# MAGEL2

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**MAGE family member L2** (MAGEL2) is a protein that in human is encoded by the *MAGEL2* [gene](/source/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](/source/USP7)-[TRIM27](/source/TRIM27) complex).[2][3]

## Gene

The MAGEL2 gene is located on the long(q) arm of [chromosome 15](/source/Chromosome_15) on position 11.2, from [base pair](/source/Base_pair) 23,643,549 to [base pair](/source/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](/source/AMPA_receptor) in hypothalamus.[6] Also it can regualte secretion of hormones such as: [oxytocin](/source/Oxytocin), [arginine vasopressin](/source/Arginine-vasopressin), [somatostatin](/source/Somatostatin), [TSH](/source/Thyroid-stimulating_hormone), [somatotropin](/source/Growth_hormone), [LH](/source/Luteinizing_hormone).[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](/source/Serotonin), [dopamine](/source/Dopamine) and [noradrenaline](/source/Norepinephrine) concentrations, in Magel2-null mice concentrations 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](/source/Prader%E2%80%93Willi_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](/source/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. Schaaf CP, Gonzalez-Garay ML, Xia F, Potocki L, Gripp KW, Zhang B, Peters BA, McElwain MA, Drmanac R, Beaudet AL, Caskey CT, Yang Y (November 2013). "Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism". *Nature Genetics*. **45** (11): 1405–1408. [doi:10.1038/ng.2776](https://doi.org/10.1038/ng.2776). [PMC 3819162](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819162). [PMID 24076603](https://pubmed.ncbi.nlm.nih.gov/24076603)

1. Florke Gee RR, Chen H, Lee AK, Daly CA, Wilander BA, Fon Tacer K, Potts PR (November 2020). "Emerging roles of the MAGE protein family in stress response pathways". *The Journal of Biological Chemistry*. **295** (47): 16121–16155. [doi:10.1074/jbc.REV120.008029](https://doi.org/10.1074/jbc.REV120.008029). [PMC 7681028](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681028). [PMID 32921631](https://pubmed.ncbi.nlm.nih.gov/32921631)

1. Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK, Potts PR (February 2013). "Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination". *Cell*. **152** (5): 1051–1064. [doi:10.1016/j.cell.2013.01.051](https://doi.org/10.1016/j.cell.2013.01.051). [PMC 3640276](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640276). [PMID 23452853](https://pubmed.ncbi.nlm.nih.gov/23452853)

1. ["Genome Data Viewer - NCBI"](https://www.ncbi.nlm.nih.gov/gdv/browser/genome/?id=GCF_000001405.40). *www.ncbi.nlm.nih.gov*. Retrieved 2025-03-07.

1. Boccaccio I, Glatt-Deeley H, Watrin F, Roëckel N, Lalande M, Muscatelli F (December 1999). "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. [doi:10.1093/hmg/8.13.2497](https://doi.org/10.1093/hmg/8.13.2497). [PMID 10556298](https://pubmed.ncbi.nlm.nih.gov/10556298)

1. 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 (January 2019). "Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance". *Neurobiology of Disease*. **121**: 58–64. [doi:10.1016/j.nbd.2018.09.017](https://doi.org/10.1016/j.nbd.2018.09.017). [PMID 30240706](https://pubmed.ncbi.nlm.nih.gov/30240706)

1. Schubert T, Schaaf CP (January 2025). "MAGEL2 (patho-)physiology and Schaaf-Yang syndrome". *Developmental Medicine and Child Neurology*. **67** (1): 35–48. [doi:10.1111/dmcn.16018](https://doi.org/10.1111/dmcn.16018). [PMC 11625468](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625468). [PMID 38950199](https://pubmed.ncbi.nlm.nih.gov/38950199)

1. Temkin P, Morishita W, Goswami D, Arendt K, Chen L, Malenka R (April 2017). "The Retromer Supports AMPA Receptor Trafficking During LTP". *Neuron*. **94** (1): 74–82.e5. [doi:10.1016/j.neuron.2017.03.020](https://doi.org/10.1016/j.neuron.2017.03.020). [PMID 28384478](https://pubmed.ncbi.nlm.nih.gov/28384478)

1. 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 (January 2019). "Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation-inhibition imbalance". *Neurobiology of Disease*. **121**: 58–64. [doi:10.1016/j.nbd.2018.09.017](https://doi.org/10.1016/j.nbd.2018.09.017). [PMID 30240706](https://pubmed.ncbi.nlm.nih.gov/30240706)

1. Luck C, Vitaterna MH, Wevrick R (August 2016). ["Dopamine pathway imbalance in mice lacking Magel2, a Prader-Willi syndrome candidate gene"](https://psycnet.apa.org/doiLanding?doi=10.1037/bne0000150). *Behavioral Neuroscience*. **130** (4): 448–459. [doi:10.1037/bne0000150](https://doi.org/10.1037/bne0000150). [PMID 27254754](https://pubmed.ncbi.nlm.nih.gov/27254754). [Archived](https://web.archive.org/web/20240603233820/https://psycnet.apa.org/doiLanding?doi=10.1037/bne0000150) 2024-06-03 at the Wayback Machine. Retrieved 2025-03-07.

1. Mercer RE, Kwolek EM, Bischof JM, van Eede M, Henkelman RM, Wevrick R (December 2009). "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. [doi:10.1002/ajmg.b.30934](https://doi.org/10.1002/ajmg.b.30934). [PMID 19199291](https://pubmed.ncbi.nlm.nih.gov/19199291)

1. Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK, Potts PR (February 2013). "Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination". *Cell*. **152** (5): 1051–1064. [doi:10.1016/j.cell.2013.01.051](https://doi.org/10.1016/j.cell.2013.01.051). [PMC 3640276](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640276). [PMID 23452853](https://pubmed.ncbi.nlm.nih.gov/23452853)

1. Fermin Gutierrez, Maria A.; Daley, Sharon F.; Mendez, Magda D. (2025), ["Prader-Willi Syndrome"](https://www.ncbi.nlm.nih.gov/books/NBK553161/), *StatPearls*, Treasure Island (FL): StatPearls Publishing, [PMID 31985954](https://pubmed.ncbi.nlm.nih.gov/31985954), retrieved 2025-03-07

1. ["Prader-Willi syndrome - Symptoms and causes"](https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997). *Mayo Clinic*. Retrieved 2025-03-07.

1. 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 (September 2020). "Loss of MAGEL2 in Prader-Willi syndrome leads to decreased secretory granule and neuropeptide production". *JCI Insight*. **5** (17). [doi:10.1172/jci.insight.138576](https://doi.org/10.1172/jci.insight.138576). [PMC 7526459](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526459). [PMID 32879135](https://pubmed.ncbi.nlm.nih.gov/32879135)

1. Schaaf CP, Marbach F (1993). ["Schaaf-Yang Syndrome"](https://www.ncbi.nlm.nih.gov/books/NBK567492/). *GeneReviews®*. Seattle (WA): University of Washington, Seattle. [PMID 33570896](https://pubmed.ncbi.nlm.nih.gov/33570896). Retrieved 2025-03-07.

1. Negishi Y, Kurosawa K, Takano K, Matsubara K, Nishiyama T, Saitoh S (December 2022). "A nationwide survey of Schaaf-Yang syndrome in Japan". *Journal of Human Genetics*. **67** (12): 735–738. [doi:10.1038/s10038-022-01089-y](https://doi.org/10.1038/s10038-022-01089-y). [PMID 36220858](https://pubmed.ncbi.nlm.nih.gov/36220858)

1. 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 (October 2020). "The adult phenotype of Schaaf-Yang syndrome". *Orphanet Journal of Rare Diseases*. **15** (1). [doi:10.1186/s13023-020-01557-8](https://doi.org/10.1186/s13023-020-01557-8). [PMC 7574436](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574436). [PMID 33076953](https://pubmed.ncbi.nlm.nih.gov/33076953)

1. Mizuno S, Yokoyama K, Yokoyama A, Nukata T, Ikeda Y, Hara S (June 2022). "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). [doi:10.1002/mgg3.1932](https://doi.org/10.1002/mgg3.1932). [PMC 9184671](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184671). [PMID 35343647](https://pubmed.ncbi.nlm.nih.gov/35343647)

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Adapted from the Wikipedia article [MAGEL2](https://en.wikipedia.org/wiki/MAGEL2) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/MAGEL2?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.