HIBCH

Chr 2AR

3-hydroxyisobutyryl-CoA hydrolase

Also known as: HIBYLCOAH

This gene encodes the enzyme responsible for hydrolysis of both HIBYL-CoA and beta-hydroxypropionyl-CoA. Mutations in this gene have been associated with 3-hyroxyisobutyryl-CoA hydrolase deficiency. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 1.191 OMIM phenotype
Clinical SummaryHIBCH
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 92 VUS of 293 total submissions
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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

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.19LOEUF
pLI 0.000
Z-score 0.81
OE 0.83 (0.591.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.29Z-score
OE missense 0.94 (0.831.06)
188 obs / 199.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.83 (0.591.19)
00.351.4
Missense OE?0.94 (0.831.06)
00.61.4
Synonymous OE?0.93
01.21.6
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

This gene — mechanism propensity

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

293 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic34
VUS92
Likely Benign93
Benign33
Conflicting11
10
Pathogenic
34
Likely Pathogenic
92
VUS
93
Likely Benign
33
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
3
0
10
Likely Pathogenic
16
16
2
0
34
VUS
3
80
4
5
92
Likely Benign
0
5
57
31
93
Benign
0
4
29
0
33
Conflicting
11
Total251069536273

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap HIBCH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HIBCH · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →