The PLCH2 gene encodes an enzyme belonging to the phosphoinositide-specific phospholipase C family. Phospholipase enzymes are responsible for hydrolyzing phospholipids into fatty acids and other lipophilic molecules. The PLCH2 enzyme is hence required for catalyzing the synthesis of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). The phospholipase activity of PLCH2 is highly sensitive to calcium concentration and is activated by G protein beta-1-gamma-2 dimers.
Apart from phosphatidylinositol and inositol phosphate metabolism and lipid catabolism, the enzyme also plays a role in intracellular signal transduction as the second messengers DAG and IP3 act as substrates for the synthesis of other important signaling molecules.
The PLCH2 gene is located on the short arm of chromosome 1. It spans a length of 89.7 kb of DNA and its coding sequence is spread across 28 exons. The gene encodes a 154 kDa protein product composed of 1416 amino acids. At least four distinct isoforms of the PLCH2 protein exist due to alternative splicing of the exons 21a, 21b, 21c and 22. The gene is primarily expressed in the nervous system, but expression is also seen in the skin, spleen and pancreas.
Monies et al. (2017) researched the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 5-year-old female, presented with a failure to thrive, fine and gross motor delay, speech delay, autistic features, hypotonia, seizures, bilateral white matter changes in the brain, poor vision, global developmental delay and epilepsy. Whole exome sequencing helped identify a homozygous mutation (c.2132G>A, p.C711Y) in exon 16 of the patient’s PLCH2 gene. This gene mutation was considered a candidate for pathogenicity as it was a novel variant located within the ‘runs of homozygosity’ and was predicted to be deleterious; and mutations in its paralog gene PLCH1 had been implicated in a disease with an overlapping phenotype. The authors noted that further studies are required to confirm this association.
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