KLRC2 Gene (Protein Coding)

Killer Cell Lectin Like Receptor C2

GC12M015060
GIFtS:
37
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. The group, designated KLRC (... See more...

Aliases for KLRC2 Gene

Aliases for KLRC2 Gene

  • Killer Cell Lectin Like Receptor C2 2 3 5
  • NKG2-C Type II Integral Membrane Protein 2 3 4
  • NKG2C 2 3 4
  • Killer Cell Lectin-Like Receptor Subfamily C, Member 2 2 3
  • CD159 Antigen-Like Family Member C 3 4
  • Natural Killer Cell Receptor G2-C 2 3
  • NKG2-C-Activating NK Receptor 3 4
  • NK Cell Receptor C 3 4
  • CD159c 2 3
  • NKG2-C 2 3
  • CD159c Antigen 4
  • KLRC2 5

External Ids for KLRC2 Gene

Previous GeneCards Identifiers for KLRC2 Gene

  • GC12P010266
  • GC12U900034
  • GC12M010484
  • GC12M010474
  • GC12M010583
  • GC12M010690
  • GC12M010719
  • GC12M012416
  • GC12M012636
  • GC12M012791
  • GC12M013376
  • GC12M010782
  • GC12M011019
  • GC12M011306
  • GC12M011540
  • GC12M011732
  • GC12M011920
  • GC12M012105
  • GC12M012282
  • GC12M013869
  • GC12M014389

Summaries for KLRC2 Gene

Entrez Gene Summary for KLRC2 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. The group, designated KLRC (NKG2) 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 KLRC (NKG2) gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. KLRC2 alternative splice variants have been described but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for KLRC2 Gene

KLRC2 (Killer Cell Lectin Like Receptor C2) is a Protein Coding gene. Diseases associated with KLRC2 include Ceftazidime Allergy and Immunodeficiency 54. Among its related pathways are Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers and RET signaling. Gene Ontology (GO) annotations related to this gene include transmembrane signaling receptor activity and MHC class I protein complex binding. An important paralog of this gene is ENSG00000255641.

UniProtKB/Swiss-Prot Summary for KLRC2 Gene

  • Immune activating receptor involved in self-nonself discrimination. In complex with KLRD1 on cytotoxic lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib HLA-E loaded with signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules, likely playing a role in the generation and effector functions of adaptive natural killer (NK) cells and in maternal-fetal tolerance during pregnancy (PubMed:9754572, PubMed:30134159). Regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, and in particular may play a role in adaptive NK cell response to viral infection (PubMed:21825173, PubMed:20952657). Upon HLA-E-peptide binding, transmits intracellular signals via the adapter protein TYROBP/DAP12, triggering the phosphorylation of proximal signaling molecules and cell activation (PubMed:9655483, PubMed:15940674).

Gene Wiki entry for KLRC2 Gene

Additional gene information for KLRC2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLRC2 Gene

Genomics for KLRC2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for KLRC2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLRC2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLRC2

Top Transcription factor binding sites by QIAGEN in the KLRC2 gene promoter:
  • AP-1
  • ATF-2
  • Bach2
  • c-Jun
  • Pax-3

Genomic Locations for KLRC2 Gene

Latest Assembly
chr12:10,426,854-10,442,300
(GRCh38/hg38)
Size:
15,447 bases
Orientation:
Minus strand

Previous Assembly
chr12:10,583,198-10,588,609
(GRCh37/hg19 by Entrez Gene)
Size:
5,412 bases
Orientation:
Minus strand

chr12:10,579,453-10,594,899
(GRCh37/hg19 by Ensembl)
Size:
15,447 bases
Orientation:
Minus strand

Genomic View for KLRC2 Gene

Genes around KLRC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLRC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLRC2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for KLRC2 Gene

Proteins for KLRC2 Gene

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  • Protein details for KLRC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P26717-NKG2C_HUMAN
    Recommended name:
    NKG2-C type II integral membrane protein
    Protein Accession:
    P26717
    Secondary Accessions:
    • O43802
    • Q52M74
    • Q9NR42

    Protein attributes for KLRC2 Gene

    Size:
    231 amino acids
    Molecular mass:
    26072 Da
    Quaternary structure:
    • Heterodimer with KLRD1; disulfide-linked. KLRD1-KLRC2 receptor complex interacts with TYROBP homodimer; this interaction is necessary for the expression on the cell surface (PubMed:20890284, PubMed:9655483). KLRD1-KLRC2 receptor complex can bind with low affinity to HLA-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia (PubMed:18083576, PubMed:9486650).

    Three dimensional structures from OCA and Proteopedia for KLRC2 Gene

neXtProt entry for KLRC2 Gene

Post-translational modifications for KLRC2 Gene

  • Glycosylation at Asn100, Asn149, and Asn178

Other Protein References for KLRC2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for KLRC2 Gene

Domains & Families for KLRC2 Gene

Gene Families for KLRC2 Gene

HGNC:
Human Protein Atlas (HPA):
  • CD markers
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for KLRC2 Gene

InterPro:

Suggested Antigen Peptide Sequences for KLRC2 Gene

GenScript: Design optimal peptide antigens:
  • NKG2-C-activating NK receptor (NKG2C_HUMAN)
  • KLRC2 protein (Q3KQS7_HUMAN)
genes like me logo Genes that share domains with KLRC2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for KLRC2 Gene

Function for KLRC2 Gene

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Molecular function for KLRC2 Gene

UniProtKB/Swiss-Prot Function:
Immune activating receptor involved in self-nonself discrimination. In complex with KLRD1 on cytotoxic lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib HLA-E loaded with signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules, likely playing a role in the generation and effector functions of adaptive natural killer (NK) cells and in maternal-fetal tolerance during pregnancy (PubMed:9754572, PubMed:30134159). Regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, and in particular may play a role in adaptive NK cell response to viral infection (PubMed:21825173, PubMed:20952657). Upon HLA-E-peptide binding, transmits intracellular signals via the adapter protein TYROBP/DAP12, triggering the phosphorylation of proximal signaling molecules and cell activation (PubMed:9655483, PubMed:15940674).
GENATLAS Biochemistry:
natural killer cell lectin-like receptor subfamily C,member 2

Phenotypes From GWAS Catalog for KLRC2 Gene

Gene Ontology (GO) - Molecular Function for KLRC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004888 transmembrane signaling receptor activity TAS 9683661
GO:0005515 protein binding IPI 9655483
GO:0023024 MHC class I protein complex binding IPI 18448674
GO:0030246 carbohydrate binding IEA --
GO:1990405 protein antigen binding IDA 18448674
genes like me logo Genes that share ontologies with KLRC2: view
genes like me logo Genes that share phenotypes with KLRC2: view

Animal Models for research

miRNA for KLRC2 Gene

miRTarBase miRNAs that target KLRC2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLRC2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for KLRC2 Gene

Localization for KLRC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLRC2 Gene

Cell membrane. Single-pass type II membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KLRC2 gene
Compartment Confidence
plasma membrane 5
extracellular 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
cytoskeleton 1
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KLRC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS,IDA 9655483
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0043235 receptor complex IDA 18448674
genes like me logo Genes that share ontologies with KLRC2: view

Pathways & Interactions for KLRC2 Gene

genes like me logo Genes that share pathways with KLRC2: view

Pathways by source for KLRC2 Gene

1 GeneGo (Thomson Reuters) pathway for KLRC2 Gene
  • Immune response Role of DAP12 receptors in NK cells

Gene Ontology (GO) - Biological Process for KLRC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002223 stimulatory C-type lectin receptor signaling pathway IDA 9655483
GO:0002228 natural killer cell mediated immunity IDA 18448674
GO:0006968 cellular defense response TAS 9683661
GO:0007165 signal transduction TAS 2007850
GO:0043323 positive regulation of natural killer cell degranulation IDA 21825173
genes like me logo Genes that share ontologies with KLRC2: view

No data available for SIGNOR curated interactions for KLRC2 Gene

Drugs & Compounds for KLRC2 Gene

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No Compound Related Data Available

Transcripts for KLRC2 Gene

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mRNA/cDNA for KLRC2 Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLRC2

Alternative Splicing Database (ASD) splice patterns (SP) for KLRC2 Gene

No ASD Table

Relevant External Links for KLRC2 Gene

GeneLoc Exon Structure for
KLRC2

Expression for KLRC2 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLRC2 Gene

mRNA expression in normal human tissues for KLRC2 Gene
mRNA expression by BioGPS for KLRC2 GenemRNA expression by GTEx for KLRC2 Gene

mRNA differential expression in normal tissues according to GTEx for KLRC2 Gene

This gene is overexpressed in Brain - Amygdala (x5.2) and Brain - Substantia nigra (x4.4).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLRC2

SOURCE GeneReport for Unigene cluster for KLRC2 Gene:

Hs.591157

mRNA Expression by UniProt/SwissProt for KLRC2 Gene:

P26717-NKG2C_HUMAN
Tissue specificity: Expressed in NK cell subsets, in particular in adaptive CD57-positive NK cells (at protein level) (PubMed:20952657, PubMed:21825173). Expressed in terminally differentiated cytotoxic gamma-delta T cells (at protein level) (PubMed:20952657). Expressed in alpha-beta T cells subsets (at protein level) (PubMed:20952657). KLRD1-KLRC1 and KLRD1-KLRC2 are differentially expressed within NK and T cell populations, with only minor subsets expressing both receptor complexes (at protein level) (PubMed:20952657).

Evidence on tissue expression from TISSUES for KLRC2 Gene

  • Liver(4.3)
  • Blood(2.5)
  • Spleen(2.2)
genes like me logo Genes that share expression patterns with KLRC2: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for KLRC2 Gene

Orthologs for KLRC2 Gene

This gene was present in the common ancestor of mammals.

Orthologs for KLRC2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia LOC101058094 29
  • 97.11 (n)
KLRC2 30
  • 94 (a)
 OneToOne
Dog
(Canis familiaris)
 Mammalia LOC609192 29
  • 74.24 (n)
-- 30
  • 54 (a)
 ManyToMany
Cow
(Bos Taurus)
 Mammalia -- 30
  • 48 (a)
 ManyToMany
Platypus
(Ornithorhynchus anatinus)
 Mammalia -- 30
  • 28 (a)
 OneToMany
Mouse
(Mus musculus)
 Mammalia Klre1 30
  • 24 (a)
 ManyToMany
Species where no ortholog for KLRC2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for KLRC2 Gene

ENSEMBL:
Gene Tree for KLRC2 (if available)
TreeFam:
Gene Tree for KLRC2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLRC2: view image
Alliance of Genome Resources:
Additional Orthologs for KLRC2

Paralogs for KLRC2 Gene

Paralogs for KLRC2 Gene

(19) SIMAP similar genes for KLRC2 Gene using alignment to 6 proteins:

  • NKG2C_HUMAN
  • F5H518_HUMAN
  • H0YFK4_HUMAN
  • H0YGY2_HUMAN
  • J3KPJ4_HUMAN
  • Q3KQS7_HUMAN

Pseudogenes.org Pseudogenes for KLRC2 Gene

genes like me logo Genes that share paralogs with KLRC2: view

Variants for KLRC2 Gene

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Polymorphic Variants from UniProtKB/Swiss-Prot for KLRC2 Gene

NKG2C_HUMAN-P26717
Two alleles are known. The sequence shown is that of allele NKG2-C*01.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLRC2 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs113695732 Benign: not provided 10,435,819(-) A/G
NM_002260.3(KLRC2):c.168T>C (p.Asp56=) 		SYNONYMOUS
rs1141715 Benign: not provided 10,434,512(-) A/G
NM_002260.3(KLRC2):c.305T>C (p.Phe102Ser) 		MISSENSE
rs28403159 Benign: not provided 10,435,982(-) T/Cp.Ser2Asn
NM_002260.3(KLRC2):c.5A>G (p.Asn2Ser) 		MISSENSE
rs75545535 Benign: not provided 10,435,931(-) C/G
NM_002260.3(KLRC2):c.56G>C (p.Arg19Pro) 		MISSENSE
VAR_013405 -- p.Ser102Phe

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for KLRC2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for KLRC2 Gene

Variant ID Type Subtype PubMed ID
dgv171e201 CNV deletion 23290073
dgv2358n54 CNV loss 21841781
dgv2359n54 CNV loss 21841781
dgv2360n54 CNV loss 21841781
dgv250e214 CNV loss 21293372
dgv263e199 CNV deletion 23128226
dgv264e199 CNV deletion 23128226
dgv270n67 CNV loss 20364138
dgv451e212 CNV loss 25503493
dgv452e212 CNV loss 25503493
esv25005 CNV loss 19812545
esv2745535 CNV deletion 23290073
esv32543 CNV loss 17666407
esv3580103 CNV loss 25503493
esv3580111 CNV loss 25503493
esv3628535 CNV loss 21293372
esv3628538 CNV loss 21293372
esv3628539 CNV loss 21293372
esv3628540 CNV gain 21293372
esv3892136 CNV loss 25118596
esv3892138 CNV loss 25118596
esv4003 CNV loss 18987735
esv8275 CNV loss 19470904
nsv1036390 CNV loss 25217958
nsv1051292 CNV loss 25217958
nsv1070507 CNV deletion 25765185
nsv1138097 CNV deletion 24896259
nsv1147689 CNV duplication 26484159
nsv1148413 CNV deletion 26484159
nsv435631 CNV deletion 17901297
nsv442633 CNV loss 18776908
nsv514645 CNV gain 21397061
nsv521062 CNV gain 19592680
nsv557465 CNV gain 21841781
nsv557475 CNV loss 21841781
nsv557476 CNV loss 21841781
nsv606 CNV deletion 18451855
nsv832328 CNV gain 17160897
nsv8914 CNV loss 18304495
nsv975447 CNV duplication 23825009
nsv975448 CNV duplication 23825009
nsv983281 CNV duplication 23825009

Variation tolerance for KLRC2 Gene

Residual Variation Intolerance Score: 88% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.30; 6.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLRC2 Gene

Human Gene Mutation Database (HGMD)
KLRC2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLRC2
Leiden Open Variation Database (LOVD)
KLRC2

SNP Genotyping and Copy Number Assays for research

Disorders for KLRC2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for KLRC2 Gene - From: COP

Disorder Aliases PubMed IDs
ceftazidime allergy
  • fortaz allergy
immunodeficiency 54
  • imd54
nk cell deficiency
  • nk cell defects
maxillary sinus adenoid cystic carcinoma
  • adenoid cystic carcinoma of maxillary sinus
thrombophlebitis migrans
- elite association - COSMIC cancer census association via MalaCards
Search KLRC2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KLRC2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with KLRC2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KLRC2 Gene

Publications for KLRC2 Gene

  1. Molecular genetic analyses of human NKG2C (KLRC2) gene deletion. (PMID: 14688071) Miyashita R … Tokunaga K (International immunology 2004) 3 22 40
  2. Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population. (PMID: 12618865) Hikami K … Tokunaga K (Genes and immunity 2003) 3 22 40
  3. Association of DAP12 with activating CD94/NKG2C NK cell receptors. (PMID: 9655483) Lanier LL … Phillips JH (Immunity 1998) 3 4 22
  4. NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease. (PMID: 20952657) Angelini DF … Battistini L (Journal of leukocyte biology 2011) 3 4
  5. Expansion of a unique CD57⁺NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. (PMID: 21825173) Lopez-Vergès S … Lanier LL (Proceedings of the National Academy of Sciences of the United States of America 2011) 3 4

ExternalLinks

View latest publications for KLRC2 gene in Mastermind

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Sources for KLRC2 Gene