NDUFV1

Chr 11AR

NADH:ubiquinone oxidoreductase core subunit V1

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

NCBI Gene: 4723ENSG00000167792UniProt: P49821

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]

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 4MIM #618225
AR
580
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NDUFV1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 123 VUS of 580 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.28Z-score
OE missense 0.95 (0.86–1.05)
281 obs / 294.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.82 (0.56–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 18 / 22.0Missense obs/exp: 281 / 294.6Syn Z: 0.14

ClinVar Variant Classifications

580 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic36
VUS123
Likely Benign217
Benign29
Conflicting38
35
Pathogenic
36
Likely Pathogenic
123
VUS
217
Likely Benign
29
Benign
38
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
4
17
0
35
Likely Pathogenic
11
15
10
0
36
VUS
0
104
18
1
123
Likely Benign
1
4
101
111
217
Benign
0
0
26
3
29
Conflicting
—38
Total26127172115478

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFV1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NDUFV1-related mitochondrial complex I deficiency

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantmissense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex I deficiency, nuclear type 4

MIM #618225

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
NDUFV1-Related Mitochondrial Complex-1 Disorders: A Retrospective Case Series and Literature Review.
Mahesan A et al.·Pediatr Neurol
2024Review
A cryptic pathogenic NDUFV1 variant identified by RNA-seq in a patient with normal complex I activity in muscle and transient magnetic resonance imaging changes.
Kiss S et al.·Am J Med Genet A
2023Case report
Compound heterozygous mutations of NDUFV1 identified in a child with mitochondrial complex I deficiency.
Tang X et al.·Genes Genomics
2022
Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening.
Li X et al.·J Exp Clin Cancer Res
2024
Leigh Syndrome Due to NDUFV1 Mutations Initially Presenting as LBSL.
Borna NN et al.·Genes (Basel)
2020Case report
Riboflavin in Neurological Diseases: A Narrative Review.
Plantone D et al.·Clin Drug Investig
2021Review
Cystic Leucoencephalopathy in NDUFV1 Mutation.
Wadhwa Y et al.·Indian J Pediatr
2018Case report
Genetic diversity of NDUFV1-dependent mitochondrial complex I deficiency.
Srivastava A et al.·Eur J Hum Genet
2018Case report
Characterization of clinically identified mutations in NDUFV1, the flavin-binding subunit of respiratory complex I, using a yeast model system.
Varghese F et al.·Hum Mol Genet
2015Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Progressive spinal cord involvement in Leigh syndrome due to an NDUFV1 variant.
Finsterer J.·Radiol Case Rep
2025🔓 Open Access
Acute profound lactic alkalosis associated with NDUFV1 compound heterozygosity in a previously healthy 6-year-old female.
Kaler SG et al.·Mol Genet Metab Rep
2025🔓 Open Access
NDUFV1 mutation presenting as isolated progressive optic neuropathy: a unique manifestation of mitochondrial complex I deficiency.
Mittal P et al.·BMJ Case Rep
2025
Mitochondrial complex I deficiency in a 4-year-old boy due to compound heterozygous NDUFV1 mutation: a case report of a new pathogenic variant.
Haddad S et al.·Oxf Med Case Reports
2025🔓 Open AccessCase report
Leigh Syndrome Caused by Compound Heterozygous Variants c.1162A_C and c.1138G_C in the NDUFV1 Gene: A Case Report.
Finsterer J.·Cureus
2024🔓 Open AccessCase report
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools