IVD

Chr 15

isovaleryl-CoA dehydrogenase

A mitochondrial matrix enzyme that catalyzes the third step in leucine catabolism, where isovaleryl-CoA (3-methylbutanoyl-CoA) is metabolized to 3-methylbut-2-enoyl-CoA (PubMed:7640268). To a lesser extent, it also participates in the first step in fatty acid beta-oxidation, in which it catalyzes the proR-proR stereospecific alpha,beta-dehydrogenation of other saturated short-chain acyl-CoA thioesters such as pentanoyl-CoA, hexanoyl-CoA and butanoyl-CoA, using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor(PubMed:7640268)

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIsovaleric acidemia

Clinical highlights

Gene-disease validity (ClinGen)
isovaleric acidemia · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
6
Active trials
693
Pubs (1 yr)
P/LP submissions
P/LP missense
1.35
LOEUF
LOF
Mechanism· G2P
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GeneReview available — IVD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.35LOEUF
pLI 0.000
Z-score 0.24
OE 0.95 (0.681.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.35Z-score
OE missense 0.94 (0.841.04)
231 obs / 246.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.95 (0.681.35)
00.351.4
Missense OE?0.94 (0.841.04)
00.61.4
Synonymous OE?0.97
01.21.6
LoF obs/exp: 22 / 23.3Missense obs/exp: 231 / 246.4Syn Z: 0.22

ClinVar

No ClinVar data available.

Protein Context — Lollipop Plot

IVD · 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