ACAT2

Chr 6Isolated cases

acetyl-CoA acetyltransferase 2

NCBI Gene: 39ENSG00000120437UniProt: O75908

The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

Primary Disease Associations & Inheritance

?ACAT2 deficiencyMIM #614055
Isolated cases
105
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ACAT2
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Gene-Disease Validity (ClinGen)
acetyl-CoA acetyltransferase-2 deficiency · UDNo Known Disease Relationship

No known disease relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 66 VUS of 105 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.14LOEUF
pLI 0.000
Z-score 1.12
OE 0.71 (0.45–1.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.70Z-score
OE missense 0.87 (0.77–0.98)
190 obs / 219.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.45–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.77–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 12 / 17.0Missense obs/exp: 190 / 219.1Syn Z: 0.42

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS66
Likely Benign9
Benign6
23
Pathogenic
1
Likely Pathogenic
66
VUS
9
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
1
0
1
VUS
1
58
7
0
66
Likely Benign
0
3
2
4
9
Benign
0
2
1
3
6
Total163347105

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

View in ClinVar →

Protein Context — Lollipop Plot

ACAT2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?ACAT2 deficiency

MIM #614055

Disorder with associated gene

Isolated cases
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Histone lactylation-driven feedback loop modulates cholesterol-linked immunosuppression in pancreatic cancer.
Yang J et al.·Gut
2025
Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learning.
Wang J et al.·Front Immunol
2022
ACAT2 may be a novel predictive biomarker and therapeutic target in lung adenocarcinoma.
Wang Z et al.·Cancer Rep (Hoboken)
2024
DNA methylation in childhood dental caries and hypomineralization.
Mj S et al.·J Dent
2022
Synergistic dual oncogenic role of CKS2 and ACAT2: Enhanced regulatory coherence and biomarker potential in adrenocortical carcinoma.
Omidi J·Cancer Genet
2025
A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder.
You MJ et al.·Transl Psychiatry
2023Cohort
Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism.
Harashima S et al.·J Steroid Biochem Mol Biol
2022
A mitochondrial lipid metabolism-related gene signature predicts prognosis and immune landscape in colorectal cancer.
Wang H et al.·Front Immunol
2025
Pan-cancer analysis reveals the oncogenic role of 3-hydroxy-3-methylglutaryl-CoA synthase 1.
Zhou C et al.·Cancer Rep (Hoboken)
2022
Human tau mutations in cerebral organoids induce a progressive dyshomeostasis of cholesterol.
Glasauer SMK et al.·Stem Cell Reports
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Pre-diabetes

Diet Impact on Hepatic Transcriptomics and Lipidomics in Pre-diabetes

ACTIVE NOT RECRUITING
NCT05965973Phase NALaval UniversityStarted 2023-06-09
Low fat dietHigh fat diet

External Resources

Links to major genomics databases and tools