Description:
MUCOLIPIDOSIS IIIA
N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE, ALPHA/BETA SUBUNITS; GNPTAB
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
10 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
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| UDP-N-acetylglucosamine--lysosomal-enzyme N-acetylglucosaminephosphotransferase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.7.8.17; 28% activity. |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 1 |
607840.0014; MUCOLIPIDOSIS IIIA |
| Identified Mutation |
LYS4GLN; In a family and a single patient with mucolipidosis IIIA (252900), Kudo et al. (Am J Hum Genet 78:451-463, 2006) found a missense mutation, lys4 to gln (K4Q), in the GNPTAB gene. |
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| Gene |
GNPTAB |
| Chromosomal Location |
12q23.3 |
| Allelic Variant 2 |
607840.0011; MUCOLIPIDOSIS II |
| Identified Mutation |
2-BP DEL, 3665TC; In 8 of 9 pedigrees with ML II (252500) and 5 of 7 with ML IIIA (252600), Kudo et al. (Am J Hum Genet 78:451-463, 2006) identified a frameshift mutation in the GNPTAB gene consisting of deletion of 2 nucleotides (3665_3666delTC) beginning at leu1168 and leading to premature termination at amino acid 1172 (L1168fsX1172). This mutation was the most frequent in their study and was found in both the homozygous and compound heterozygous state, in combination with severe mutations (i.e., mutations preventing the generation of active enzyme) in ML II and with mild mutations (i.e., mutations allowing the generation of active enzyme) in ML IIIA. |
| Remarks |
Deficient Alpha-L-iduronidase, beta-glucuronidase, beta-galactosidase, and neuraminidase; 28% of normal level of N-acetylglucosaminylphosphotransferase activity; GlcNAc-Phosphotransferase activity = 14% (measured as specific activity in cell lysate and reported as percentage of activity in normal fibroblasts); donor subject is a compound heterozygote: one allele has an A>C transversion at nucleotide 174 in exon 1 of the GNPTAB gene [174A>C] resulting in a substitution of glutamine for lysine at codon 4 [Lys4Gln (K4Q)] and a second allele has a 2-bp deletion in exon 19 of the GNPTAB gene [3665_3666delTC] resulting in a frameshift and truncation of the protein in the beta subunit [L1168fsX1172]. |
| Flint M, Chatterjee P, Lin DL, McMullan LK, Shrivastava-Ranjan P, Bergeron É, Lo MK, Welch SR, Nichol ST, Tai AW, Spiropoulou CF, A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus Nature communications10:285 2018 |
| PubMed ID: 30655525 |
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| Kudo M, Brem MS, Canfield WM, Mucolipidosis II (I-Cell Disease) and Mucolipidosis IIIA (Classical Pseudo-Hurler Polydystrophy) Are Caused by Mutations in the GlcNAc-Phosphotransferase alpha / beta -Subunits Precursor Gene. Am J Hum Genet78(3):451-63 2006 |
| PubMed ID: 16465621 |
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| Reitman ML, Varki A, Kornfeld S, Fibroblasts from patients with I-cell disease and pseudo-Hurler polydystrophy are deficient in uridine 5'-diphosphate-N- acetylglucosamine: glycoprotein N-acetylglucosaminylphosphotransferase activity. J Clin Invest67:1574-9 1981 |
| PubMed ID: 6262380 |
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| Varki AP, Reitman ML, Kornfeld S, Identification of a variant of mucolipidosis III (pseudo-Hurler polydystrophy): a catalytically active N- acetylglucosaminylphosphotransferase that fails to phosphorylate lysosomal enzymes. Proc Natl Acad Sci U S A78:7773-7 1981 |
| PubMed ID: 6461005 |
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| Kress BC, Freeze HH, Herd JK, Alhadeff JA, Miller AL, Purification and characterization of I-cell disease alpha-L-fucosidase. J Biol Chem255:955-61 1980 |
| PubMed ID: 7356669 |
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| Herd JK, Dvorak AD, Wiltse HE, Eisen JD, Kress BC, Miller AL, Mucolipidosis type III. Multiple elevated serum and urine enzyme activities. Am J Dis Child132:1181-6 1978 |
| PubMed ID: 152578 |
| Passage Frozen |
10 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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