IDUA

Chr 4AR

alpha-L-iduronidase

Also known as: IDA, MPS1, MPSI

NCBI Gene: 3425 ENSG00000127415 UniProt: P35475 OMIM: 252800

The encoded enzyme hydrolyzes terminal alpha-L-iduronic acid residues from dermatan sulfate and heparan sulfate, enabling lysosomal degradation of these glycosaminoglycans. Mutations cause autosomal recessive mucopolysaccharidosis type I (MPS I), which presents as a spectrum including severe Hurler syndrome (MPS Ih), intermediate Hurler-Scheie syndrome (MPS Ih/s), and mild Scheie syndrome (MPS Is). Enzymatic deficiency results in lysosomal accumulation of undegraded glycosaminoglycans, leading to progressive multisystem disease.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mucopolysaccharidosis IhMIM #607014

Mucopolysaccharidosis Ih/sMIM #607015

Mucopolysaccharidosis IsMIM #607016

Clinical highlights

Gene-disease validity (ClinGen)

mucopolysaccharidosis type 1 · 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.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — IDUA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — IDUA

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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 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

Mucopolysaccharidosis I

Long Term Follow-Up for RGX-111

ENROLLING BY INVITATION

NCT06103487REGENXBIO Inc.Started 2023-07-24

No Intervention

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 LVV, encoding for the α-L-iduronidase cDNA, in their final formulation medium.

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system

Kim S et al.·Mol Genet Metab Rep

2022

Quantification of Idua Enzymatic Activity Combined with Observation of Phenotypic Change in Zebrafish Embryos Provide a Preliminary Assessment of Mutated idua Correlated with Mucopolysaccharidosis Type I

Lin CY et al.·J Pers Med

2022Functional

Intra-Articular AAV9 alpha-l-Iduronidase Gene Replacement in the Canine Model of Mucopolysaccharidosis Type I

Wang RY et al.·Adv Cell Gene Ther

2023Functional

Improving yield of a recombinant biologic in a Brassica hairy root manufacturing process

Gutierrez-Valdes N et al.·Biotechnol Bioeng

2022

Functional assessment of IDUA variants of uncertain significance identified by newborn screening

Yu SH et al.·NPJ Genom Med

2024Functional

Top 5 full-text resultsSearch PubTator3 ↗

Key Publications

Landmark & review papers · by relevance

PubMed

Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome.

Gentner B et al.·N Engl J Med

2021Clinical trial

Newborn screening in mucopolysaccharidoses.

Donati MA et al.·Ital J Pediatr

2018Review

Identification of incompletely penetrant variants and interallelic interactions in autosomal recessive disorders by a population-genetic approach.

Mikó Á et al.·Hum Mutat

2021

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

Top 5 results · since 2015Search PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Variant classification for mucopolysaccharidosis type I; ACMG/AMP specification for IDUA from the ClinGen lysosomal diseases variant curation expert panel.

Lacaria M et al.·Mol Genet Metab

2026

Homozygous R383H variant in IDUA gene causing pericentric retinitis pigmentosa in attenuated mucopolysaccharidosis type I.

Chattannavar G et al.·Ophthalmic Genet

2026

Case Report: Compound heterozygous mutations in the IDUA gene causing mucopolysaccharidosis type I with uterine developmental abnormality.

Xu Y et al.·Front Pediatr

2026Open AccessCase report

Reclassifying IDUA c.250G>A (p.Gly84Ser): Evidence for a Possible Pseudodeficiency Allele.

Connolly C et al.·Int J Neonatal Screen

2025Open 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

2025Open AccessCohort

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

IDUA

Primary Disease Associations & Inheritance

Clinical highlights

Population Genetics & Constraint

ClinVar Variant Classifications

Protein Context — Lollipop Plot

Tissue Expression

Transcripts & Isoforms

Transcript architecture

DECIPHER · Gene2Phenotype

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Clinical Trials

External Resources

Transcripts & Isoforms