ACSS2
protein-codingacyl-CoA synthetase short chain family member 2, the group of Acyl-CoA synthetase family
Gene summary
This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]
- ACAS2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.8 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 ACSS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018677.4. 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 | 8 | 2 | 10 | |||
| missense | 80 | 7 | 3 | 90 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 85 | 15 | 5 | 105 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061147.1 | 18 | MANE Select | |
| Ensembl | ENSP00000353804.2 | 18 | MANE Select | |
| RefSeq | NP_001070020.2 | 19 | Standard | |
| RefSeq | NP_001229322.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyruvate metabolism - Homo sapiens (human)
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Propanoate metabolism - Homo sapiens (human)
- Pyruvate Dehydrogenase Complex Deficiency
- Disulfiram Action Pathway
Biological Process
- ethanol oxidation
- lipid biosynthetic process
- acetate biosynthetic process
- acetyl-CoA biosynthetic process from acetate
- propionate biosynthetic process
Molecular Function
- acetate-CoA ligase activity
- ATP binding
- AMP binding
Cellular Component
- nucleoplasm
- cytoplasm
- mitochondrial matrix
- cytosol
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253382
- Coding exons
- 19
- Length
- 55821
- Individuals with no LoFs
- 125682
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 66
- Defined
- 125748
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 333 | 393 | 0.846 | 0.0000213 | 4651 |
| Missense (PolyPhen) | 166 | 202.51 | 0.81972 | 2380 | ||
| Synonymous | 2.25 | 108 | 142 | 0.760 | 0.00000738 | 1379 |
| Loss of Function | 2.05 | 27 | 41.2 | 0.655 | 0.00000208 | 473 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0.00052 | 0.00052 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activates acetate so that it can be used for lipid synthesis or for energy generation.;
Recessive Scores
- pRec
- 0.457
Intolerance Scores
- LoFtool
- 0.962
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.859
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |