NDUFB3

Chr 2

NADH:ubiquinone oxidoreductase subunit B3

Also known as: B12, CI-B12, MC1DN25

NCBI Gene: 4709 ENSG00000119013 UniProt: O43676

This protein is an accessory subunit of mitochondrial Complex I (NADH dehydrogenase), which transfers electrons from NADH to the respiratory chain as the first enzyme in mitochondrial electron transport. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation (pLI ~0, LOEUF 1.94), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which is the first enzyme in the electron transport chain of mitochondria. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. Mutations in this gene contribute to mitochondrial complex 1 deficiency. Alternative splicing results in multiple transcript variants encoding the same protein. Humans have multiple pseudogenes of this gene. [provided by RefSeq, Mar 2012]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.94

Clinical Summary— NDUFB3

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 24 VUS of 50 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.94LOEUF

pLI 0.000

Z-score -1.10

OE 1.61 (0.79–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.32Z-score

OE missense 0.88 (0.69–1.12)

45 obs / 51.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.61 (0.79–1.94)

0≤0.351.4

Missense OE?0.88 (0.69–1.12)

0≤0.61.4

Synonymous OE?0.70

0≤1.21.6

LoF obs/exp: 6 / 3.7Missense obs/exp: 45 / 51.4Syn Z: 0.98

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveNDUFB3-related mitochondrial complex I deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7131th %ile

GOF

0.5071th %ile

LOF

0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic3

VUS24

Likely Benign7

Benign8

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	2	1	0	0	3
VUS	0	23	1	0	24
Likely Benign	0	0	4	3	7
Benign	0	0	8	0	8
Conflicting	—				2
Total	4	24	13	3	46

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap NDUFB3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →