IVD

Chr 15AR

isovaleryl-CoA dehydrogenase

Also known as: ACAD2, IVDH

Isovaleryl-CoA dehydrogenase catalyzes the third step in leucine catabolism within the mitochondrial matrix. Mutations cause isovaleric acidemia, an autosomal recessive disorder characterized by accumulation of toxic isovaleric acid that damages the central nervous system. The pathogenic mechanism involves loss of enzyme function leading to substrate accumulation and metabolic toxicity.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.351 OMIM phenotype
Clinical SummaryIVD
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Gene-Disease Validity (ClinGen)
isovaleric acidemia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — IVD
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
1.35LOEUF
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 OE0.95 (0.681.35)
00.351.4
Missense OE0.94 (0.841.04)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 22 / 23.3Missense obs/exp: 231 / 246.4Syn Z: 0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveIVD-related isovaleric acidemiaLOFAR

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

DN
0.7326th %ile
GOF
0.6737th %ile
LOF
0.3647th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IVD · 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

T-Cell Lymphoproliferative Disorder

Pivotal, Clinical Study for the Accuracy Evaluation of the IdentiClone Dx TRG Assay

NOT YET RECRUITING
NCT06876571Invivoscribe, Inc.Started 2025-06-02
IdentiClone Dx TRG Assay
COVID-19

Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.

ACTIVE NOT RECRUITING
NCT05515042Phase PHASE2The Aurum Institute NPCStarted 2022-07-25
Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)
Metastatic Colorectal Cancer (mCRC)

DHF-20-1839-2: Clinical Performance Study Protocol for Therascreen® KRAS RGQ PCR Kit

RECRUITING
NCT06645236Phase NAQIAGEN Gaithersburg, IncStarted 2023-12-22
therascreen® KRAS RGQ PCR Kit
Breast Cancer

Precision Oncology Clinical Diagnostic Study In Primary and Metastatic Breast Cancer (PRISM)

RECRUITING
NCT07425002Phase NACancer Trials IrelandStarted 2025-11-11
TSO500 Assay
Solid Tumor, AdultColorectal CancerNon-Small Cell Lung

A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression

RECRUITING
NCT06682793Phase PHASE1, PHASE2A2 Biotherapeutics Inc.Started 2025-05-22
A2B395xT CDx with HLA-LOH assay
Carcinoma, Non-small Cell Lung Cancer (NSCLC)

Next Generation Sequencing Method for the Detection of EGFR Gene Mutations in the Plasma of Patients With Lung Cancer

ACTIVE NOT RECRUITING
NCT06595498Phase NAIstituto Oncologico Veneto IRCCSStarted 2024-07-01
Plasma- SeqSensei™ Solid Cancer IVD Kit (Sysmex)cobas® EGFR Mutation Test v2 (Roche)
Solid Tumor, AdultColorectal CancerNSCLC

A Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Logic-gated CAR T, in Participants With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

RECRUITING
NCT06051695Phase PHASE1, PHASE2A2 Biotherapeutics Inc.Started 2024-04-03
A2B694A2B543xT CDx with HLA-LOH Assay
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
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