ACACA

protein-coding

acetyl-CoA carboxylase alpha

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. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

ACAC
ACC

MANE transcript

NM_198834.3

Inheritance

ClinVar variants

P:2U:225B:94

Top phenotype

Acetyl-CoA carboxylase deficiency

Max pathogenic AF

—

Genomic locus

chr17:37,084,992-37,406,836

External References & Databases

Ensembl (ENSG00000278540)

Transcript & Mutation Effects

hg38 • Region Span ~321.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

acetyl-coa carboxylase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013493

Submitter: PanelApp Australia

acetyl-coa carboxylase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013493

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Acetyl-CoA carboxylase deficiencyAR

Manifestation: Biochemical; Neurologic

Intervention: Biochemical

Rationale: The conditon can manifest with early-onset neurological sequelae, and medical and dietary management (eg, with vitamin B2, carnitine, and medium chain triglycerides) has been reported as potentially beneficial

Refs: 34552920; 36709796

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACACA variants in ClinVar

6 Conditions Cataloged

not providedTotal: 285

not specifiedTotal: 138

ACACA-related disorderTotal: 38

Acetyl-CoA: carboxylase deficiencyTotal: 7

Hereditary breast ovarian cancer syndromeTotal: 1

Cardiac anomalies - developmental delay - facial dysmorphism syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198834.3. 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			6 clinvar	79 clinvar	7 clinvar	92
missense	1 clinvar	1 clinvar	201 clinvar	6 clinvar	2 clinvar	211
nonsense			7 clinvar			7
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	1	1	225	85	9	321

Highest pathogenic variant AF is 0.000011772199

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198834.3	RefSeq	NP_942131.1	56	MANE Select
ENST00000616317.5	Ensembl	ENSP00000483300.1	56	MANE Select
NM_198836.3	RefSeq	NP_942133.1	54	Standard
NM_198837.2	RefSeq	NP_942134.1	54	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyruvate metabolism - Homo sapiens (human)
Propanoate metabolism - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
Glucagon signaling pathway - Homo sapiens (human)
Fatty acid biosynthesis - Homo sapiens (human)

Biological Process

tissue homeostasis
acetyl-CoA metabolic process
fatty acid biosynthetic process
carnitine shuttle
protein metabolic process

Molecular Function

acetyl-CoA carboxylase activity
biotin carboxylase activity
protein binding
ATP binding
identical protein binding

Cellular Component

fibrillar center
cytosol
actin cytoskeleton

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. {ECO:0000269|PubMed:20952656}.;
Disease: DISEASE: Acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:613933]: An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth. {ECO:0000269|PubMed:6114432}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.732

Intolerance Scores

LoFtool: 0.0461
RVIS EVS: -1.61
RVIS percentile EVS: 2.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.983

Gene Damage Prediction

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