ACSM3

protein-coding

acyl-CoA synthetase medium chain family member 3, the group of Acyl-CoA synthetase family

Gene summary

Enables medium-chain fatty acid-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

MANE transcript

NM_005622.4

Inheritance

—

ClinVar variants

U:97B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr16:20,610,243-20,797,581

External References & Databases

Ensembl (ENSG00000005187)

Transcript & Mutation Effects

hg38 • Region Span ~187.3 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 ACSM3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 91

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005622.4. 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	4 clinvar		6
missense			88 clinvar	5 clinvar		93
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	97	9	0	106

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 127 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005622.4	RefSeq	NP_005613.2	13	MANE Select
ENST00000289416.10	Ensembl	ENSP00000289416.5	13	MANE Select
NM_202000.3	RefSeq	NP_973729.1	8	Standard
ENST00000440284.6	Ensembl	ENSP00000394565.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Butanoate metabolism - Homo sapiens (human)
Valproic Acid Pathway, Pharmacokinetics
Metabolism of lipids
Beta oxidation of butanoyl-CoA to acetyl-CoA
mitochondrial fatty acid beta-oxidation of saturated fatty acids

Biological Process

fatty acid biosynthetic process
acyl-CoA metabolic process
regulation of blood pressure
cholesterol homeostasis

Molecular Function

molecular_function
acyl-CoA ligase activity
fatty-acyl-CoA synthase activity
ATP binding
fatty acid ligase activity

Cellular Component

cellular_component
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000289416
Coding exons: 13
Length: 187339
Individuals with no LoFs: 123187
Homozygous LoFs: 22
Heterozygous LoFs: 2539
Defined: 125748
p: 0.0102

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.456	290	313	0.927	0.0000158	3828
Missense (PolyPhen)		115	125.21	0.91847		1544
Synonymous	1.14	95	110	0.862	0.00000567	1115
Loss of Function	1.30	26	34.2	0.761	0.00000196	381

Population LoF Frequency

Population	CAF	p-value	Status
African	0.040	0.040	notable
Latino/Admixed American	0.0088	0.0087	notable
Ashkenazi Jewish	0.0078	0.0078	notable
East Asian	0.00077	0.00076	rare
Finnish	0.0018	0.0018	notable
European (Non-Finnish)	0.010	0.010	notable
South Asian	0.0088	0.0088	notable
Other	0.0090	0.0090	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has medium-chain fatty acid:CoA ligase activity with broad substrate specificity (in vitro). Acts on acids from C(4) to C(11) and on the corresponding 3-hydroxy- and 2,3- or 3,4- unsaturated acids (in vitro) (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.455

Intolerance Scores

LoFtool: 0.959
RVIS EVS: 1.29
RVIS percentile EVS: 93.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.276

Gene Damage Prediction

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