NDUFA8

Chr 9AR

NADH:ubiquinone oxidoreductase subunit A8

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

The protein encoded by this gene belongs to the complex I 19 kDa subunit family. Mammalian complex I is composed of 45 different subunits. This protein has NADH dehydrogenase activity and oxidoreductase activity. It plays an important role in transfering electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.721 OMIM phenotype
Clinical SummaryNDUFA8
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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
3 unique Pathogenic / Likely Pathogenic· 30 VUS of 42 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.72LOEUF
pLI 0.344
Z-score 2.10
OE 0.23 (0.090.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.48Z-score
OE missense 0.86 (0.721.03)
86 obs / 99.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.23 (0.090.72)
00.351.4
Missense OE?0.86 (0.721.03)
00.61.4
Synonymous OE?0.87
01.21.6
LoF obs/exp: 2 / 8.7Missense obs/exp: 86 / 99.5Syn Z: 0.63
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNDUFA8-related developmental disorderLOFAR

This gene — mechanism propensity

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

42 submitted variants in ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS30
Likely Benign2
2
Pathogenic
1
Likely Pathogenic
30
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
0
0
2
Likely Pathogenic
1
0
0
0
1
VUS
0
30
0
0
30
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total1330135

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap NDUFA8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NDUFA8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →