NDUFB9

Chr 8AR

NADH:ubiquinone oxidoreductase subunit B9

Also known as: B22, CI-B22, LYRM3, MC1DN24, UQOR22

The protein is an accessory subunit of mitochondrial complex I (NADH dehydrogenase) that functions in electron transfer from NADH to ubiquinone in the respiratory chain. Mutations cause mitochondrial complex I deficiency with autosomal recessive inheritance, though the specific clinical phenotype associated with NDUFB9 mutations remains uncertain. Complex I deficiencies typically present with variable manifestations including neonatal disease, cardiomyopathy, liver disease, and neurodegenerative disorders.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Mitochondrial complex I deficiency, nuclear type 24MIM #618245
AR
0
Active trials
7
Pubs (1 yr)
55
P/LP submissions
2%
P/LP missense
1.04
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryNDUFB9
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 62 VUS of 188 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.45
OE 0.58 (0.341.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.00Z-score
OE missense 1.00 (0.851.18)
104 obs / 104.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.341.04)
00.351.4
Missense OE1.00 (0.851.18)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 8 / 13.8Missense obs/exp: 104 / 104.0Syn Z: 0.10
DN
0.7228th %ile
GOF
0.72top 25%
LOF
0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

188 submitted variants in ClinVar

Classification Summary

Pathogenic55
VUS62
Likely Benign43
Benign16
Conflicting6
55
Pathogenic
62
VUS
43
Likely Benign
16
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
54
0
55
Likely Pathogenic
0
0
0
0
0
VUS
4
48
10
0
62
Likely Benign
0
2
21
20
43
Benign
0
1
14
1
16
Conflicting
6
Total4529921182

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

View in ClinVar →

Protein Context — Lollipop Plot

NDUFB9 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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