ACAA1

Chr 3

acetyl-CoA acyltransferase 1

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

NCBI Gene: 30ENSG00000060971UniProt: P09110OMIM: 604054

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.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.12
Clinical Summary— ACAA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 67 VUS of 104 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ACAA1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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 OE0.74 (0.50–1.12)
0≤0.351.4
Missense OE0.78 (0.70–0.88)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 16 / 21.7Missense obs/exp: 195 / 249.0Syn Z: -0.65
DN
0.7229th %ile
GOF
0.5954th %ile
LOF
0.4037th %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

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS67
Likely Benign8
Benign2
10
Pathogenic
1
Likely Pathogenic
67
VUS
8
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
60
7
0
67
Likely Benign
0
3
2
3
8
Benign
0
1
0
1
2
Total06420488

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

View in ClinVar →

Protein Context — Lollipop Plot

ACAA1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Effect of the ACAA1 Gene on Preadipocyte Differentiation in Sheep
Wang Y et al.·Front Genet
2021
The Identification of Functional Genes Affecting Fat-Related Meat Traits in Meat-Type Pigeons Using Double-Digest Restriction-Associated DNA Sequencing and Molecular Docking Analysis
Yuan S et al.·Animals (Basel)
2023Functional
Inactivation of Acetyl-CoA Acyltransferase 1 enhances the proliferation and motility of nasopharyngeal carcinoma cells.
Wei W et al.·Mol Cell Oncol
2025
Inhibition of ACAA1 Restrains Proliferation and Potentiates the Response to CDK4/6 Inhibitors in Triple-Negative Breast Cancer.
Peng WT et al.·Cancer Res
2023
Comparative Genomic Analysis of the Thiolase Family and Functional Characterization of the Acetyl-Coenzyme A Acyltransferase-1 Gene for Milk Biosynthesis and Production of Buffalo and Cattle.
Deng T et al.·J Agric Food Chem
2023Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome.
Yang F et al.·J Transl Med
2024
Turning off the ferroptosis switch: ACAA1-Driven PI3K/AKT/Nrf2 signaling as a novel driver of endometrial cancer progression.
Lang T et al.·Free Radic Biol Med
2025
A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.
Luo R et al.·Signal Transduct Target Ther
2021
Genetic adaptation of skin pigmentation in highland Tibetans.
Yang Z et al.·Proc Natl Acad Sci U S A
2022
Interposition Intracranial-Intracranial Bypass Based on Anterior Cerebral Artery A1 Donor Anastomosis: Technical Advances, Outcomes, and Literature Review.
Liu P et al.·Oper Neurosurg
2023Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients