IDUA alpha-L-iduronidase [Homo sapiens (human)] - Gene

Summary

Official Symbol: IDUAprovided by HGNC
Official Full Name: alpha-L-iduronidaseprovided by HGNC
Primary source: HGNC:HGNC:5391
See related: Ensembl:ENSG00000127415 MIM:252800
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IDA; MPS1; MPSI
Summary: This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in spleen (RPKM 4.2), stomach (RPKM 4.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 4p16.3

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	4	NC_000004.12 (986997..1004564)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (980785..998317)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

"Missing mutations" in MPS I: Identification of two novel copy number variations by an IDUA-specific in house MLPA assay.
Title: "Missing mutations" in MPS I: Identification of two novel copy number variations by an IDUA-specific in house MLPA assay.
IDUA gene mutation is associated with mucopolysaccharidosis type 1.
Title: Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1.
Missense mutations in IUDA gene are associated with mucopolysaccharidosis type I.
Title: Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I.
pathogenic sequence variations in IDUA gene, which cause the development of mucopolysaccharidosis type 1 in Iranian patients
Title: Mutation Analysis of the IDUA Gene in Iranian Patients with Mucopolysaccharidosis Type 1: Identification of Four Novel Mutations.
IDUA rs6831280 is associated with bone mineral density in the elderly Chinese population may serve as a marker for the genetic susceptibility to osteoporotic fractures.
Title: Associations of IDUA and PTCH1 with Bone Mineral Density, Bone Turnover Markers, and Fractures in Chinese Elderly Patients with Osteoporosis.
the p.X654R mutation is an intermediate IDUA allele yielding residual IDUA activity in Thai patients with intermediate mucopolysaccharidosis type I
Title: p.X654R IDUA variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS-7 cells.
Enzyme activities (acid alpha-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), alpha-galactosidase A (GLA), alpha-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk
Title: Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry.
Using lysosomal storage disease mucopolysaccharidosis type I (MPS I) dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS
Title: Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model.
IDUA deletion mutation is associate with with mucopolysaccharidosis type I .
Title: [IDUA gene mutation analysis and prenatal diagnosis of two families affected with mucopolysaccharidosis type I].
Functional characterization of all the novel sequence variants identified in the study would be helpful to confirm the clinical significance and to determine the effect of these variations on the function of respective proteins (IDUA and IDS)
Title: Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hurler syndrome MedGen: C0086795 OMIM: 607014 GeneReviews: Mucopolysaccharidosis Type I	Compare labs
Mucopolysaccharidosis, MPS-I-H/S MedGen: C0086431 OMIM: 607015 GeneReviews: Mucopolysaccharidosis Type I	Compare labs
Mucopolysaccharidosis, MPS-I-S MedGen: C0026708 OMIM: 607016 GeneReviews: Mucopolysaccharidosis Type I	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-67320 (e-PCR)
- UniSTS:85805

GDB:375196 (e-PCR)
- UniSTS:157009

GDB:375201 (e-PCR)
- UniSTS:157010

GDB:375204 (e-PCR)
- UniSTS:157011

GDB:375207 (e-PCR)
- UniSTS:157012

GDB:375210 (e-PCR)
- UniSTS:157013

GDB:375213 (e-PCR)
- UniSTS:157014

GDB:375216 (e-PCR)
- UniSTS:157015

GDB:375219 (e-PCR)
- UniSTS:157016

GDB:375222 (e-PCR)
- UniSTS:157017

GDB:375225 (e-PCR)
- UniSTS:157018

GDB:375228 (e-PCR)
- UniSTS:157019

GDB:375231 (e-PCR)
- UniSTS:157020

GDB:375234 (e-PCR)
- UniSTS:157021

SHGC4-969 (e-PCR)
- UniSTS:84878

GDB:194363 (e-PCR)
- UniSTS:155791

GDB:196305 (e-PCR)
- UniSTS:155820

SHGC-59739 (e-PCR)
- UniSTS:73434

D4S111 (e-PCR)
- UniSTS:92391

SLC26A1_1601 (e-PCR)
- UniSTS:277737

RH119306 (e-PCR)
- UniSTS:133868

SHGC-67289 (e-PCR)
- UniSTS:88812

Homology

Homologs of the IDUA gene: The IDUA gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 318 organisms have orthologs with human gene IDUA
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
L-iduronidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
L-iduronidase activity	IDA Inferred from Direct Assay more info	PubMed
L-iduronidase activity	TAS Traceable Author Statement more info
hydrolase activity, hydrolyzing O-glycosyl compounds	IBA Inferred from Biological aspect of Ancestor more info	PubMed
signaling receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
chondroitin sulfate catabolic process	TAS Traceable Author Statement more info
dermatan sulfate catabolic process	IDA Inferred from Direct Assay more info	PubMed
disaccharide metabolic process	TAS Traceable Author Statement more info	PubMed
glycosaminoglycan catabolic process	TAS Traceable Author Statement more info
heparin catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
coated vesicle	IEA Inferred from Electronic Annotation more info
extracellular exosome	HDA more info	PubMed
lysosomal lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: alpha-L-iduronidase

Names: iduronidase alpha-L-; mucopolysaccharidosis type I

NP_000194.2

EC 3.2.1.76

NP_001350505.1

EC 3.2.1.76

XP_011511763.1

EC 3.2.1.76

XP_016863652.1

EC 3.2.1.76

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008103.1 RefSeqGene

Range

5048..22568

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000203.5 → NP_000194.2 alpha-L-iduronidase isoform a precursor

See identical proteins and their annotated locations for NP_000194.2

Status: REVIEWED

Source sequence(s)

AC019103, M74715

Consensus CDS

CCDS3343.1

UniProtKB/Swiss-Prot

P35475

Related

ENSP00000425081.2, ENST00000514224.2

Conserved Domains (2) summary

cl21522
Location:544 → 636

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cl23725
Location:30 → 543

Glyco_hydro_1; Glycosyl hydrolase family 1
NM_001363576.1 → NP_001350505.1 alpha-L-iduronidase isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

AC019103, AK098805

Consensus CDS

CCDS87198.1

Related

ENST00000652070.1

Conserved Domains (1) summary

cl23725
Location:1 → 411

Glyco_hydro_1; Glycosyl hydrolase family 1

RNA

NR_110313.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC019103, AK125223, BC029959, BC099922, DA488352

Related

ENST00000514698.5

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p13 Primary Assembly

Range

986997..1004564

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017008163.1 → XP_016863652.1 alpha-L-iduronidase isoform X3
XM_011513461.2 → XP_011511763.1 alpha-L-iduronidase isoform X1

Conserved Domains (2) summary

cl21522
Location:475 → 567

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cl23725
Location:31 → 474

Glyco_hydro_1; Glycosyl hydrolase family 1