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- W2016227601 abstract "The overwhelming amount of available genomic sequence variation information demands a streamlined approach to examine known pathogenic mutations of any given protein. Here we seek to outline a strategy to easily classify pathogenic missense mutations that cause protein misfolding and are thus good candidates for chaperone-based therapeutic strategies, using previously identified mutations in the gene CASK. We applied a battery of bioinformatics algorithms designed to predict potential impact on protein structure to five pathogenic missense mutations in the protein CASK that have been shown to underlie pathologies ranging from X-linked mental retardation to autism spectrum disorder. A successful classification of the mutations as damaging was not consistently achieved despite the known pathogenicity. In addition to the bioinformatics analyses, we performed molecular modeling and phylogenetic comparisons. Finally, we developed a simple high-throughput imaging assay to measure the misfolding propensity of the CASK mutants in situ. Our data suggests that a phylogenetic analysis may be a robust method for predicting structurally damaging mutations in CASK. Mutations in two evolutionarily invariant residues (Y728C and W919R) exhibited a strong propensity to misfold and form visible aggregates in the cytosolic milieu. The remaining mutations (R28L, Y268H, and P396S) showed no evidence of aggregation and maintained their interactions with known CASK binding partners liprin-α3 Mint-1, and Veli, indicating an intact structure. Intriguingly, the protein aggregation caused by the Y728C and W919R mutations was reversed by treating the cells with a chemical chaperone (glycerol), providing a possible therapeutic strategy for treating structural mutations in CASK in the future." @default.
- W2016227601 created "2016-06-24" @default.
- W2016227601 creator A5002775620 @default.
- W2016227601 creator A5009100929 @default.
- W2016227601 creator A5086502784 @default.
- W2016227601 date "2014-02-05" @default.
- W2016227601 modified "2023-09-25" @default.
- W2016227601 title "Identification and Glycerol-Induced Correction of Misfolding Mutations in the X-Linked Mental Retardation Gene CASK" @default.
- W2016227601 cites W14541597 @default.
- W2016227601 cites W1510612347 @default.
- W2016227601 cites W1585995761 @default.
- W2016227601 cites W1607931568 @default.
- W2016227601 cites W1919311176 @default.
- W2016227601 cites W1963697504 @default.
- W2016227601 cites W1966771308 @default.
- W2016227601 cites W1972796001 @default.
- W2016227601 cites W1973160416 @default.
- W2016227601 cites W1975405079 @default.
- W2016227601 cites W1977677498 @default.
- W2016227601 cites W1980740976 @default.
- W2016227601 cites W1981434287 @default.
- W2016227601 cites W1982714879 @default.
- W2016227601 cites W1985006546 @default.
- W2016227601 cites W1985903139 @default.
- W2016227601 cites W1991103963 @default.
- W2016227601 cites W1992426410 @default.
- W2016227601 cites W1996423252 @default.
- W2016227601 cites W1997990960 @default.
- W2016227601 cites W1998096683 @default.
- W2016227601 cites W1999369847 @default.
- W2016227601 cites W2008722691 @default.
- W2016227601 cites W2023490488 @default.
- W2016227601 cites W2024663595 @default.
- W2016227601 cites W2030776726 @default.
- W2016227601 cites W2031553026 @default.
- W2016227601 cites W2032179525 @default.
- W2016227601 cites W2032233949 @default.
- W2016227601 cites W2032244100 @default.
- W2016227601 cites W2032258216 @default.
- W2016227601 cites W2036634847 @default.
- W2016227601 cites W2042920344 @default.
- W2016227601 cites W2048796422 @default.
- W2016227601 cites W2050939226 @default.
- W2016227601 cites W2053820259 @default.
- W2016227601 cites W2055193239 @default.
- W2016227601 cites W2059145105 @default.
- W2016227601 cites W2060043254 @default.
- W2016227601 cites W2069337540 @default.
- W2016227601 cites W2069974072 @default.
- W2016227601 cites W2075725530 @default.
- W2016227601 cites W2077596705 @default.
- W2016227601 cites W2081868581 @default.
- W2016227601 cites W2085344563 @default.
- W2016227601 cites W2091738825 @default.
- W2016227601 cites W2093202312 @default.
- W2016227601 cites W2093807978 @default.
- W2016227601 cites W2094014906 @default.
- W2016227601 cites W2097866765 @default.
- W2016227601 cites W2098500786 @default.
- W2016227601 cites W2099387330 @default.
- W2016227601 cites W2099540110 @default.
- W2016227601 cites W2099564671 @default.
- W2016227601 cites W2099589970 @default.
- W2016227601 cites W2102978407 @default.
- W2016227601 cites W2105908180 @default.
- W2016227601 cites W2109453395 @default.
- W2016227601 cites W2110110505 @default.
- W2016227601 cites W2111256689 @default.
- W2016227601 cites W2114520383 @default.
- W2016227601 cites W2115734610 @default.
- W2016227601 cites W2120587971 @default.
- W2016227601 cites W2120772351 @default.
- W2016227601 cites W2126802086 @default.
- W2016227601 cites W2127322768 @default.
- W2016227601 cites W2131104106 @default.
- W2016227601 cites W2131965976 @default.
- W2016227601 cites W2132629607 @default.
- W2016227601 cites W2132911146 @default.
- W2016227601 cites W2133425057 @default.
- W2016227601 cites W2135159333 @default.
- W2016227601 cites W2136513422 @default.
- W2016227601 cites W2138039051 @default.
- W2016227601 cites W2140490140 @default.
- W2016227601 cites W2144221219 @default.
- W2016227601 cites W2146624371 @default.
- W2016227601 cites W2147645629 @default.
- W2016227601 cites W2151624292 @default.
- W2016227601 cites W2153187042 @default.
- W2016227601 cites W2156678798 @default.
- W2016227601 cites W2157048103 @default.
- W2016227601 cites W2161199282 @default.
- W2016227601 cites W2161910692 @default.
- W2016227601 cites W2164683872 @default.
- W2016227601 cites W2165554927 @default.
- W2016227601 cites W2168621448 @default.
- W2016227601 cites W2168749685 @default.
- W2016227601 cites W2169150541 @default.
- W2016227601 cites W2172034373 @default.