DDAH2

Chr 6

DDAH family member 2, ADMA-independent

Also known as: DDAH, DDAHII, G6a, HEL-S-277, NG30

NCBI Gene: 23564ENSG00000213722UniProt: O95865

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]

26
ClinVar variants
7
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— DDAH2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 17 VUS of 26 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.86LOEUF
pLI 0.014
Z-score 1.92
OE 0.41 (0.21–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.31Z-score
OE missense 0.53 (0.45–0.63)
102 obs / 192.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.21–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.45–0.63)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.69
0≤1.21.6
LoF obs/exp: 5 / 12.3Missense obs/exp: 102 / 192.3Syn Z: 2.27

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS17
Benign2
5
Pathogenic
2
Likely Pathogenic
17
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
13
4
0
17
Likely Benign
0
0
0
0
0
Benign
0
1
1
0
2
Total01412026

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DDAH2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Protective role of DDAH2 (rs805304) gene polymorphism in patients with myocardial infarction.
Pérez-Hernández N et al.·Exp Mol Pathol
2014Cohort
Pharmacology and clinical pharmacology of methylarginines used as inhibitors of nitric oxide synthases.
Kittel A et al.·Curr Pharm Des
2014Review
Sequence variation in DDAH1 and DDAH2 genes is strongly and additively associated with serum ADMA concentrations in individuals with type 2 diabetes.
Abhary S et al.·PLoS One
2010
Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients.
Tongu Y et al.·Sci Rep
2025Cohort
The Second Life of Methylarginines as Cardiovascular Targets.
Jarzebska N et al.·Int J Mol Sci
2019Review
Common genetic variation in DDAH2 is associated with intracerebral haemorrhage in a Chinese population: a multi-centre case-control study in China.
Bai Y et al.·Clin Sci (Lond)
2009
Association study of dimethylarginine dimethylaminohydrolase 2 gene polymorphisms and coronary heart disease.
Xu AG et al.·Mol Med Rep
2012
Evidence for a protective role for the rs805305 single nucleotide polymorphism of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in septic shock through the regulation of DDAH activity.
Lambden S et al.·Crit Care
2018
A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is associated with chronic kidney disease.
Sesti G et al.·Atherosclerosis
2013Functional
A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is associated with myocardial infarction in type 2 diabetic patients.
Mannino GC et al.·Cardiovasc Diabetol
2019Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
[Retracted] DDAH2 alleviates myocardial fibrosis in diabetic cardiomyopathy through activation of the DDAH/ADMA/NOS/NO pathway in rats.
Zhu ZD et al.·Int J Mol Med
2026🔓 Open Access
KLF3 aggravates renal fibrosis in chronic kidney disease through transcriptional activation of DDAH2.
Zhang J et al.·Biochem Pharmacol
2025
Association of NOS3 (rs1799983) and DDAH2 (rs805305) Gene Polymorphisms With Coronary Artery Disease in the Northern Indian Cohort.
Shiraz Rizvi SM et al.·Cureus
2025🔓 Open AccessCohort
Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes.
Mendes FS et al.·Rev Bras Ginecol Obstet
2024🔓 Open Access
Assessment of DDAH1 and DDAH2 Contributions to Psychiatric Disorders via In Silico Methods.
Kozlova AA et al.·Int J Mol Sci
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chronic Obstructive Pulmonary Disease (COPD)

Intermittent Hypoxemia, Lung Function Decline, Morbidity, and Mortality in COPD (PROSA Study).

NOT YET RECRUITING
NCT06265623Universitätsklinikum Hamburg-EppendorfStarted 2024-03-01
No active intervention, but observational follow-up

External Resources

Links to major genomics databases and tools