NDUFAB1

Chr 16

NADH:ubiquinone oxidoreductase subunit AB1

Also known as: ACP, ACP1, FASN2A, SDAP

NCBI Gene: 4706 ENSG00000004779 UniProt: O14561 OMIM: 603836

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables mitochondrial large ribosomal subunit binding activity. Involved in [2Fe-2S] cluster assembly and protein lipoylation. Located in mitochondrial inner membrane and nucleoplasm. Part of mitochondrial [2Fe-2S] assembly complex and respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.75

Clinical Summary— NDUFAB1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 29 VUS of 44 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.75LOEUF

pLI 0.527

Z-score 1.96

OE 0.16 (0.06–0.75)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.16Z-score

OE missense 0.95 (0.80–1.14)

82 obs / 86.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.06–0.75)

0≤0.351.4

Missense OE?0.95 (0.80–1.14)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 1 / 6.3Missense obs/exp: 82 / 86.2Syn Z: 0.12

This gene — mechanism propensity

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

44 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS29

Likely Benign2

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	3	0	3
Likely Pathogenic	0	0	0	0
VUS	29	0	0	29
Likely Benign	2	0	0	2
Benign	1	0	1	2
Total	32	3	1	36

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap NDUFAB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →