CLEC2A Gene

HGNC Family	C-type lectin domain family (CLEC)
Name	C-type lectin domain family 2, member A
Description	Enables protein homodimerization activity. Predicted to be involved in natural killer cell mediated cytotoxicity. Predicted to act upstream of or within several processes, including T cell receptor signaling pathway; regulation of actin filament polymerization; and regulation of interleukin-2 production. Located in plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLEC2A is an orphan member of the CLEC2 family that, through alternative splicing, gives rise to several protein variants with distinct transmembrane and C‐type lectin-like domains. Notably, the CLEC2A gene encodes keratinocyte-associated C-type lectin (KACL), which is predominantly expressed in the skin (particularly by keratinocytes and select dermal cell types) and at lower levels in certain hematopoietic and gonadal tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Functional studies have demonstrated that KACL exists as a non-disulfide-linked homodimer at the cell surface and engages in high-affinity interactions with the activating natural killer (NK) cell receptor NKp65. This interaction, which relies on specific amino acid residues on KACL rather than its glycosylation status, triggers NK cell cytotoxicity and the secretion of proinflammatory cytokines."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " In a distinct context, CLEC2A expression by dermal fibroblasts has been shown to orchestrate a crosstalk with NK cells, thereby contributing to immune surveillance of the skin. Loss or down-regulation of CLEC2A in fibroblasts—observed in conditions such as xeroderma pigmentosum or in cancer-associated fibroblasts—disrupts this communication and may promote squamous cell carcinoma invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jessica Spreu, Eike C Kienle, Birgit Schrage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLEC2A: a novel, alternatively spliced and skin-associated member of the NKC-encoded AICL-CD69-LLT1 family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunogenetics (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00251-007-0263-1"}], "href": "https://doi.org/10.1007/s00251-007-0263-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18046548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18046548"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jessica Spreu, Sabrina Kuttruff, Veronika Stejfova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0913108107"}], "href": "https://doi.org/10.1073/pnas.0913108107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20194751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20194751"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yili Li, Qian Wang, Sharon Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1303300110"}], "href": "https://doi.org/10.1073/pnas.1303300110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23803857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23803857"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Björn Bauer, Jessica Spreu, Christina Rohe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Key residues at the membrane-distal surface of KACL, but not glycosylation, determine the functional interaction of the keratinocyte-specific C-type lectin-like receptor KACL with its high-affinity receptor NKp65."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/imm.12432"}], "href": "https://doi.org/10.1111/imm.12432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25510854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25510854"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maria Gonçalves-Maia, Yannick Gache, Miguel Basante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NK Cell and Fibroblast-Mediated Regulation of Skin Squamous Cell Carcinoma Invasion by CLEC2A Is Compromised in Xeroderma Pigmentosum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2020.01.021"}], "href": "https://doi.org/10.1016/j.jid.2020.01.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32061658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32061658"}]}]}]}
Synonyms	PILAR, UNQ5792, INPE5792, KACL
Proteins	CLC2A_HUMAN
NCBI Gene ID	387836
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLEC2A has 1,547 functional associations with biological entities spanning 8 categories (molecular profile, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 53 datasets.

Click the + buttons to view associations for CLEC2A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLEC2A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CLEC2A gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CLEC2A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLEC2A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLEC2A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLEC2A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLEC2A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CLEC2A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLEC2A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLEC2A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CLEC2A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLEC2A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLEC2A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLEC2A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CLEC2A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CLEC2A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CLEC2A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLEC2A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLEC2A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLEC2A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CLEC2A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CLEC2A from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of CLEC2A gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GO Biological Process Annotations 2015	biological processes involving CLEC2A gene from the curated GO Biological Process Annotations 2015 dataset.
	GO Biological Process Annotations 2023	biological processes involving CLEC2A gene from the curated GO Biological Process Annotations 2023 dataset.
	GO Biological Process Annotations 2025	biological processes involving CLEC2A gene from the curated GO Biological Process Annotations2025 dataset.
	GO Cellular Component Annotations 2015	cellular components containing CLEC2A protein from the curated GO Cellular Component Annotations 2015 dataset.
	GO Molecular Function Annotations 2015	molecular functions performed by CLEC2A gene from the curated GO Molecular Function Annotations 2015 dataset.
	GO Molecular Function Annotations 2023	molecular functions performed by CLEC2A gene from the curated GO Molecular Function Annotations 2023 dataset.
	GO Molecular Function Annotations 2025	molecular functions performed by CLEC2A gene from the curated GO Molecular Function Annotations 2025 dataset.
	GTEx eQTL 2025	SNPs regulating expression of CLEC2A gene from the GTEx eQTL 2025 dataset.
	GTEx Tissue Gene Expression Profiles	tissues with high or low expression of CLEC2A gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
	GTEx Tissue Gene Expression Profiles 2023	tissues with high or low expression of CLEC2A gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
	GWAS Catalog SNP-Phenotype Associations 2025	phenotypes associated with CLEC2A gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
	GWASdb SNP-Disease Associations	diseases associated with CLEC2A gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
	GWASdb SNP-Phenotype Associations	phenotypes associated with CLEC2A gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
	Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles	cell lines with high or low expression of CLEC2A gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
	HPA Tissue Protein Expression Profiles	tissues with high or low expression of CLEC2A protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
	InterPro Predicted Protein Domain Annotations	protein domains predicted for CLEC2A protein from the InterPro Predicted Protein Domain Annotations dataset.
	JASPAR Predicted Human Transcription Factor Targets 2025	transcription factors regulating expression of CLEC2A gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
	JASPAR Predicted Transcription Factor Targets	transcription factors regulating expression of CLEC2A gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
	Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLEC2A gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
	LOCATE Predicted Protein Localization Annotations	cellular components predicted to contain CLEC2A protein from the LOCATE Predicted Protein Localization Annotations dataset.
	PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of CLEC2A gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	Roadmap Epigenomics Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLEC2A gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
	RummaGEO Drug Perturbation Signatures	drug perturbations changing expression of CLEC2A gene from the RummaGEO Drug Perturbation Signatures dataset.
	RummaGEO Gene Perturbation Signatures	gene perturbations changing expression of CLEC2A gene from the RummaGEO Gene Perturbation Signatures dataset.
	TargetScan Predicted Nonconserved microRNA Targets	microRNAs regulating expression of CLEC2A gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
	TCGA Signatures of Differentially Expressed Genes for Tumors	tissue samples with high or low expression of CLEC2A gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
	TISSUES Curated Tissue Protein Expression Evidence Scores	tissues with high expression of CLEC2A protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
	TISSUES Curated Tissue Protein Expression Evidence Scores 2025	tissues with high expression of CLEC2A protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
	TISSUES Experimental Tissue Protein Expression Evidence Scores 2025	tissues with high expression of CLEC2A protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
	TISSUES Text-mining Tissue Protein Expression Evidence Scores	tissues co-occuring with CLEC2A protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
	TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025	tissues co-occuring with CLEC2A protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.