GNE (gene) explained

Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is an enzyme that in humans is encoded by the GNE gene.^{[1] [2] [3]}

The bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase/N-acetylmannosamine kinase) regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. UDP-GlcNAc 2-epimerase activity is rate-limiting for the biosynthesis of sialic acid and is required for sialylation in hematopoietic cells. The activity of the enzyme can be controlled at the transcriptional level and can affect the sialylation and function of specific cell surface molecules expressed on B cells and myeloid cells. Modification of cell surface molecules with sialic acid is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free NeuAc.^[3]

Further reading

• Wilcken B, Don N, Greenaway R . Sialuria: a second case. . J. Inherit. Metab. Dis. . 10 . 2 . 97–102 . 1987 . 2443758 . 10.1007/BF01800030 . 35287967 . etal.
• Weiss P, Tietze F, Gahl WA . Identification of the metabolic defect in sialuria. . J. Biol. Chem. . 264 . 30 . 17635–6 . 1989 . 10.1016/S0021-9258(19)84615-X . 2808337 . etal. free .
• Krasnewich DM, Tietze F, Krause W . Clinical and biochemical studies in an American child with sialuria. . Biochem. Med. Metab. Biol. . 49 . 1 . 90–6 . 1993 . 8439453 . 10.1006/bmmb.1993.1010 . etal.
• Mitrani-Rosenbaum S, Argov Z, Blumenfeld A . Hereditary inclusion body myopathy maps to chromosome 9p1-q1. . Hum. Mol. Genet. . 5 . 1 . 159–163 . 1996 . 8789455 . 10.1093/hmg/5.1.159 . etal. free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Seppala R, Lehto VP, Gahl WA . Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. . Am. J. Hum. Genet. . 64 . 6 . 1563–9 . 1999 . 10330343 . 10.1086/302411 . 1377899 .
• Keppler OT, Hinderlich S, Langner J . UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation. . Science . 284 . 5418 . 1372–6 . 1999 . 10334995 . 10.1126/science.284.5418.1372 . 1999Sci...284.1372K . etal.
• Ferreira H, Seppala R, Pinto R . Sialuria in a Portuguese girl: clinical, biochemical, and molecular characteristics. . Mol. Genet. Metab. . 67 . 2 . 131–7 . 1999 . 10356312 . 10.1006/mgme.1999.2852 . etal.
• Lucka L, Krause M, Danker K . Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis. . FEBS Lett. . 454 . 3 . 341–4 . 1999 . 10431835 . 10.1016/S0014-5793(99)00837-6 . 31863212 . etal. free .
• Leroy JG, Seppala R, Huizing M . Dominant inheritance of sialuria, an inborn error of feedback inhibition. . Am. J. Hum. Genet. . 68 . 6 . 1419–27 . 2001 . 11326336 . 10.1086/320598 . 1226128 . etal.
• Eisenberg I, Avidan N, Potikha T . The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. . Nat. Genet. . 29 . 1 . 83–7 . 2001 . 11528398 . 10.1038/ng718 . 9941510 . etal.
• Kovach MJ, Waggoner B, Leal SM . Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. . Mol. Genet. Metab. . 74 . 4 . 458–75 . 2002 . 11749051 . 10.1006/mgme.2001.3256 . etal. 6277059 .
• Kayashima T, Matsuo H, Satoh A . Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE). . J. Hum. Genet. . 47 . 2 . 77–9 . 2002 . 11916006 . 10.1007/s100380200004 . etal. free .
• Tomimitsu H, Ishikawa K, Shimizu J . Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene. . Neurology . 59 . 3 . 451–4 . 2002 . 12177386 . 10.1212/wnl.59.3.451. 38623700 . etal.
• Arai A, Tanaka K, Ikeuchi T . A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees. . Ann. Neurol. . 52 . 4 . 516–9 . 2002 . 12325084 . 10.1002/ana.10341 . 23825084 . etal.
• Darvish D, Vahedifar P, Huo Y . Four novel mutations associated with autosomal recessive inclusion body myopathy (MIM: 600737). . Mol. Genet. Metab. . 77 . 3 . 252–6 . 2003 . 12409274 . 10.1016/S1096-7192(02)00141-5 .
• Nishino I, Noguchi S, Murayama K . Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy. . Neurology . 59 . 11 . 1689–93 . 2003 . 12473753 . 10.1212/01.wnl.0000041631.28557.c6. 45523943 . etal.
• Vasconcelos OM, Raju R, Dalakas MC . GNE mutations in an American family with quadriceps-sparing IBM and lack of mutations in s-IBM. . Neurology . 59 . 11 . 1776–9 . 2003 . 12473769 . 10.1212/01.wnl.0000039780.13681.ad. 42238112 .

External links

• • • GeneReviews/NCBI/NIH/UW entry on Sialuria

Notes and References

1. Hinderlich S, Stasche R, Zeitler R, Reutter W . A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase . J Biol Chem . 272 . 39 . 24313–8 . Oct 1997 . 9305887 . 10.1074/jbc.272.39.24313 . free .
2. Stasche R, Hinderlich S, Weise C, Effertz K, Lucka L, Moormann P, Reutter W . A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase . J Biol Chem . 272 . 39 . 24319–24 . Oct 1997 . 9305888 . 10.1074/jbc.272.39.24319 . free .
3. Web site: Entrez Gene: GNE glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase.