ACSM2A
protein-codingacyl-CoA synthetase medium chain family member 2A, the group of Acyl-CoA synthetase family
Gene summary
This gene encodes a mitochondrial acyl-coenzyme A synthetase that is specific for medium chain fatty acids. These enzymes catalyze fatty acid activation, the first step of fatty acid metabolism, through the transfer of acyl-CoA. These enzymes also participate in the glycine conjugation pathway in the detoxification of xenobiotics such as benzoate and ibuprofen. Expression levels of this gene in the kidney may be correlated with kidney function. This gene and its paralog ACSM2B (Gene ID: 348158), both present on chromosome 16, likely arose from a chromosomal duplication event. [provided by RefSeq, May 2017]
- ACSM2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.2 kbGenCC 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 ACSM2A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001308172.2. 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 | 1 | 2 | |||
| missense | 83 | 5 | 1 | 89 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 87 | 7 | 2 | 96 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001295101.1 | 13 | MANE Select | |
| Ensembl | ENSP00000459451.1 | 13 | MANE Select | |
| RefSeq | NP_001295098.1 | 12 | Standard | |
| RefSeq | NP_001295883.1 | 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
- medium-chain fatty-acyl-CoA metabolic process
- glucose homeostasis
- triglyceride homeostasis
Molecular Function
- acyl-CoA ligase activity
- fatty-acyl-CoA synthase activity
- ATP binding
- fatty acid ligase activity
- metal ion binding
Cellular Component
- mitochondrion
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000573854
- Coding exons
- 13
- Length
- 36209
- Individuals with no LoFs
- 118166
- Homozygous LoFs
- 464
- Heterozygous LoFs
- 7118
- Defined
- 125748
- p
- 0.0306
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.79 | 411 | 321 | 1.28 | 0.0000168 | 3732 |
| Missense (PolyPhen) | 132 | 109.92 | 1.2008 | 1331 | ||
| Synonymous | -1.89 | 145 | 119 | 1.22 | 0.00000613 | 1129 |
| Loss of Function | -0.131 | 34 | 33.2 | 1.02 | 0.00000184 | 332 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0034 | 0.0034 | notable |
| Latino/Admixed American | 0.042 | 0.042 | notable |
| Ashkenazi Jewish | 0.043 | 0.044 | notable |
| East Asian | 0.21 | 0.21 | notable |
| Finnish | 0.0071 | 0.0071 | notable |
| European (Non-Finnish) | 0.012 | 0.012 | notable |
| South Asian | 0.020 | 0.020 | notable |
| Other | 0.025 | 0.026 | notable |
dbNSFP Gene Annotations
Source:
- 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
- 0.0680
Intolerance Scores
- LoFtool
- 0.970
- RVIS EVS
- 0.41
- RVIS percentile EVS
- 76.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.107
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |