DDAH2 Gene

Name	dimethylarginine dimethylaminohydrolase 2
Description	This gene encodes a dimethylarginine dimethylaminohydrolase. The encoded enzyme functions in nitric oxide generation by regulating the cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. The protein may be localized to the mitochondria. Alternative splicing resulting in multiple transcript variants. [provided by RefSeq, Dec 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dimethylarginine dimethylaminohydrolase‐2 (DDAH2) is emerging as a key enzyme in the local regulation of nitric oxide (NO) bioavailability through its ability to metabolize asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. DDAH2‐mediated ADMA clearance is essential for maintaining vascular homeostasis, as reduced DDAH2 expression or activity leads to ADMA accumulation and consequent NO deficiency, which contributes to endothelial dysfunction in a variety of clinical conditions. For example, transgenic overexpression of DDAH2 has been shown to lower plasma ADMA and elevate cardiac NO levels, thereby protecting against ADMA‐induced vascular injury and attenuating cardiac oxidative stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In sepsis and allergic airway inflammation, genetic polymorphisms and modulated promoter activity of the DDAH2 gene correlate with increased ADMA levels and organ dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, epigenetic modifications—such as promoter hypermethylation observed in certain cancers—can suppress DDAH2 expression, linking altered DDAH2 regulation to impaired endothelial progenitor cell function and possibly to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Genetic variation in DDAH2 has also been associated with changes in ADMA levels in type 2 diabetes, suggesting that altered DDAH2 function may contribute to metabolic dysregulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, DDAH2 is expressed in extravillous trophoblasts, where its activity increases NO and cyclic guanosine monophosphate production, thereby promoting cell motility and invasion that are critical for placental development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In endothelial cells, DDAH2 expression is subject to transcriptional regulation by factors such as Nrf2, which, together with a positive interplay with other pathways, helps preserve NO synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In metabolic tissues, DDAH2 overexpression has been linked to improved glucose‐stimulated insulin secretion, underscoring its role in the cross‐talk between vascular function and metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, in conditions of elevated homocysteine—a recognized cardiovascular risk factor—suppression of DDAH2 contributes to ADMA accumulation and impaired NO production, while DDAH2 overexpression can counteract these deleterious effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, recent evidence indicates that oxidative pathways, for instance those involving vascular peroxidase‐1 and its production of hypochlorous acid, can negatively modulate both DDAH2 activity and endothelial NO synthase function, providing a potential therapeutic target to restore vascular function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazuhiro Hasegawa, Shu Wakino, Satoru Tatematsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of asymmetric dimethylarginine in vascular injury in transgenic mice overexpressing dimethylarginie dimethylaminohydrolase 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.107.156901"}], "href": "https://doi.org/10.1161/CIRCRESAHA.107.156901"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17601800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17601800"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael J O'Dwyer, Felicity Dempsey, Vivion Crowley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Crit Care (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/cc5053"}], "href": "https://doi.org/10.1186/cc5053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17002794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17002794"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tanveer Ahmad, Ulaganathan Mabalirajan, Balaram Ghosh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered asymmetric dimethyl arginine metabolism in allergically inflamed mouse lungs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2009-0137RC"}], "href": "https://doi.org/10.1165/rcmb.2009-0137RC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19648472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19648472"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Goot Heah Khor, Gabriele Ruth Anisah Froemming, Rosnah Binti Zain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation profiling revealed promoter hypermethylation-induced silencing of p16, DDAH2 and DUSP1 in primary oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Med Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijms.6884"}], "href": "https://doi.org/10.7150/ijms.6884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24155659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24155659"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pan-Pan Niu, Yu Cao, Ting Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1479-5876-12-170"}], "href": "https://doi.org/10.1186/1479-5876-12-170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24934151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24934151"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sotoodeh Abhary, Kathryn P Burdon, Abraham Kuot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sequence variation in DDAH1 and DDAH2 genes is strongly and additively associated with serum ADMA concentrations in individuals with type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0009462"}], "href": "https://doi.org/10.1371/journal.pone.0009462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20209122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20209122"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "L J Ayling, G St J Whitley, J D Aplin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dimethylarginine dimethylaminohydrolase (DDAH) regulates trophoblast invasion and motility through effects on nitric oxide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/del111"}], "href": "https://doi.org/10.1093/humrep/del111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16920729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16920729"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zaiming Luo, Shakil Aslam, William J Welch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of nuclear factor erythroid 2-related factor 2 coordinates dimethylarginine dimethylaminohydrolase/PPAR-γ/endothelial nitric oxide synthase pathways that enhance nitric oxide generation in human glomerular endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.114.04760"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.114.04760"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25691623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25691623"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Kazuhiro Hasegawa, Shu Wakino, Masumi Kimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hydrolase DDAH2 enhances pancreatic insulin secretion by transcriptional regulation of secretagogin through a Sirt1-dependent mechanism in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.12-226092"}], "href": "https://doi.org/10.1096/fj.12-226092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23430976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23430976"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Li-Hua Liu, Zheng Guo, Mei Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protection of DDAH2 overexpression against homocysteine-induced impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000343329"}], "href": "https://doi.org/10.1159/000343329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23171931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23171931"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Zhaoya Liu, Yanbo Liu, Qian Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of vascular peroxidase 1 in regulating endothelial nitric oxide synthase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2017.02.022"}], "href": "https://doi.org/10.1016/j.redox.2017.02.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28264790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28264790"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "James Leiper, Judith Murray-Rust, Neil McDonald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.212269799"}], "href": "https://doi.org/10.1073/pnas.212269799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12370443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12370443"}]}]}]}
Synonyms	NG30, HEL-S-277, DDAHII, DDAH, G6A
Proteins	DDAH2_HUMAN
NCBI Gene ID	23564
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DDAH2 has 7,519 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 116 datasets.

Click the + buttons to view associations for DDAH2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DDAH2 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 DDAH2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DDAH2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DDAH2 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 DDAH2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DDAH2 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 DDAH2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DDAH2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DDAH2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DDAH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DDAH2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DDAH2 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 DDAH2 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 DDAH2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DDAH2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DDAH2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DDAH2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DDAH2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 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 DDAH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DDAH2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for DDAH2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DDAH2 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 DDAH2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DDAH2 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 DDAH2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DDAH2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.