Biology:MAGEL2

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Short description: Protein-coding gene in the species Homo sapiens

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


MAGE family member L2 (MAGEL2) 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.[1] This protein is a part of MUST complex (which consists of MAGEL2-USP7-TRIM27 complex).[2][3]

Gene

The MAGEL2 gene is located on the long(q) arm of chromosome 15 on position 11.2, from base pair 23,643,549 to base pair 23,647,867.[4] This gene is expressed from the paternal chromosome 15.[5]

Function

This protein is known to regulate AMPA receptors in hypothalamus.[6] Also it can regualte secretion of hormones such as: oxytocin, arginine vasopressin, somatostatin, TSH, somatotropin, LH.[7] 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.[8][9]

MAGEL2 is required for balance of serotonin, dopamine and noradrenaline concentrations, in Magel2-null mice concetrations of that neurotransmitters had been decreased.[10][11]

As mentioned above MAGEL2 participates in MUST complex, which promotes endosomal F-actin polymerization.[12]

Clinical significance

Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a rare genetic disorder that is caused by maternal UPD(15) or deletions/epimutations on paternal chromosome 15.[13] 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.[14]

Deletion of MAGEL2 (and other genes that are located on the same region) contributes to symptoms in PWS.[15]

Schaaf-Yang syndrome

Schaaf-Yang syndrome (SYS) is a rare genetic disorder that is caused by a mutation in a paternally expressed gene MAGEL2.[16] 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.[17]

As mentioned above, SYS is caused by LoF variants of the paternal copy of MAGEL2.[18][19]

References

  1. ↑ "Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism". Nature Genetics 45 (11): 1405–1408. November 2013. doi:10.1038/ng.2776. PMID 24076603. 
  2. ↑ "Emerging roles of the MAGE protein family in stress response pathways". The Journal of Biological Chemistry 295 (47): 16121–16155. November 2020. doi:10.1074/jbc.REV120.008029. PMID 32921631. 
  3. ↑ "Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination". Cell 152 (5): 1051–1064. February 2013. doi:10.1016/j.cell.2013.01.051. PMID 23452853. 
  4. ↑ "Genome Data Viewer - NCBI". https://www.ncbi.nlm.nih.gov/gdv/browser/genome/?id=GCF_000001405.40. 
  5. ↑ "The human MAGEL2 gene and its mouse homologue are paternally expressed and mapped to the Prader-Willi region". Human Molecular Genetics 8 (13): 2497–2505. December 1999. doi:10.1093/hmg/8.13.2497. PMID 10556298. 
  6. ↑ "Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance". Neurobiology of Disease 121: 58–64. January 2019. doi:10.1016/j.nbd.2018.09.017. PMID 30240706. 
  7. ↑ "MAGEL2 (patho-)physiology and Schaaf-Yang syndrome". Developmental Medicine and Child Neurology 67 (1): 35–48. January 2025. doi:10.1111/dmcn.16018. PMID 38950199. 
  8. ↑ "The Retromer Supports AMPA Receptor Trafficking During LTP". Neuron 94 (1): 74–82.e5. April 2017. doi:10.1016/j.neuron.2017.03.020. PMID 28384478. 
  9. ↑ "Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance". Neurobiology of Disease 121: 58–64. January 2019. doi:10.1016/j.nbd.2018.09.017. PMID 30240706. 
  10. ↑ "Dopamine pathway imbalance in mice lacking Magel2, a Prader-Willi syndrome candidate gene". Behavioral Neuroscience 130 (4): 448–459. August 2016. doi:10.1037/bne0000150. PMID 27254754. https://psycnet.apa.org/doiLanding?doi=10.1037/bne0000150. Retrieved 2025-03-07. 
  11. ↑ "Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 150B (8): 1085–1099. December 2009. doi:10.1002/ajmg.b.30934. PMID 19199291. 
  12. ↑ "Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination" (in English). Cell 152 (5): 1051–1064. February 2013. doi:10.1016/j.cell.2013.01.051. PMID 23452853. 
  13. ↑ Fermin Gutierrez, Maria A.; Daley, Sharon F.; Mendez, Magda D. (2025), "Prader-Willi Syndrome", StatPearls (Treasure Island (FL): StatPearls Publishing), PMID 31985954, https://www.ncbi.nlm.nih.gov/books/NBK553161/, retrieved 2025-03-07 
  14. ↑ "Prader-Willi syndrome - Symptoms and causes" (in en). https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997. 
  15. ↑ "Loss of MAGEL2 in Prader-Willi syndrome leads to decreased secretory granule and neuropeptide production". JCI Insight 5 (17). September 2020. doi:10.1172/jci.insight.138576. PMID 32879135. 
  16. ↑ "Schaaf-Yang Syndrome". GeneReviews®. Seattle (WA): University of Washington, Seattle. 1993. https://www.ncbi.nlm.nih.gov/books/NBK567492/. Retrieved 2025-03-07. 
  17. ↑ "A nationwide survey of Schaaf-Yang syndrome in Japan". Journal of Human Genetics 67 (12): 735–738. December 2022. doi:10.1038/s10038-022-01089-y. PMID 36220858. 
  18. ↑ "The adult phenotype of Schaaf-Yang syndrome". Orphanet Journal of Rare Diseases 15 (1). October 2020. doi:10.1186/s13023-020-01557-8. PMID 33076953. 
  19. ↑ "Longitudinal analysis of electroencephalography pattern changes in an infant with Schaaf-Yang syndrome and a novel mutation in melanoma antigen L2 (MAGEL2)". Molecular Genetics & Genomic Medicine 10 (6). June 2022. doi:10.1002/mgg3.1932. PMID 35343647. 



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