NDUFAF4

Chr 6AR

NADH:ubiquinone oxidoreductase complex assembly factor 4

Also known as: C6orf66, HRPAP20, HSPC125, MC1DN15, My013, bA22L21.1

NDUFAF4 encodes a complex I assembly factor required for proper assembly of NADH:ubiquinone oxidoreductase (complex I), which catalyzes electron transfer from NADH to ubiquinone and proton translocation across the inner mitochondrial membrane. Autosomal recessive mutations cause mitochondrial complex I deficiency (nuclear type 15) through impaired complex I assembly. The pathogenic mechanism involves disrupted mitochondrial respiratory chain function due to defective complex I assembly rather than direct enzymatic dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.721 OMIM phenotype
Clinical SummaryNDUFAF4
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.72LOEUF
pLI 0.553
Z-score 2.02
OE 0.15 (0.050.72)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.06Z-score
OE missense 0.98 (0.831.17)
90 obs / 91.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.050.72)
00.351.4
Missense OE0.98 (0.831.17)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 1 / 6.6Missense obs/exp: 90 / 91.7Syn Z: -0.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NDUFAF4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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