NDUFB4

Chr 3

NADH:ubiquinone oxidoreductase subunit B4

Also known as: B15, CI-B15

NCBI Gene: 4710 ENSG00000065518 UniProt: O95168 OMIM: 603840

This gene encodes an accessory subunit of mitochondrial complex I (NADH dehydrogenase), which transfers electrons from NADH to ubiquinone in the electron transport chain. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, typically presenting in infancy or early childhood with neurological symptoms, developmental delay, and multi-organ involvement. The gene shows low constraint to loss-of-function variants, consistent with recessive disease requiring biallelic mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a non-catalytic subunit of the multisubunit NADH:ubiquinone oxidoreductase, the first enzyme complex in the mitochondrial electron transport chain (complex I). Mammalian complex I is composed of 45 different subunits and transfers electrons from NADH to ubiquinone. [provided by RefSeq, Dec 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.006

Z-score 0.85

OE 0.63 (0.31–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.39Z-score

OE missense 1.13 (0.94–1.35)

82 obs / 72.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.31–1.43)

0≤0.351.4

Missense OE?1.13 (0.94–1.35)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 4 / 6.3Missense obs/exp: 82 / 72.7Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in NDUFB4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 440

182 rare PASS variants

Rare truncating (LoF)

1 in 2,400

29 rare PASS variants

Rare synonymous (reference)

1 in 1,400

74 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFB4. 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 500	1 in 3,400
South Asian	~43k	1 in 430	1 in 1,300
Remaining (unassigned)	~30k	1 in 410	1 in 2,300
European (Finnish)	~27k	1 in 1,300	1 in 1,400
Admixed American	~22k	1 in 200	1 in 2,100
African / African American	~21k	1 in 290	1 in 1,900
East Asian	~20k	1 in 290	1 in 2,100
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,884	1 in 360	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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓