ACSF2

protein-coding

acyl-CoA synthetase family member 2, the group of Acyl-CoA synthetase family

Gene summary

Enables medium-chain fatty acid-CoA ligase activity. Predicted to be involved in fatty acid metabolic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_025149.6

Inheritance

—

ClinVar variants

U:93B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr17:50,426,158-50,474,845

External References & Databases

Ensembl (ENSG00000167107)

Transcript & Mutation Effects

hg38 • Region Span ~48.7 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 ACSF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 141

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025149.6. 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						0
missense			90 clinvar	3 clinvar		93
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	93	3	0	96

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025149.6	RefSeq	NP_079425.3	16	MANE Select
ENST00000300441.9	Ensembl	ENSP00000300441.4	16	MANE Select
NM_001288968.2	RefSeq	NP_001275897.1	17	Standard
NM_001288969.2	RefSeq	NP_001275898.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitochondrial LC-Fatty Acid Beta-Oxidation
Liver steatosis AOP
Metabolism of lipids
Mitochondrial Fatty Acid Beta-Oxidation
Metabolism

Biological Process

fatty acid metabolic process
acyl-CoA metabolic process

Molecular Function

acyl-CoA ligase activity
protein binding
ATP binding

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300441
Coding exons: 16
Length: 48688
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125748
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.98	249	354	0.704	0.0000202	3983
Missense (PolyPhen)		108	168.2	0.64208		1828
Synonymous	0.988	130	145	0.896	0.00000916	1197
Loss of Function	3.12	14	33.4	0.419	0.00000170	377

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00051	0.00049	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA. Has some preference toward medium-chain substrates. Plays a role in adipocyte differentiation. {ECO:0000269|PubMed:16380219, ECO:0000269|PubMed:17762044}.;

Recessive Scores

pRec: 0.201

Intolerance Scores

LoFtool: 0.622
RVIS EVS: -0.18
RVIS percentile EVS: 40.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0833

Gene Damage Prediction

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