HIBCH: 3-Hydroxyisobutyryl-CoA Hydrolase
Mitochondrial enzyme in valine catabolism and potential biomarker for HIBCH deficiency
Gene Information Card
| Symbol | HIBCH |
|---|---|
| Full Name | 3-Hydroxyisobutyryl-CoA Hydrolase |
| Gene Type | Protein coding |
| Chromosomal Location | 2q32.2 |
| NCBI Gene ID | 26275 ncbi.nlm.nih.gov/gene/26275 |
| Ensembl ID | ENSG00000163026 |
| UniProt ID | Q6NVY1 |
| OMIM ID | 610690 |
| HGNC ID | 4908 |
| Aliases | HIBYL-CoA-H, HIBCOAH |
Description
HIBCH encodes the mitochondrial enzyme 3-hydroxyisobutyryl-CoA hydrolase, which catalyzes the hydrolysis of 3-hydroxyisobutyryl-CoA to 3-hydroxyisobutyrate and CoA in the valine catabolic pathway. Deficiency of HIBCH leads to accumulation of toxic metabolites, causing a rare autosomal recessive neurometabolic disorder characterized by progressive neurodegeneration, basal ganglia lesions, and developmental regression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIBCH deficiency (3-hydroxyisobutyryl-CoA hydrolase deficiency) | Loss-of-function mutations impair valine catabolism, leading to accumulation of 3-hydroxyisobutyryl-CoA and methacrylyl-CoA, causing mitochondrial toxicity and neurodegeneration. | OMIM #250620; ClinVar; multiple case reports (PubMed) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 9.8 | Medium |
| Heart | 7.5 | Medium |
| Brain | 5.2 | Low |
| Skeletal Muscle | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Hepatocellular carcinoma cell line |
| HEK293 | 6.4 | Embryonic kidney cells |
| SH-SY5Y | 3.8 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.302G>A (p.Arg101Gln) | Missense | Rare | Reduced enzyme activity; associated with HIBCH deficiency |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein; severe phenotype |
| c.424C>T (p.Arg142*) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported HIBCH mutations are loss-of-function, leading to enzyme deficiency and valine catabolism block.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • 3-hydroxyisobutyryl-CoA hydrolase activity (GO:0003860) | • mitochondrion (GO:0005739) |
| • valine catabolic process (GO:0006574) | • identical protein binding (GO:0042802) |
Pathways
• Valine
• leucine and isoleucine degradation (KEGG: hsa00280)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
Protein Summary
HIBCH is a 386-amino acid mitochondrial hydrolase that catalyzes the penultimate step of valine catabolism. The enzyme forms a homodimer and requires CoA for activity. Deficiency results in accumulation of methacrylyl-CoA, which reacts with glutathione and causes mitochondrial dysfunction, particularly in the basal ganglia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HIBCH Knockout HEK293 Cell Line | EDJ-KQ8497 | Human | 26275 | Details Get a Quote |
| HIBCH Knockout HCT 116 Cell Line | EDJ-KQ33309 | Human | 26275 | Details Get a Quote |
| HIBCH Knockout A-549 Cell Line | EDJ-KQ34620 | Human | 26275 | Details Get a Quote |
| HIBCH Knockout HeLa Cell Line | EDJ-KQ34621 | Human | 26275 | Details Get a Quote |
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