IDUA

Chr 4AR

alpha-L-iduronidase

Also known as: IDA, MPS1, MPSI

NCBI Gene: 3425ENSG00000127415UniProt: P35475OMIM: 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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.173 OMIM phenotypes
Clinical Summary— IDUA
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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.
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ClinVar Variants
92 unique Pathogenic / Likely Pathogenic· 167 VUS of 500 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — IDUA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
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
-0.60Z-score
OE missense 1.09 (1.00–1.19)
373 obs / 341.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.82 (0.58–1.17)
0≤0.351.4
Missense OE1.09 (1.00–1.19)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 22 / 26.9Missense obs/exp: 373 / 341.9Syn Z: -2.69

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic52
VUS167
Likely Benign204
Benign8
Conflicting11
40
Pathogenic
52
Likely Pathogenic
167
VUS
204
Likely Benign
8
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
4
13
0
40
Likely Pathogenic
32
17
3
0
52
VUS
4
142
10
11
167
Likely Benign
0
9
42
153
204
Benign
0
3
1
4
8
Conflicting
—11
Total5917569168482

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Compound heterozygous mutations in the IDUA gene causing mucopolysaccharidosis type I with uterine developmental abnormality.
Xu Y et al.·Front Pediatr
2026Case 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
Prognostic Modeling of Deleterious IDUA Mutations L238Q and P385R in Hurler Syndrome Through Molecular Dynamics Simulations.
Priya Nanda Kumar M et al.·Pharmaceuticals (Basel)
2025Open 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
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