AUH

Chr 9AR

AU RNA binding methylglutaconyl-CoA hydratase

This gene encodes bifunctional mitochondrial protein that has both RNA-binding and hydratase activities. The encoded protein is a methylglutaconyl-CoA hydratase that catalyzes the hydration of 3-methylglutaconyl-CoA to 3-hydroxy-3-methyl-glutaryl-CoA, a critical step in the leucine degradation pathway. This protein also binds AU-rich elements (AREs) found in the 3' UTRs of rapidly decaying mRNAs including c-fos, c-myc and granulocyte/ macrophage colony stimulating factor. ARE elements are involved in directing RNA to rapid degradation and deadenylation. This protein is localizes to the mitochondrial matrix and the inner mitochondrial membrane and may be involved in mitochondrial protein synthesis. Mutations in this gene are the cause of 3-methylglutaconic aciduria, type I. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.961 OMIM phenotype
Clinical SummaryAUH
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Gene-Disease Validity (ClinGen)
3-methylglutaconic aciduria type 1 · 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.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 136 VUS of 293 total submissions
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.96LOEUF
pLI 0.000
Z-score 1.68
OE 0.58 (0.360.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.34Z-score
OE missense 0.93 (0.821.05)
169 obs / 182.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.58 (0.360.96)
00.351.4
Missense OE?0.93 (0.821.05)
00.61.4
Synonymous OE?0.97
01.21.6
LoF obs/exp: 11 / 18.9Missense obs/exp: 169 / 182.0Syn Z: 0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveAUH-related 3-methylglutaconic aciduriaLOFAR

This gene — mechanism propensity

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

DN
0.7133th %ile
GOF
0.6248th %ile
LOF
0.3162th %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

Pathogenic20
Likely Pathogenic16
VUS136
Likely Benign78
Benign19
Conflicting13
20
Pathogenic
16
Likely Pathogenic
136
VUS
78
Likely Benign
19
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
2
4
0
20
Likely Pathogenic
10
5
1
0
16
VUS
1
115
17
3
136
Likely Benign
0
2
39
37
78
Benign
0
1
17
1
19
Conflicting
13
Total251257841282

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap AUH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

AUH · 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

Hypercholesterolemia, Autosomal DominantHypercholesterolemia, Autosomal RecessiveFamilial Combined Hypercholesterolemia

Integrating Whole Genome Sequencing and Digital Twins Into the Management of Hypercholesterolemia in Emiratis

RECRUITING
NCT06535542Phase NAAbu Dhabi Health Services CompanyStarted 2024-07-29
Whole Genome Sequencing
Safety and Impact of Medically Supervised Performance Enhancing Substance Usage in Healthy Elite Athletes

Impact of Medically Supervised Performance-Enhancing Substances (PES) on Elite Athletes

ENROLLING BY INVITATION
NCT07568574Phase NAEnhanced Emirates LimitedStarted 2026-03-12
Testosterone EnanthateTestosterone CypionateTestosterone Propionate
Acute Myeloid Leukemia

Ivosidenib and Azacitidine With or Without Venetoclax in Adult Patients With Newly Diagnosed IDH1-Mutated AML or MDS/AML Considered Ineligible for Intensive Chemotherapy

RECRUITING
NCT07075016Phase PHASE3Stichting Hemato-Oncologie voor Volwassenen NederlandStarted 2025-08-05
Venetoclax 400Placebo
HematologyDiffused Large B Cell Lymphoma

A Multicenter Observational Study to Understand the Clinical Characteristics, Treatment Patterns and Access to Novel Therapies of Patients With Diffuse Large B-Cell Lymphoma in the MEA Region

RECRUITING
NCT07065344AstraZenecaStarted 2025-07-23
Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)

ACTIVE NOT RECRUITING
NCT05456191Phase PHASE3Novartis PharmaceuticalsStarted 2022-11-21
AsciminibNilotinib
Male InfertilityMale Subfertility

Assessing the Correlation Between Phospholipase C Zeta Measurements and Semen Parameters

RECRUITING
NCT07684339Fakih IVF Fertility CenterStarted 2026-07-01
No Intervention: Observational Cohort
HealthyHealthy Nutrition

The BEGIN Study Bifidobacterium Infantis to Newborns: Effects of Modulating the Gut Microbial Composition on Growth, Immune Function and Inflammatory Conditions - a Randomized Placebo-controlled Double-blinded Intervention Trial

RECRUITING
NCT06452199Phase NAUniversity of AarhusStarted 2024-06-10
B. infantisPlacebo