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FLASH GENE

Symbol

MAGEL2

contributors: mct - updated : 20-11-2024

HGNC name	MAGE-like 2
HGNC id	6814

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE
text	associated with a 5'differentiated methylated region (DMR)
STRUCTURE	4.30 kb     1 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - MKRN3 - NDN - MAGEL2 - SNURF - SNRPN - PAR5 - IPW - PAR1 - UBE3A - NDNL2 - ATP10A - APBA2 - qter
Authors	Lee (00), Herzing (02)

regionally located

41kb telomeric to NDN (head to tail) within the PWCR region

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_019066 1 - 4298 NP_061939 - 1249 - 2000 10915770

EXPRESSION

Type	restricted

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine       Mus musculus Nervous brain diencephalon hypothalamus suprachiasmatic nuclei predominantly Mus musculus   brain midbrain       Mus musculus   brain forebrain       Mus musculus   ganglia sensory ganglia dorsal root     Mus musculus Reproductive female system placenta       Mus musculus   male system bulbourethral gland       Mus musculus

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	several tissues (brain, kidney, liver, lung)

IMPRINTING	maternally
text	paternally in brain fetal and adult
	only expressed from the paternal allele

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal half of MAGEL2 might be required for the interaction with regulators of RNA metabolism
	a C terminal domain of homology with the MAGE (essentially MAGED1) and NDN proteins

HOMOLOGY

Homologene

FAMILY

MAGE gene family

CATEGORY

antigen

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
text	MAGEL2 shuttles between the cytoplasm and the nucleus

basic FUNCTION	induces the redistribution of the subcellular localization of CLOCK towards the cytoplasm, in contrast to the nucleus-directed effect of ARNTL on CLOCK subcellular localization
	normally promotes potentially negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins
	MAGED1 and MAGEL2 are thus both essential for the proper regulation of food intake
	ubiquitin ligase activity of MAGEL2-TRIM27 is important for proper retrograde transport
	has an essential role in neuronal development
	plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway
	plays a key role in modulating bone remodeling and mass in PWS by affecting N-oleoyl serine (OS) levels and activity
	act as a tissue-specific regulator of the retromer-dependent endosomal protein recycling pathway and, by doing so, ensures proper secretory granule formation and maturation
	involvement of MAGEL2 in biological processes such as RNA stabilization, chromosome condensation, and transcription

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

E3 RING ubiquitin ligase, MAGEL2-TRIM27, localizes to endosomes through interactions with the retromer complex

INTERACTION

DNA

RNA

small molecule

protein	MAGEL2 interacts with ARNTL and with PER2
	TRIM27 was identified as a major binding partner of MAGEL2, and MAGEL2-TRIM27 is likely required for endosome-to-Golgi retrograde transport
	bind USP7 and TRIM27 proteins, thus forming the MUST complex
	MAGEL2 was identified to interact with VPS35 and VPS26A two components of the endosomal retromer complex
	VPS35 recruits MAGEL2-TRIM27 to retromer-positive endosomes by binding to MAGEL2
	NDN necdin, MAGED1, MAGEF1 and MAGEL2 bound to PIAS1 but not to NSMCE2 or CBX4
	interacts with proteins involved in transcription regulation and RNA metabolism (PMUID: 38908375)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

PWS , PWLAD , AMCN5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in the hippocampus of patients with incipient Alzheimer disease constitutional       loss of function leads to the disruption of hypothalamic feeding circuits, an effect that appears to be independent of the neurodevelopmental effects of leptin and ghrelin and likely involves a direct neurotrophic effect of MAGEL2

Susceptibility

Variant & Polymorphism

Candidate gene	regulation of normal circadian rhythm
Marker
Therapy target

ANIMAL & CELL MODELS

	Magel2-null mice exhibit neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood as seen in PWS patients
	mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency
	paternally Magel2-null mice have reduced embryonic viability but otherwise normal embryonic growth in survivors, followed by post-natal growth retardation and excessive weight gain, recapitulating aspects of the PWS phenotype