NUDT8

Chr 11

nudix hydrolase 8

NCBI Gene: 254552 ENSG00000167799 UniProt: Q8WV74

NUDT8 encodes an acyl-CoA diphosphatase that hydrolyzes CoA and CoA esters in mitochondria, with highest activity against free CoA and medium-chain acyl-CoAs. The gene is not highly constrained against loss-of-function variants (pLI 0.0001, LOEUF 1.8), and no established human disease associations have been reported for NUDT8 mutations.

ResearchSummary from RefSeq, UniProt

Predicted to enable coenzyme A diphosphatase activity; magnesium ion binding activity; and manganese ion binding activity. Predicted to be involved in nucleoside phosphate catabolic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.80

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.80LOEUF

pLI 0.000

Z-score -0.09

OE 1.04 (0.56–1.80)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.83–1.13)

122 obs / 126.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.04 (0.56–1.80)

0≤0.351.4

Missense OE?0.97 (0.83–1.13)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 6 / 5.8Missense obs/exp: 122 / 126.0Syn Z: 1.04

Background carrier burden — how many people carry a rare variant somewhere in NUDT8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

360 rare PASS variants

Rare truncating (LoF)

1 in 620

69 rare PASS variants

Rare synonymous (reference)

1 in 420

179 rare PASS variants

Rare missense and truncating variants are carried at similar rates in NUDT8; this gene does not show strong loss-of-function constraint by this measure. 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 270	1 in 1,200
South Asian	~43k	1 in 140	1 in 540
Remaining (unassigned)	~30k	1 in 140	1 in 790
European (Finnish)	~27k	1 in 640	1 in 1,800
Admixed American	~22k	1 in 170	1 in 490
African / African American	~21k	1 in 110	1 in 830
East Asian	~20k	1 in 360	1 in 1,200
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 160	≈ 1 in 600

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 4.? see exons ↓