The Na+ leak channel (NALCN) is highly expressed in the brain, where it mediates a persistent current that contributes to resting membrane potential (RMP) of neurons. This regulates neuronal excitability underlying processes, such as locomotion and circadian rhythm. Recently, we have shown, co-expression UNC80, UNC79 FAM155A required form functional NALCN complex heterologous systems. To date, ...

Proprotein Convertase Subtilisin Kexin type 9 (PCSK9), comprises 12 exons, encoded for an enzyme which plays a critical role in the regulation of circulating low density lipoprotein. The gain-of-function (GOF) mutations aggravate degradation LDL receptors, resulting familial hypercholesterolemia (FH), while loss-of-function (LOF) lead to higher levels lower cholesterol, and preventing from card...

Abstract Hereditary a-tryptasemia (HaT) is a genetic trait defined by elevated serum tryptase caused increased TPSAB1 copy number and associated with multiple phenotypes including pain. CACNA1H encoding the voltage-gated calcium channel Ca V3.2 overlaps locus where partial gain-of-function (GOF) haplotype containing 3 linked variants has been shown to be co-inherited HaT in ~2/3 of individuals....

Abstract The coordinated effort of the immune system in host defense is dependent upon proper release and interpretation different cytokine signals. Several examples monogenic diseases targeting JAK-STAT pathway reveal there still a critical need to understand basic principles signaling output. For example, patients with STAT1 gain-of-function (GOF) mutations exhibit type 1/IFN-gamma bias that ...

Most mutant alleles in the Fz-PCP pathway genes were discovered in classic Drosophila screens looking for recessive loss-of-function (LOF) mutations. Nonetheless, although Fz-PCP signaling is sensitive to increased doses of PCP gene products, not many screens have been performed in the wing under genetically engineered Fz overexpression conditions, mostly because the Fz phenotypes were strong a...

p53 deficiency enhances the efficiency of somatic cell reprogramming to a pluripotent state. As p53 is usually mutated in human tumors and many mutated forms of p53 gain novel activities, we studied the influence of mutant p53 (mut-p53) on somatic cell reprogramming. Our data indicate a novel gain of function (GOF) property for mut-p53, which markedly enhanced the efficiency of the reprogrammin...

Prion diseases are disorders that share several characteristics that are typical of many neurodegenerative diseases. Recently, several studies have extended the prion concept to pathological aggregation in malignant tumors involving misfolded p53, a tumor-suppressor protein. The aggregation of p53 and its coaggregation with p53 family members, p63 and p73, have been shown. Certain p53 mutants e...