ACAT1

acetyl-CoA acetyltransferase 1

Basic information

Region (hg38): 11:108116695-108148957

Previous symbols: [ "ACAT" ]

Links

ENSG00000075239 ∙ NCBI:38 ∙ OMIM:607809 ∙ HGNC:93 ∙ Uniprot:P24752 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• beta-ketothiolase deficiency (Definitive), mode of inheritance: AR
• beta-ketothiolase deficiency (Strong), mode of inheritance: AR
• beta-ketothiolase deficiency (Strong), mode of inheritance: AR
• beta-ketothiolase deficiency (Definitive), mode of inheritance: AR
• beta-ketothiolase deficiency (Supportive), mode of inheritance: AR
• beta-ketothiolase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alpha-methylacetoacetic aciduria	AR	Biochemical	Individuals typically present with hypoglycemic or hyperglycemic ketoacidosis due to fasting, illnesses, and dietary changes (eg, increased protein), which can result in severe neurologic sequelae or death, and diagnosis can allow dietary and medical management (eg, protein restriction and l-carnitine supplementation) to avoid acute crises and subsequent sequelae	Biochemical; Neurologic	4143539; 4690360; 4812006; 8103405; 8103405; 9700610; 15877211; 17236799; 18511318; 16950638; 20046049; 20157782; 21669895; 23430882; 23920042; 23958592

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACAT1 gene.

• Deficiency of acetyl-CoA acetyltransferase (84 variants)
• not provided (6 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACAT1 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	1	164	4	170
missense	6	45	90	2	1	144
nonsense	19	5	1			25
start loss	4					4
frameshift	40	23	2			65
inframe indel	1	4	4			9
splice donor/acceptor (+/-2bp)	11	19				30
splice region	2	2	6	28	5	43
non coding	2	3	9	110	38	162
Total	83	100	107	276	43

Highest pathogenic variant AF is 0.0000394

Variants in ACAT1

This is a list of pathogenic ClinVar variants found in the ACAT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-108121200-CAA-C			Benign (Jun 18, 2021)
11-108121537-T-A		Deficiency of acetyl-CoA acetyltransferase	Uncertain significance (Jan 12, 2018)
11-108121579-T-A		Deficiency of acetyl-CoA acetyltransferase	Benign (Jan 12, 2018)
11-108121585-C-G		Deficiency of acetyl-CoA acetyltransferase	Benign (Jul 01, 2021)
11-108121585-C-T		Deficiency of acetyl-CoA acetyltransferase	Uncertain significance (Jan 13, 2018)
11-108121592-C-G		not specified • Deficiency of acetyl-CoA acetyltransferase	Benign (Oct 16, 2023)
11-108121598-T-A		not specified • Deficiency of acetyl-CoA acetyltransferase	Benign (Jul 01, 2021)
11-108121602-C-T		Deficiency of acetyl-CoA acetyltransferase	Uncertain significance (Jan 13, 2018)
11-108121607-A-C		Deficiency of acetyl-CoA acetyltransferase	Pathogenic (Feb 25, 2024)
11-108121607-A-G		Deficiency of acetyl-CoA acetyltransferase	Pathogenic (May 11, 2024)
11-108121608-T-A		Deficiency of acetyl-CoA acetyltransferase	Pathogenic (May 05, 2019)
11-108121608-T-C		Deficiency of acetyl-CoA acetyltransferase	Pathogenic (Oct 03, 2023)
11-108121611-C-T		Deficiency of acetyl-CoA acetyltransferase	Uncertain significance (Sep 01, 2021)
11-108121615-G-A		Deficiency of acetyl-CoA acetyltransferase	Likely benign (Jan 28, 2024)
11-108121616-C-G		Deficiency of acetyl-CoA acetyltransferase	Uncertain significance (Jul 14, 2021)
11-108121616-C-T		Deficiency of acetyl-CoA acetyltransferase	Likely benign (Mar 21, 2023)
11-108121619-G-C		not specified • Deficiency of acetyl-CoA acetyltransferase	Benign (Feb 01, 2024)
11-108121620-C-T		Deficiency of acetyl-CoA acetyltransferase	Uncertain significance (Aug 31, 2022)
11-108121621-G-C		Deficiency of acetyl-CoA acetyltransferase	Conflicting classifications of pathogenicity (Dec 22, 2021)
11-108121621-G-T		Deficiency of acetyl-CoA acetyltransferase	Likely benign (Jul 27, 2022)
11-108121624-A-G		Deficiency of acetyl-CoA acetyltransferase	Likely benign (Jun 28, 2023)
11-108121627-T-G		Deficiency of acetyl-CoA acetyltransferase	Likely benign (Jul 25, 2022)
11-108121628-C-T		Deficiency of acetyl-CoA acetyltransferase • ACAT1-related disorder	Likely benign (Nov 17, 2023)
11-108121630-G-T		Deficiency of acetyl-CoA acetyltransferase	Likely benign (Oct 24, 2022)
11-108121633-C-T		Deficiency of acetyl-CoA acetyltransferase	Likely benign (May 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACAT1	protein_coding	protein_coding	ENST00000265838	12	26261

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.85e-8	0.774	125695	0	52	125747	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.906	193	232	0.833	0.0000110	2766
Missense in Polyphen		63	93.942	0.67063		1136
Synonymous	-0.645	85	77.8	1.09	0.00000393	855
Loss of Function	1.39	14	20.8	0.672	9.77e-7	265

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000656	0.000655
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000382	0.000381
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000185	0.000185
Middle Eastern	0.000382	0.000381
South Asian	0.000136	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a major role in ketone body metabolism.
• Disease: DISEASE: 3-ketothiolase deficiency (3KTD) [MIM:203750]: An autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype. {ECO:0000269|PubMed:1346617, ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Butanoate metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);Synthesis and degradation of ketone bodies - Homo sapiens (human);Terpenoid backbone biosynthesis - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);Long chain acyl-CoA dehydrogenase deficiency (LCAD);Pyruvate Dehydrogenase Complex Deficiency;Lysine Degradation;3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Hyperlysinemia I, Familial;Malonyl-coa decarboxylase deficiency;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;2-aminoadipic 2-oxoadipic aciduria;Trifunctional protein deficiency;Carnitine palmitoyl transferase deficiency (II);Very-long-chain acyl coa dehydrogenase deficiency (VLCAD);Medium chain acyl-coa dehydrogenase deficiency (MCAD);Malonic Aciduria;Leigh Syndrome;Pyridoxine dependency with seizures;Saccharopinuria/Hyperlysinemia II;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency);Fatty acid Metabolism;Maple Syrup Urine Disease;Propanoate Metabolism;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Pyruvate Metabolism;Glutaric Aciduria Type I;Glutaric Aciduria Type I;Ethylmalonic Encephalopathy;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Mitochondrial Beta-Oxidation of Short Chain Saturated Fatty Acids;Succinyl CoA: 3-ketoacid CoA transferase deficiency;Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (SCHAD);Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Hyperlysinemia II or Saccharopinuria;Ketone Body Metabolism;Butyrate Metabolism;Beta-Ketothiolase Deficiency;Carnitine palmitoyl transferase deficiency (I);Fatty Acid Beta Oxidation;Synthesis and Degradation of Ketone Bodies;Tryptophan metabolism;ketogenesis;ketolysis;Butanoate metabolism;Metabolism of lipids;Citrate cycle;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Saturated fatty acids beta-oxidation;Metabolism;Lysine degradation;superpathway of cholesterol biosynthesis;Synthesis of Ketone Bodies;Utilization of Ketone Bodies;Ketone body metabolism;isoleucine degradation;Pyruvate metabolism;glutaryl-CoA degradation;Tryptophan degradation;mevalonate pathway;superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) (Consensus)

Recessive Scores

• pRec: 0.480

Intolerance Scores

• loftool: 0.301
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.333
• hipred: N
• hipred_score: 0.285
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acat1

Gene ontology

• Biological process: liver development;acetyl-CoA biosynthetic process;isoleucine catabolic process;fatty acid beta-oxidation;brain development;branched-chain amino acid catabolic process;response to hormone;response to organic cyclic compound;coenzyme A metabolic process;coenzyme A biosynthetic process;response to starvation;acetyl-CoA catabolic process;ketone body biosynthetic process;ketone body catabolic process;protein homooligomerization;adipose tissue development;metanephric proximal convoluted tubule development;ketone body metabolic process;propionyl-CoA biosynthetic process
• Cellular component: mitochondrion;mitochondrial matrix;extracellular exosome
• Molecular function: acetyl-CoA C-acetyltransferase activity;acetyl-CoA C-acyltransferase activity;carbon-carbon lyase activity;ligase activity, forming carbon-carbon bonds;enzyme binding;protein homodimerization activity;metal ion binding;coenzyme binding