NDUFS7

Chr 19AR

NADH:ubiquinone oxidoreductase core subunit S7

Also known as: CI-20, CI-20KD, MC1DN3, MY017, PSST

NCBI Gene: 374291ENSG00000115286UniProt: O75251OMIM: 601825

This protein is a subunit of mitochondrial respiratory complex I (NADH:ubiquinone oxidoreductase) that functions in electron transfer from NADH to the respiratory chain. Biallelic mutations cause autosomal recessive mitochondrial complex I deficiency, which presents as Leigh syndrome with severe neurological deterioration and characteristic bilaterally symmetrical necrotic lesions in subcortical brain regions. The pathogenic mechanism involves impaired mitochondrial electron transport and cellular energy production.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.391 OMIM phenotype
Clinical Summary— NDUFS7
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 67 VUS of 306 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — NDUFS7
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.39LOEUF
pLI 0.914
Z-score 2.98
OE 0.08 (0.03–0.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.99Z-score
OE missense 0.78 (0.67–0.90)
121 obs / 155.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.03–0.39)
0≤0.351.4
Missense OE0.78 (0.67–0.90)
0≤0.61.4
Synonymous OE1.28
0≤1.21.6
LoF obs/exp: 1 / 12.3Missense obs/exp: 121 / 155.8Syn Z: -1.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNDUFS7-related mitochondrial respiratory chain complex I deficiencyLOFAR

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

DN
0.6454th %ile
GOF
0.3888th %ile
LOF
0.59top 25%

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

306 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic14
VUS67
Likely Benign188
Benign15
Conflicting5
12
Pathogenic
14
Likely Pathogenic
67
VUS
188
Likely Benign
15
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
9
0
12
Likely Pathogenic
11
2
1
0
14
VUS
0
53
12
2
67
Likely Benign
0
1
98
89
188
Benign
0
0
14
1
15
Conflicting
—5
Total135713492301

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFS7 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
NDUFS7 variant in dogs with Leigh syndrome and its functional validation in a Drosophila melanogaster model
Christen M et al.·Sci Rep
2024Functional
First-in-Class NADH/Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) Antagonist for the Treatment of Pancreatic Cancer.
Xu Y et al.·ACS Pharmacol Transl Sci
2023
Systematic selection of suitable reference genes for quantitative real-time PCR normalization studies of gene expression in Lutjanus erythropterus
Chen L et al.·Sci Rep
2024
Copper Transporter 1-Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.
Mouawad R et al.·ACS Pharmacol Transl Sci
2026
Exploring mito-nuclear genetic factors in Leber's hereditary optic neuropathy: insights from comprehensive profiling of unique cases
Chermakani P et al.·EXCLI J
2023Cohort
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
SLC7A11-mediated cystine import protects against NDUFS7 deficiency-induced cell death in HEK293T cells.
Chen J et al.·Biochem Biophys Res Commun
2024
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
Novel intronic variant in NDUFS7 gene results in mitochondrial complex I assembly defect with early basal ganglia and midbrain involvement with progressive neuroimaging findings.
Oikarainen J et al.·Mitochondrion
2025Case report
Genomic landscape of paired primary and peritoneal metastatic lesions in gastric cancer highlights evolutionary dynamics and mutational drivers.
Li S et al.·J Adv Res
2026
Multiomics analyses reveals Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria.
Li R et al.·BMC Microbiol
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients