Affinage

Showing IDUA — MPS1 is a alias.

IDUA

Alpha-L-iduronidase · UniProt P35475

Length
653 aa
Mass
72.7 kDa
Annotated
2026-06-10
73 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IDUA encodes alpha-L-iduronidase, a lysosomal hydrolase that degrades the glycosaminoglycans heparan sulfate and dermatan sulfate, and loss of its activity causes the lysosomal storage disorder mucopolysaccharidosis type I (MPS I) (PMID:2220820, PMID:19751987). The enzyme is translated with a signal peptide that directs it to the lysosome, and a mutation reducing and restructuring this signal peptide is associated with an attenuated, predominantly skeletal phenotype (PMID:25256405). The IDUA locus has a housekeeping-gene architecture (GC-rich, Sp1-bound promoter lacking TATA/CAAT motifs) (PMID:1339393). Disease-causing lesions span the full allelic spectrum — missense, nonsense, frameshift, and splice-site mutations — and act through distinct molecular routes: destabilizing the folded protein, disrupting the substrate-binding site, abolishing protein production, or generating aberrantly spliced transcripts with intron retention, exon skipping, or premature termination codons (PMID:8328452, PMID:8213840, PMID:19396826, PMID:29282708, PMID:39132856). Catalytic activity correlates directly with clinical severity; missense changes in the hydrophobic core and the C-terminal ~130 residues are severe, surface changes are attenuated, and folding/stability defects rather than direct catalytic impairment underlie many hypomorphic alleles (PMID:19396826, PMID:39702574). Enzyme specific activity provides a quantitative functional classifier that separates pathogenic, pseudodeficiency, and benign variants, and combinations of individually benign variants in cis can drop activity into the pathogenic range (PMID:33198351, PMID:40359731). Loss of IDUA blocks lysosomal GAG catabolism and secondarily impairs lysosomal acidification and autophagosome-lysosome fusion, blocking autophagy flux and shifting metabolism toward glycolysis and lipogenesis (PMID:35011691); in vivo it acts upstream of TP53 and LC3/GABARAP-mediated autophagy signaling (PMID:37347427). Because secreted enzyme can be taken up by distant tissues, as little as 1% of normal activity normalizes GAG storage, a principle that underlies enzyme-replacement, gene-transfer, and nonsense-suppression therapeutic strategies (PMID:15703491, PMID:22056610).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1990 High

    Establishing that IDUA encodes the lysosomal hydrolase degrading heparan and dermatan sulfate and mapping it to 4p16.3 anchored the gene to its enzymatic function and chromosomal location.

    Evidence In situ hybridization and Southern blot of human-mouse hybrids with enzyme activity assay

    PMID:2220820

    Open questions at the time
    • Did not define gene structure or catalytic mechanism
    • No mutation-to-phenotype correlation yet
  2. 1992 High

    Cloning the orthologous canine gene revealed a 14-exon housekeeping-gene architecture and showed a splice-donor mutation causes intron retention and premature termination, framing how splice lesions disrupt IDUA.

    Evidence Gene cloning, RT-PCR, primer extension and genomic sequencing in canine MPS I

    PMID:1339393

    Open questions at the time
    • Human gene structure inferred by analogy
    • Did not address protein folding or substrate binding
  3. 1993 High

    Expression of mutagenized human cDNAs established that individual IDUA mutations produce distinct molecular consequences — trace activity, residual activity, low mRNA, exon skipping, cryptic splicing — explaining phenotypic variability from mild Scheie to severe disease.

    Evidence Transfection of mutant cDNAs into COS cells, enzyme assays, RT-PCR splice analysis; chemical-cleavage mutation detection

    PMID:8213840 PMID:8328452

    Open questions at the time
    • Limited number of variants
    • No structural basis for activity loss
  4. 1998 Medium

    Polymorphic residues were shown to modulate enzyme specific activity, indicating sequence context tunes IDUA output beyond simple loss-of-function.

    Evidence Site-directed mutagenesis and expression in COS-7 cells with activity assays

    PMID:9536518

    Open questions at the time
    • Single study
    • Physiological relevance of activity gains unclear
  5. 2002 Medium

    Demonstrating that clinical aminoglycosides suppress IDUA nonsense mutations to restore full-length protein opened nonsense-readthrough as a therapeutic avenue and identified the termination context as the key determinant.

    Evidence Readthrough reporter and IDUA premature-stop cDNA constructs in a mammalian translation system

    PMID:12072912

    Open questions at the time
    • In vitro only
    • Suppression efficiency low and context-dependent
  6. 2005 Medium

    Lentiviral gene transfer in MPS I mice showed secreted enzyme cross-corrects distant tissues and that 1% of normal activity suffices to normalize GAG, defining the therapeutic threshold and metabolic cross-correction principle.

    Evidence In vivo lentiviral delivery in MPS I mice with vector PCR, enzyme assay, tissue GAG quantification

    PMID:15703491

    Open questions at the time
    • CNS correction not addressed
    • Durability and integration safety not resolved
  7. 2009 Medium

    Combining expression assays with structural modeling established that core-localized missense mutations are severe while surface mutations are attenuated, and that the C-terminal ~130 residues are functionally essential.

    Evidence Transient CHO expression with enzyme assays and 3D protein modeling of MPS I variants

    PMID:19396826

    Open questions at the time
    • Modeling-based structural inference
    • Folding versus catalytic contributions not separated
  8. 2010 High

    The Idua-W392X knock-in mouse provided a faithful null model recapitulating MPS I-H biochemistry and pathology, enabling mechanistic and preclinical work.

    Evidence Gene-targeted knock-in with enzyme assay, GAG quantification, histology, EM, and X-ray imaging

    PMID:19751987

    Open questions at the time
    • Models a single nonsense allele
    • Secondary cellular pathways not dissected
  9. 2011 High

    Designer aminoglycoside NB84 and a blood-brain-barrier-penetrant antibody-IDUA fusion demonstrated that both stop-codon suppression and receptor-mediated brain delivery can restore activity and reverse storage in vivo, including in the CNS.

    Evidence Suppression assays in MEFs and Idua-W392X mice; cTfRMAb-IDUA fusion enzyme activity and intravenous correction with brain inclusion-body quantitation

    PMID:21667973 PMID:22056610

    Open questions at the time
    • Long-term efficacy and toxicity unaddressed
    • Limited to specific alleles/delivery systems
  10. 2011 Medium

    Characterization of novel missense and splice variants (p.E276K; c.1727+3G>C) confirmed pathogenicity and showed C-terminal truncation is the deleterious driver, while documenting exon 4 skipping as a normal regulatory splicing event.

    Evidence COS-7 transient expression with enzyme assays; RT-PCR transcript analysis of leukocyte RNA

    PMID:21364962 PMID:21831683

    Open questions at the time
    • Function of physiological exon-4 skipping unproven
    • Single-variant resolution
  11. 2013 Medium

    Chloramphenicol's ~100-fold activity increase in W402X patient fibroblasts, with no detectable nonsense allele transcript, revealed that nonsense alleles undergo nonsense-mediated decay and that some drugs act independently of readthrough.

    Evidence Patient fibroblast drug treatment, enzyme assay, and cDNA sequencing

    PMID:23167761

    Open questions at the time
    • Mechanism of chloramphenicol action undefined
    • Single cell line/genotype
  12. 2017 Medium

    The C-terminally extended p.X654R allele was shown to produce an enlarged, near-inactive protein causing intermediate MPS I, while nonsense variants yielded no detectable protein, refining genotype-phenotype rules for hypomorphic alleles.

    Evidence COS-7 expression, enzyme assay, Western blot, and 3'RACE of mutant mRNA

    PMID:29282708

    Open questions at the time
    • Mechanism of activity loss from C-terminal extension not detailed
    • Single lab
  13. 2020 Medium

    An isogenic HAP1/HEK293 expression platform quantitatively distinguished pseudodeficiency, pathogenic, and VUS variants by specific activity, providing a functional framework for newborn-screening interpretation.

    Evidence Viral delivery of variants into IDUA-deficient HAP1 cells, single-cell cloning, fluorescence activity assay, Western blot

    PMID:33198351

    Open questions at the time
    • Recombinant expression may not capture tissue context
    • Single-lab platform
  14. 2021 Medium

    Drosophila IDUA knockdown linked enzyme loss to impaired lysosome acidification, blocked autophagosome-lysosome fusion, and a glycolytic/lipogenic metabolic shift, all reversible by starvation, establishing secondary autophagy and metabolic dysregulation downstream of IDUA deficiency.

    Evidence RNAi knockdown in Drosophila with lysosome imaging, autophagy flux assays, metabolic analysis, and starvation rescue

    PMID:35011691

    Open questions at the time
    • Ortholog model
    • Direct relevance of metabolic shift to human MPS I unconfirmed
  15. 2022 Medium

    Zebrafish mRNA injection showed enzymatic activity correlates directly with phenotype, with a dominant-negative allele (z-idua-L346R) and a residual-activity frameshift allele behaving differently, reinforcing activity as the disease determinant.

    Evidence Zebrafish morpholino knockdown and mutant mRNA microinjection with enzyme assays and phenotypic scoring

    PMID:35893292

    Open questions at the time
    • Dominant-negative mechanism not molecularly defined
    • Ortholog model
  16. 2023 Medium

    Zebrafish knockdown and human IDUA mRNA rescue placed IDUA upstream of TP53 signaling, LC3/GABARAP autophagy, and leukotriene A4 hydrolase-mediated arachidonic acid metabolism, connecting enzyme loss to defined signaling cascades.

    Evidence Zebrafish IDUA morpholino knockdown, transcriptome profiling, and wild-type mRNA rescue

    PMID:37347427

    Open questions at the time
    • Mechanistic links between GAG storage and TP53/autophagy unproven
    • Transcriptome correlations not validated at protein level
  17. 2024 Medium

    Systematic characterization of over 30 variants showed many act through folding, processing, and stability defects rather than direct catalytic loss, establishing relative specific activity as a first-level functional classifier.

    Evidence HEK293 expression of >30 variants with fluorescence activity assay and semi-quantitative Western blotting

    PMID:39702574

    Open questions at the time
    • Folding defects inferred from protein abundance, not direct biophysics
    • Single-lab platform
  18. 2024 Medium

    Heterozygous IDUA loss-of-function exerted a gene-dosage effect on brain Abeta40 and increased plaque burden in the 5xFAD model, implicating partial IDUA deficiency in amyloid processing beyond classic MPS I.

    Evidence Mouse genetics (IDUA heterozygous knockout crossed with 5xFAD), interstitial fluid Abeta40 measurement, plaque quantification (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mechanism linking IDUA to amyloid metabolism unknown
  19. 2025 Medium

    Demonstrating that combinations of individually benign IDUA variants in cis lower activity into the pathogenic range showed complex-allele additivity as a genotype mechanism in MPS I.

    Evidence Viral delivery of single and combined variant constructs in HAP1 cells with specific activity assay and Western blot

    PMID:40359731

    Open questions at the time
    • Recombinant system; clinical cases of such complex alleles not confirmed
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GAG storage mechanistically triggers TP53 activation, autophagy blockade, metabolic reprogramming, and altered amyloid processing — and whether these secondary pathways are therapeutic targets in human MPS I — remains unresolved.
  • No direct mechanistic link from GAG accumulation to TP53/autophagy in human cells
  • Amyloid finding is a single preprint
  • No structural model defining catalytic versus stability determinants experimentally validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005764 lysosome 3
Pathway
R-HSA-9612973 Autophagy 2 R-HSA-1430728 Metabolism 1 R-HSA-1643685 Disease 1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 IDUA (alpha-L-iduronidase) was chromosomally localized to human chromosome 4p16.3 by in situ hybridization and Southern blot analysis of human-mouse hybrid cell lines, confirming IDUA encodes the lysosomal hydrolase responsible for degrading glycosaminoglycans heparan sulfate and dermatan sulfate. In situ hybridization, Southern blot analysis of human-mouse somatic cell hybrids, enzyme activity assay American journal of human genetics High 2220820
1992 The canine IDUA gene contains 14 exons spanning 13 kb, has a GC-rich promoter with Sp1 binding sites but no TATA box or CAAT motif (housekeeping gene architecture), and the canine MPS I mutation is a G→A transition at the donor splice site of intron 1, causing intron 1 retention in the RNA and a premature termination codon at the exon-intron junction. Gene cloning, restriction analysis, RT-PCR, primer extension, sequence analysis of genomic DNA Genomics High 1339393
1993 Missense mutations Thr366→Pro and Ter→Cys in IDUA permit expression of only trace alpha-L-iduronidase activity; Gly409→Arg permits expression of ~60% normal activity. Nonsense mutation Tyr64→Ter causes very low mRNA levels and exon 2 skipping; Gln310→Ter causes use of a cryptic splice site. Established that specific IDUA mutations have distinct molecular consequences on RNA processing and enzyme activity. Transfection of mutagenized cDNAs into COS-1 cells, enzyme activity assay, RT-PCR analysis of RNA processing American journal of human genetics High 8328452
1993 The R89Q missense mutation in IDUA results in reduced stability and activity of the mutant protein. The 678-7g→a splice site mutation allows a very small amount of normal mRNA to be produced, accounting for the mild (Scheie) phenotype. Both the 5' and 3' splice site mutations (1060+2t→c and 678-7g→a) result in high proportions of mature mRNAs containing introns. Chemical cleavage mutation detection, direct PCR sequencing, expression of R89Q in cells, RT-PCR of splice variants American journal of human genetics High 8213840
1998 Polymorphic amino acid changes Q105 (R105Q), T361 (A361T), and I454 (V454I) individually and in combination increase alpha-L-iduronidase specific activity when expressed in COS-7 cells, demonstrating that these polymorphic positions modulate IDUA enzymatic activity. Site-directed mutagenesis of IDUA cDNA, expression in COS-7 cells, enzyme activity assay Proceedings of the National Science Council, Republic of China. Part B, Life sciences Medium 9536518
2002 Clinically approved aminoglycosides gentamicin, tobramycin, and amikacin can suppress naturally occurring IDUA premature stop mutations (disease-associated nonsense mutations) in a mammalian translation system, restoring full-length protein. Suppression efficiency is context-dependent, determined primarily by the tetranucleotide termination signal (stop codon plus +1 nucleotide). Readthrough reporter constructs and IDUA cDNA constructs with premature stop mutations in mammalian translation system, enzyme activity assay Journal of molecular medicine Medium 12072912
2005 Lentiviral-mediated IDUA gene transfer resulted in IDUA transgene expression highest in liver and spleen; secretion of corrective enzyme from these tissues into plasma allowed cross-correction of distant tissues (kidney, heart, lung) via uptake of secreted enzyme, demonstrating that 1% of normal IDUA activity is sufficient to normalize GAG levels in urine, liver, and spleen of MPS I mice. In vivo lentiviral vector injection (tail vein) in MPS I mice, PCR for integration, enzyme activity assay, GAG quantification in tissues Human gene therapy Medium 15703491
2010 The knock-in Idua-W392X mouse (analogous to human IDUA-W402X) shows no detectable alpha-L-iduronidase activity, increased sulfated GAG excretion in urine and storage in multiple tissues, bone abnormalities, and altered metabolism, establishing this as a faithful model of MPS I-H with complete loss of lysosomal enzyme function. Gene targeting/knock-in, enzyme activity assay, GAG quantification, histology, electron microscopy, X-ray imaging Molecular genetics and metabolism High 19751987
2011 The designer aminoglycoside NB84 suppresses the Idua-W392X premature termination codon more efficiently than conventional aminoglycosides (gentamicin, G418, amikacin, paromomycin), restoring sufficient functional alpha-L-iduronidase activity to partially reverse lysosomal GAG accumulation in mouse embryonic fibroblasts and significantly reduce urine and tissue GAG storage in vivo. Suppression assay in mouse embryonic fibroblasts, enzyme activity assay, GAG quantification, in vivo drug administration to Idua-W392X mice Molecular genetics and metabolism High 22056610
2011 Murine IDUA fused to the carboxyl terminus of a chimeric anti-transferrin receptor monoclonal antibody (cTfRMAb-IDUA fusion protein) retains comparable enzyme activity (776 ± 79 units/μg protein) to recombinant IDUA, crosses the blood-brain barrier via transferrin receptor-mediated transport, and reverses pre-existing lysosomal inclusion bodies in brain by 73% and reduces GAGs in peripheral tissues of MPS I mice. Fusion protein engineering, enzyme activity assay, intravenous administration to MPS I null mice, GAG quantification, semithin brain section quantitation of lysosomal inclusion bodies Molecular pharmaceutics High 21667973
2011 A novel IDUA splice site mutation (c.1727+3G>C) causes aberrant splicing of intron 12 (insertion of GTCC), introducing a frameshift and premature termination codon (p.Cys577SerfsX15), with the deleterious effect primarily due to C-terminal truncation. Additionally, exon 4 skipping is a normal alternative splicing event (25–34% of transcripts in healthy individuals), potentially regulating iduronidase activity levels. Sequence analysis of IDUA transcripts, RT-PCR of leukocyte RNA, gene expression studies Molecular genetics and metabolism Medium 21831683
2013 Chloramphenicol treatment of MPS I patient fibroblasts (carrying p.W402X/p.W402X) produced a ~100-fold increase in IDUA activity; cDNA sequencing showed only alleles without the nonsense mutation were amplified even after treatment, indicating that nonsense alleles are targeted to nonsense-mediated mRNA decay and that chloramphenicol acts through a mechanism other than stop codon readthrough. Cell culture treatment of patient fibroblasts, IDUA enzyme activity assay, cDNA sequencing Current pharmaceutical biotechnology Medium 23167761
2009 Expression of novel MPS I mutations (including p.V620F, p.W626X) in Chinese hamster ovary (CHO) cells confirmed pathogenicity. Missense mutations localized to the hydrophobic core of IDUA are associated with severe phenotype, while surface-localized missense mutations cause attenuated phenotypes. Mutations in the C-terminal 130 amino acids cause clinical disease, establishing functional importance of the IDUA C-terminus. Transient expression in CHO cells, enzyme activity assay, 3D protein modeling American journal of medical genetics. Part A Medium 19396826
2011 Novel p.E276K IDUA missense mutation significantly reduces alpha-L-iduronidase activity when expressed in COS-7 cells by transient transfection, confirming it as a disease-causing variant. Transient transfection of mutant IDUA construct into COS-7 cells, enzyme activity assay Molecular vision Medium 21364962
2017 The p.X654R (c.*1T>C) IDUA variant produces an mRNA encoding a protein with 38 additional amino acids (C-terminal extension); COS-7 cells expressing this variant show an elevated apparent molecular mass by Western blot and extremely low enzyme activity, while p.W312X and p.Q380X produce no detectable protein by Western blot. This established that p.X654R is a hypomorphic allele with residual activity resulting in intermediate MPS I. Expression in COS-7 cells, enzyme activity assay, Western blot, 3'RACE sequencing of mutant mRNA Annals of human genetics Medium 29282708
2014 The p.L18P IDUA mutation alters the signal peptide structure (reducing it to 25 amino acids and altering its secondary structure), likely impairing lysosomal targeting of alpha-L-iduronidase, based on bioinformatics analysis of signal peptide properties and clinical correlation with attenuated phenotype featuring bone/cartilage symptoms without visceral or cognitive involvement. Bioinformatics signal peptide analysis, clinical phenotyping Clinical genetics Low 25256405
2018 Triazole-iduronic acid hybrid molecules synthesized by click chemistry were identified as the first small molecules that inhibit and thermally stabilize recombinant human alpha-L-iduronidase (rh-α-IDUA) in vitro, suggesting pharmacological chaperone potential. Enzyme inhibition assay, thermal denaturation/stability assay of rh-α-IDUA with library compounds Chemical communications Medium 29473068
2020 A functional HEK293-based expression platform combining fluorescence-based alpha-iduronidase activity assay and semi-quantitative Western blotting determined that pseudodeficiency IDUA variants (p.His82Gln, p.Ala79Thr, p.Val322Glu, p.Asp223Asn) variably reduce but do not abolish specific activity, while pathogenic variants (p.Ser633Leu, p.His240Arg) show very low activity. p.His240Arg showed 5-fold higher specific activity than p.Ser633Leu despite both causing Scheie syndrome, and p.Ser586Phe and p.Ile272Leu VUS variants had specific activities in the pseudodeficiency range. Viral delivery of IDUA variants into IDUA-deficient HAP1 cells, single-cell cloning, enzyme activity assay, Western blot for protein quantification International journal of neonatal screening Medium 33198351
2021 Reduction of D-idua (Drosophila IDUA ortholog) by RNAi causes lethality at the pupal stage, increased lysosome number and size in brain and muscle, impaired lysosome acidification leading to dysfunctional lysosome-autophagosome fusion and autophagy flux blockade, and a metabolic shift toward glycolysis and lipogenesis. Starvation rescued both autophagy/lysosome phenotypes and metabolic alterations, establishing that IDUA deficiency causes secondary autophagy impairment and metabolic dysregulation. RNAi-mediated knockdown in Drosophila, lysosome staining and imaging, autophagy flux assay, metabolic pathway analysis, starvation rescue experiment Cells Medium 35011691
2022 Injection of mutated z-idua-L346R mRNA into zebrafish embryos reduced z-Idua enzymatic activity and caused dominant negative defective phenotypes (compared to wild-type injected), while z-idua-E540-frameshift mRNA provided partial enzymatic activity and did not cause defective phenotypes, establishing that enzymatic activity of IDUA directly correlates with disease phenotype in this model system. Zebrafish morpholino knockdown, mRNA microinjection of mutant idua, z-Idua enzymatic activity assay, phenotypic scoring Journal of personalized medicine Medium 35893292
2023 IDUA morpholino knockdown in zebrafish larvae upregulates TP53 signaling and LC3/GABARAP family protein-mediated autophagy, and upregulates leukotriene A4 hydrolase-mediated arachidonic acid metabolism; introduction of wild-type human IDUA mRNA rescued developmental defects and aberrant signaling, placing IDUA upstream of these pathways. Zebrafish IDUA morpholino knockdown, transcriptome profiling, rescue with wild-type IDUA mRNA, IDUA enzyme activity assay Annals of the New York Academy of Sciences Medium 37347427
2024 Heterozygous loss-of-function mutations in IDUA have a gene-dosage effect on Aβ40 levels in brain interstitial fluid in C57BL/6 mice and significantly increase Aβ plaque formation in the 5xFAD Alzheimer's disease mouse model, establishing that partial IDUA deficiency is sufficient to perturb amyloid processing. In vivo mouse genetics (IDUA heterozygous knock-out crossed with 5xFAD), brain interstitial fluid Aβ40 measurement, amyloid plaque quantification bioRxiv (preprint)preprint Medium
2024 Characterization of over 30 IDUA variants using HEK293 expression platform revealed that different variants have distinct effects on enzyme folding, processing, and stability (not just catalytic activity), and that relative specific activity serves as a first-level functional classifier. Some variants reduce activity primarily through folding/stability defects rather than direct catalytic impairment. HEK293-based expression of IDUA variants, fluorescence enzyme activity assay, semi-quantitative Western blotting for protein folding/processing assessment NPJ genomic medicine Medium 39702574
2024 The novel IDUA splice variant c.159-9T>A causes two aberrant splicing events—exon 2 skipping and intron 1 retention—as demonstrated by minigene splicing assay, establishing the molecular consequence of this mutation on IDUA mRNA processing. Minigene splicing assay, WES, SNP array, Sanger sequencing Molecular genetics & genomic medicine Medium 39132856
2025 The novel IDUA deletion p.His356_Gln362del disrupts the protein's substrate-binding site, causing structural deformation and complete loss of enzymatic activity; the missense mutation p.Pro533Arg affects protein stability and flexibility by introducing a bulkier arginine residue that interferes with the contact region between the β-sheet structure and substrate-bound helix, reducing substrate affinity. Sanger sequencing, SWISS-MODEL structural homology modeling, DynaMut stability prediction, clinical phenotyping Molecular genetics and metabolism reports Low 40291162
2025 Combining two or more clinically benign IDUA variants in cis on a single allele reduces the specific activity of the resulting enzyme into the pathogenic range (comparable to attenuated or severe MPS I-associated variants), as measured by the established HAP1-cell functional platform. Viral delivery of single and combined IDUA variant constructs into IDUA-deficient HAP1 cells, single-cell cloning, enzyme specific activity assay, Western blot Molecular genetics and metabolism Medium 40359731

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Clinically relevant aminoglycosides can suppress disease-associated premature stop mutations in the IDUA and P53 cDNAs in a mammalian translation system. Journal of molecular medicine (Berlin, Germany) 116 12072912
1993 Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area. American journal of human genetics 84 8328452
1992 Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis I. Genomics 81 1339393
2020 Inulin Exerts Beneficial Effects on Non-Alcoholic Fatty Liver Disease via Modulating gut Microbiome and Suppressing the Lipopolysaccharide-Toll-Like Receptor 4-Mψ-Nuclear Factor-κB-Nod-Like Receptor Protein 3 Pathway via gut-Liver Axis in Mice. Frontiers in pharmacology 80 33390939
1993 Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes. American journal of human genetics 80 8213840
2019 Inulin Ameliorates Alcoholic Liver Disease via Suppressing LPS-TLR4-Mψ Axis and Modulating Gut Microbiota in Mice. Alcoholism, clinical and experimental research 73 30589437
1990 Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3. American journal of human genetics 71 2220820
2005 Gene therapy for a mucopolysaccharidosis type I murine model with lentiviral-IDUA vector. Human gene therapy 61 15703491
2011 IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles. Human mutation 59 21394825
2011 The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua-W392X mouse. Molecular genetics and metabolism 58 22056610
2011 Reversal of lysosomal storage in brain of adult MPS-I mice with intravenous Trojan horse-iduronidase fusion protein. Molecular pharmaceutics 54 21667973
2010 Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation. Molecular genetics and metabolism 51 19751987
2018 Worldwide distribution of common IDUA pathogenic variants. Clinical genetics 32 29393969
2002 Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human alpha-L-iduronidase (IDUA) gene. Genetics in medicine : official journal of the American College of Medical Genetics 31 12509712
2009 Mucopolysaccharidosis type I in 21 Czech and Slovak patients: mutation analysis suggests a functional importance of C-terminus of the IDUA protein. American journal of medical genetics. Part A 29 19396826
1999 An Mpsi-containing heterologous RNA, but not env mRNA, is efficiently packaged into avian retroviral particles. Journal of virology 28 10515997
2015 Identification of IDUA and WNT16 Phosphorylation-Related Non-Synonymous Polymorphisms for Bone Mineral Density in Meta-Analyses of Genome-Wide Association Studies. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 26256109
2022 MPSI Manifestations and Treatment Outcome: Skeletal Focus. International journal of molecular sciences 18 36232472
2019 Targeting a Pre-existing Anti-transgene T Cell Response for Effective Gene Therapy of MPS-I in the Mouse Model of the Disease. Molecular therapy : the journal of the American Society of Gene Therapy 18 31060789
2017 IDUA mutational profile and genotype-phenotype relationships in UK patients with Mucopolysaccharidosis Type I. Human mutation 17 28752568
2013 Chloramphenicol enhances IDUA activity on fibroblasts from mucopolysaccharidosis I patients. Current pharmaceutical biotechnology 16 23167761
1991 PCR of a KpnI RFLP in the alpha-L-iduronidase (IDUA) gene. Nucleic acids research 15 1682883
2017 Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I. Scientific reports 14 28842642
2016 Evaluation and identification of IDUA gene mutations in Turkishpatients with mucopolysaccharidosis type I. Turkish journal of medical sciences 12 27511503
1992 Linkage, but not gene order, of homologous loci, including alpha-L-iduronidase (Idua), is conserved in the Huntington disease region of the mouse and human genomes. Mammalian genome : official journal of the International Mammalian Genome Society 12 1533802
2020 Ocular Tolerability and Immune Response to Corneal Intrastromal AAV-IDUA Gene Therapy in New Zealand White Rabbits. Molecular therapy. Methods & clinical development 11 32542182
2018 A combinatorial approach towards the synthesis of non-hydrolysable triazole-iduronic acid hybrid inhibitors of human α-l-iduronidase: discovery of enzyme stabilizers for the potential treatment of MPSI. Chemical communications (Cambridge, England) 11 29473068
2017 An Integrated Computational Framework to Assess the Mutational Landscape of α-L-Iduronidase IDUA Gene. Journal of cellular biochemistry 11 28608934
1992 PCR detection of two RFLPs in exon I of the alpha-L-iduronidase (IDUA) gene. Human genetics 10 1362562
2021 Drosophila D-idua Reduction Mimics Mucopolysaccharidosis Type I Disease-Related Phenotypes. Cells 9 35011691
2012 Intracerebroventricular transplantation of human bone marrow-derived multipotent progenitor cells in an immunodeficient mouse model of mucopolysaccharidosis type I (MPS-I). Cell transplantation 9 22472595
2011 A novel p.E276K IDUA mutation decreasing α-L-iduronidase activity causes mucopolysaccharidosis type I. Molecular vision 9 21364962
2021 Which Is the Best In Silico Program for the Missense Variations in IDUA Gene? A Comparison of 33 Programs Plus a Conservation Score and Evaluation of 586 Missense Variants. Frontiers in molecular biosciences 8 34746235
2019 Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1. Journal of pediatric endocrinology & metabolism : JPEM 8 31473686
2013 Treatment of MPS I mice with microencapsulated cells overexpressing IDUA: effect of the prednisolone administration. Journal of microencapsulation 8 23418953
2016 Maternal mosaicism for IDUA deletion clarifies recurrence risk in MPS I. Human genome variation 7 27766162
2014 p.L18P: a novel IDUA mutation that causes a distinct attenuated phenotype in mucopolysaccharidosis type I patients. Clinical genetics 7 25256405
2020 A deletion of IDUA exon 10 in a family of Golden Retriever dogs with an attenuated form of mucopolysaccharidosis type I. Journal of veterinary internal medicine 6 32785987
2017 p.X654R IDUA variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS-7 cells. Annals of human genetics 6 29282708
2019 Associations of IDUA and PTCH1 with Bone Mineral Density, Bone Turnover Markers, and Fractures in Chinese Elderly Patients with Osteoporosis. Disease markers 5 31275456
2012 Treatment of adult MPSI mouse brains with IDUA-expressing mesenchymal stem cells decreases GAG deposition and improves exploratory behavior. Genetic vaccines and therapy 5 22520214
2024 Functional assessment of IDUA variants of uncertain significance identified by newborn screening. NPJ genomic medicine 4 39702574
2020 A Biochemical Platform to Define the Relative Specific Activity of IDUA Variants Identified by Newborn Screening. International journal of neonatal screening 4 33198351
2019 Mutation Analysis of the IDUA Gene in Iranian Patients with Mucopolysaccharidosis Type 1: Identification of Four Novel Mutations. Genetic testing and molecular biomarkers 4 31298590
2019 "Missing mutations" in MPS I: Identification of two novel copy number variations by an IDUA-specific in house MLPA assay. Molecular genetics & genomic medicine 4 31319022
2019 Identification of a novel compound heterozygous IDUA mutation underlies Mucopolysaccharidoses type I in a Chinese pedigree. Molecular genetics & genomic medicine 4 31758674
2018 Novel splice site IDUA gene mutation in Tunisian pedigrees with hurler syndrome. Diagnostic pathology 3 29843745
2017 Novel frameshift variant in the IDUA gene underlies Mucopolysaccharidoses type I in a consanguineous Yemeni pedigree. Molecular genetics and metabolism reports 3 28649516
2024 Whole paternal uniparental disomy of chromosome 4 with a novel homozygous IDUA splicing variant, c.159-9T>A, in a Chinese patient with mucopolysaccharidosis type I. Molecular genetics & genomic medicine 2 39132856
2024 Long-Term Health Outcomes of Individuals With Pseudodeficiency Alleles in IDUA May Inform Newborn Screening Practices for Mucopolysaccharidosis Type I. American journal of medical genetics. Part A 2 39559959
2023 Phenotypic characterisation of the Mucopolysaccharidosis Type I (MPSI) Idua-W392X mouse model reveals increased anxiety-related traits in female mice. Molecular genetics and metabolism 2 37473537
2022 Quantification of Idua Enzymatic Activity Combined with Observation of Phenotypic Change in Zebrafish Embryos Provide a Preliminary Assessment of Mutated idua Correlated with Mucopolysaccharidosis Type I. Journal of personalized medicine 2 35893292
2011 A novel mucopolysaccharidosis type I associated splice site mutation and IDUA splice variants. Molecular genetics and metabolism 2 21831683
1998 Human alpha-L-iduronidase (IDUA) gene: correlation of polymorphic DNA haplotype and IDUA activity in Chinese population. Proceedings of the National Science Council, Republic of China. Part B, Life sciences 2 9536518
2025 Combining clinically benign IDUA variants in cis reduces enzymatic activity of the resulting enzyme within the pathogenic range. Molecular genetics and metabolism 1 40359731
2025 Long-term safety outcomes and patient preferences for home-based intravenous enzyme replacement therapy (ERT) in Pompe disease and Mucopolysaccharidosis Type I (MPS-I): final results of two-year observation. Orphanet journal of rare diseases 1 41272769
2024 Intrathecal or intravenous AAV9-IDUA/RGX-111 at minimal effective dose prevents cardiac, skeletal and neurologic manifestations of murine MPS I. Molecular therapy. Methods & clinical development 1 39687731
2023 Identification of an α-l-iduronidase (IDUA) M1T mutation in a Chinese family with autosomal recessive mucopolysaccharidosis I. Annals of the New York Academy of Sciences 1 37347427
2021 IDUA Gene Variants and Response to Zoledronic Acid Treatment in Chinese Women with Postmenopausal Osteoporosis. Pharmacogenomics and personalized medicine 1 34285554
2017 [IDUA gene mutation analysis and prenatal diagnosis of two families affected with mucopolysaccharidosis type I]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 28604952
2016 Analysis of the env gene variability of the IDU-A HIV-1 variant in the outbreak of the HIV infection epidemic in Perm region of Russia (1996-2011). Voprosy virusologii 1 29323855
2013 Efficient IDUA Gene Mutation Detection with Combined Use of dHPLC and Dried Blood Samples. ISRN molecular biology 1 27335677
1999 Linkage disequilibrium between IDUA kpnI-VNTR haplotype in Mexican patients with MPS-I. Archives of medical research 1 10596456
2026 Case Report: Compound heterozygous mutations in the IDUA gene causing mucopolysaccharidosis type I with uterine developmental abnormality. Frontiers in pediatrics 0 41837196
2026 Homozygous R383H variant in IDUA gene causing pericentric retinitis pigmentosa in attenuated mucopolysaccharidosis type I. Ophthalmic genetics 0 42161901
2026 Variant classification for mucopolysaccharidosis type I; ACMG/AMP specification for IDUA from the ClinGen lysosomal diseases variant curation expert panel. Molecular genetics and metabolism 0 42190545
2025 Genetic variations in the IDUA gene in Tunisian MPS I families: Identification of a novel microdeletion disrupting substrate binding and structural insights. Molecular genetics and metabolism reports 0 40291162
2025 Congenital Dermal Melanocytosis Exhibited in Two Patients with Hurler Syndrome: Clinical Characterization and Report of a Recurrent IDUA Allele in Colombia. International journal of molecular sciences 0 41226457
2025 Reclassifying IDUA c.250G>A (p.Gly84Ser): Evidence for a Possible Pseudodeficiency Allele. International journal of neonatal screening 0 41283362
2022 [Analysis of a child with mucopolysaccharidoses type I due to compound heterozygous variants of IDUA gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 36184100
2014 Mutation c.1190-1delG/N in intron 8 and c.1708G>C/N in exon 12 not reported in the IDUA gene developed a clinical phenotype of Scheie syndrome. Investigacion clinica 0 25558755
2005 Haplotypes Eco47 III-Nsp I sites frequencies on the IDUA gene in Mexican native population. European journal of medical genetics 0 15953403
1998 Human alpha-L-iduronidase (IDUA) gene: apparent recombination in intron 2 by haplotype analysis in a Taiwanese population. Journal of the Formosan Medical Association = Taiwan yi zhi 0 9700243

Missed literature

Know a paper Affinage missed for IDUA? Flag it for the maintainers and the community.

No submissions yet.