The sequence variant c.1501T>A in exon 12 changes cysteine in amino acid position 501 to serine (p.Cys501Ser). It has only been detected on the same allele (in cis) as the more severe missense mutation p.Arg950Pro. p.Cys501 is conserved among species and is involved in a disulphide-bridge with Cys493, which supports a conserved glycosylation at position 497. However, studies in transfected cells show that p.Ser501 is active and localized to the lysosomes but shows slightly abnormal intracellular processing. Its role in the development of alpha-mannosidosis is unclear. |
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