ACAA1

Chr 3

acetyl-CoA acyltransferase 1

Also known as: ACAA, Lnc-Myd88, PTHIO, THIO

NCBI Gene: 30 ENSG00000060971 UniProt: P09110

The ACAA1 protein catalyzes the thiolytic cleavage of 3-oxoacyl-CoAs in peroxisomal fatty acid beta-oxidation, processing fatty acids of varying chain lengths. Mutations cause pseudo-Zellweger syndrome, which follows autosomal recessive inheritance. This gene is not highly constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, UniProt

This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

Mechanism· predicted

📖

GeneReview available — ACAA1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 1.14

OE 0.74 (0.50–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.22Z-score

OE missense 0.78 (0.70–0.88)

195 obs / 249.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.50–1.12)

0≤0.351.4

Missense OE?0.78 (0.70–0.88)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 16 / 21.7Missense obs/exp: 195 / 249.0Syn Z: -0.65

Background carrier burden — how many people carry a rare variant somewhere in ACAA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

555 rare PASS variants

Rare truncating (LoF)

1 in 1,700

100 rare PASS variants

Rare synonymous (reference)

1 in 130

245 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACAA1. 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 130	1 in 2,600
South Asian	~43k	1 in 100	1 in 430
Remaining (unassigned)	~30k	1 in 71	1 in 1,700
European (Finnish)	~27k	1 in 420	1 in 2,400
Admixed American	~22k	1 in 88	1 in 1,300
African / African American	~21k	1 in 85	1 in 750
East Asian	~20k	1 in 110	1 in 580
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 84	1 in 570

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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓