IDUA Gene (Alpha-L-Iduronidase): Function, Mutations, and Associated Diseases
Comprehensive biomedical overview of the IDUA gene, including genomic context, protein function, disease associations, expression data, and mutation landscape.
Gene Information Card
| Symbol | IDUA |
|---|---|
| Full Name | Alpha-L-Iduronidase |
| Gene Type | Protein coding |
| Chromosomal Location | 4p16.3 |
| NCBI Gene ID | 3425 ncbi.nlm.nih.gov/gene/3425 |
| Ensembl ID | ENSG00000127415 |
| UniProt ID | P35475 |
| OMIM ID | 252800 |
| HGNC ID | 5391 |
| Aliases | MPS1, IDA, alpha-L-iduronidase |
Description
The IDUA gene encodes alpha-L-iduronidase, a lysosomal enzyme that catalyzes the hydrolysis of terminal alpha-L-iduronic acid residues in dermatan sulfate and heparan sulfate. This enzyme is essential for the degradation of glycosaminoglycans (GAGs). Mutations in IDUA lead to deficiency of the enzyme, causing mucopolysaccharidosis type I (MPS I), an autosomal recessive lysosomal storage disorder. The clinical spectrum ranges from severe (Hurler syndrome) to attenuated (Scheie syndrome) forms, depending on residual enzyme activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucopolysaccharidosis type I (MPS I) | Loss-of-function mutations in IDUA result in deficient alpha-L-iduronidase activity, leading to accumulation of dermatan sulfate and heparan sulfate in lysosomes, causing cellular and tissue damage. | OMIM 252800; ClinVar; multiple publications |
| Hurler syndrome (severe MPS I) | Severe or complete loss of enzyme activity due to homozygous or compound heterozygous mutations (e.g., W402X, Q70X) leading to early-onset progressive multisystem involvement. | OMIM 607014; ClinVar; literature |
| Hurler-Scheie syndrome (intermediate MPS I) | Partial enzyme deficiency due to missense mutations (e.g., P533R) resulting in milder but still progressive phenotype. | OMIM 607015; ClinVar |
| Scheie syndrome (attenuated MPS I) | Milder mutations (e.g., R89Q) retain some enzyme activity, leading to later onset and less severe symptoms. | OMIM 607016; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.4 | Medium |
| Kidney | 8.7 | Low |
| Lung | 7.9 | Low |
| Spleen | 6.5 | Low |
| Brain | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| A549 | 9.8 | Lung carcinoma cell line; moderate expression |
| MCF7 | 7.1 | Breast cancer cell line; low expression |
| K562 | 5.3 | Chronic myelogenous leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| W402X | Nonsense | Common in severe MPS I (allelic frequency ~20% in some populations) | Truncated protein, complete loss of enzyme activity |
| Q70X | Nonsense | Common in severe MPS I (allelic frequency ~10%) | Truncated protein, complete loss of enzyme activity |
| P533R | Missense | Associated with intermediate phenotype | Reduced enzyme activity, protein misfolding |
| R89Q | Missense | Associated with attenuated phenotype | Partial enzyme activity retained |
Mutation functional classification
Loss of Function (LOF)
Most IDUA mutations are loss-of-function, leading to reduced or absent enzyme activity. This is the primary mechanism for MPS I.
Gain of Function (GOF)
No gain-of-function mutations have been reported for IDUA.
Dominant Negative (DN)
IDUA is not known to have dominant-negative effects; the disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • alpha-L-iduronidase activity | • hydrolase activity |
| • glycosaminoglycan binding | • lysosome |
| • extracellular region | • carbohydrate metabolic process |
| • glycosaminoglycan catabolic process |
Pathways
• Glycosaminoglycan degradation
• Lysosome
• Metabolism of glycosaminoglycans
Protein Summary
Alpha-L-iduronidase is a 653-amino acid glycoprotein localized to lysosomes. It is synthesized as a preproenzyme and processed to a mature form. The enzyme cleaves terminal alpha-L-iduronic acid residues from dermatan sulfate and heparan sulfate. Deficiency leads to lysosomal accumulation of these GAGs, causing cellular dysfunction and clinical manifestations. Enzyme replacement therapy (laronidase) and hematopoietic stem cell transplantation are treatment options for MPS I.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IDUA Knockout HEK293 Cell Line | EDJ-KQ2272 | Human | 3425 | Details Get a Quote |
| IDUA Knockout A-549 Cell Line | EDJ-KQ23983 | Human | 3425 | Details Get a Quote |
| IDUA Knockout HCT 116 Cell Line | EDJ-KQ23984 | Human | 3425 | Details Get a Quote |
| IDUA Knockout HeLa Cell Line | EDJ-KQ23985 | Human | 3425 | Details Get a Quote |
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