HIBCH

Chr 2AR

3-hydroxyisobutyryl-CoA hydrolase

Also known as: HIBYLCOAH

NCBI Gene: 26275ENSG00000198130UniProt: Q6NVY1OMIM: 610690

The protein functions as a mitochondrial enzyme that hydrolyzes both 3-hydroxyisobutyryl-CoA and beta-hydroxypropionyl-CoA in the valine catabolic pathway. Mutations cause 3-hydroxyisobutyryl-CoA hydrolase deficiency, an autosomal recessive disorder of branched-chain amino acid metabolism. Disease results from loss of enzyme function leading to accumulation of toxic metabolites.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.191 OMIM phenotype
Clinical Summary— HIBCH
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 83 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — HIBCH
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.000
Z-score 0.81
OE 0.83 (0.59–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.29Z-score
OE missense 0.94 (0.83–1.06)
188 obs / 199.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.83 (0.59–1.19)
0≤0.351.4
Missense OE0.94 (0.83–1.06)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 22 / 26.5Missense obs/exp: 188 / 199.7Syn Z: 0.46
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHIBCH-related 3-hydroxyisobutryl-CoA hydrolase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7227th %ile
GOF
0.5367th %ile
LOF
0.2872th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic19
VUS83
Likely Benign63
Benign2
Conflicting3
10
Pathogenic
19
Likely Pathogenic
83
VUS
63
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
8
0
10
Likely Pathogenic
10
7
2
0
19
VUS
3
69
6
5
83
Likely Benign
0
3
37
23
63
Benign
0
0
2
0
2
Conflicting
—3
Total15795528180

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HIBCH · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients