DDAH1

Chr 1

dimethylarginine dimethylaminohydrolase 1

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

NCBI Gene: 23576 ENSG00000153904 UniProt: O94760 OMIM: 604743

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the dimethylarginine dimethylaminohydrolase (DDAH) gene family. The encoded enzyme plays a role in nitric oxide generation by regulating cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.48 (0.26–0.95)

0≤0.351.4

Missense OE?0.66 (0.56–0.78)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 6 / 12.4Missense obs/exp: 98 / 149.3Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in DDAH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

351 rare PASS variants

Rare truncating (LoF)

1 in 3,200

56 rare PASS variants

Rare synonymous (reference)

1 in 180

170 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DDAH1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 420	1 in 6,100
South Asian	~43k	1 in 180	1 in 4,700
Remaining (unassigned)	~30k	1 in 240	1 in 3,700
European (Finnish)	~27k	1 in 240	≈ 1 in 21,000
Admixed American	~22k	1 in 130	1 in 3,300
African / African American	~21k	1 in 220	1 in 3,000
East Asian	~20k	1 in 170	1 in 1,500
Ashkenazi Jewish	~13k	1 in 320	≈ 1 in 5,900
Middle Eastern	~2,884	1 in 160	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓