ACACA

acetyl-CoA carboxylase alpha

Basic information

Region (hg38): 17:37084992-37406836

Previous symbols: [ "ACAC", "ACC" ]

Links

ENSG00000278540 ∙ NCBI:31 ∙ OMIM:200350 ∙ HGNC:84 ∙ Uniprot:Q13085 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acetyl-coa carboxylase deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acetyl-CoA carboxylase deficiency	AR	Biochemical	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	Biochemical; Neurologic	34552920; 36709796

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACACA gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACACA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	59	9	70
missense			108	3	2	113
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			9	17	5	31
non coding			3	41	21	65
Total	0	0	118	103	32

Variants in ACACA

This is a list of pathogenic ClinVar variants found in the ACACA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-37087350-C-T			Uncertain significance (Dec 18, 2022)
17-37087388-C-G			Likely benign (Dec 02, 2022)
17-37087425-T-C		not specified	Uncertain significance (Jan 20, 2023)
17-37088918-G-A			Benign (Jun 16, 2024)
17-37088926-C-T			Likely benign (Dec 28, 2021)
17-37088927-G-A			Likely benign (Aug 14, 2023)
17-37088952-G-A		ACACA-related disorder	Benign (Dec 10, 2023)
17-37088958-G-A			Likely benign (Dec 09, 2023)
17-37088997-C-T			Likely benign (Nov 27, 2023)
17-37089042-C-T		ACACA-related disorder	Benign (Nov 05, 2024)
17-37089043-G-A		Acetyl-CoA: carboxylase deficiency	Uncertain significance (Jun 10, 2023)
17-37089058-T-C		not specified	Uncertain significance (Jun 02, 2024)
17-37097008-T-C			Likely benign (Jun 27, 2022)
17-37097011-C-T			Likely benign (Nov 21, 2023)
17-37097064-C-G		not specified	Uncertain significance (Aug 28, 2024)
17-37097075-T-C		not specified	Uncertain significance (Apr 28, 2022)
17-37097148-T-A			Uncertain significance (Jun 05, 2022)
17-37097816-A-C			Likely benign (Jun 15, 2024)
17-37097827-T-TA			Uncertain significance (Apr 14, 2023)
17-37097856-G-A		not specified	Uncertain significance (Dec 06, 2022)
17-37097868-C-T		not specified	Uncertain significance (Oct 13, 2023)
17-37097909-G-T		Acetyl-CoA: carboxylase deficiency	Pathogenic/Likely pathogenic (Jan 31, 2024)
17-37097916-G-A		ACACA-related disorder	Benign (Jan 13, 2025)
17-37097957-C-T			Uncertain significance (Jan 29, 2024)
17-37097958-G-A		Acetyl-CoA: carboxylase deficiency	Uncertain significance (Oct 29, 2024)

GnomAD

Source: gnomAD

dbNSFP

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.
• Pathway: 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);Insulin signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;Pyruvate Dehydrogenase Complex Deficiency;Malonyl-coa decarboxylase deficiency;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Malonic Aciduria;Leigh Syndrome;Propanoate Metabolism;Pyruvate Metabolism;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Methylmalonic Aciduria Due to Cobalamin-Related Disorders;Fatty Acid Biosynthesis;AMP-activated Protein Kinase (AMPK) Signaling;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Leptin signaling pathway;Corticotropin-releasing hormone signaling pathway;JAK-STAT;Mesodermal Commitment Pathway;Fatty Acid Biosynthesis;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Leptin and adiponectin;Lipid Metabolism Pathway;Liver steatosis AOP;Pathways in clear cell renal cell carcinoma;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Biotin transport and metabolism;reversal of insulin resistance by leptin;Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Ghrelin;Fatty acid metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;fatty acid biosynthesis initiation;biotin-carboxyl carrier protein assembly;Pyruvate metabolism (Consensus)

Recessive Scores

• pRec: 0.732

Intolerance Scores

• loftool: 0.0461
• rvis_EVS: -1.61
• rvis_percentile_EVS: 2.96

Haploinsufficiency Scores

• pHI: 0.468
• hipred: Y
• hipred_score: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acaca
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; embryo phenotype; liver/biliary system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Gene ontology

• Biological process: tissue homeostasis;acetyl-CoA metabolic process;fatty acid biosynthetic process;carnitine shuttle;protein metabolic process;positive regulation of cellular metabolic process;regulation of cholesterol biosynthetic process;fatty-acyl-CoA biosynthetic process;protein homotetramerization;lipid homeostasis;cellular response to prostaglandin E stimulus;malonyl-CoA biosynthetic process
• Cellular component: fibrillar center;cytosol;actin cytoskeleton
• Molecular function: acetyl-CoA carboxylase activity;biotin carboxylase activity;protein binding;ATP binding;identical protein binding;metal ion binding