Abstract
UCHL1 (Ubiquitin Carboxy-terminal hydrolase L1) is a deubiquitinating enzyme that is selectively expressed in neurons and repairs the neurons after injury by removing abnormal proteins through autophagy and UPP (ubiquitin proteasome pathway). It co-localizes with α-synuclein in Nigral Lewy bodies causing sporadic Parkinson's disease (PD) and UCHL1 S18Y variant has been identified as a risk factor. Additionally, p.E7A, p.R178Q and p.A216D are associated with early onset progressive neuro-degeneration. A total of 3518 SNPs (Single Nucleotide Polymorphisms) within UCHL1 are documented in NCBI and no comprehensive studies have addressed the effects of these SNPs. We analysed thirty non-synonymous (ns) SNPs using Ensembl Variant Effect Predictor (VEP) and iSTABLE prediction tools and eleven nsSNPs were found to be deleterious, possibly/probably damaging and alter protein stability. ConSurf analysis revealed that 8/11 nsSNPs were conserved and these SNPs were subjected to 3D molecular dynamic studies. Furthermore, PolymiRTS database 2.0 analysis indicated that 4/24, 3′-UTR SNPs affected the conserved miRNA target site or created a new target site for other miRNAs. Also, GeneMANIA predicted that UCHL1 forms interactome with several neuronal and ubiquitin pathway genes. To conclude, SNP analysis of UCHL1 has predicted eight ns-SNPs and four 3′- UTR SNPs that show divergence from its normal activity and may affect the function of other gene components within its interacting network.
Published Version
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