ACACA

Chr 17AR

acetyl-CoA carboxylase alpha

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

NCBI Gene: 31 ENSG00000278540 UniProt: Q13085 OMIM: 200350

Acetyl-CoA carboxylase alpha catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. Biallelic mutations cause acetyl-CoA carboxylase deficiency with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.221 OMIM phenotype

Clinical Summary— ACACA

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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.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 217 VUS of 471 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.15 (0.10–0.22)

0≤0.351.4

Missense OE?0.44 (0.41–0.47)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 20 / 134.5Missense obs/exp: 569 / 1304.8Syn Z: 1.85

ClinVar Variant Classifications

471 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS217

Likely Benign156

Benign41

Conflicting5

Pathogenic

Likely Pathogenic

217

VUS

156

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	1	0	0	1
VUS	8	192	14	3	217
Likely Benign	1	4	72	79	156
Benign	2	2	29	8	41
Conflicting	—				5
Total	11	200	115	90	421

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

View in ClinVar →

138 pathogenic / likely-pathogenic (of 152) ClinVar copy-number / structural variants overlap ACACA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →