NDUFS7

Chr 19AR

NADH:ubiquinone oxidoreductase core subunit S7

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

NCBI Gene: 374291ENSG00000115286UniProt: O75251

This gene encodes a protein that is a subunit of one of the complexes that forms the mitochondrial respiratory chain. This protein is one of over 40 subunits found in complex I, the nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase. This complex functions in the transfer of electrons from NADH to the respiratory chain, and ubiquinone is believed to be the immediate electron acceptor for the enzyme. Mutations in this gene cause Leigh syndrome due to mitochondrial complex I deficiency, a severe neurological disorder that results in bilaterally symmetrical necrotic lesions in subcortical brain regions. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Mitochondrial complex I deficiency, nuclear type 3MIM #618224
AR
200
ClinVar variants
28
Pathogenic / LP
0.91
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NDUFS7
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
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.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 12 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
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?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.
0.99Z-score
OE missense 0.78 (0.67–0.90)
121 obs / 155.8 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.0.08 (0.03–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.67–0.90)
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.1.28
0≤1.21.6
LoF obs/exp: 1 / 12.3Missense obs/exp: 121 / 155.8Syn Z: -1.73

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic11
VUS12
Likely Benign127
Benign19
Conflicting14
17
Pathogenic
11
Likely Pathogenic
12
VUS
127
Likely Benign
19
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
16
0
17
Likely Pathogenic
6
1
4
0
11
VUS
0
5
6
1
12
Likely Benign
0
1
76
50
127
Benign
0
1
18
0
19
Conflicting
—14
Total6912051200

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.

Gene2Phenotype Curations

NDUFS7-related mitochondrial respiratory chain complex I deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex I deficiency, nuclear type 3

MIM #618224

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NDUFS7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
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
SLC7A11-mediated cystine import protects against NDUFS7 deficiency-induced cell death in HEK293T cells.
Chen J et al.·Biochem Biophys Res Commun
2024
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
Clinical and molecular findings in children with complex I deficiency.
Bugiani M et al.·Biochim Biophys Acta
2004
Sequence analysis of nuclear genes encoding functionally important complex I subunits in children with encephalomyopathy.
Hinttala R et al.·J Mol Med (Berl)
2005Functional
A novel mutation in the human complex I NDUFS7 subunit associated with Leigh syndrome.
Lebon S et al.·Mol Genet Metab
2007Case report
Genetic variants of Complex I in multiple sclerosis.
Vyshkina T et al.·J Neurol Sci
2005
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
Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects.
Pagniez-Mammeri H et al.·Mol Genet Metab
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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