CD6 Gene

HGNC Family	CD molecules (CD)
Name	CD6 molecule
Description	This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CD6 is a multifunctional lymphocyte surface receptor that plays a pivotal role in modulating T‐cell activation, adhesion, and migration. Genetic studies have implicated CD6 as a susceptibility gene in autoimmune conditions such as multiple sclerosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", where specific allelic variants alter the expression of full‐length CD6 and, consequently, T‐cell proliferative responses. Structurally, the extracellular portion of CD6 contains three scavenger receptor cysteine‐rich domains that mediate interactions with its classical ligand, activated leukocyte cell adhesion molecule (ALCAM/CD166)"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ", as well as with the more recently identified ligand CD318."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " These adhesive interactions facilitate not only leukocyte trafficking—such as the transmigration of T cells across the blood–brain barrier—but also the stabilization of the immunological synapse during antigen recognition."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its adhesive role, CD6 participates directly in T‐cell signaling. Its cytoplasmic domain contains key tyrosine residues (e.g., tyrosine 662) that, when phosphorylated, recruit adaptor proteins such as SLP-76"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and syntenin-1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", linking CD6 to the T-cell receptor (TCR) signalosome. Notably, CD6 appears to have a dual function; in the absence of ligand engagement it can attenuate T-cell activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", whereas binding to its ligands (ALCAM or CD318) provides costimulatory signals that enhance T-cell proliferation and effector responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, recombinant forms of the CD6 ectodomain exhibit pathogen-binding properties—akin to pattern recognition receptors—by binding bacterial components and aggregating diverse microbial strains."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the complex yet critical roles of CD6 in regulating lymphocyte function. By both dampening basal T-cell activation and promoting costimulation when engaged with appropriate ligands, CD6 contributes to immune homeostasis and influences the pathogenesis of autoimmune diseases. Its ability to mediate cell–cell adhesion and to participate in signal transduction through interactions with multiple intracellular partners further positions CD6 as a potential therapeutic target in settings of dysregulated immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Philip L De Jager, Xiaoming Jia, Joanne Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.401"}], "href": "https://doi.org/10.1038/ng.401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19525953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19525953"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David M Kofler, Christopher A Severson, Narine Mousissian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CD6 multiple sclerosis susceptibility allele is associated with alterations in CD4+ T cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1100626"}], "href": "https://doi.org/10.4049/jimmunol.1100626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21849685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21849685"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Romain Cayrol, Karolina Wosik, Jennifer L Berard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1551"}], "href": "https://doi.org/10.1038/ni1551"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18157132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18157132"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fumio Arai, Osamu Ohneda, Takeshi Miyamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20011700"}], "href": "https://doi.org/10.1084/jem.20011700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12070283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12070283"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "P Nair, R Melarkode, D Rajkumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD6 synergistic co-stimulation promoting proinflammatory response is modulated without interfering with the activated leucocyte cell adhesion molecule interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2249.2010.04235.x"}], "href": "https://doi.org/10.1111/j.1365-2249.2010.04235.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20726988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20726988"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gospel Enyindah-Asonye, Yan Li, Jeffrey H Ruth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD318 is a ligand for CD6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1704008114"}], "href": "https://doi.org/10.1073/pnas.1704008114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28760953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28760953"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Romain Roncagalli, Simon Hauri, Fréderic Fiore, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2843"}], "href": "https://doi.org/10.1038/ni.2843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24584089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24584089"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Namir J Hassan, Stephen J Simmonds, Nicholas G Clarkson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP-76."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00688-06"}], "href": "https://doi.org/10.1128/MCB.00688-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16914752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16914752"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Idoia Gimferrer, Anna Ibáñez, Montse Farnós, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The lymphocyte receptor CD6 interacts with syntenin-1, a scaffolding protein containing PDZ domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.175.3.1406"}], "href": "https://doi.org/10.4049/jimmunol.175.3.1406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16034076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16034076"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marta I Oliveira, Carine M Gonçalves, Mafalda Pinto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD6 attenuates early and late signaling events, setting thresholds for T-cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201040528"}], "href": "https://doi.org/10.1002/eji.201040528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21956609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21956609"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Maria-Rosa Sarrias, Montserrat Farnós, Rubén Mota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0702815104"}], "href": "https://doi.org/10.1073/pnas.0702815104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17601777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17601777"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Marc Orta-Mascaró, Marta Consuegra-Fernández, Esther Carreras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD6 modulates thymocyte selection and peripheral T cell homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20151785"}], "href": "https://doi.org/10.1084/jem.20151785"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27377588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27377588"}]}]}]}
Synonyms	TP120
Proteins	CD6_HUMAN
NCBI Gene ID	923
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CD6 has 5,458 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 109 datasets.

Click the + buttons to view associations for CD6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CD6 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CD6 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 CD6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CD6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CD6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CD6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CD6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CD6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CD6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CD6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CD6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CD6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CD6 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 CD6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CD6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CD6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CD6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CD6 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 CD6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CD6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with CD6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CD6 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CD6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CD6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CD6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CD6 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 CD6 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 CD6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CD6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CD6 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 CD6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CD6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CD6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CD6 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CD6 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CD6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CD6 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 CD6 from the GeneSigDB Published Gene Signatures dataset.