protein
MAGE-like protein 2
Gene
MAGEL2
Organism
Homo sapiens(9606)
Length
1249 aa
Mass
132,822 Da
MAGEL2 (MAGE-like protein 2) is a 1249-amino acid protein that functions as a regulator of ubiquitin ligase activity and cellular trafficking (UniProt: Q9UJ55). It enhances E3 ubiquitin-protein ligase activity, likely by recruiting or stabilizing conjugating enzymes at E3:substrate complexes. MAGEL2 also acts as a retrograde transport regulator through interaction with VPS35 and promotes endosomal F-actin assembly by facilitating polyubiquitin chain formation on WASHC1. Additionally, it regulates circadian rhythm by repressing the transcriptional activity of the CLOCK-BMAL1 heterodimer and promoting CLOCK cytoplasmic accumulation.
MAGEL2 is associated with Schaaf-Yang syndrome (SHFYNG, MIM 615547), a disease characterized by neonatal hypotonia, feeding difficulties, developmental delay, short stature, hypogonadism, and obesity—features overlapping with Prader-Willi syndrome (UniProt: Q9UJ55). Patients with this condition also manifest autism spectrum disorder and may present with dysmorphic facial features.
MAGEL2 is classified as a SFARI category S, syndromic gene (SFARI Cat S), reflecting its established association with autism as a component of Schaaf-Yang syndrome rather than as a standalone autism-risk factor.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Probably enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases, possibly through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. Acts as a regulator of retrograde transport via its interaction with VPS35. Recruited to retromer-containing endosomes and promotes the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1 together with TRIM27, leading to promote endosomal F-actin assembly (PubMed:23452853). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Significantly promotes the cytoplasmic accumulation of CLOCK (By similarity)
Disease associations
Schaaf-Yang syndromeSHFYNG
A disease characterized by clinical features of Prader-Willi syndrome, including neonatal hypotonia with poor suck, feeding problems in infancy, obesity, developmental delay, short stature, and hypogonadism. Additionally, patients manifest autism spectrum disorder. Some patients have dysmorphic facial features.
Sources
Last updated 5/6/2026, 5:24:20 AM