NDUFV3

Chr 21

NADH:ubiquinone oxidoreductase subunit V3

Also known as: CI-10k, CI-9KD

NCBI Gene: 4731 ENSG00000160194 UniProt: P56181 OMIM: 602184

The NDUFV3 protein is an accessory subunit of mitochondrial respiratory chain Complex I (NADH dehydrogenase), which transfers electrons from NADH to ubiquinone in cellular energy production. Mutations cause mitochondrial complex I deficiency, typically presenting as a multisystem disorder affecting high-energy demanding organs including the brain, heart, and skeletal muscle with autosomal recessive inheritance. This gene is extremely intolerant to loss-of-function variants, indicating that even single functional copies are insufficient for normal cellular function.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is one of at least forty-one subunits that make up the NADH-ubiquinone oxidoreductase complex. This complex is part of the mitochondrial respiratory chain and serves to catalyze the rotenone-sensitive oxidation of NADH and the reduction of ubiquinone. The encoded protein is one of three proteins found in the flavoprotein fraction of the complex. The specific function of the encoded protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.87

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.000

Z-score -1.50

OE 1.40 (1.00–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.05 (0.95–1.17)

270 obs / 256.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.40 (1.00–1.87)

0≤0.351.4

Missense OE?1.05 (0.95–1.17)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 23 / 16.4Missense obs/exp: 270 / 256.0Syn Z: -0.49

Background carrier burden — how many people carry a rare variant somewhere in NDUFV3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

625 rare PASS variants

Rare truncating (LoF)

1 in 280

112 rare PASS variants

Rare synonymous (reference)

1 in 230

258 rare PASS variants

Rare missense and truncating variants are carried at similar rates in NDUFV3; 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 110	1 in 400
South Asian	~43k	1 in 71	1 in 1,100
Remaining (unassigned)	~30k	1 in 70	1 in 680
European (Finnish)	~27k	1 in 200	1 in 560
Admixed American	~22k	1 in 80	1 in 370
African / African American	~21k	1 in 61	1 in 420
East Asian	~20k	1 in 91	1 in 1,300
Ashkenazi Jewish	~13k	1 in 460	1 in 930
Middle Eastern	~2,884	1 in 67	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓