IDUA

Chr 4

alpha-L-iduronidase

Also known as: IDA, MPS1, MPSI

NCBI Gene: 3425 ENSG00000127415 UniProt: P35475

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMucopolysaccharidosis 1H

UniProtMucopolysaccharidosis 1H/S

UniProtMucopolysaccharidosis 1S

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mucopolysaccharidosis type 1 · AR · ClinGen 2020

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)

—

P/LP submissions

—

P/LP missense

1.17

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.82 (0.58–1.17)

0≤0.351.4

Missense OE?1.09 (1.00–1.19)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 22 / 26.9Missense obs/exp: 373 / 341.9Syn Z: -2.69

Background carrier burden — how many people carry a rare variant somewhere in IDUA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 39

1,156 rare PASS variants

Rare truncating (LoF)

1 in 410

185 rare PASS variants

Rare synonymous (reference)

1 in 100

503 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IDUA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 63	1 in 420
South Asian	~43k	1 in 39	1 in 650
Remaining (unassigned)	~30k	1 in 35	1 in 740
European (Finnish)	~26k	1 in 140	1 in 670
Admixed American	~22k	1 in 43	1 in 370
African / African American	~21k	1 in 41	1 in 600
East Asian	~20k	1 in 62	1 in 360
Ashkenazi Jewish	~13k	1 in 170	1 in 2,100
Middle Eastern	~2,884	1 in 43	1 in 330

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.