NDUFS5

Chr 1

NADH:ubiquinone oxidoreductase subunit S5

Also known as: CI-15k, CI15K

NCBI Gene: 4725ENSG00000168653UniProt: O43920OMIM: 603847

The encoded protein is an accessory subunit of mitochondrial complex I (NADH dehydrogenase), which transfers electrons from NADH to ubiquinone in the respiratory chain. Mutations cause Leigh syndrome and mitochondrial complex I deficiency, typically presenting in infancy or early childhood with progressive neurodegeneration affecting the brain, brainstem, and spinal cord. These conditions follow autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.35
Clinical Summary— NDUFS5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 17 VUS of 34 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.35LOEUF
pLI 0.026
Z-score 1.03
OE 0.53 (0.24–1.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.01Z-score
OE missense 1.00 (0.82–1.22)
69 obs / 69.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.24–1.35)
0≤0.351.4
Missense OE1.00 (0.82–1.22)
0≤0.61.4
Synonymous OE0.73
0≤1.21.6
LoF obs/exp: 3 / 5.6Missense obs/exp: 69 / 69.3Syn Z: 0.95
DN
0.7229th %ile
GOF
0.6346th %ile
LOF
0.1993th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS17
Likely Benign3
Benign2
5
Pathogenic
2
Likely Pathogenic
17
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
12
5
0
17
Likely Benign
0
2
1
0
3
Benign
0
0
1
1
2
Total01414129

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFS5 · 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
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 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