IDUA

alpha-L-iduronidase, the group of Glycoside hydrolases

Basic information

Region (hg38): 4:986997-1004564

Links

ENSG00000127415 ∙ NCBI:3425 ∙ OMIM:252800 ∙ HGNC:5391 ∙ Uniprot:P35475 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 1 (Definitive), mode of inheritance: AR
• Hurler syndrome (Strong), mode of inheritance: AR
• Scheie syndrome (Strong), mode of inheritance: AR
• Hurler-Scheie syndrome (Strong), mode of inheritance: AR
• Scheie syndrome (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 1 (Definitive), mode of inheritance: AR
• Hurler syndrome (Supportive), mode of inheritance: AR
• Scheie syndrome (Supportive), mode of inheritance: AR
• Hurler-Scheie syndrome (Supportive), mode of inheritance: AR
• Scheie syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type I (Mucopolysaccharidosis Ih; Mucopolysaccharidosis Is; Mucopolysaccharidosis Ih/s)	AR	Biochemical	Enzyme replacement therapy, the timing of which affects outcome is available, but may not affect cerebral manifestations; HSCT and umbilical cord blood transplantation has been described as beneficial	Biochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	6139633; 9516162; 7550242; 11735025; 11172140; 15128896; 19748810; 20301341; 21502868; 25103575; 28595941; 31127942
The conditions includes a wide degree of severity, and multiple subtypes, including Scheie syndrome, Hurler-Scheie syndrome, and Hurler syndrome

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDUA gene.

• Mucopolysaccharidosis_type_1 (1521 variants)
• not_provided (784 variants)
• Inborn_genetic_diseases (354 variants)
• Hurler_syndrome (260 variants)
• Nephrolithiasis_susceptibility_caused_by_SLC26A1 (182 variants)
• Hypersulfaturia (180 variants)
• Mucopolysaccharidosis,_MPS-I-H/S (121 variants)
• Mucopolysaccharidosis,_MPS-I-S (91 variants)
• not_specified (78 variants)
• Nephrolithiasis,_calcium_oxalate (50 variants)
• IDUA-related_disorder (28 variants)
• SLC26A1-related_disorder (25 variants)
• Hyperoxaluria (4 variants)
• Mucopolysaccharidosis (3 variants)
• See_cases (3 variants)
• Interstitial_pneumonitis (2 variants)
• Mucopolysaccharidosis,_MPS-II (1 variants)
• Familial_hypokalemia-hypomagnesemia (1 variants)
• Hereditary_disease (1 variants)
• IDUA-related_core_myopathy (1 variants)
• Epileptic_encephalopathy (1 variants)
• Autosomal_recessive_IDUA-related_disorders (1 variants)
• IDUA_PSEUDODEFICIENCY (1 variants)
• Mucopolysaccharidosis,_MPS-IV-A (1 variants)
• Disorder_of_lung (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDUA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000203.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		3	24	513	1	541
missense	23	99	470	32	3	627
nonsense	48	26	2			76
start loss	5	1				6
frameshift	72	63	3			138
splice donor/acceptor (+/-2bp)	27	43	2	3		75
Total	175	235	501	548	4

Highest pathogenic variant AF is 0.0012653201

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDUA	protein_coding	protein_coding	ENST00000247933	14	17532

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125525	0	153	125678	0.000609

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.598	373	342	1.09	0.0000191	4038
Missense in Polyphen		151	145.32	1.0391		1738
Synonymous	-2.69	205	162	1.27	0.0000102	1379
Loss of Function	0.882	22	26.9	0.817	0.00000120	298

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000248	0.000243
Ashkenazi Jewish	0.00	0.00
East Asian	0.000339	0.000326
Finnish	0.00178	0.00176
European (Non-Finnish)	0.000924	0.000880
Middle Eastern	0.000339	0.000326
South Asian	0.0000981	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Mucopolysaccharidosis 1H (MPS1H) [MIM:607014]: A severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age. {ECO:0000269|PubMed:10466419, ECO:0000269|PubMed:10735634, ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:1301941, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:24036510, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:7951228, ECO:0000269|PubMed:8019563, ECO:0000269|PubMed:8328452, ECO:0000269|PubMed:8401515, ECO:0000269|Ref.20}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mucopolysaccharidosis 1H/S (MPS1H/S) [MIM:607015]: A form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. {ECO:0000269|PubMed:10466419, ECO:0000269|PubMed:10735634, ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8401515}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mucopolysaccharidosis 1S (MPS1S) [MIM:607016]: A mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding. {ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:25256405, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8213840}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Metabolism of carbohydrates;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;CS/DS degradation;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Metabolism;dermatan sulfate degradation (metazoa) (Consensus)

Recessive Scores

• pRec: 0.0988

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.278

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: disaccharide metabolic process;glycosaminoglycan catabolic process;chondroitin sulfate catabolic process;dermatan sulfate catabolic process;heparin catabolic process
• Cellular component: coated vesicle;lysosomal lumen;extracellular exosome
• Molecular function: L-iduronidase activity;signaling receptor binding