CD4 Gene

HGNC Family	Immunoglobulin superfamily domain containing, CD molecules (CD)
Name	CD4 molecule
Description	This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class II MHC molecules. The CD4 antigen is also a primary receptor for entry of the human immunodeficiency virus through interactions with the HIV Env gp120 subunit. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, May 2020]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CD4<sup>+</sup> T lymphocytes function as central regulators of adaptive immunity by differentiating into distinct effector lineages that either promote or suppress immune responses. For example, a major subset of CD4<sup>+</sup> cells expresses the transcription factor Foxp3 and, together with surface markers such as CD25 and low levels of CD127, defines naturally arising regulatory T (T<sub>reg</sub>) cells that enforce self‐tolerance and prevent autoimmunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In addition, upon appropriate cytokine stimulation, naive CD4<sup>+</sup> T cells can differentiate into interleukin‑17–producing T helper 17 (T<sub>H</sub>17) cells that are instrumental in host defense and inflammatory processes, with developmental cues provided by transforming growth factor‑β, IL‑6, IL‑1β, and IL‑23."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, a specialized CD4<sup>+</sup> subset—T follicular helper (T<sub>FH</sub>) cells—provides critical help to B cells to enable germinal center reactions and effective antibody production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The balance between these pro‐inflammatory and regulatory CD4<sup>+</sup> T cell responses is fine‑tuned by multiple factors, including metabolic cues mediated by molecules such as hypoxia‑inducible factor 1α (HIF1α) and mTOR that help to determine whether activated CD4<sup>+</sup> T cells adopt an effector phenotype (e.g. T<sub>H</sub>17) or switch to a more quiescent, regulatory program."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In chronic infections such as HIV, CD4<sup>+</sup> T cells exhibit upregulated inhibitory receptors—most notably programmed death‑1 (PD‑1)—which correlate with impaired function and overall disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, PD‑L1 signals can directly promote the induction and maintenance of inducible T<sub>reg</sub> cells (iT<sub>reg</sub>), underscoring an additional mechanism by which the PD‑1/PD‑L1 pathway modulates CD4<sup>+</sup> T cell fate and helps maintain peripheral tolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight the multifaceted role of CD4<sup>+</sup> T cells: they not only direct adaptive immune responses through the differentiation into specific effector subsets, such as T<sub>H</sub>17 and T<sub>FH</sub> cells, but they also mediate immune regulation via T<sub>reg</sub> cells. As such, CD4<sup>+</sup> T cells are master orchestrators of immune activation, tolerance, and homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shohei Hori, Takashi Nomura, Shimon Sakaguchi "}, {"type": "b", "children": [{"type": "t", "text": "Control of regulatory T cell development by the transcription factor Foxp3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1079490"}], "href": "https://doi.org/10.1126/science.1079490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12522256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12522256"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jason D Fontenot, Marc A Gavin, Alexander Y Rudensky "}, {"type": "b", "children": [{"type": "t", "text": "Foxp3 programs the development and function of CD4+CD25+ regulatory T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni904"}], "href": "https://doi.org/10.1038/ni904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12612578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12612578"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Roli Khattri, Tom Cox, Sue-Ann Yasayko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An essential role for Scurfin in CD4+CD25+ T regulatory cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni909"}], "href": "https://doi.org/10.1038/ni909"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12612581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12612581"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kajsa Wing, Yasushi Onishi, Paz Prieto-Martin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CTLA-4 control over Foxp3+ regulatory T cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1160062"}], "href": "https://doi.org/10.1126/science.1160062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18845758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18845758"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marc Veldhoen, Richard J Hocking, Christopher J Atkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2006.01.001"}], "href": "https://doi.org/10.1016/j.immuni.2006.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16473830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16473830"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Paul R Mangan, Laurie E Harrington, Darrell B O'Quinn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transforming growth factor-beta induces development of the T(H)17 lineage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature04754"}], "href": "https://doi.org/10.1038/nature04754"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16648837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16648837"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Spencer C Liang, Xiang-Yang Tan, Deborah P Luxenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20061308"}], "href": "https://doi.org/10.1084/jem.20061308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16982811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16982811"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Eva V Acosta-Rodriguez, Laura Rivino, Jens Geginat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1467"}], "href": "https://doi.org/10.1038/ni1467"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17486092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17486092"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Robert J Johnston, Amanda C Poholek, Daniel DiToro, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20110278"}], "href": "https://doi.org/10.1084/jem.20110278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21708926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21708926"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Cheryl L Day, Daniel E Kaufmann, Photini Kiepiela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature05115"}], "href": "https://doi.org/10.1038/nature05115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16921384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16921384"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Loise M Francisco, Victor H Salinas, Keturah E Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PD-L1 regulates the development, maintenance, and function of induced regulatory T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20090847"}], "href": "https://doi.org/10.1084/jem.20090847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20008522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20008522"}]}]}]}
Synonyms	CD4MUT
Proteins	CD4_HUMAN
NCBI Gene ID	920
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CD4 has 17,378 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 126 datasets.

Click the + buttons to view associations for CD4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CD4 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CD4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CD4 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 CD4 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 CD4 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 CD4 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 CD4 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 CD4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving CD4 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CD4 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 CD4 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 CD4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CD4 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 CD4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CD4 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 CD4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CD4 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 CD4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CD4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CD4 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CD4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CD4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CD4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CD4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CD4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CD4 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 CD4 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 CD4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CD4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CD4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CD4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CD4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CD4 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 CD4 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 CD4 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 CD4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CD4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CD4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CD4 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 CD4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CD4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.