NDUFAB1

Chr 16

NADH:ubiquinone oxidoreductase subunit AB1

Also known as: ACP, ACP1, FASN2A, SDAP

The NDUFAB1 protein functions as an accessory subunit of mitochondrial respiratory chain complex I and serves as a regulatory component of the iron-sulfur cluster assembly machinery that is essential for mitochondrial protein biogenesis. Mutations cause autosomal recessive mitochondrial complex I deficiency presenting with early-onset neurodegeneration, developmental delay, and multisystem involvement including cardiac and hepatic dysfunction. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in mitochondrial energy metabolism.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.75
Clinical SummaryNDUFAB1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.75LOEUF
pLI 0.527
Z-score 1.96
OE 0.16 (0.060.75)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.16Z-score
OE missense 0.95 (0.801.14)
82 obs / 86.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.060.75)
00.351.4
Missense OE0.95 (0.801.14)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 1 / 6.3Missense obs/exp: 82 / 86.2Syn Z: 0.12
DN
0.6357th %ile
GOF
0.5071th %ile
LOF
0.4430th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NDUFAB1 · 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.

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Clinical Literature
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