NDUFV2

Chr 18AR

NADH:ubiquinone oxidoreductase core subunit V2

Also known as: CI-24k, MC1DN7

The NDUFV2 protein is the 24 kDa subunit of mitochondrial respiratory chain complex I that participates in electron transfer from NADH to ubiquinone. Mutations cause mitochondrial complex I deficiency, nuclear type 7, inherited in an autosomal recessive pattern, with reported presentations including early onset hypertrophic cardiomyopathy and encephalopathy. The pathogenic mechanism appears to be dominant negative, where mutant protein disrupts normal complex I function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.831 OMIM phenotype
Clinical SummaryNDUFV2
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 31 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.006
Z-score 2.02
OE 0.42 (0.230.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.55Z-score
OE missense 1.14 (0.991.30)
149 obs / 131.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.42 (0.230.83)
00.351.4
Missense OE1.14 (0.991.30)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 6 / 14.2Missense obs/exp: 149 / 131.1Syn Z: 0.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateNDUFV2-related mitochondrial complex I deficiency, nuclearOTHERAR

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

DN
0.6939th %ile
GOF
0.5856th %ile
LOF
0.3843th %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

100 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic3
VUS31
Likely Benign22
Benign11
Conflicting3
30
Pathogenic
3
Likely Pathogenic
31
VUS
22
Likely Benign
11
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
28
0
30
Likely Pathogenic
1
1
1
0
3
VUS
1
21
8
1
31
Likely Benign
0
0
17
5
22
Benign
0
0
11
0
11
Conflicting
3
Total422656100

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFV2 · 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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