DDAH1

Chr 1

dimethylarginine dimethylaminohydrolase 1

Also known as: DDAH, DDAH-1, DDAHI, HEL-S-16

NCBI Gene: 23576ENSG00000153904UniProt: O94760

The encoded enzyme hydrolyzes asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine (MMA), which are endogenous inhibitors of nitric oxide synthase, thereby regulating nitric oxide production. The gene shows low constraint against loss-of-function variants (pLI = 0.003, LOEUF = 0.95), and no established Mendelian disease associations have been reported for DDAH1 mutations in pediatric patients.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
23
Pubs (1 yr)
17
P/LP submissions
0%
P/LP missense
0.95
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DDAH1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 39 VUS of 68 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.003
Z-score 1.69
OE 0.48 (0.26–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.49Z-score
OE missense 0.66 (0.56–0.78)
98 obs / 149.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.26–0.95)
0≤0.351.4
Missense OE0.66 (0.56–0.78)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 6 / 12.4Missense obs/exp: 98 / 149.3Syn Z: 0.28
DN
0.6841th %ile
GOF
0.6344th %ile
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic3
VUS39
Likely Benign2
Benign1
14
Pathogenic
3
Likely Pathogenic
39
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
3
0
3
VUS
0
33
6
0
39
Likely Benign
0
1
1
0
2
Benign
0
0
1
0
1
Total03425059

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

View in ClinVar →

Protein Context — Lollipop Plot

DDAH1 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated machine learning reveals the role of tryptophan metabolism in clear cell renal cell carcinoma and its association with patient prognosis.
Li F et al.·Biol Direct
2024
CHIT1 and DDAH1 levels relate to amyloid-related imaging abnormalities risk profile in Alzheimer's disease patients.
Oosthoek M et al.·Alzheimers Res Ther
2025Cohort
AK4 promotes nasopharyngeal carcinoma metastasis and chemoresistance by activating NLRP3 inflammatory complex.
Liu SL et al.·Cell Death Dis
2025
DDAH1 mediates gastric cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway.
Ye J et al.·Mol Oncol
2017
DDAH1 SNP rs480414 that protects against the development of pulmonary hypertension in bronchopulmonary dysplasia results in lower nitric oxide production in neonatal cord blood-derived lymphoblastoid cell lines.
Milton AD et al.·J Neonatal Perinatal Med
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients