ACAA2

Chr 18

acetyl-CoA acyltransferase 2

Also known as: DSAEC, T1

NCBI Gene: 10449ENSG00000167315UniProt: P42765

The encoded protein catalyzes the final step of mitochondrial fatty acid beta-oxidation, breaking down medium- to long-chain fatty acids into acetyl-CoA for energy production. Mutations cause autosomal recessive 3-methylglutaconicaciduria with early-onset neurodegeneration, developmental delay, and metabolic dysfunction affecting the central nervous system and energy metabolism. This gene is highly intolerant to loss-of-function variants, indicating its critical role in cellular energy production.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
29
Pubs (1 yr)
40
P/LP submissions
0%
P/LP missense
1.31
LOEUF
DN
Mechanism· predicted
Clinical Summary— ACAA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 66 VUS of 128 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.000
Z-score 0.56
OE 0.86 (0.58–1.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.27Z-score
OE missense 1.05 (0.94–1.18)
220 obs / 209.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.58–1.31)
0≤0.351.4
Missense OE1.05 (0.94–1.18)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 16 / 18.6Missense obs/exp: 220 / 209.0Syn Z: 0.90
DN
0.7229th %ile
GOF
0.6151th %ile
LOF
0.4528th %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

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic1
VUS66
Likely Benign4
Benign6
37
Pathogenic
1
Likely Pathogenic
66
VUS
4
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
1
0
1
VUS
0
59
7
0
66
Likely Benign
0
2
2
0
4
Benign
0
2
4
0
6
Total063510114

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

View in ClinVar →

Protein Context — Lollipop Plot

ACAA2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
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