NDUFV1

Chr 11AR

NADH:ubiquinone oxidoreductase core subunit V1

Also known as: CI-51K, CI51KD, MC1DN4, UQOR1

NCBI Gene: 4723 ENSG00000167792 UniProt: P49821 OMIM: 161015

The protein is a 51 kDa subunit of mitochondrial complex I that contains the NADH-binding site and flavin mononucleotide and iron-sulfur binding sites essential for electron transport in oxidative phosphorylation. Biallelic mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, presenting as myopathies, encephalomyopathies, and neurodegenerative disorders including Leigh syndrome. Disease results from loss of function leading to impaired mitochondrial energy production.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The mitochondrial respiratory chain provides energy to cells via oxidative phosphorylation and consists of four membrane-bound electron-transporting protein complexes (I-IV) and an ATP synthase (complex V). This gene encodes a 51 kDa subunit of the NADH:ubiquinone oxidoreductase complex I; a large complex with at least 45 nuclear and mitochondrial encoded subunits that liberates electrons from NADH and channels them to ubiquinone. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-biding sites. Defects in complex I are a common cause of mitochondrial dysfunction; a syndrome that occurs in approximately 1 in 10,000 live births. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.211 OMIM phenotype

Clinical Summary— NDUFV1

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Gene-Disease Validity (ClinGen)

Leigh syndrome · 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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ClinVar Variants

72 unique Pathogenic / Likely Pathogenic· 169 VUS of 559 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — NDUFV1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.000

Z-score 0.80

OE 0.82 (0.56–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.28Z-score

OE missense 0.95 (0.86–1.05)

281 obs / 294.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.56–1.21)

0≤0.351.4

Missense OE?0.95 (0.86–1.05)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 18 / 22.0Missense obs/exp: 281 / 294.6Syn Z: 0.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveNDUFV1-related mitochondrial complex I deficiencyLOFAR

This gene — mechanism propensity

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

0.6649th %ile

GOF

0.6053th %ile

LOF

0.4430th %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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

559 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic45

VUS169

Likely Benign239

Benign28

Conflicting40

Pathogenic

Likely Pathogenic

169

VUS

239

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	4	2	0	27
Likely Pathogenic	23	19	3	0	45
VUS	0	157	10	2	169
Likely Benign	1	5	109	124	239
Benign	0	0	25	3	28
Conflicting	—				40
Total	45	185	149	129	548

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap NDUFV1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →