NDUFS1

Chr 2AR

NADH:ubiquinone oxidoreductase core subunit S1

Also known as: CI-75Kd, CI-75k, MC1DN5, PRO1304

NCBI Gene: 4719ENSG00000023228UniProt: P28331

The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 5MIM #618226
AR
544
ClinVar variants
53
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— NDUFS1
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 208 VUS of 544 total submissions
Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 502

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

544 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic27
VUS208
Likely Benign136
Benign63
Conflicting21
26
Pathogenic
27
Likely Pathogenic
208
VUS
136
Likely Benign
63
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
23
0
26
Likely Pathogenic
10
12
5
0
27
VUS
0
169
35
4
208
Likely Benign
0
0
94
42
136
Benign
0
0
63
0
63
Conflicting
—21
Total1318122046481

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFS1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NDUFS1-related mitochondrial complex I deficiency

definitive
ARUndeterminedAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
missense 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 5

MIM #618226

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Target oxidative stress-induced disulfidptosis: novel therapeutic avenues in Parkinson's disease.
Zhang J et al.·Mol Brain
2025
MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network.
Elkholi R et al.·Mol Cell
2019
Correlation of disulfidptosis and periodontitis: New insights and clinical significance.
Fan Y et al.·Arch Oral Biol
2024
Genetic variant in NDUFS1 gene is associated with schizophrenia and negative symptoms in Han Chinese.
Zhu Y et al.·J Hum Genet
2015
MiR-3130-5p is an intermediate modulator of 2q33 and influences the invasiveness of lung adenocarcinoma by targeting NDUFS1.
Zhan J et al.·Cancer Med
2021
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
Roberts JL et al.·Gene
2014
Identification of a novel disulfidptosis-related gene signature in osteoarthritis using bioinformatics analysis and experimental validation.
Wei M et al.·Sci Rep
2025
Identifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses.
Li S et al.·Neurobiol Dis
2025
[Progressive cavitating leukoencephalopathy: four cases and literatures review].
Ren CH et al.·Zhonghua Er Ke Za Zhi
2017Review
A homozygous mutation in the NDUFS1 gene presents with a mild cavitating leukoencephalopathy.
Kashani A et al.·Neurogenetics
2014Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Role of NDUFS1 in mitochondrial dysfunction and oxidative stress in glaucomatous retinal ganglion cells.
Zhang J et al.·Exp Eye Res
2026
ER-localized ERO1α and caspase-3-mediated cleavage of mitochondrial NDUFS1 drives trichothecene-induced ROS accumulation in liver.
Zhong Z et al.·Free Radic Biol Med
2026
Mechanisms of sorafenib-induced cardiotoxicity: ER stress induces upregulation of ATF3, leading to downregulation of NDUFS1 expression and mitochondrial dysfunction.
Yan M et al.·Front Pharmacol
2025🔓 Open AccessFunctional
PCBP2 alleviates myocardial infarction by inhibiting cardiomyocyte ferroptosis via the NDUFS1/NRF2 pathway.
Zhang Q et al.·Mol Immunol
2025
NDUFS1 upregulates ENaCα by NAD+ to promote alveolar fluid clearance in acute lung injury.
Wang M et al.·Int J Med Sci
2025🔓 Open Access
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