HIBADH

Chr 7

3-hydroxyisobutyrate dehydrogenase

Also known as: NS5ATP1

NCBI Gene: 11112ENSG00000106049UniProt: P31937

This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]

76
ClinVar variants
26
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— HIBADH
🧬
Gene-Disease Validity (ClinGen)
3-hydroxyisobutyric aciduria · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 48 VUS of 76 total submissions
Some data sources returned errors (2)

clinvar: TypeError: fetch failed

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.006
Z-score 2.02
OE 0.42 (0.23–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.13Z-score
OE missense 0.97 (0.86–1.10)
167 obs / 171.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.23–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.86–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 6 / 14.2Missense obs/exp: 167 / 171.8Syn Z: -0.50

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic3
VUS48
Likely Benign2
23
Pathogenic
3
Likely Pathogenic
48
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
3
0
3
VUS
1
42
5
0
48
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total14431076

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

View in ClinVar →

Protein Context — Lollipop Plot

HIBADH · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lnc-HIBADH-4 Regulates Autophagy-Lysosome Pathway in Amyotrophic Lateral Sclerosis by Targeting Cathepsin D.
Huang J et al.·Mol Neurobiol
2024
Shared genetic correlations between kidney diseases and sepsis.
Zhang T et al.·Front Endocrinol (Lausanne)
2024Meta-analysis
3-Hydroxyisobutyric acid dehydrogenase deficiency: Expanding the clinical spectrum and quantitation of D- and L-3-Hydroxyisobutyric acid by an LC-MS/MS method.
Sasarman F et al.·J Inherit Metab Dis
2022
Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition.
Xu G et al.·J Proteome Res
2023
3-Hydroxyisobutyrate dehydrogenase (HIBADH) deficiency-A novel disorder of valine metabolism.
Meyer M et al.·J Inherit Metab Dis
2021Case report
Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria.
Loupatty FJ et al.·Mol Genet Metab
2006Case report
Effect of endurance exercise on microRNAs in myositis skeletal muscle-A randomized controlled study.
Boehler JF et al.·PLoS One
2017
HOXA genes cluster: clinical implications of the smallest deletion.
Pezzani L et al.·Ital J Pediatr
2015Case report
Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia.
Curtis D et al.·Ann Hum Genet
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools