HIBCH

3-hydroxyisobutyryl-CoA hydrolase

Basic information

Region (hg38): 2:190189734-190344193

Links

ENSG00000198130 ∙ NCBI:26275 ∙ OMIM:610690 ∙ HGNC:4908 ∙ Uniprot:Q6NVY1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-hydroxyisobutyryl-CoA hydrolase deficiency (Definitive), mode of inheritance: AR
• 3-hydroxyisobutyryl-CoA hydrolase deficiency (Strong), mode of inheritance: AR
• 3-hydroxyisobutyryl-CoA hydrolase deficiency (Strong), mode of inheritance: AR
• 3-hydroxyisobutyryl-CoA hydrolase deficiency (Strong), mode of inheritance: AR
• 3-hydroxyisobutyryl-CoA hydrolase deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR
• 3-hydroxyisobutyryl-CoA hydrolase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-hydroxyisobutryl-CoA hydrolase deficiency	AR	Biochemical	Dietary measures (eg, low-protein, high carbohydrate) especially in ketosis, as well as medical treatment (eg, carnitine) may be beneficial)	Biochemical;Neurologic	7122152; 17160907; 24299452; 26026795; 26163321

ClinVar

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

• Beta-hydroxyisobutyryl-CoA deacylase deficiency (133 variants)
• not provided (63 variants)
• not specified (21 variants)
• Inborn genetic diseases (15 variants)
• See cases (5 variants)
• HIBCH-related condition (1 variants)
• Neurodegeneration due to 3-hydroxyisobutyryl coenzyme A hydrolase deficiency (1 variants)
• Mitochondrial disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIBCH 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			4	17		21
missense		11	57		3	71
nonsense	4	2				6
start loss					1	1
frameshift		4	1			5
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	1	7	1			9
splice region			5	6		11
non coding				39	28	67
Total	5	25	64	56	32

Highest pathogenic variant AF is 0.0000526

Variants in HIBCH

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

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

Position	Type	Phenotype	Significance	ClinVar
2-190199998-G-C		not specified	Uncertain significance (Oct 29, 2021)
2-190204963-T-A			Benign (Jun 29, 2018)
2-190205025-G-C			Likely benign (May 12, 2021)
2-190205114-A-G		not specified	Likely benign (Mar 22, 2016)
2-190205129-A-G		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Likely benign (Feb 07, 2023)
2-190205139-C-T		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Uncertain significance (Feb 21, 2022)
2-190205145-G-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
2-190205149-TA-T		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Uncertain significance (Oct 13, 2022)
2-190205149-T-TA		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Likely pathogenic (Jul 11, 2022)
2-190205155-GATT-G			Likely pathogenic (Mar 03, 2017)
2-190205160-T-C		See cases	Uncertain significance (-)
2-190205175-G-A		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Uncertain significance (Aug 22, 2022)
2-190205194-C-T		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Uncertain significance (Jul 01, 2022)
2-190205225-A-C		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Uncertain significance (Jan 06, 2022)
2-190205230-A-G		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Likely benign (Nov 19, 2023)
2-190205240-G-A		not specified	Likely benign (Apr 28, 2016)
2-190205356-A-T			Likely benign (May 12, 2021)
2-190208668-A-AT			Benign (May 13, 2021)
2-190208668-A-ATT			Benign (May 13, 2021)
2-190208668-A-ATTT			Benign (May 21, 2021)
2-190208668-A-ATTTT			Benign (May 18, 2021)
2-190208739-T-C			Benign (Jun 03, 2021)
2-190208775-T-G			Benign (Jun 29, 2018)
2-190208880-C-G		Beta-hydroxyisobutyryl-CoA deacylase deficiency	Uncertain significance (Jun 05, 2022)
2-190208887-A-T		not specified • Beta-hydroxyisobutyryl-CoA deacylase deficiency • HIBCH-related disorder	Benign/Likely benign (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIBCH	protein_coding	protein_coding	ENST00000359678	14	154459

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.58e-13	0.131	125692	0	53	125745	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.293	188	200	0.942	0.00000934	2535
Missense in Polyphen		48	61.907	0.77536		746
Synonymous	0.463	62	66.8	0.928	0.00000323	693
Loss of Function	0.808	22	26.5	0.831	0.00000135	313

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000553	0.000550
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000109	0.000109
South Asian	0.000327	0.000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA. {ECO:0000269|PubMed:8824301}.
• Pathway: beta-Alanine metabolism - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Malonyl-coa decarboxylase deficiency;Malonic Aciduria;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;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;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Beta-Ketothiolase Deficiency;Amino Acid metabolism;Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Metabolism;valine degradation;Valine, leucine and isoleucine degradation;Propanoate metabolism (Consensus)

Recessive Scores

• pRec: 0.180

Intolerance Scores

• loftool: 0.955
• rvis_EVS: 0.75
• rvis_percentile_EVS: 86.57

Haploinsufficiency Scores

• pHI: 0.0949
• hipred: N
• hipred_score: 0.251
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hibch

Gene ontology

• Biological process: valine catabolic process;fatty acid beta-oxidation;branched-chain amino acid catabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: 3-hydroxyisobutyryl-CoA hydrolase activity