NDUFAF3

Chr 3

NADH:ubiquinone oxidoreductase complex assembly factor 3

Also known as: 2P1, C3orf60, E3-3, MC1DN18

NCBI Gene: 25915 ENSG00000178057 UniProt: Q9BU61

The protein encoded by this gene is a mitochondrial complex I assembly protein that interacts with complex I subunits to facilitate proper assembly of the respiratory chain complex. Mutations cause mitochondrial complex I deficiency (nuclear type 18), a fatal neonatal disorder of the oxidative phosphorylation system, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted assembly of complex I, leading to defective mitochondrial respiratory chain function.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a mitochondrial complex I assembly protein that interacts with complex I subunits. Mutations in this gene cause mitochondrial complex I deficiency, a fatal neonatal disorder of the oxidative phosphorylation system. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2009]

ResearchGenerating clinical summary…

LOEUF 1.07

Clinical Summary— NDUFAF3

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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 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 65 VUS of 136 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?

1.07LOEUF

pLI 0.005

Z-score 1.43

OE 0.51 (0.26–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.49Z-score

OE missense 1.14 (0.98–1.32)

120 obs / 105.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.51 (0.26–1.07)

0≤0.351.4

Missense OE?1.14 (0.98–1.32)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 5 / 9.8Missense obs/exp: 120 / 105.7Syn Z: -0.47

ClinVar Variant Classifications

136 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic3

VUS65

Likely Benign39

Benign2

Conflicting15

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	1	4	0	0	5
Likely Pathogenic	2	1	0	0	3
VUS	1	45	17	2	65
Likely Benign	0	1	22	16	39
Benign	0	0	1	1	2
Conflicting	—				15
Total	4	51	40	19	129

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap NDUFAF3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →