KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders.
Xinchen TengAbdel AouacheriaLoïc LionnardKyle A MetzLucian SoaneAtsushi KamiyaJ Marie HardwickPublished in: CNS neuroscience & therapeutics (2020)
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.
Keyphrases
- bipolar disorder
- healthcare
- genome wide
- metabolic syndrome
- cell death
- magnetic resonance
- oxidative stress
- single cell
- autism spectrum disorder
- risk assessment
- gene expression
- dna methylation
- squamous cell carcinoma
- multiple sclerosis
- weight loss
- resting state
- intellectual disability
- adipose tissue
- bioinformatics analysis
- blood brain barrier
- high throughput
- human health
- cerebral ischemia
- lymph node metastasis
- genome wide analysis
- single molecule