NDUFB8

Chr 10

NADH:ubiquinone oxidoreductase subunit B8

Also known as: ASHI, CI-ASHI, MC1DN32

Predicted to enable NADH dehydrogenase (ubiquinone) activity. Predicted to be involved in mitochondrial electron transport, NADH to ubiquinone and proton motive force-driven mitochondrial ATP synthesis. Located in mitochondrial inner membrane. Part of respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency 32. Biomarker of Alzheimer's disease and Parkinson's disease. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.98
Clinical SummaryNDUFB8
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 54 VUS of 108 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.98LOEUF
pLI 0.007
Z-score 1.61
OE 0.47 (0.240.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.11Z-score
OE missense 1.03 (0.891.20)
121 obs / 117.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.47 (0.240.98)
00.351.4
Missense OE?1.03 (0.891.20)
00.61.4
Synonymous OE?0.93
01.21.6
LoF obs/exp: 5 / 10.7Missense obs/exp: 121 / 117.5Syn Z: 0.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNDUFB8-related mitochondrial complex I deficiencyLOFAR

This gene — mechanism propensity

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

DN
0.6355th %ile
GOF
0.5758th %ile
LOF
0.3068th %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

108 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS54
Likely Benign34
Benign9
Conflicting1
4
Pathogenic
1
Likely Pathogenic
54
VUS
34
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
1
0
4
Likely Pathogenic
1
0
0
0
1
VUS
3
47
3
1
54
Likely Benign
0
3
12
19
34
Benign
0
3
4
2
9
Conflicting
1
Total4562022103

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap NDUFB8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NDUFB8 · 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 →