ACACB

acetyl-CoA carboxylase beta

Basic information

Region (hg38): 12:109116587-109268226

Links

ENSG00000076555 ∙ NCBI:32 ∙ OMIM:601557 ∙ HGNC:85 ∙ Uniprot:O00763 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated cleft palate (Limited), mode of inheritance: Unknown

ClinVar

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

• not_specified (397 variants)
• ACACB-related_disorder (79 variants)
• not_provided (61 variants)
• HIGH_DENSITY_LIPOPROTEIN_CHOLESTEROL_LEVEL_QUANTITATIVE_TRAIT_LOCUS_6 (1 variants)
• Autism_spectrum_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACACB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001093.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	38	12	58
missense			392	29	6	427
nonsense						0
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			11			11
Total	0	0	412	67	18

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACACB	protein_coding	protein_coding	ENST00000338432	52	151632

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125336	1	411	125748	0.00164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	1347	1.52e+3	0.887	0.0000978	16104
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00341	0.00334
Ashkenazi Jewish	0.00418	0.00418
East Asian	0.00246	0.00245
Finnish	0.000370	0.000370
European (Non-Finnish)	0.00127	0.00126
Middle Eastern	0.00246	0.00245
South Asian	0.00276	0.00268
Other	0.00131	0.00130

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Glucagon signaling pathway - Homo sapiens (human);Fatty acid biosynthesis - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Metformin Pathway, Pharmacodynamic;AMP-activated Protein Kinase (AMPK) Signaling;Leptin signaling pathway;Activation of gene expression by SREBF (SREBP);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;Fatty Acid Biosynthesis;VEGFA-VEGFR2 Signaling Pathway;Liver steatosis AOP;Pathways in clear cell renal cell carcinoma;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Biotin transport and metabolism;Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of steroids;Metabolism of vitamins and cofactors;fatty acid biosynthesis initiation;biotin-carboxyl carrier protein assembly;Pyruvate metabolism;Leptin;Activation of gene expression by SREBF (SREBP) (Consensus)

Recessive Scores

• pRec: 0.412

Intolerance Scores

• loftool: 0.0976
• rvis_EVS: -1.97
• rvis_percentile_EVS: 1.78

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.422

Gene Damage Prediction

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

Gene ontology

• Biological process: acetyl-CoA metabolic process;fatty acid biosynthetic process;carnitine shuttle;negative regulation of gene expression;positive regulation of lipid storage;regulation of glucose metabolic process;response to organic cyclic compound;positive regulation of cellular metabolic process;response to nutrient levels;negative regulation of fatty acid beta-oxidation;response to drug;negative regulation of catalytic activity;regulation of cholesterol biosynthetic process;protein homotetramerization;positive regulation of heart growth;energy homeostasis;malonyl-CoA biosynthetic process
• Cellular component: nucleus;mitochondrion;mitochondrial outer membrane;cytosol;endomembrane system
• Molecular function: acetyl-CoA carboxylase activity;biotin carboxylase activity;protein binding;ATP binding;biotin binding;identical protein binding;metal ion binding