ACSM5

protein-coding

acyl-CoA synthetase medium chain family member 5, the group of Acyl-CoA synthetase family

Gene summary

Predicted to enable fatty acid 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_017888.3

Inheritance

—

ClinVar variants

U:86B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr16:20,409,534-20,441,336

External References & Databases

Ensembl (ENSG00000183549)

Transcript & Mutation Effects

hg38 • Region Span ~31.8 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 ACSM5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017888.3. 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			83 clinvar	4 clinvar		87
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	86	6	0	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017888.3	RefSeq	NP_060358.2	13	MANE Select
ENST00000331849.8	Ensembl	ENSP00000327916.4	13	MANE Select
NM_001324371.2	RefSeq	NP_001311300.1	13	Standard
NM_001324372.2	RefSeq	NP_001311301.1	13	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
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
GTP binding
fatty acid ligase activity

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331849
Coding exons: 13
Length: 31803
Individuals with no LoFs: 125376
Homozygous LoFs: 0
Heterozygous LoFs: 372
Defined: 125748
p: 0.00148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.621	367	335	1.10	0.0000190	3732
Missense (PolyPhen)		118	114.93	1.0267		1312
Synonymous	-2.11	165	134	1.23	0.00000814	1161
Loss of Function	0.402	29	31.4	0.923	0.00000158	327

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0016	notable
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0011	0.0011	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00043	0.00043	rare
South Asian	0.0082	0.0082	notable
Other	0.00049	0.00049	rare

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: 0.0925

Intolerance Scores

LoFtool: 0.816
RVIS EVS: 3.18
RVIS percentile EVS: 99.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.176

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High