The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

IDUA  -  iduronidase, alpha-L-

Homo sapiens

Synonyms: Alpha-L-iduronidase, IDA, MPS1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of IDUA

  • A deficiency of IDUA in humans leads to the accumulation of these glycosaminoglycans and results in the lysosomal storage disorder mucopolysaccharidosis type I. We have isolated and sequenced cDNA clones containing part of the human IDUA coding region and used PCR from reverse-transcribed RNA to obtain the full IDUA sequence [1].
  • 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 [2].
  • Mucopolysaccharidosis type I (i.e., Hurler, Hurler-Scheie, and Scheie syndromes) and type II (i.e., Hunter syndrome) are lysosomal storage disorders resulting from alpha-L-iduronidase (IDUA) deficiency and iduronate-2-sulfatase (IDS) deficiency, respectively [3].
  • We have previously shown in a murine model the therapeutic potential of lentiviral IDUA vector-mediated gene therapy, in which human IDUA cDNA was driven by the cytomegalovirus promoter [4].
  • Two retroviral vectors containing a full-length human IDUA cDNA were constructed using Moloney murine leukemia virus (MoMLV)-based vector backbones [5].

Psychiatry related information on IDUA


High impact information on IDUA

  • We report on the mapping of a gene causing ACH/HCH to human chromosome 4p16.3, by linkage to the iduronidase A (IDUA) locus, in 15 informative families (Z max = 3.01 at theta = 0 for ACH; Z max = 4.71 at theta = 0 for ACH/HCH) [8].
  • A positive lod score of z = 3.35 with no recombinants was obtained with an intragenic marker for IDUA [9].
  • Our results reveal Mps1 as a critical regulator of chromosome number in zebrafish, and demonstrate how slight genetic perturbation of a mitotic checkpoint factor can dramatically reduce the fidelity of chromosome segregation during vertebrate meiosis [10].
  • These data are consistent with a model that predicts that the MPS-1-dependent phosphorylation of KVS-1 sustains cell excitability by controlling K+ flux [11].
  • Electrophysiological analysis in Chinese hamster ovary (CHO) cells demonstrates that MPS-1 activity leads to a significant decrease in the macroscopic current [11].

Chemical compound and disease context of IDUA

  • Hurler syndrome (mucopolysaccharidosis IH or MPS IH) is a congenital mucopolysaccharide storage disorder resulting from a genetic deficiency of alpha-L-iduronidase (IDUA), which is required for lysosomal degradation of glycosaminoglycans heparan sulfate and dermatan sulfate [5].
  • We found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity [12].
  • Mucopolysaccharidosis type I (MPS I, Hurler and Scheie syndromes) is an autosomal recessive lysosomal storage disorder that results from a deficiency of the hydrolase alpha-L-iduronidase (IDUA) which is involved in the lysosomal degradation of both heparan sulphate (HS) and dermatan sulphate (DS) [13].
  • Effective therapeutic strategies for mucopolysaccharidosis type I (MPSI) rely on mannose-6-phosphate receptor-mediated uptake of extracellular alpha-l-iduronidase (IDUA), the missing lysosomal enzyme in this disease, by deficient cells [14].
  • Hepatobiliary imaging with the various technetium-labeled IDA compounds is more than 90% sensitive and specific for the diagnosis of acute cholecystitis [15].

Biological context of IDUA

  • Notably, a new IDUA mutation A300T was also identified in the proband, his sister, and his mother, accounting for reduced IDUA activity in these individuals; the asymptomatic sister, whose cells demonstrated normal glycosaminoglycan metabolism, is thus a compound heterozygote for W402X and the new allele [3].
  • Measurement of expressed human IDUA activity in human-mouse hybrid cell lines confirmed that IDUA is on chromosome 4 [16].
  • Multiple techniques, including automated sequencing of the entire IDS and IDUA coding regions, were employed to unravel the molecular genetic basis of these intriguing observations [3].
  • The two-mutation allele was identified in a family from Gaza; the other three alleles were found in seven families, five of them Druze, residing in a very small area of northern Israel. Since such clustering suggests a classic founder effect, the presence of three mutant alleles of the IDUA gene was unexpected [2].
  • Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype [17].

Anatomical context of IDUA

  • Northern blot analysis with IDUA cDNA detected only a single 2.3-kilobase mRNA species in human placental RNA; however, PCR analysis of fibroblast, liver, kidney, and placental RNA showed the existence of alternatively spliced mRNA from the IDUA gene [1].
  • However, since cloning of the IDUA gene, mutation analysis has provided some molecular explanations for the range of MPS-I phenotypes, in turn facilitating the selection and evaluation of patients undergoing experimental treatment protocols such as bone marrow transplantation [18].
  • These mutations lead to a deficiency of the glycosidase alpha-L-iduronidase (IDUA), which is required for the degradation of heparan sulphate and dermatan sulphate and thus the storage of these glycosaminoglycans in the lysosome [18].
  • Eight- to 10-week-old mice were injected via the tail vein with a lentiviral vector expressing human IDUA cDNA driven by the albumin gene promoter selectively expressed in hepatocytes [4].
  • In transfected COS-7 cells, R619G caused significant reduction in enzyme activity (1.5% of normal activity), although it did not cause significant reduction in IDUA mRNA or protein level [19].

Associations of IDUA with chemical compounds

  • The lysosomal hydrolase alpha-L-iduronidase (IDUA) is one of the enzymes in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate [16].
  • Enzyme produced by the progeny of the transduced human CD34+ cells carrying IDUA cDNA corrected Hurler fibroblasts via mannose-6-phosphate receptors [5].
  • In an attempt to avoid maturation of the N-linked glycans of IDUA, the same IDUA transgene was introduced into the Arabidopsis cgl background, which is deficient in the activity of N-acetylglucosaminyl transferase I (EC, the first enzyme in the pathway of complex glycan biosynthesis [20].
  • IDUA protein was easily detected on Western blots of extracts from the T(2) seeds, and extracts contained IDUA activity as high as 2.9 nmol 4-methylumbelliferone (4 MU)/min/mg total soluble protein (TSP), corresponding to approximately 0.06 microg IDUA/mg TSP [20].
  • In this study we investigated whether the aminoglycoside gentamicin can suppress stop mutations within the IDUA gene [12].

Other interactions of IDUA


Analytical, diagnostic and therapeutic context of IDUA


  1. Human alpha-L-iduronidase: cDNA isolation and expression. Scott, H.S., Anson, D.S., Orsborn, A.M., Nelson, P.V., Clements, P.R., Morris, C.P., Hopwood, J.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  2. 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. Bach, G., Moskowitz, S.M., Tieu, P.T., Matynia, A., Neufeld, E.F. Am. J. Hum. Genet. (1993) [Pubmed]
  3. Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency. Aronovich, E.L., Pan, D., Whitley, C.B. Am. J. Hum. Genet. (1996) [Pubmed]
  4. Limited transgene immune response and long-term expression of human alpha-L-iduronidase in young adult mice with mucopolysaccharidosis type I by liver-directed gene therapy. Di Domenico, C., Di Napoli, D., Gonzalez Y Reyero, E., Lombardo, A., Naldini, L., Di Natale, P. Hum. Gene Ther. (2006) [Pubmed]
  5. Retrovirus-mediated transfer of the human alpha-L-iduronidase cDNA into human hematopoietic progenitor cells leads to correction in trans of Hurler fibroblasts. Huang, M.M., Wong, A., Yu, X., Kakkis, E., Kohn, D.B. Gene Ther. (1997) [Pubmed]
  6. Huntington disease-linked locus D4S111 exposed as the alpha-L-iduronidase gene. MacDonald, M.E., Scott, H.S., Whaley, W.L., Pohl, T., Wasmuth, J.J., Lehrach, H., Morris, C.P., Frischauf, A.M., Hopwood, J.J., Gusella, J.F. Somat. Cell Mol. Genet. (1991) [Pubmed]
  7. First pregnancy and life after preimplantation genetic diagnosis by polar body analysis for mucopolysaccharidosis type I. Tomi, D., Schultze-Mosgau, A., Eckhold, J., Schopper, B., Al-Hasani, S., Steglich, C., Gal, A., Axt-Fliedner, R., Schwinger, E., Diedrich, K., Griesinger, G. Reprod. Biomed. Online (2006) [Pubmed]
  8. A gene for achondroplasia-hypochondroplasia maps to chromosome 4p. Le Merrer, M., Rousseau, F., Legeai-Mallet, L., Landais, J.C., Pelet, A., Bonaventure, J., Sanak, M., Weissenbach, J., Stoll, C., Munnich, A. Nat. Genet. (1994) [Pubmed]
  9. The gene for achondroplasia maps to the telomeric region of chromosome 4p. Velinov, M., Slaugenhaupt, S.A., Stoilov, I., Scott, C.I., Gusella, J.F., Tsipouras, P. Nat. Genet. (1994) [Pubmed]
  10. Germ cell aneuploidy in zebrafish with mutations in the mitotic checkpoint gene mps1. Poss, K.D., Nechiporuk, A., Stringer, K.F., Lee, C., Keating, M.T. Genes Dev. (2004) [Pubmed]
  11. MPS-1 is a K+ channel beta-subunit and a serine/threonine kinase. Cai, S.Q., Hernandez, L., Wang, Y., Park, K.H., Sesti, F. Nat. Neurosci. (2005) [Pubmed]
  12. Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation. Keeling, K.M., Brooks, D.A., Hopwood, J.J., Li, P., Thompson, J.N., Bedwell, D.M. Hum. Mol. Genet. (2001) [Pubmed]
  13. Recombinant alpha-L-iduronidase: characterization of the purified enzyme and correction of mucopolysaccharidosis type I fibroblasts. Unger, E.G., Durrant, J., Anson, D.S., Hopwood, J.J. Biochem. J. (1994) [Pubmed]
  14. alpha-L-Iduronidase transport in neurites. Chen, F., Vitry, S., Hocquemiller, M., Desmaris, N., Ausseil, J., Heard, J.M. Mol. Genet. Metab. (2006) [Pubmed]
  15. Congenital absence of the gallbladder: another cause of false-positive hepatobiliary image. Dickinson, C.Z., Powers, T.A., Sandler, M.P., Partain, C.L. J. Nucl. Med. (1984) [Pubmed]
  16. Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3. Scott, H.S., Ashton, L.J., Eyre, H.J., Baker, E., Brooks, D.A., Callen, D.F., Sutherland, G.R., Morris, C.P., Hopwood, J.J. Am. J. Hum. Genet. (1990) [Pubmed]
  17. Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype. Scott, H.S., Nelson, P.V., Litjens, T., Hopwood, J.J., Morris, C.P. Hum. Mol. Genet. (1993) [Pubmed]
  18. Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Scott, H.S., Bunge, S., Gal, A., Clarke, L.A., Morris, C.P., Hopwood, J.J. Hum. Mutat. (1995) [Pubmed]
  19. Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity. Lee-Chen, G.J., Lin, S.P., Tang, Y.F., Chin, Y.W. Clin. Genet. (1999) [Pubmed]
  20. Synthesis of enzymatically active human alpha-L-iduronidase in Arabidopsis cgl (complex glycan-deficient) seeds. Downing, W.L., Galpin, J.D., Clemens, S., Lauzon, S.M., Samuels, A.L., Pidkowich, M.S., Clarke, L.A., Kermode, A.R. Plant Biotechnol. J. (2006) [Pubmed]
  21. Retroviral vector design studies toward hematopoietic stem cell gene therapy for mucopolysaccharidosis type I. Pan, D., Aronovich, E., McIvor, R.S., Whitley, C.B. Gene Ther. (2000) [Pubmed]
  22. Nonviral in vivo gene transfer in the mucopolysaccharidosis I murine model. Camassola, M., Braga, L.M., Delgado-Cañedo, A., Dalberto, T.P., Matte, U., Burin, M., Giugliani, R., Nardi, N.B. J. Inherit. Metab. Dis. (2005) [Pubmed]
  23. Thyroid volume measurement by ultrasound in children as a tool for the assessment of mild iodine deficiency. Vitti, P., Martino, E., Aghini-Lombardi, F., Rago, T., Antonangeli, L., Maccherini, D., Nanni, P., Loviselli, A., Balestrieri, A., Araneo, G. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  24. In vitro and in vivo evidence of metallopanstimulin-1 in gastric cancer progression and tumorigenicity. Wang, Y.W., Qu, Y., Li, J.F., Chen, X.H., Liu, B.Y., Gu, Q.L., Zhu, Z.G. Clin. Cancer Res. (2006) [Pubmed]
WikiGenes - Universities