GeneBe

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Mucopolysaccharidosis type I (Mucopolysaccharidosis Ih; Mucopolysaccharidosis Is; Mucopolysaccharidosis Ih/s)ARBiochemicalEnzyme 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 beneficialBiochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary6139633; 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 (1470 variants)
  • not_provided (738 variants)
  • Inborn_genetic_diseases (326 variants)
  • Hurler_syndrome (255 variants)
  • Nephrolithiasis_susceptibility_caused_by_SLC26A1 (182 variants)
  • Hypersulfaturia (180 variants)
  • Mucopolysaccharidosis,_MPS-I-H/S (119 variants)
  • Mucopolysaccharidosis,_MPS-I-S (91 variants)
  • not_specified (63 variants)
  • Nephrolithiasis,_calcium_oxalate (50 variants)
  • IDUA-related_disorder (27 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)
  • Epileptic_encephalopathy (1 variants)
  • Familial_hypokalemia-hypomagnesemia (1 variants)
  • IDUA_PSEUDODEFICIENCY (1 variants)
  • Hereditary_disease (1 variants)
  • Mucopolysaccharidosis,_MPS-IV-A (1 variants)
  • IDUA-related_core_myopathy (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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
21
clinvar
501
clinvar
1
clinvar
 526
missense
24
clinvar
91
clinvar
453
clinvar
30
clinvar
5
clinvar
 603
nonsense
49
clinvar
25
clinvar
2
clinvar
 76
start loss
5
1
 6
frameshift
67
clinvar
63
clinvar
3
clinvar
 133
splice donor/acceptor (+/-2bp)
21
clinvar
44
clinvar
3
clinvar
 68
Total 166 227 479 534 6

Highest pathogenic variant AF is 0.0012653201

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
IDUAprotein_codingprotein_codingENST00000247933 1417532
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
3.76e-130.16112552501531256780.000609
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.5983733421.090.00001914038
Missense in Polyphen151145.321.03911738
Synonymous-2.692051621.270.00001021379
Loss of Function0.8822226.90.8170.00000120298

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002480.000243
Ashkenazi Jewish0.000.00
East Asian0.0003390.000326
Finnish0.001780.00176
European (Non-Finnish)0.0009240.000880
Middle Eastern0.0003390.000326
South Asian0.00009810.0000980
Other0.0001640.000163

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

Haploinsufficiency Scores

pHI
0.0841
hipred
N
hipred_score
0.342
ghis
0.583

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Idua
Phenotype
renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;

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