MAGEL2


MAGE family member L2 is a protein that in human is encoded by the MAGEL2 gene. This protein is a ubuquitin ligase enhancer which is necessary for endsomal protein recycling. This protein is a part of MUST complex.

Gene

The MAGEL2 gene is located on the long arm of chromosome 15 on position 11.2, from base pair 23,643,549 to base pair 23,647,867. This gene is expressed from the paternal chromosome 15.

Function

This protein is known to regulate AMPA receptors in hypothalamus. Also it can regualte secretion of hormones such as: oxytocin, arginine vasopressin, somatostatin, TSH, somatotropin, LH. Loss of that protein showed decreased neuoronal activity in hypothalamus and hippocampus of mice via AMPA receptor trafficking defects, consequently neuronal activity gets disrupted and synaptic excitation/inhibition balance is lost.
MAGEL2 is required for balance of serotonin, dopamine and noradrenaline concentrations, in Magel2-null mice concetrations of that neurotransmitters had been decreased.
As mentioned above MAGEL2 participates in MUST complex, which promotes endosomal F-actin polymerization.

Clinical significance

Prader-Willi syndrome

Prader-Willi syndrome is a rare genetic disorder that is caused by maternal UPD or deletions/epimutations on paternal chromosome 15. PWS can cause variety of symptoms from hypotoniain infancy to behavioural problems in early childhood. Some symptoms can be found in infants aside from hypotonia, are a poor eye coordination, almond-shaped eyes, thin upper lip, also, due to hypotonia, problems with sucking reflex. Their cries are weak and they have difficulty of waking up.
Deletion of MAGEL2 contributes to symptoms in PWS.

Schaaf-Yang syndrome

Schaaf-Yang syndrome is a rare genetic disorder that is caused by a mutation in a paternally expressed gene MAGEL2. The signs of this disease are: hypotonia, developmental delay and contractures of joints, also another signs of that disease are unique facial features, small hands, problems with eye and short stature.
As mentioned above, SYS is caused by LoF variants of the paternal copy of MAGEL2.