IDUA
alpha-L-iduronidase, the group of Glycoside hydrolases
Basic information
Region (hg38): 4:986997-1004564
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Mucopolysaccharidosis type 1 (134 variants)
- not provided (41 variants)
- Hurler syndrome (38 variants)
- Mucopolysaccharidosis, MPS-I-H/S (9 variants)
- Hurler syndrome;Mucopolysaccharidosis, MPS-I-H/S;Mucopolysaccharidosis, MPS-I-S (8 variants)
- IDUA-related disorder (4 variants)
- Mucopolysaccharidosis, MPS-I-S (4 variants)
- Interstitial pneumonitis (2 variants)
- Mucopolysaccharidosis, MPS-I-S;Hurler syndrome;Mucopolysaccharidosis, MPS-I-H/S (2 variants)
- Inborn genetic diseases (2 variants)
- See cases (2 variants)
- Mucopolysaccharidosis (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.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 460 | 473 | ||||
| missense | 17 | 51 | 370 | 12 | 456 | |
| nonsense | 44 | 21 | 67 | |||
| start loss | 6 | |||||
| frameshift | 55 | 37 | 94 | |||
| inframe indel | 25 | 34 | ||||
| splice donor/acceptor (+/-2bp) | 20 | 32 | 54 | |||
| splice region | 1 | 1 | 12 | 71 | 5 | 90 |
| non coding | 208 | 324 | 45 | 579 | ||
| Total | 146 | 148 | 611 | 798 | 60 |
Highest pathogenic variant AF is 0.000859
Variants in IDUA
This is a list of pathogenic ClinVar variants found in the IDUA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-987014-C-T | Mucopolysaccharidosis type 1 • Mucopolysaccharidosis, MPS-I-S;Hurler syndrome;Mucopolysaccharidosis, MPS-I-H/S | Uncertain significance (Aug 04, 2021) | ||
| 4-987056-AGCCCCGCAGTCCCCGAGCACGCGTGGCCATGCGTCCCCTGC-A | Mucopolysaccharidosis type 1 | Pathogenic (May 22, 2023) | ||
| 4-987064-AGTCCCCGAGCACGCGTGGCCATGC-A | Mucopolysaccharidosis type 1 | Pathogenic (Sep 10, 2023) | ||
| 4-987083-C-T | Mucopolysaccharidosis type 1 | Uncertain significance (Aug 14, 2020) | ||
| 4-987085-A-C | Hurler syndrome • Mucopolysaccharidosis type 1 | Pathogenic (Mar 14, 2023) | ||
| 4-987085-A-G | Mucopolysaccharidosis type 1 | Pathogenic (Dec 08, 2023) | ||
| 4-987086-T-C | Mucopolysaccharidosis type 1 | Pathogenic (Aug 31, 2023) | ||
| 4-987087-G-A | Hurler syndrome • Mucopolysaccharidosis type 1 | Likely pathogenic (Jul 28, 2023) | ||
| 4-987089-G-C | Mucopolysaccharidosis type 1 | Uncertain significance (Sep 17, 2021) | ||
| 4-987090-T-C | Mucopolysaccharidosis type 1 | Likely benign (Jul 17, 2023) | ||
| 4-987092-C-A | Mucopolysaccharidosis type 1 | Uncertain significance (Feb 28, 2022) | ||
| 4-987093-C-T | Mucopolysaccharidosis type 1 | Likely benign (Apr 28, 2023) | ||
| 4-987094-C-T | Mucopolysaccharidosis type 1 | Likely benign (Apr 30, 2023) | ||
| 4-987095-T-C | Mucopolysaccharidosis type 1 • Inborn genetic diseases | Conflicting classifications of pathogenicity (Jan 31, 2024) | ||
| 4-987098-G-GC | Mucopolysaccharidosis type 1 | Pathogenic (Aug 05, 2022) | ||
| 4-987099-C-A | Mucopolysaccharidosis type 1 | Likely benign (Feb 27, 2022) | ||
| 4-987099-C-G | Mucopolysaccharidosis type 1 | Likely benign (Nov 12, 2022) | ||
| 4-987099-C-T | Mucopolysaccharidosis type 1 | Likely benign (Mar 11, 2022) | ||
| 4-987102-C-T | Mucopolysaccharidosis type 1 | Likely benign (Dec 11, 2023) | ||
| 4-987105-C-A | Mucopolysaccharidosis type 1 | Likely benign (Mar 25, 2020) | ||
| 4-987106-G-T | Mucopolysaccharidosis type 1 | Uncertain significance (Aug 27, 2021) | ||
| 4-987106-GC-G | Mucopolysaccharidosis, MPS-I-H/S | Likely pathogenic (Mar 30, 2022) | ||
| 4-987108-C-A | not specified • Mucopolysaccharidosis type 1 | Benign (Feb 01, 2024) | ||
| 4-987109-GC-AT | Mucopolysaccharidosis type 1 | Uncertain significance (Aug 09, 2022) | ||
| 4-987110-C-G | Mucopolysaccharidosis type 1 | Uncertain significance (Feb 24, 2022) |
GnomAD
Source:
| 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 |
|---|---|---|---|---|---|---|
| 3.76e-13 | 0.161 | 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:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
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