Mucopolysaccharidosis: genes and variants

Genes linked to Mucopolysaccharidosis

• 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.

  80 disease-causing and 299 uncertain variants in IDUA are linked to Mucopolysaccharidosis.

• IDS: Iduronate 2-sulfatase

  It removes sulfate groups from iduronate-containing glycosaminoglycans during lysosomal degradation. Loss-of-function variants cause X-linked Hunter syndrome, with progressive accumulation of dermatan and heparan sulfate affecting multiple organs and, in severe disease, the nervous system.

  0 disease-causing and 0 uncertain variants in IDS are linked to Mucopolysaccharidosis.

Known disease-causing variants in Mucopolysaccharidosis

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Uncertain variants in Mucopolysaccharidosis that look disease-causing

Which prediction tools work for Mucopolysaccharidosis

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• SIFT: 89 out of 100
• CADD: 89 out of 100
• phyloP: 88 out of 100
• CATVariant: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Hurler syndrome is also caused by IDUA variants; they fall in the same places as the Mucopolysaccharidosis variants (16 disease-causing).

Diseases related to Mucopolysaccharidosis

• Mucopolysaccharidosis, MPS-II, also linked to IDS
• Familial hypokalemia-hypomagnesemia, also linked to IDUA
• Hurler syndrome, also linked to IDUA
• Mucopolysaccharidosis, MPS-I-S, also linked to IDUA
• Mucopolysaccharidosis, MPS-III-A, also linked to IDS
• Mucopolysaccharidosis, MPS-I-H/S, also linked to IDUA

Frequently asked questions

Which genes are linked to Mucopolysaccharidosis?

In CATVariant, Mucopolysaccharidosis is linked to 2 analyzed proteins: IDUA (Alpha-L-iduronidase) and IDS (Iduronate 2-sulfatase).

How many genetic variants are linked to Mucopolysaccharidosis?

528 variants: 80 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 299 are of uncertain significance or have conflicting reports.

Which uncertain variants in Mucopolysaccharidosis look disease-causing?

14 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example IDUA T179A, IDUA R383C, IDUA P302T, IDUA T364A and IDUA N348D. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Mucopolysaccharidosis?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.89, based on 70 disease-causing and 64 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.

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