ADA Gene

Name	adenosine deaminase
Description	This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Adenosine deaminases comprise a diverse family of enzymes that play multifaceted roles in cellular physiology and disease. One major subgroup—the ADAR (adenosine deaminase acting on RNA) family—catalyzes adenosine‐to‐inosine (A‐to‐I) RNA editing, a process that modulates transcript diversity and prevents inappropriate activation of innate immune sensors. For example, ADAR1‐mediated editing of endogenous double‐stranded RNA is essential to suppress interferon pathways and PKR activation, thereby protecting cells from autoinflammatory responses and aberrant viral signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In cancer and hematopoietic transformation, dysregulated ADAR activity can alter the function of key transcripts and microRNAs, contributing to tumor progression and stem cell self‐renewal"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while ADAR1 also acts as a restriction factor during viral infections."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast to these intracellular RNA editors, the extracellular enzyme adenosine deaminase 2 (ADA2)—encoded by the CECR1 gene—functions as a growth factor that is critical for vascular integrity and immune regulation. Loss‐of‐function mutations in ADA2 are associated with a spectrum of vasculopathic and inflammatory disorders, including early‐onset strokes, systemic vasculopathy, and polyarteritis nodosa."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, the “classical” adenosine deaminase (ADA) plays key roles in purine metabolism and immune homeostasis. Its regulated expression during embryogenesis is vital for proper trophoblast proliferation at the maternal–fetal interface."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " At the immune synapse, ADA forms complexes with surface molecules such as CD26 and DPP4 on T cells and antigen‐presenting cells, thereby enhancing costimulatory signals and modulating dendritic cell function. In addition, ADA bound to DPP4 can compete with viruses for receptor binding, as demonstrated in studies showing that adenosine deaminase can function as a natural antagonist to viral entry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that adenosine deaminases are not limited to a single function; instead, they regulate RNA editing to maintain cellular homeostasis and modulate innate immune responses, serve as extracellular growth factors critical for vascular and inflammatory integrity, and participate in immune cell costimulation as well as antiviral defense. \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brian J Liddicoat, Robert Piskol, Alistair M Chalk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aac7049"}], "href": "https://doi.org/10.1126/science.aac7049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26275108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26275108"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Niamh M Mannion, Sam M Greenwood, Robert Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNA-editing enzyme ADAR1 controls innate immune responses to RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2014.10.041"}], "href": "https://doi.org/10.1016/j.celrep.2014.10.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25456137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25456137"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jochen C Hartner, Carolin Schmittwolf, Andreas Kispert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M311347200"}], "href": "https://doi.org/10.1074/jbc.M311347200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14615479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14615479"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Konstantinos Stellos, Aikaterini Gatsiou, Kimon Stamatelopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4172"}], "href": "https://doi.org/10.1038/nm.4172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27595325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27595325"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maria Anna Zipeto, Angela C Court, Anil Sadarangani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2016.05.004"}], "href": "https://doi.org/10.1016/j.stem.2016.05.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27292188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27292188"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Simone V Ward, Cyril X George, Megan J Welch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1017241108"}], "href": "https://doi.org/10.1073/pnas.1017241108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21173229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21173229"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qing Zhou, Dan Yang, Amanda K Ombrello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Early-onset stroke and vasculopathy associated with mutations in ADA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa1307361"}], "href": "https://doi.org/10.1056/NEJMoa1307361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24552284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24552284"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Paulina Navon Elkan, Sarah B Pierce, Reeval Segel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa1307362"}], "href": "https://doi.org/10.1056/NEJMoa1307362"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24552285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24552285"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Uwe Werling, Hubert Schorle "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor gene AP-2 gamma essential for early murine development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.9.3149-3156.2002"}], "href": "https://doi.org/10.1128/MCB.22.9.3149-3156.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11940672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11940672"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jixin Zhong, Xiaoquan Rao, Jeffrey Deiuliis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-induced visceral inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db12-0230"}], "href": "https://doi.org/10.2337/db12-0230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22936179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22936179"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "V Stalin Raj, Saskia L Smits, Lisette B Provacia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.02935-13"}], "href": "https://doi.org/10.1128/JVI.02935-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24257613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24257613"}]}]}]}
Proteins	ADA_HUMAN
NCBI Gene ID	100
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ADA has 10,787 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

ADA 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 ADA 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 ADA gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ADA 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 ADA 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 ADA 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 ADA 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 ADA 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 ADA 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 ADA 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 ADA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ADA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ADA 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 ADA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ADA 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 ADA 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 ADA gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ADA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ADA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ADA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ADA 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 ADA 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 ADA 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 ADA 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 ADA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ADA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ADA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ADA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ADA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ADA gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ADA gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ADA 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 ADA 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 ADA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ADA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ADA protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ADA 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 ADA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ADA 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 ADA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ADA gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.