DDAH1 (Dimethylarginine Dimethylaminohydrolase 1)
Key regulator of nitric oxide synthase via ADMA degradation; implicated in cardiovascular, renal, and metabolic disorders.
Gene Information Card
| Symbol | DDAH1 |
|---|---|
| Full Name | Dimethylarginine dimethylaminohydrolase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p22.3 |
| NCBI Gene ID | 23576 ncbi.nlm.nih.gov/gene/23576 |
| Ensembl ID | ENSG00000115414 |
| UniProt ID | O94760 |
| OMIM ID | 604743 |
| HGNC ID | 2715 |
| Aliases | DDAH, MGC6784 |
Description
DDAH1 encodes dimethylarginine dimethylaminohydrolase 1, an enzyme that specifically metabolizes asymmetric dimethylarginine (ADMA) and N(G),N(G)-dimethyl-L-arginine, which are endogenous inhibitors of nitric oxide synthase (NOS). By regulating ADMA levels, DDAH1 plays a critical role in nitric oxide production, influencing vascular tone, endothelial function, and various physiological processes. The enzyme is widely expressed, with high levels in the kidney, liver, and pancreas. DDAH1 has been implicated in cardiovascular, renal, and metabolic diseases, and its expression is regulated by oxidative stress and inflammatory cytokines.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiovascular disease | Reduced DDAH1 activity leads to elevated ADMA, inhibiting NOS and reducing nitric oxide bioavailability, contributing to endothelial dysfunction and atherosclerosis. | Multiple studies; e.g., PMID: 15699074 (NCBI Gene reference) |
| Chronic kidney disease | Impaired DDAH1 function in renal tissue may increase ADMA, worsening renal hemodynamics and progression of kidney disease. | Clinical observations; e.g., PMID: 18480255 |
| Diabetes mellitus | Hyperglycemia-induced oxidative stress downregulates DDAH1, leading to ADMA accumulation and endothelial dysfunction in diabetic patients. | Experimental evidence; e.g., PMID: 17641245 |
| Pulmonary hypertension | DDAH1 deficiency may contribute to pulmonary vascular remodeling via reduced NO production. | Animal models; e.g., PMID: 21749996 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 89.2 | High |
| Liver | 78.5 | High |
| Pancreas | 65.3 | High |
| Lung | 45.1 | Medium |
| Heart | 38.7 | Medium |
| Brain | 22.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 72.3 | Liver cancer cell line |
| A549 | 55.8 | Lung carcinoma |
| HEK293 | 48.9 | Embryonic kidney |
| MCF7 | 30.2 | Breast cancer |
| K562 | 12.5 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6669292 | SNV (intronic) | ~30% (global) | Associated with altered DDAH1 expression; may affect ADMA levels. |
| rs233112 | SNV (intronic) | ~25% | Linked to cardiovascular risk in some populations. |
| c.115G>A (p.Gly39Ser) | Missense | Rare (<0.1%) | Potential loss of function; not well characterized. |
| c.374C>T (p.Thr125Met) | Missense | Rare | Reported in ClinVar; uncertain significance. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce DDAH1 enzymatic activity lead to ADMA accumulation, impairing NO synthesis and contributing to endothelial dysfunction.
Gain of Function (GOF)
No clear gain-of-function mutations reported; increased DDAH1 expression may enhance ADMA degradation, but not linked to specific mutations.
Dominant Negative (DN)
No evidence for dominant-negative effects; DDAH1 functions as a homodimer, but no such mutations documented.
View complete mutation data：
Gene Ontology (GO)
| • dimethylargininase activity | • hydrolase activity |
| • protein homodimerization activity | • response to oxidative stress |
| • nitric oxide biosynthetic process | • arginine metabolic process |
Pathways
• Arginine and proline metabolism
• Nitric oxide signaling pathway
• ADMA metabolism
Protein Summary
DDAH1 is a 285-amino acid enzyme that hydrolyzes ADMA to citrulline and dimethylamine. It exists as a homodimer and requires zinc for catalytic activity. The protein is predominantly cytosolic and expressed in tissues with high metabolic activity. DDAH1 plays a central role in regulating nitric oxide production by controlling ADMA levels. Its activity is modulated by oxidative stress, and it interacts with various cellular proteins. Structural studies reveal a conserved catalytic site essential for substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDAH1 Knockout HEK293 Cell Line | EDJ-KQ8075 | Human | 23576 | Details Get a Quote |
| DDAH1 Knockout A-549 Cell Line | EDJ-KQ33905 | Human | 23576 | Details Get a Quote |
| DDAH1 Knockout HCT 116 Cell Line | EDJ-KQ33906 | Human | 23576 | Details Get a Quote |
| DDAH1 Knockout HeLa Cell Line | EDJ-KQ33907 | Human | 23576 | Details Get a Quote |
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