chromatin IP Primers for KLRC3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat KLRC3


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

Entrez Gene cytogenetic band: 12p13   Ensembl cytogenetic band:  12p13.2   HGNC cytogenetic band: 12p13

KLRC3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
KLRC3 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M010564:  view genomic region     (about GC identifiers)

Start:
10,564,911 bp from pter      End:
10,573,194 bp from pter
Size:
8,284 bases      Orientation:
minus 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, 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., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NKG2E_HUMAN, Q07444 (See protein sequence)
Recommended Name: NKG2-E type II integral membrane protein  
Size: 240 amino acids; 27100 Da
Subunit: Can form disulfide-bonded heterodimer with CD94
Secondary accessions: Q8WXA4 Q96RL0 Q9UP04
Alternative splicing: 2 isoforms:  Q07444-1   Q07444-2   

Explore the universe of human proteins at neXtProt for KLRC3: NX_Q07444

Explore proteomics data for KLRC3 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn100, Asn149, Asn179

  • See KLRC3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_002252.2  NP_031359.2  

    ENSEMBL proteins: 
     ENSP00000379716   ENSP00000371328   ENSP00000371329  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    KLR: Killer cell lectin-like receptors

    3 InterPro protein domains:
     IPR016187 C-type_lectin_fold
     IPR016186 C-type_lectin-like
     IPR001304 C-type_lectin

    Graphical View of Domain Structure for InterPro Entry Q07444

    ProtoNet protein and cluster: Q07444

    UniProtKB/Swiss-Prot: NKG2E_HUMAN, Q07444
    Similarity: Contains 1 C-type lectin domain


    KLRC3 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,
    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, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NKG2E_HUMAN, Q07444
    Function: Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some
    cytotoxic T-cells

         Genatlas biochemistry entry for KLRC3:
    natural killer cell lectin-like receptor subfamily C,member 3

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004888transmembrane signaling receptor activity TAS9683661
    GO:0030246carbohydrate binding IEA--
         
    KLRC3 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for KLRC3:
     Increased gamma-H2AX phosphory  Wnt reporter downregulated 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for KLRC3
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    hsa-mir-335-5p (MIRT018845)

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    (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
    NKG2E_HUMAN, Q07444: Membrane; Single-pass type II membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol2
    endoplasmic reticulum2
    extracellular2
    golgi apparatus2
    nucleus2
    peroxisome1
    plasma membrane1

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0016021integral component of membrane IEA--

    KLRC3 for ontologies           About GeneDecksing


    (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 KLRC3 About    
    See pathways by source

    SuperPathContained pathways About
    1Immune response Role of DAP12 receptors in NK cells
    Immune response Role of DAP12 receptors in NK cells0.33
    Natural killer cell mediated cytotoxicity0.31
    2Allograft rejection
    Antigen processing and presentation0.36

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 GeneGo (Thomson Reuters) Pathway for KLRC3
        Immune response Role of DAP12 receptors in NK cells



    2 Kegg Pathways  (Kegg details for KLRC3):
        Antigen processing and presentation
    Natural killer cell mediated cytotoxicity


    KLRC3 for pathways           About GeneDecksing

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for KLRC3
    Interactions:

        Search GeneGlobe Interaction Network for KLRC3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 7)

    Selected Interacting proteins for KLRC3 (Q074443 ENSP000003713284) via UniProtKB, MINT, STRING, and/or I2D (see all 7)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    KLRD1Q132413, ENSP000003381304I2D: score=3 STRING: ENSP00000338130
    TYROBPO439143, ENSP000002626294I2D: score=1 STRING: ENSP00000262629
    ENSG00000223532ENSP000004008424STRING: ENSP00000400842
    ENSG00000229252ENSP000004099104STRING: ENSP00000409910
    ENSG00000237216ENSP000004091324STRING: ENSP00000409132
    About this table

    Gene Ontology (GO): 2 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006968cellular defense response TAS9683661
    GO:0007165signal transduction TAS9683661

    KLRC3 for ontologies           About GeneDecksing



    (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
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    Browse Tocris compounds for KLRC3 (NKG2E)



    (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, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for KLRC3 gene (2 alternative transcripts): 
    NM_002261.2  NM_007333.2  

    Unigene Cluster for KLRC3:

    Killer cell lectin-like receptor subfamily C, member 3
    Hs.654362  [show with all ESTs]
    Unigene Representative Sequence: NM_002261
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000396439(uc001qyf.3 uc021qvc.1) ENST00000381903(uc001qyi.1 uc021qvd.1)
    ENST00000381904
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      QuantiFast Probe-based Assays in human, mouse, rat KLRC3

    Additional mRNA sequence: 

    AF078550.1 AF350016.1 AF350017.1 AK307860.1 AK311162.1 L14542.1 

    5 DOTS entries:

    DT.95373143  DT.452120  DT.121197032  DT.121197040  DT.75132896 

    Selected AceView cDNA sequences (see all 84):

    AF439512 AF260135 CR607215 CR597595 CB216677 CB241686 BM456777 AA361092 
    BC017784 AF350018 BI909601 BQ708055 X54870 BX099329 BI253358 NM_007360 
    BI765191 BI333629 AF461811 BG392353 AA738439 BM740579 BG682117 U96845 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    KLRC3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TACCATTTAG
    KLRC3 Expression
    About this image


    KLRC3 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 3 entries
             Natural Killer Cells Peripheral Blood
     
     Thymus (Hematopoietic System)
             T-Cytotoxic Cells Thymus
     
     Brain (Nervous System)
             Oligodendrocyte Precursor Cells Forebrain White Matter
    KLRC3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    KLRC3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.654362

    UniProtKB/Swiss-Prot: NKG2E_HUMAN, Q07444
    Tissue specificity: Natural killer cells

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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 human and mouse.

    Orthologs for KLRC3 gene from Selected species (see all 5)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Klrc35 killer cell lectin-like receptor subfamily C, member more   --   6 (63.44 cM) 129639085 


    ENSEMBL Gene Tree for KLRC3 (if available)
    TreeFam Gene Tree for KLRC3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for KLRC3 gene
    KLRC22  KLRD12  KLRK12  KLRC42  KLRC4-KLRK12  ENSG000002556412  KLRC12  
    9 SIMAP similar genes for KLRC3 using alignment to 2 protein entries:     NKG2E_HUMAN (see all proteins):
    NKG2-E    KLRC2    KLRC1    KLRC4    KLRC4-KLRK1    FCER2
    KLRK1    REG1A    KLRD1

    KLRC3 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), 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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    Selected SNPs for KLRC3 (see all 286)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs774980361,2
    F--10564819(+) ACTCTC/TATTGA 1 -- ds50011Minor allele frequency- T:0.04WA 118
    rs1898018751,2
    --10564909(+) CCACTA/CATTAT 1 -- ds50010--------
    rs1439744811,2
    --10564925(+) TCATTC/GATTTA 1 -- ut310--------
    rs1460389511,2
    --10564945(+) CATAAC/TGGTCT 1 -- ut310--------
    rs26825061,2
    C,F,A--10564963(-) ATATTA/CATATT 1 -- ut311Minor allele frequency- C:0.04WA 118
    rs175489831,2
    C,F--10565113(-) AAGCCA/GCCGCC 1 -- ut31 ese35Minor allele frequency- G:0.17NA WA 244
    rs617430851,2
    C--10565212(+) ACCCCG/ATCTCT 2 /R /W mis11Minor allele frequency- A:0.01NS 76
    rs1121948231,2
    C,F--10565408(+) AATATG/ATTTTT 1 -- int11Minor allele frequency- A:0.50CSA 2
    rs15457501,2
    C,F,A,H--10565453(+) ATATAA/GTTGAA 1 -- int117Minor allele frequency- G:0.00NA NS EA WA CSA 1195
    rs1421890871,2
    C--10565463(+) ATAAAA/GTGAAC 1 -- int10--------

    HapMap Linkage Disequilibrium report for KLRC3 (10564911 - 10573194 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for KLRC3 (see all 18):    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv263e199CNV Deletion23128226
    esv4003CNV Deletion18987735
    nsv435631CNV Deletion17901297
    esv2745535CNV Deletion23290073
    esv32543CNV Loss17666407
    nsv898759CNV Loss21882294
    nsv898763CNV Loss21882294
    nsv606CNV Loss18451855
    esv25005CNV Loss19812545
    dgv1371n71CNV Loss21882294

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602892    OMIM disorders: --

    1 disease for KLRC3:    
    About MalaCards
    monkeypox

    1 disease from the University of Copenhagen DISEASES database for KLRC3:
    Monkeypox

    KLRC3 for disorders           About GeneDecksing


    Export disorders for KLRC3 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 KLRC3 gene, integrated from 10 sources (see all 12):
    (articles sorted by number of sources associating them with KLRC3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Conservation and variation in human and common chimpanzee CD94 and NKG2 genes. (PubMed id 11751968)1, 2, 9 Shum B.P.... Parham P. (J. Immunol. 2002)
    2. Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39 heterodimer. (PubMed id 10201920)1, 2, 9 Bellon T.... Aparicio P. (J. Immunol. 1999)
    3. The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex. (PubMed id 9683661)1, 2 Glienke J.... Francis F. (Immunogenetics 1998)
    4. Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes. (PubMed id 9598306)1, 3 Plougastel B. and Trowsdale J. (Genomics 1998)
    5. Natural killer lectin-like receptors have divergent carboxy-termini, distinct from C-type lectins. (PubMed id 8276468)1, 2 Adamkiewicz T.V.... Houchins J.P. (Immunogenetics 1994)
    6. The finished DNA sequence of human chromosome 12. (PubMed id 16541075)2 Scherer S.E.... Gibbs R.A. (Nature 2006)
    7. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. (PubMed id 8943374)1 Lazetic S....Phillips J.H. (J. Immunol. 1996)
    8. Multiple transcription factor elements collaborate with estrogen receptor alpha to activate an inducible estrogen response element in the NKG2E gene. (PubMed id 17395694)9 Levy N....Leitman D.C. (Endocrinology 2007)
    9. Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics. (PubMed id 15728498)9 Kaiser B.K....Strong R.K. (J. Immunol. 2005)
    10. CD94 transcripts imply a better prognosis in nasal-type extranodal NK/T-cell lymphoma. (PubMed id 12816864)9 Lin C.W....Hsu S.M. (Blood 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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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: 3823 HGNC: 6376 AceView: KLRK1 Ensembl:ENSG00000205810 euGenes: HUgn3823
    ECgene: KLRC3 Kegg: 3823 H-InvDB: KLRC3

    (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 KLRC3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for KLRC3 Genetics and Cytogenetics in Oncology and Haematology
    Functional Glycomics Gateway - Glycan Bindinghttp://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_247

    (Patent information from GeneIP,
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    Patent Information for KLRC3 gene:
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