MAGEL2
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
MAGEL2 (HGNC:6814) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
MAGE family member L2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
NDNL1
Alias symbols
nM15
%HI
84.66(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
Cytoband
15q11.2
Genomic Coordinates
GRCh37/hg19: chr15:23888696-23893014 NCBI Ensembl UCSC
GRCh38/hg38: chr15:23643549-23647867 NCBI Ensembl UCSC
MANE Select Transcript
NM_019066.5 ENST00000650528.1 (Read more about MANE Select)
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... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-16618
ClinGen Curation ID:
CCID:007427
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
05/22/2018

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Evidence Comments:
This gene is located in the commonly deleted region associated with Prader Willi syndrome (and is imprinted, expressed from the paternal allele). Paternally truncating mutations in MAGEL2 cause Schaaf-Yang syndrome (Fountain et al., 2017, PMID 27195816; Jobling et al., 2018, PMID 29599419). However, it is unclear if the underlying mechanism of mutation is a dominant-negative effect as suggested by Fountain, et al. or if haploinsufficiency plays a role. There are two instances of whole gene deletions outside of the common Prader-Willi deletion. Kanber et al., 2009, PMID 19066619 reported 1 patient with an unbalanced X;15 translocation, resulting in a deletion of MAGEL2 and 2 other genes in a patient with intellectual disability and obesity. Buiting et al., 2014, PMID 24661356 reported a patient with a 3.9Mb deletion including MAGEL2 with hypotonia, mild feeding difficulties, and slight fine/motor delays. For both of these cases, there were other genes involved, thus it is unclear what haploinsufficiency of MAGEL2 contributes to the reported phenotype.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Of note: PMID:18925931 Cai et al. (2008) identified a de novo 120 kb maternally-derived duplication including MKRN3, MAGEL2, and NDN using MLPA probes in monozygotic twins with autism.

Genomic View

Select assembly: (NC_000015.9) (NC_000015.10)