IDUA

Chr 4AR

alpha-L-iduronidase

NCBI Gene: 3425ENSG00000127415UniProt: P35475

Primary Disease Associations & Inheritance

Mucopolysaccharidosis IhMIM #607014
AR
Mucopolysaccharidosis Ih/sMIM #607015
AR
Mucopolysaccharidosis IsMIM #607016
AR
582
ClinVar variants
118
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— IDUA
🧬
Gene-Disease Validity (ClinGen)
mucopolysaccharidosis 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
118 Pathogenic / Likely Pathogenic· 279 VUS of 582 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

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.
1.17LOEUF
pLI 0.000
Z-score 0.88
OE 0.82 (0.58–1.17)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.60Z-score
OE missense 1.09 (1.00–1.19)
373 obs / 341.9 exp
Tolerant

Tolerant to missense variation

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.0.82 (0.58–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (1.00–1.19)
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.1.27
0≤1.21.6
LoF obs/exp: 22 / 26.9Missense obs/exp: 373 / 341.9Syn Z: -2.69

ClinVar Variant Classifications

582 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic65
VUS279
Likely Benign175
Benign2
Conflicting8
53
Pathogenic
65
Likely Pathogenic
279
VUS
175
Likely Benign
2
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
4
32
0
53
Likely Pathogenic
33
18
14
0
65
VUS
6
243
19
11
279
Likely Benign
0
4
70
101
175
Benign
0
0
2
0
2
Conflicting
—8
Total56269137112582

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

View in ClinVar →

Protein Context — Lollipop Plot

IDUA · protein map & ClinVar variants

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

Gene2Phenotype Curations

IDUA-related mucopolysaccharidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mucopolysaccharidosis Ih

MIM #607014

Molecular basis of disorder known

Autosomal recessive

Mucopolysaccharidosis Ih/s

MIM #607015

Molecular basis of disorder known

Autosomal recessive

Mucopolysaccharidosis Is

MIM #607016

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — IDUA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Worldwide distribution of common IDUA pathogenic variants.
Poletto E et al.·Clin Genet
2018Review
Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome.
Gentner B et al.·N Engl J Med
2021Clinical trial
Mucopolysaccharidosis type I.
Wraith JE et al.·Pediatr Endocrinol Rev
2014Review
Newborn screening in mucopolysaccharidoses.
Donati MA et al.·Ital J Pediatr
2018Review
Circulating ECM proteins decorin and alpha-L-iduronidase differentiate ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF.
Tubben A et al.·Cardiovasc Res
2024
Open issues in Mucopolysaccharidosis type I-Hurler.
Parini R et al.·Orphanet J Rare Dis
2017Review
Mucopolysaccharidoses type I gene therapy.
Hurt SC et al.·J Inherit Metab Dis
2021Review
Clinical applications of and molecular insights from RNA sequencing in a rare disease cohort.
Stark JC et al.·Genome Med
2025Cohort
Identification of an α-l-iduronidase (IDUA) M1T mutation in a Chinese family with autosomal recessive mucopolysaccharidosis I.
Liu D et al.·Ann N Y Acad Sci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Reclassifying IDUA c.250G>A (p.Gly84Ser): Evidence for a Possible Pseudodeficiency Allele.
Connolly C et al.·Int J Neonatal Screen
2025🔓 Open Access
Congenital Dermal Melanocytosis Exhibited in Two Patients with Hurler Syndrome: Clinical Characterization and Report of a Recurrent IDUA Allele in Colombia.
Vanegas S et al.·Int J Mol Sci
2025🔓 Open AccessCohort
Prognostic Modeling of Deleterious IDUA Mutations L238Q and P385R in Hurler Syndrome Through Molecular Dynamics Simulations.
Priya Nanda Kumar M et al.·Pharmaceuticals (Basel)
2025🔓 Open AccessFunctional
Combining clinically benign IDUA variants in cis reduces enzymatic activity of the resulting enzyme within the pathogenic range.
Yu SH et al.·Mol Genet Metab
2025
Genetic variations in the IDUA gene in Tunisian MPS I families: Identification of a novel microdeletion disrupting substrate binding and structural insights.
Rebai M et al.·Mol Genet Metab Rep
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Mucopolysaccharidosis IH

Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant

ACTIVE NOT RECRUITING
NCT03488394Phase PHASE1, PHASE2Orchard TherapeuticsStarted 2018-05-11
Frozen autologous CD34+ hematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LV, encoding for the α-L-iduronidase cDNA, in their final formulation medium.
MPS-IH (Hurler Syndrome)

A Study to Investigate the Efficacy and Safety of OTL-203 in Subjects With MPS-IH Compared With Standard of Care With Allogeneic HSCT

ACTIVE NOT RECRUITING
NCT06149403Phase PHASE3Orchard TherapeuticsStarted 2023-12-11
Experimental: OTL-203Active Comparator: Allo-HSCT
Mucopolysaccharidosis I

Long Term Follow-Up for RGX-111

ENROLLING BY INVITATION
NCT06103487REGENXBIO Inc.Started 2023-07-24
No Intervention
Mucopolysaccharidosis Type I

A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of JWK008 in Patients With Mucopolysaccharidosis Type I

RECRUITING
NCT06519552Phase PHASE1West China HospitalStarted 2024-07-22
JWK008 Single intravenous infusion administration

External Resources

Links to major genomics databases and tools