Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase

ction, tumorigenicity and metastatic behavior of malignant cells. Defects in GNE are a cause of sialuria (SIALURIA); also known as sialuria French type. In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant. Defects in GNE are the cause of inclusion body myopathy type 2 (IBM2). Hereditary inclusion body myopathies are a group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. IBM2 is an autosomal recessive disorder affecting mainly leg muscles, but with an unusual distribution that spares the quadriceps as also observed in Nonaka myopathy. Defects in GNE are the cause of Nonaka myopathy (NM); also known as distal myopathy with rimmed vacuoles (DMRV). NM is an autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens. 5 isoforms of the human protein are produced by alternative splicing.

Protein type: Carbohydrate Metabolism - amino sugar and nucleotide sugar; Cell adhesion; Cytoskeletal; EC 2.7.1.60; EC 3.2.1.183; Isomerase; Kinase, other; Motility/polarity/chemotaxis

Chromosomal Location of Human Ortholog: 9p13.3

Cellular Component: cytoplasm; cytosol

Molecular Function: N-acylmannosamine kinase activity; protein binding; UDP-N-acetylglucosamine 2-epimerase activity

Biological Process: cell adhesion; N-acetylneuraminate metabolic process

Disease: Inclusion Body Myopathy 2, Autosomal Recessive; Nonaka Myopathy; Sialuria