ACSS3

protein-coding

acyl-CoA synthetase short chain family member 3, the group of MicroRNA protein coding host genes|Acyl-CoA synthetase family

Gene summary

Enables propionate-CoA ligase activity. Predicted to be involved in ketone body biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_024560.4

Inheritance

—

ClinVar variants

U:99B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr12:80,936,414-81,261,210

External References & Databases

Ensembl (ENSG00000111058)

Transcript & Mutation Effects

hg38 • Region Span ~324.8 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 ACSS3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 95

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024560.4. 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			2 clinvar			2
missense			95 clinvar	6 clinvar		101
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	99	6	0	105

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024560.4	RefSeq	NP_078836.1	16	MANE Select
ENST00000548058.6	Ensembl	ENSP00000449535.1	16	MANE Select
NM_001330242.2	RefSeq	NP_001317171.1	16	Standard
NM_001330243.2	RefSeq	NP_001317172.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Propanoate metabolism - Homo sapiens (human)
Malonyl-coa decarboxylase deficiency
Malonic Aciduria
Propanoate Metabolism
Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids

Biological Process

ketone body biosynthetic process

Molecular Function

acetate-CoA ligase activity
ATP binding

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000548058
Coding exons: 16
Length: 318940
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125748
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.146	375	383	0.979	0.0000195	4396
Missense (PolyPhen)		144	149.34	0.96425		1756
Synonymous	-1.39	160	139	1.15	0.00000740	1374
Loss of Function	1.79	25	36.7	0.681	0.00000177	452

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00023	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.00062	0.00052	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates acetate so that it can be used for lipid synthesis or for energy generation. {ECO:0000250}.;

Recessive Scores

pRec: 0.0919

Intolerance Scores

LoFtool: 0.908
RVIS EVS: -0.42
RVIS percentile EVS: 25.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.291

Gene Damage Prediction

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