CLC-Related Proteins in Diseases

Date

2023

Authors

Bretag, A.H.
Ma, L.
Hryciw, D.H.

Editors

Zheng, J.
Trudeau, M.C.

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Book chapter

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Source details - Title: Textbook of Ion Channels Volume III: Regulation, Physiology, and Diseases, 2023 / Zheng, J., Trudeau, M.C. (ed./s), vol.3, Ch.11, pp.189-205

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Abstract

All nine CLC proteins (with over 1000 genetic variations in total) and three different CLC auxiliary subunits (with more than 70 genetic variations) have now been associated with some 20 distinct human diseases. This chapter adds new neurological and endocrine disorders associated with ClC-2, ClC-3, ClC-4, ClC-6 and ClC-7 to the wide variety of diseases already linked to CLC-related proteins. Considerable advances have been made in understanding how mutated CLC protein dysfunction causes disease, most apparent where altered membrane Cl– flux can be related to transmembrane voltage, to ion homeostasis or to transepithelial transport. For many CLC-related proteins, however, the precise relationship between mutation and disease remains unknown, especially in neurodegeneration. Also, still perplexing is the variability in disease expression, and the penetrance and apparent dominant or recessive inheritance involving the same genetic variant in one or different pedigrees.

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Copyright 2023 selection and editorial matter, Jie Zheng and Matthew C. Trudeau; individual chapters, the contributors

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