ACACB
protein-codingacetyl-CoA carboxylase beta
Gene summary
Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. [provided by RefSeq, Oct 2022]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~151.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007336
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ACACB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001093.4. 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 | 43 | 12 | 63 | ||
| missense | 412 | 32 | 5 | 449 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 13 | 13 | ||||
| Total | 0 | 0 | 434 | 75 | 17 | 526 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001084.3 | 52 | MANE Select | |
| Ensembl | ENSP00000341044.7 | 52 | MANE Select | |
| RefSeq | NP_001399663.1 | 52 | Standard | |
| RefSeq | NP_001399664.1 | 52 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyruvate metabolism - Homo sapiens (human)
- Adipocytokine signaling pathway - Homo sapiens (human)
- Insulin resistance - Homo sapiens (human)
- Propanoate metabolism - Homo sapiens (human)
- AMPK signaling pathway - Homo sapiens (human)
Biological Process
- acetyl-CoA metabolic process
- fatty acid biosynthetic process
- carnitine shuttle
- negative regulation of gene expression
- positive regulation of lipid storage
Molecular Function
- acetyl-CoA carboxylase activity
- biotin carboxylase activity
- protein binding
- ATP binding
- biotin binding
Cellular Component
- nucleus
- mitochondrion
- mitochondrial outer membrane
- cytosol
- endomembrane system
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338432
- Coding exons
- 52
- Length
- 151632
- Individuals with no LoFs
- 125336
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 411
- Defined
- 125748
- p
- 0.00164
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.57 | 1347 | 1.52e+3 | 0.887 | 0.0000978 | 16104 |
| Missense (PolyPhen) | 505 | 579.9 | 0.87084 | 6015 | ||
| Synonymous | -0.142 | 628 | 623 | 1.01 | 0.0000437 | 4856 |
| Loss of Function | 2.93 | 92 | 128 | 0.720 | 0.00000682 | 1393 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0017 | notable |
| Latino/Admixed American | 0.0017 | 0.0016 | notable |
| Ashkenazi Jewish | 0.0042 | 0.0042 | notable |
| East Asian | 0.0025 | 0.0024 | notable |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.0013 | 0.0013 | notable |
| South Asian | 0.0028 | 0.0027 | notable |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in inhibition of fatty acid and glucose oxidation and enhancement of fat storage (By similarity). May play a role in regulation of mitochondrial fatty acid oxidation through malonyl- CoA-dependent inhibition of carnitine palmitoyltransferase 1 (By similarity). {ECO:0000250|UniProtKB:E9Q4Z2, ECO:0000269|PubMed:20952656}.;
Recessive Scores
- pRec
- 0.412
Intolerance Scores
- LoFtool
- 0.0976
- RVIS EVS
- -1.97
- RVIS percentile EVS
- 1.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.422
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | Medium | High |