Hurler syndrome: genes and variants
Hurler syndrome is linked to 1 analyzed protein (IDUA). 16 DNA variants are known to cause it; 25 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Hurler syndrome
IDUA: Alpha-L-iduronidase
It removes terminal alpha-L-iduronic acid residues during lysosomal degradation of dermatan and heparan sulfate. Biallelic loss-of-function variants cause mucopolysaccharidosis type I, spanning severe Hurler syndrome to attenuated Scheie-spectrum disease.
16 disease-causing and 25 uncertain variants in IDUA are linked to Hurler syndrome.
Known disease-causing variants in Hurler syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| IDUA E178K | 178 | Disease-causing (★★) | |
| IDUA D349Y | 349 | Disease-causing (★★) | |
| IDUA R489P | 489 | Disease-causing (★★) | |
| IDUA R492P | 492 | Disease-causing (★★) | |
| IDUA A319E | 319 | Disease-causing (★★) | |
| IDUA L490P | 490 | Disease-causing (★★) | |
| IDUA A327P | 327 | Disease-causing (★★) | |
| IDUA S423R | 423 | Disease-causing (★★) | |
| IDUA R621P | 621 | Disease-causing (★★) | |
| IDUA L623P | 623 | Disease-causing (★★) | |
| IDUA R89W | 89 | Disease-causing (★★) | |
| IDUA G630D | 630 | Disease-causing (★) | |
| IDUA F177C | 177 | Disease-causing (★) | |
| IDUA L121P | 121 | Disease-causing | |
| IDUA T366P | 366 | Disease-causing | |
| IDUA G409R | 409 | Disease-causing |
Which prediction tools work for Hurler syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 86 out of 100
- PolyPhen-2: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 80 out of 100
- phyloP: 72 out of 100
Same protein, different disease
- Mucopolysaccharidosis is also caused by IDUA variants; they fall mostly in different places as the Hurler syndrome variants (80 disease-causing).
Diseases related to Hurler syndrome
- Familial hypokalemia-hypomagnesemia, also linked to IDUA
- Mucopolysaccharidosis, also linked to IDUA
- Mucopolysaccharidosis, MPS-I-S, also linked to IDUA
- Mucopolysaccharidosis, MPS-I-H/S, also linked to IDUA
Frequently asked questions
Which genes are linked to Hurler syndrome?
In CATVariant, Hurler syndrome is linked to 1 analyzed protein: IDUA (Alpha-L-iduronidase).
How many genetic variants are linked to Hurler syndrome?
62 variants: 16 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 25 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hurler syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Hurler syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.86, based on 11 disease-causing and 18 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center