NDUFA8

Chr 9AR

NADH:ubiquinone oxidoreductase subunit A8

Also known as: CI-19KD, CI-PGIV, MC1DN37, PGIV

NCBI Gene: 4702ENSG00000119421UniProt: P51970OMIM: 603359

The protein is an accessory subunit of mitochondrial respiratory chain complex I that functions in electron transfer from NADH to ubiquinone. Biallelic mutations cause mitochondrial complex I deficiency, nuclear type 37, inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired mitochondrial respiratory chain function leading to cellular energy deficiency.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.721 OMIM phenotype
Clinical Summary— NDUFA8
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
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ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 31 VUS of 71 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
0.72LOEUF
pLI 0.344
Z-score 2.10
OE 0.23 (0.09–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.48Z-score
OE missense 0.86 (0.72–1.03)
86 obs / 99.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.09–0.72)
0≤0.351.4
Missense OE0.86 (0.72–1.03)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 2 / 8.7Missense obs/exp: 86 / 99.5Syn Z: 0.63
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNDUFA8-related developmental disorderLOFAR

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

DN
0.6259th %ile
GOF
0.5856th %ile
LOF
0.2385th %ile

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.

ClinVar Variant Classifications

71 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic2
VUS31
Likely Benign2
29
Pathogenic
2
Likely Pathogenic
31
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
27
0
29
Likely Pathogenic
1
0
1
0
2
VUS
0
30
1
0
31
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total13329164

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFA8 · 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 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
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