NDUFAB1

Chr 16

NADH:ubiquinone oxidoreductase subunit AB1

Also known as: ACP, ACP1, FASN2A, SDAP, mt-ACP, mtACP

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 and structural molecule activity. Involved in [2Fe-2S] cluster assembly; mitochondrial large ribosomal subunit assembly; and protein lipoylation. Located in mitochondrial inner membrane. Part of mitochondrial [2Fe-2S] assembly complex and respiratory chain complex I. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.75

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in NDUFAB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

191 rare PASS variants

Rare truncating (LoF)

1 in 17,000

19 rare PASS variants

Rare synonymous (reference)

1 in 720

90 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDUFAB1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 360	1 in 15,000
South Asian	~43k	1 in 360	≈ 1 in 20,000
Remaining (unassigned)	~30k	1 in 340	none seen
European (Finnish)	~27k	1 in 2,600	≈ 1 in 25,000
Admixed American	~22k	1 in 330	none seen
African / African American	~21k	1 in 260	≈ 1 in 21,000
East Asian	~20k	1 in 470	none seen
Ashkenazi Jewish	~13k	1 in 2,500	none seen
Middle Eastern	~2,884	1 in 410	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 4.? see exons ↓