Open AccessKCTD : A new gene family involved in neurodevelopmental and neuropsychiatric disorders
Author(s) -
Teng Xinchen,
Aouacheria Abdel,
Lionnard Loïc,
Metz Kyle A.,
Soane Lucian,
Kamiya Atsushi,
Hardwick J. Marie
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13156
Subject(s) - schizophrenia (object oriented programming) , neurocognitive , neuroscience , disease , neurodegeneration , autism , biology , bipolar disorder , bioinformatics , psychology , medicine , psychiatry , cognition , pathology
The underlying molecular basis for neurodevelopmental or neuropsychiatric disorders is not known. In contrast, mechanistic understanding of other brain disorders including neurodegeneration has advanced considerably. Yet, these do not approach the knowledge accrued for many cancers with precision therapeutics acting on well‐characterized targets. Although the identification of genes responsible for neurodevelopmental and neuropsychiatric disorders remains a major obstacle, the few causally associated genes are ripe for discovery by focusing efforts to dissect their mechanisms. Here, we make a case for delving into mechanisms of the poorly characterized human KCTD gene family. Varying levels of evidence support their roles in neurocognitive disorders ( KCTD3 ), neurodevelopmental disease ( KCTD7 ), bipolar disorder ( KCTD12 ), autism and schizophrenia ( KCTD13 ), movement disorders ( KCTD17 ), cancer ( KCTD11 ), and obesity ( KCTD15 ). Collective knowledge about these genes adds enhanced value, and critical insights into potential disease mechanisms have come from unexpected sources. Translation of basic research on the KCTD‐related yeast protein Whi2 has revealed roles in nutrient signaling to mTORC1 (KCTD11) and an autophagy‐lysosome pathway affecting mitochondria (KCTD7). Recent biochemical and structure‐based studies (KCTD12, KCTD13, KCTD16) reveal mechanisms of regulating membrane channel activities through modulation of distinct GTPases. We explore how these seemingly varied functions may be disease related.