Defective GNE does not phosphorylate ManNAc to ManNAc-6-P

Stable Identifier
R-HSA-4088322
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective GNE does not phosphorylate ManNAc to ManNAc-6-P
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
UDP N acetylglucosamine 2 epimerase, N acetylmannosamine kinase (GNE) is a bifunctional enzyme in the cytosol that is involved in the first two critical, rate limiting steps of sialic acid (Neu5Ac, N acetylneuraminic acid) biosynthesis. In the second reaction, GNE phosphorylates N-acetylmannosamine (ManNAc) to ManNAc-6-P. There are various disorders associated with defects in the GNE gene. Defects in GNE can cause sialuria (MIM:269921), an inborn error of metabolism characterised by cytoplasmic accumulation and increased urinary excretion of Neu5Ac (Seppala et al. 1999). Mutations causing sialuria are R266W, R266Q and R263L (Seppala et al. 1999). Defects in GNE can also cause hereditary inclusion body myopathy (IBM2; MIM:600737), an autosomal recessive neuromuscular disorder characterised by adult-onset, progressive distal and proximal muscle weakness and wastage. Muscle pathology shows rimmed vacuoles and filamentous inclusions (Eisenberg et al. 2001). The common M712T mutation can cause IBM2, as well as heterozygosity with the mutation M171V (Eisenberg et al. 2001, Argov et al. 2003, Broccolini et al. 2002). Defects in GNE can also cause Nonaka myopathy (NM; MIM:605820), an early adulthood-onset muscular disorder characterised by weakness and wastage of the lower limbs and rimmed vacuoles (Nonaka et al. 1981, Eisenberg et al. 2001). Mutations causing NK include the common V572L, either homozygous or heterozygous with C303V (Tomimitsu et al. 2002, Kayashima et al. 2002) and the heterozygous M712T with A631V indicated that NK and IBM2 are allelic, if not identical, disorders (Tomimitsu et al. 2004).
Literature References
PubMed ID Title Journal Year
7252518 Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation

Nonaka, I, Sunohara, N, Ishiura, S, Satoyoshi, E

J. Neurol. Sci. 1981
11528398 The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy

Eisenberg, I, Avidan, N, Potikha, T, Hochner, H, Chen, M, Olender, T, Barash, M, Shemesh, M, Sadeh, M, Grabov-Nardini, G, Shmilevich, I, Friedmann, A, Karpati, G, Bradley, WG, Baumbach, L, Lancet, D, Asher, EB, Beckmann, JS, Argov, Z, Mitrani-Rosenbaum, S

Nat. Genet. 2001
12473780 An Italian family with autosomal recessive inclusion-body myopathy and mutations in the GNE gene

Broccolini, A, Pescatori, M, D'Amico, A, Sabino, A, Silvestri, G, Ricci, E, Servidei, S, Tonali, PA, Mirabella, M

Neurology 2002
11916006 Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE)

Kayashima, T, Matsuo, H, Satoh, A, Ohta, T, Yoshiura, K, Matsumoto, N, Nakane, Y, Niikawa, N, Kishino, T

J. Hum. Genet. 2002
12743242 Hereditary inclusion body myopathy: the Middle Eastern genetic cluster

Argov, Z, Eisenberg, I, Grabov-Nardini, G, Sadeh, M, Wirguin, I, Soffer, D, Mitrani-Rosenbaum, S

Neurology 2003
12177386 Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene

Tomimitsu, H, Ishikawa, K, Shimizu, J, Ohkoshi, N, Kanazawa, I, Mizusawa, H

Neurology 2002
10330343 Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme

Seppala, R, Lehto, VP, Gahl, WA

Am. J. Hum. Genet. 1999
15136692 Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant

Tomimitsu, H, Shimizu, J, Ishikawa, K, Ohkoshi, N, Kanazawa, I, Mizusawa, H

Neurology 2004
Participants
Input
Participates
as an event of
Catalyst Activity

N-acylmannosamine kinase activity of GNE mutants [cytosol]

Physical Entity
GNE mutants [cytosol] (Homo sapiens)
Activity
N-acylmannosamine kinase activity (GO:0009384)
Normal reaction
GNE phosphorylates ManNAc to ManNAc-6-P (Homo sapiens)
Functional status

Loss of function of GNE mutants [cytosol]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
sialuria DOID:3659
inclusion body myositis DOID:3429 Inclusion body myositis (disorder), inclusion body myositis
Cross References
Mondo
Authored
Jassal, B  (2013-08-13)
Reviewed
Spillmann, D  (2015-04-30)
Created
Jassal, B  (2013-08-13)
Cite Us!