The ABHD6 gene encodes a lipase enzyme responsible for the hydrolysis of medium-chain saturated monoacylglycerols such as 2-arachidonoylglycerol. By controlling the accumulation of 2-arachidonoylglycerol at the cannabinoid receptors, it is involved in the regulation of endocannabinoid signaling pathways. ABHD6 also has phospholipase activity, and is involved in the catabolism of lysophosphatidylglycerol. Based on orthologue studies, the ABHD6 protein has also been implicated in the negative regulation of cell migration and long term synaptic depression.
The enzyme is an integral membrane protein consisting of a conserved alpha/beta-hydrolase domain (ABHD), an N-terminal signal sequence and two transmembrane domains. The residues ser148, asp278, and his306 form a catalytic triad that is required for enzyme function.
The ABHD6 gene is located on the short arm of chromosome 3 at position 3p14.3. It spans a length of 58.1 kb of DNA and its coding sequence is spread across 10 exons. The gene encodes a 38.3 kDa protein consisting of 337 amino acids. The gene is found to be expressed in several tissues including the liver, kidney, ovary, nervous system, lung and skin.
Monies et al. (2017) discussed the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 6-year-old female, presented with speech and fine motor delay, intellectual disability, autistic features, pachygyria, diffuse white matter and signal changes. Using whole exome sequencing, a homozygous mutation (185A>C, p.Y62S) was identified in exon 3 of the patient’s ABHD6 gene. This gene mutation was considered a candidate for pathogenicity as it was a novel variant located within the autozygome that was predicted to be deleterious, and the gene had been reported to be involved in synapse function. The authors noted that further studies were required to confirm this association.
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