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.

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.

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			1	35	10	46
missense			162	20	6	188
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				12	4	16
non coding				7	7	14
Total	0	0	163	62	23

Variants in ACACB

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

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

Position	Type	Phenotype	Significance	ClinVar
12-109139409-G-A		not specified	Likely benign (Nov 05, 2021)
12-109139424-C-T		ACACB-related disorder	Benign (Dec 31, 2019)
12-109139509-G-A		not specified	Uncertain significance (Nov 08, 2022)
12-109139533-C-T		not specified • ACACB-related disorder	Likely benign (Jan 12, 2024)
12-109139534-G-A		ACACB-related disorder	Likely benign (Aug 14, 2024)
12-109139539-A-G		ACACB-related disorder	Conflicting classifications of pathogenicity (Oct 25, 2022)
12-109139545-C-A		not specified	Uncertain significance (Apr 07, 2022)
12-109139578-C-T		not specified	Likely benign (Aug 16, 2021)
12-109139631-C-T		not specified	Uncertain significance (Dec 16, 2023)
12-109139665-G-A		not specified	Likely benign (Apr 14, 2022)
12-109139671-G-T		not specified	Uncertain significance (Nov 15, 2023)
12-109139686-C-T		not specified	Uncertain significance (Jun 10, 2022)
12-109139711-C-A			Likely benign (Dec 14, 2023)
12-109139727-G-A		not specified	Uncertain significance (Apr 09, 2024)
12-109139760-G-A		not specified	Uncertain significance (Mar 01, 2023)
12-109139783-G-C		not specified	Uncertain significance (Jun 22, 2023)
12-109139794-C-G		not specified	Uncertain significance (May 14, 2024)
12-109139896-A-G		not specified	Uncertain significance (Jul 05, 2023)
12-109139937-G-C		not specified	Uncertain significance (Feb 12, 2024)
12-109139959-G-A		not specified	Conflicting classifications of pathogenicity (May 01, 2024)
12-109139971-G-A		ACACB-related disorder	Likely benign (Feb 07, 2022)
12-109139977-G-A		not specified	Uncertain significance (Aug 04, 2023)
12-109140042-C-T		not specified	Uncertain significance (Oct 06, 2023)
12-109140043-G-A		not specified	Uncertain significance (Jun 05, 2023)
12-109140045-G-A		not specified	Likely benign (Jun 03, 2024)

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
7.65e-47	0.191	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

Haploinsufficiency Scores

• pHI: 0.164
• hipred: Y
• hipred_score: 0.526
• ghis: 0.566

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

Mouse Genome Informatics

• Gene name: Acacb
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

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