HIBCH

3-hydroxyisobutyryl-CoA hydrolase

Basic information

Region (hg38): 2:190189735-190344193

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.

• 3-hydroxyisobutyryl-CoA_hydrolase_deficiency (162 variants)
• not_provided (46 variants)
• Inborn_genetic_diseases (40 variants)
• not_specified (15 variants)
• HIBCH-related_disorder (6 variants)
• See_cases (5 variants)
• Mitochondrial_disease (1 variants)
• Neurodegeneration_due_to_3-hydroxyisobutyryl_coenzyme_A_hydrolase_deficiency (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. These statistics are base on transcript: NM_000014362.4. 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			5	28		33
missense	2	17	71	8	2	100
nonsense	5	2	1			8
start loss						0
frameshift		7	1			8
splice donor/acceptor (+/-2bp)	1	8	1			10
Total	8	34	79	36	2

Highest pathogenic variant AF is 0.0000317155

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