Defective SLC17A5 does not cotransport Neu5Ac, H+ from lysosomal lumen to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
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SLC17A5 encodes a lysosomal sialic acid transporter, sialin (AST, membrane glycoprotein HP59) which exports sialic acid (N-acetylneuraminic acid, Neu5Ac) derived from the degradation of glycoconjugates from lysosomes. This export is dependent on the proton electrochemical gradient across the lysosomal membrane. SLC17A5 is present in the pathological tumor vasculature of the lung, breast, colon, and ovary, but not in the normal vasculature, suggesting that the protein may be critical to pathological angiogenesis. SLC17A5 is not expressed in a variety of normal tissues, but is significantly expressed in human fetal lung. Defects in SLC17A5 cause Salla disease (SD) and infantile sialic acid storage disorder (ISSD aka N-acetylneuraminic acid storage disease, NSD). These diseases belong to the sialic acid storage diseases (SASDs) and are autosomal recessive neurodegenerative disorders characterised by hypotonia, cerebellar ataxia, mental retardation with patients excreting large amounts of free Neu5Ac in the urine (Verheijen et al. 1999, Aula et al. 2000). SD is an adult form of SASD and is particularly found in Northern Finland. The build-up of Neu5Ac in the brain and other tissues result in the clinical phenotype. Mutations that can cause SD include the founder mutation R39C and K136E (Verheijen et al. 1999, Aula et al. 2000, Biancheri et al. 2005). Mutations causing the more severe ISSD include T178Nfs*34, I373Lfs*26, H183R and R334R (Verheijen et al. 1999).
Literature References
PubMed ID Title Journal Year
10581036 A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases

Peltonen, Leena, van der Spek, PJ, Verbeek, E, Joosse, M, Galjaard, H, Aula, P, Aula, N, Havelaar, AC, Verheijen, FW, Mancini, GM, Beerens, CE

Nat Genet 1999
10947946 The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage diseases indicates some genotype-phenotype correlation

Peltonen, Leena, Mancini, G, Månsson, JE, Aula, P, Aula, N, Timonen, R, Verheijen, F, Salomäki, P

Am J Hum Genet 2000
16170568 Homozygosity for the p.K136E mutation in the SLC17A5 gene as cause of an Italian severe Salla disease

Mancini, GM, Verbeek, HA, Minetti, C, Corsolini, F, Schot, R, Assereto, S, Verheijen, FW, Rossi, A, Filocamo, M, Biancheri, R

Neurogenetics 2005
Catalyst Activity

sialic acid:proton symporter activity of SLC17A5 mutants [lysosomal membrane]

Normal reaction
Functional status

Loss of function of SLC17A5 mutants [lysosomal membrane]

Name Identifier Synonyms
inherited metabolic disorder DOID:655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
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