Topic: loss-of-function

Affective disorders, which can be categorized into depressive and bipolar disorders, represent a leading cause of disability worldwide. Despite their considerable prevalence, the intricate molecular and cellular mechanisms underlying these conditions remain elusive, mainly due to their complex etiologies and heterogeneous clinical presentations. Over the past years, the serotonergic system has emerged as a focal point in understanding the pathophysiological and therapeutic responses of affective disorders. Among the major regulators of this system, the serotonin transporter (SERT), which media

The DPYSL5 (Dihydropyrimidinase like 5) gene encodes a cytosolic protein which regulates axonal guidance and neuritic growth. We initially described two missense mutations (p.Glu41Lys, recurrent ; p.Gly47Arg) in DPYSL5 gene in nine individuals presenting intellectual disability and agenesis of the corpus callosum. Interestingly, both variants caused abnormal neuronal development and impaired interaction between DPYSL5 and MAP2 and TUBB3 proteins. Recently, a third de novo variant (p.Glu25Lys) was identified in four individuals with a similar clinical phenotype. Various studies described DPYSL5

Glioblastoma (GBM) patients have a poor prognosis due to glioblastoma stem cells (GSCs) that resist current treatments. Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins, particularly Lrig1, play a role in growth factor signaling in various stem cells. In this study, the function of Lrig1 in glioblastoma stem cells was investigated using gain- and loss-of-function experiments. Removing Lrig1 in cultured GBM stem cells increased proliferation and reduced quiescence, while overexpression of Lrig1 enhanced quiescence and reduced proliferation. Mice transplanted with Lrig1-defic

Kv7.2 and Kv7.3 are neuronal voltage-gated potassium channel subunits encoded by KCNQ2 and KCNQ3 genes, underlying the M-current, a slowly activating and non-inactivating current involved in neuronal excitability control. Kv7.2 mutations lead to neonatal-onset epilepsies including developmental and epileptic encephalopathies (DEE), characterized by seizures, electroencephalographic abnormalities, and developmental delay. When expressed in vitro, most Kv7.2 variants cause loss-of-function (LoF) effects. In this study, we aimed to functionally characterize a de novo KCNQ2 mutation in the pore of