KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders

Xinchen Teng, Abdel Aouacheria, Loïc Lionnard, Kyle A. Metz, Lucian Soane, Atsushi Kamiya, J. Marie Hardwick

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)887-902
Number of pages16
JournalCNS Neuroscience and Therapeutics
Volume25
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • KCTD11
  • KCTD13
  • KCTD7
  • Neurodegeneration
  • Neurodevelopmental disorders

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders'. Together they form a unique fingerprint.

Cite this