NDUFS1

Chr 2AR

NADH:ubiquinone oxidoreductase core subunit S1

NCBI Gene: 4719 ENSG00000023228 OMIM: 157655

The NDUFS1 protein is the largest subunit of mitochondrial complex I and functions as an NADH dehydrogenase that transfers electrons from NADH to ubiquinone in the respiratory chain, forming part of the active site where NADH is oxidized. Mutations cause mitochondrial complex I deficiency, nuclear type 5, which follows an autosomal recessive inheritance pattern. The pathogenic mechanism involves impaired electron transport chain function due to defective complex I assembly or activity.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.811 OMIM phenotype

Clinical Summary— NDUFS1

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.53

OE 0.57 (0.41–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.08Z-score

OE missense 1.01 (0.93–1.10)

413 obs / 408.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.41–0.81)

0≤0.351.4

Missense OE?1.01 (0.93–1.10)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 23 / 40.3Missense obs/exp: 413 / 408.7Syn Z: -0.41

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveNDUFS1-related mitochondrial complex I deficiencyOTHERAR

This gene — mechanism propensity

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

0.6260th %ile

GOF

0.5170th %ile

LOF

0.4037th %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.