MAGEL2

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.{{Cite web |title=Genome Data Viewer - NCBI |url=https://www.ncbi.nlm.nih.gov/gdv/browser/genome/?id=GCF_000001405.40 |access-date=2025-03-07 |website=www.ncbi.nlm.nih.gov}} This gene is expressed from the paternal chromosome 15.{{cite journal | vauthors = Boccaccio I, Glatt-Deeley H, Watrin F, Roëckel N, Lalande M, Muscatelli F | title = The human MAGEL2 gene and its mouse homologue are paternally expressed and mapped to the Prader-Willi region | journal = Human Molecular Genetics | volume = 8 | issue = 13 | pages = 2497–2505 | date = December 1999 | pmid = 10556298 | doi = 10.1093/hmg/8.13.2497 }}

This protein is known to regulate AMPA receptors in hypothalamus.{{cite journal | vauthors = Ates T, Oncul M, Dilsiz P, Topcu IC, Civas CC, Alp MI, Aklan I, Ates Oz E, Yavuz Y, Yilmaz B, Sayar Atasoy N, Atasoy D | title = Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance | journal = Neurobiology of Disease | volume = 121 | pages = 58–64 | date = January 2019 | pmid = 30240706 | doi = 10.1016/j.nbd.2018.09.017 }} Also it can regualte secretion of hormones such as: oxytocin, arginine vasopressin, somatostatin, TSH, somatotropin, LH.{{cite journal | vauthors = Schubert T, Schaaf CP | title = MAGEL2 (patho-)physiology and Schaaf-Yang syndrome | journal = Developmental Medicine and Child Neurology | volume = 67 | issue = 1 | pages = 35–48 | date = January 2025 | pmid = 38950199 | pmc = 11625468 | doi = 10.1111/dmcn.16018 }} 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.{{cite journal | vauthors = Temkin P, Morishita W, Goswami D, Arendt K, Chen L, Malenka R | title = The Retromer Supports AMPA Receptor Trafficking During LTP | journal = Neuron | volume = 94 | issue = 1 | pages = 74–82.e5 | date = April 2017 | pmid = 28384478 | doi = 10.1016/j.neuron.2017.03.020 | doi-access = free }}{{cite journal | vauthors = Ates T, Oncul M, Dilsiz P, Topcu IC, Civas CC, Alp MI, Aklan I, Ates Oz E, Yavuz Y, Yilmaz B, Sayar Atasoy N, Atasoy D | title = Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance | journal = Neurobiology of Disease | volume = 121 | pages = 58–64 | date = January 2019 | pmid = 30240706 | doi = 10.1016/j.nbd.2018.09.017 }}

MAGEL2 is required for balance of serotonin, dopamine and noradrenaline concentrations, in Magel2-null mice concetrations of that neurotransmitters had been decreased.{{cite journal | vauthors = Luck C, Vitaterna MH, Wevrick R | title = Dopamine pathway imbalance in mice lacking Magel2, a Prader-Willi syndrome candidate gene | journal = Behavioral Neuroscience | volume = 130 | issue = 4 | pages = 448–459 | date = August 2016 | pmid = 27254754 | doi = 10.1037/bne0000150 | url = https://psycnet.apa.org/doiLanding?doi=10.1037/bne0000150 | archive-url = http://web.archive.org/web/20240603233820/https://psycnet.apa.org/doiLanding?doi=10.1037/bne0000150 | archive-date = 2024-06-03 | url-access = subscription }}{{cite journal | vauthors = Mercer RE, Kwolek EM, Bischof JM, van Eede M, Henkelman RM, Wevrick R | title = Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2 | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 150B | issue = 8 | pages = 1085–1099 | date = December 2009 | pmid = 19199291 | doi = 10.1002/ajmg.b.30934 }}

As mentioned above MAGEL2 participates in MUST complex, which promotes endosomal F-actin polymerization.{{cite journal | vauthors = Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK, Potts PR | title = Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination | language = English | journal = Cell | volume = 152 | issue = 5 | pages = 1051–1064 | date = February 2013 | pmid = 23452853 | pmc = 3640276 | doi = 10.1016/j.cell.2013.01.051 }}

Prader-Willi syndrome (PWS) is a rare genetic disorder that is caused by maternal UPD(15) or deletions/epimutations on paternal chromosome 15.{{Citation |last1=Fermin Gutierrez |first1=Maria A. |title=Prader-Willi Syndrome |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK553161/ |access-date=2025-03-07 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31985954 |last2=Daley |first2=Sharon F. |last3=Mendez |first3=Magda D.}} 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.{{Cite web |title=Prader-Willi syndrome - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997 |access-date=2025-03-07 |website=Mayo Clinic |language=en}}

Deletion of MAGEL2 (and other genes that are located on the same region) contributes to symptoms in PWS.{{cite journal | vauthors = Chen H, Victor AK, Klein J, Tacer KF, Tai DJ, de Esch C, Nuttle A, Temirov J, Burnett LC, Rosenbaum M, Zhang Y, Ding L, Moresco JJ, Diedrich JK, Yates JR, Tillman HS, Leibel RL, Talkowski ME, Billadeau DD, Reiter LT, Potts PR | title = Loss of MAGEL2 in Prader-Willi syndrome leads to decreased secretory granule and neuropeptide production | journal = JCI Insight | volume = 5 | issue = 17 | date = September 2020 | pmid = 32879135 | pmc = 7526459 | doi = 10.1172/jci.insight.138576 }}

Schaaf-Yang syndrome (SYS) is a rare genetic disorder that is caused by a mutation in a paternally expressed gene MAGEL2.{{Citation |last1=Schaaf |first1=Christian P. |title=Schaaf-Yang Syndrome |date=1993 |work=GeneReviews® |editor-last=Adam |editor-first=Margaret P. |url=https://www.ncbi.nlm.nih.gov/books/NBK567492/ |access-date=2025-03-07 |place=Seattle (WA) |publisher=University of Washington, Seattle |pmid=33570896 |last2=Marbach |first2=Felix |editor2-last=Feldman |editor2-first=Jerry |editor3-last=Mirzaa |editor3-first=Ghayda M. |editor4-last=Pagon |editor4-first=Roberta A.}} 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.{{cite journal | vauthors = Negishi Y, Kurosawa K, Takano K, Matsubara K, Nishiyama T, Saitoh S | title = A nationwide survey of Schaaf-Yang syndrome in Japan | journal = Journal of Human Genetics | volume = 67 | issue = 12 | pages = 735–738 | date = December 2022 | pmid = 36220858 | doi = 10.1038/s10038-022-01089-y }}

As mentioned above, SYS is caused by LoF variants of the paternal copy of MAGEL2.{{cite journal | vauthors = Marbach F, Elgizouli M, Rech M, Beygo J, Erger F, Velmans C, Stumpel CT, Stegmann AP, Beck-Wödl S, Gillessen-Kaesbach G, Horsthemke B, Schaaf CP, Kuechler A | title = The adult phenotype of Schaaf-Yang syndrome | journal = Orphanet Journal of Rare Diseases | volume = 15 | issue = 1 | pages = 294 | date = October 2020 | pmid = 33076953 | pmc = 7574436 | doi = 10.1186/s13023-020-01557-8 | doi-access = free }}

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Category:Human proteins

Category:Human genetics