AACS

protein-coding

acetoacetyl-CoA synthetase, the group of Acyl-CoA synthetase family

Gene summary

Predicted to enable acetoacetate-CoA ligase activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_023928.5

Inheritance

—

ClinVar variants

U:127B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr12:125,065,434-125,143,333

External References & Databases

Ensembl (ENSG00000081760)

Transcript & Mutation Effects

hg38 • Region Span ~77.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AACS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 114

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023928.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar	4 clinvar	8
missense			119 clinvar		1 clinvar	120
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	127	3	5	135

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023928.5	RefSeq	NP_076417.2	18	MANE Select
ENST00000316519.11	Ensembl	ENSP00000324842.6	18	MANE Select
NM_001319839.2	RefSeq	NP_001306768.1	17	Standard
NM_001319840.2	RefSeq	NP_001306769.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Butanoate metabolism - Homo sapiens (human)
Valine, leucine and isoleucine degradation - Homo sapiens (human)
Butanoate metabolism
Metabolism of lipids
Metabolism

Biological Process

liver development
fatty acid metabolic process
response to nutrient
response to purine-containing compound
positive regulation of insulin secretion

Molecular Function

protein binding
ATP binding
acetoacetate-CoA ligase activity
butyrate-CoA ligase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316519
Coding exons: 18
Length: 77949
Individuals with no LoFs: 125616
Homozygous LoFs: 1
Heterozygous LoFs: 131
Defined: 125748
p: 0.000525

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.200	397	408	0.972	0.0000241	4402
Missense (PolyPhen)		132	140.78	0.9376		1554
Synonymous	0.667	162	173	0.936	0.0000121	1263
Loss of Function	1.13	29	36.3	0.798	0.00000163	432

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00092	0.00092	rare
Latino/Admixed American	0.00081	0.00081	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0019	0.0018	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00036	0.00036	rare
South Asian	0.00048	0.00046	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates acetoacetate to acetoacetyl-CoA. May be involved in utilizing ketone body for the fatty acid-synthesis during adipose tissue development (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.239

Intolerance Scores

LoFtool: 0.887
RVIS EVS: -1.17
RVIS percentile EVS: 6.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.780

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium