ACACA

Chr 17AR

acetyl-CoA carboxylase alpha

Also known as: ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA, ACCalpha, Acac1

NCBI Gene: 31ENSG00000278540UniProt: Q13085

Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Acetyl-CoA carboxylase deficiencyMIM #613933
AR
466
ClinVar variants
122
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ACACA
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
122 Pathogenic / Likely Pathogenic· 202 VUS of 466 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.22LOEUF
pLI 1.000
Z-score 9.15
OE 0.15 (0.10–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
7.24Z-score
OE missense 0.44 (0.41–0.47)
569 obs / 1304.8 exp
Constrained

Extremely missense-constrained (top ~0.01%)

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.0.15 (0.10–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.41–0.47)
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.0.89
0≤1.21.6
LoF obs/exp: 20 / 134.5Missense obs/exp: 569 / 1304.8Syn Z: 1.85

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic109
Likely Pathogenic13
VUS202
Likely Benign113
Benign26
Conflicting3
109
Pathogenic
13
Likely Pathogenic
202
VUS
113
Likely Benign
26
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
108
0
109
Likely Pathogenic
0
0
13
0
13
VUS
4
172
24
2
202
Likely Benign
1
3
54
55
113
Benign
2
1
15
8
26
Conflicting
—3
Total717721465466

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

View in ClinVar →

Protein Context — Lollipop Plot

ACACA · 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

Acetyl-CoA carboxylase deficiency

MIM #613933

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy in the physiological endometrium and cancer.
Devis-Jauregui L et al.·Autophagy
2021Review
Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.
Wang K et al.·Autophagy
2023
Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.
Zheng ZG et al.·Autophagy
2021
The third patient of ACACA-related acetyl-CoA carboxylase deficiency with seizure and literature review.
Shafieipour N et al.·Eur J Med Genet
2023Review
Integrated single-cell and bulk RNA sequencing analysis reveals ACACA as a potential prognostic and immunotherapeutic biomarker across cancers.
He H et al.·Front Immunol
2025
DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy.
Puustinen P et al.·Autophagy
2020
A MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth.
Morelli E et al.·Blood
2023
Regulation of human Th9 cell differentiation by lipid modulators targeting PPAR-γ and acetyl-CoA-carboxylase 1.
Peesari S et al.·Front Immunol
2024
Exosomal PKM2: A Noninvasive Diagnostic Marker Linking Macrophage Metabolic Reprogramming to Gastric Cancer Pathogenesis.
Yuan M et al.·Cancer Sci
2025
Prenatal diagnosis, ultrasound findings, and pregnancy outcome of 17q12 deletion and duplication syndromes: a retrospective case series.
Luo X et al.·Arch Gynecol Obstet
2024Cohort
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools