ACSM4

protein-coding

acyl-CoA synthetase medium chain family member 4, the group of Acyl-CoA synthetase family

Gene summary

Predicted to enable decanoate-CoA ligase activity and fatty-acyl-CoA synthase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001080454.2

Inheritance

—

ClinVar variants

U:69B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr12:7,304,072-7,328,719

External References & Databases

Ensembl (ENSG00000215009)

Transcript & Mutation Effects

hg38 • Region Span ~24.6 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 ACSM4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 71

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080454.2. 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		1
missense			68 clinvar	3 clinvar		71
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	69	4	0	73

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080454.2	RefSeq	NP_001073923.1	13	MANE Select
ENST00000399422.5	Ensembl	ENSP00000382349.4	13	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Butanoate metabolism - Homo sapiens (human)
Valproic Acid Pathway, Pharmacokinetics
Conjugation of salicylate with glycine
Conjugation of carboxylic acids
Amino Acid conjugation

Biological Process

fatty acid biosynthetic process
acyl-CoA metabolic process

Molecular Function

acyl-CoA ligase activity
fatty-acyl-CoA synthase activity
ATP binding
fatty acid ligase activity
metal ion binding

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399422
Coding exons: 13
Length: 24441
Individuals with no LoFs: 114123
Homozygous LoFs: 317
Heterozygous LoFs: 10616
Defined: 125056
p: 0.0447

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.908	274	320	0.857	0.0000174	3765
Missense (PolyPhen)		104	110.26	0.94327		1302
Synonymous	1.24	100	117	0.855	0.00000656	1100
Loss of Function	0.471	30	32.9	0.911	0.00000184	350

Population LoF Frequency

Population	CAF	p-value	Status
African	0.096	0.096	notable
Latino/Admixed American	0.051	0.051	notable
Ashkenazi Jewish	0.067	0.067	notable
East Asian	0.0075	0.0074	notable
Finnish	0.029	0.028	notable
European (Non-Finnish)	0.046	0.045	notable
South Asian	0.036	0.036	notable
Other	0.054	0.053	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}.;

Intolerance Scores

LoFtool: 0.959
RVIS EVS: -0.46
RVIS percentile EVS: 23.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0828

Gene Damage Prediction

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