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• W2947796056 abstract "Zimmermann-Laband syndrome (ZLS) is characterized by coarse facial features with gingival enlargement, intellectual disability (ID), hypertrichosis, and hypoplasia or aplasia of nails and terminal phalanges. De novo missense mutations in KCNH1 and KCNK4, encoding K+ channels, have been identified in subjects with ZLS and ZLS-like phenotype, respectively. We report de novo missense variants in KCNN3 in three individuals with typical clinical features of ZLS. KCNN3 (SK3/KCa2.3) constitutes one of three members of the small-conductance Ca2+-activated K+ (SK) channels that are part of a multiprotein complex consisting of the pore-forming channel subunits, the constitutively bound Ca2+ sensor calmodulin, protein kinase CK2, and protein phosphatase 2A. CK2 modulates Ca2+ sensitivity of the channels by phosphorylating SK-bound calmodulin. Patch-clamp whole-cell recordings of KCNN3 channel-expressing CHO cells demonstrated that disease-associated mutations result in gain of function of the mutant channels, characterized by increased Ca2+ sensitivity leading to faster and more complete activation of KCNN3 mutant channels. Pretreatment of cells with the CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole revealed basal inhibition of wild-type and mutant KCNN3 channels by CK2. Analogous experiments with the KCNN3 p.Val450Leu mutant previously identified in a family with portal hypertension indicated basal constitutive channel activity and thus a different gain-of-function mechanism compared to the ZLS-associated mutant channels. With the report on de novo KCNK4 mutations in subjects with facial dysmorphism, hypertrichosis, epilepsy, ID, and gingival overgrowth, we propose to combine the phenotypes caused by mutations in KCNH1, KCNK4, and KCNN3 in a group of neurological potassium channelopathies caused by an increase in K+ conductance." @default.
• W2947796056 created "2019-06-07" @default.
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• W2947796056 date "2019-06-01" @default.
• W2947796056 modified "2023-10-18" @default.
• W2947796056 title "Gain-of-Function Mutations in KCNN3 Encoding the Small-Conductance Ca2+-Activated K+ Channel SK3 Cause Zimmermann-Laband Syndrome" @default.
• W2947796056 cites W1138668481 @default.
• W2947796056 cites W1490915066 @default.
• W2947796056 cites W1602259950 @default.
• W2947796056 cites W1808711893 @default.
• W2947796056 cites W1937251821 @default.
• W2947796056 cites W1966296397 @default.
• W2947796056 cites W1967333038 @default.
• W2947796056 cites W1968073531 @default.
• W2947796056 cites W1969992726 @default.
• W2947796056 cites W1971888448 @default.
• W2947796056 cites W1976461271 @default.
• W2947796056 cites W1977021728 @default.
• W2947796056 cites W1984068087 @default.
• W2947796056 cites W1996558914 @default.
• W2947796056 cites W1999982652 @default.
• W2947796056 cites W2000197503 @default.
• W2947796056 cites W2008370397 @default.
• W2947796056 cites W2011867116 @default.
• W2947796056 cites W2012863615 @default.
• W2947796056 cites W2015123704 @default.
• W2947796056 cites W2032019404 @default.
• W2947796056 cites W2032855201 @default.
• W2947796056 cites W2033849297 @default.
• W2947796056 cites W2035798975 @default.
• W2947796056 cites W2043207949 @default.
• W2947796056 cites W2045949101 @default.
• W2947796056 cites W2046656676 @default.
• W2947796056 cites W2048492290 @default.
• W2947796056 cites W2060809301 @default.
• W2947796056 cites W2062436839 @default.
• W2947796056 cites W2068182798 @default.
• W2947796056 cites W2069065045 @default.
• W2947796056 cites W2071698136 @default.
• W2947796056 cites W2071889282 @default.
• W2947796056 cites W2077182790 @default.
• W2947796056 cites W2078261825 @default.
• W2947796056 cites W2090344118 @default.
• W2947796056 cites W2093852589 @default.
• W2947796056 cites W2098699260 @default.
• W2947796056 cites W2099219138 @default.
• W2947796056 cites W2113755495 @default.
• W2947796056 cites W2114130324 @default.
• W2947796056 cites W2119180969 @default.
• W2947796056 cites W2120411875 @default.
• W2947796056 cites W2122289819 @default.
• W2947796056 cites W2124120257 @default.
• W2947796056 cites W2131952724 @default.
• W2947796056 cites W2132926880 @default.
• W2947796056 cites W2137493532 @default.
• W2947796056 cites W2137833069 @default.
• W2947796056 cites W2145166145 @default.
• W2947796056 cites W2145387500 @default.
• W2947796056 cites W2152226130 @default.
• W2947796056 cites W2156578605 @default.
• W2947796056 cites W2185631784 @default.
• W2947796056 cites W2185899532 @default.
• W2947796056 cites W2207522740 @default.
• W2947796056 cites W2256016639 @default.
• W2947796056 cites W2270303516 @default.
• W2947796056 cites W2275079805 @default.
• W2947796056 cites W2289344921 @default.
• W2947796056 cites W2319026022 @default.
• W2947796056 cites W2320847165 @default.
• W2947796056 cites W2332426614 @default.
• W2947796056 cites W2337841958 @default.
• W2947796056 cites W2342335209 @default.
• W2947796056 cites W2413664424 @default.
• W2947796056 cites W2481614397 @default.
• W2947796056 cites W2565872039 @default.
• W2947796056 cites W2594218383 @default.
• W2947796056 cites W2598890256 @default.
• W2947796056 cites W2735199155 @default.
• W2947796056 cites W2784083776 @default.
• W2947796056 cites W2801595722 @default.
• W2947796056 cites W2864963571 @default.
• W2947796056 cites W2894763404 @default.
• W2947796056 cites W2894810571 @default.
• W2947796056 cites W2910797603 @default.
• W2947796056 cites W333157481 @default.
• W2947796056 doi "https://doi.org/10.1016/j.ajhg.2019.04.012" @default.
• W2947796056 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6562147" @default.
• W2947796056 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31155282" @default.

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