MAGEL2
Homo sapiens
Gene Name: MAGE-like 2
Aliases: NDNL1, nM15
Chromosome No: 15
Chromosome Band: 15q11.2
Genetic Category: Syndromic-Rare single gene variant--Functional
Associated Syndrome(s): Schaaf-Yang syndrome
Aliases: NDNL1, nM15
Chromosome No: 15
Chromosome Band: 15q11.2
Genetic Category: Syndromic-Rare single gene variant--Functional
Associated Syndrome(s): Schaaf-Yang syndrome
Summary Statistics:
ASD Reports: 25
Recent Reports: 4
Annotated variants: 56
Associated CNVs: 14
Evidence score: 4
ASD Reports: 25
Recent Reports: 4
Annotated variants: 56
Associated CNVs: 14
Evidence score: 4
| Associated Disorders: |
|
Relevance to Autism
Truncating variants on the paternal allele of the MAGEL2 gene were identified in four individuals presenting with autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of Prader-Willi syndrome (PWS) (Schaaf et al., 2013).
Molecular Function
The protein encoded by this paternally-imprinted gene may enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases and has been proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. This gene may play a role in Prader-Willi syndrome (PWS, OMIM 176270), a contiguous gene syndrome characterized by muscular hypotonia, mental retardation, short stature, obesity, hypogonadotropic hypogonadism, and small hands and feet that results from inactivity of the paternal copies of a number of genes on 15q11, through deletion or disruption of these genes or maternal uniparental disomy 15.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism.
Schaaf-Yang syndrome
ASD, ID
Support
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
Schaaf-Yang syndrome
DD, microcephaly
Support
A Novel Mutation of MAGEL2 in a Patient with Schaaf-Yang Syndrome and Hypopituitarism.
Schaaf-Yang syndrome
ASD
Support
Deficiency of the paternally inherited gene Magel2 alters the development of separation-induced vocalization and maternal behavior in mice
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
ID
Support
Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders.
Chitayat-Hall syndrome
ASD
Support
Phenotypic spectrum and mechanism analysis of Schaff Yang syndrome: A case report on new mutation of MAGEL2 gene
Schaaf-Yang syndrome
DD, ID, autistic features
Support
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders.
Schaaf-Yang syndrome
DD, ASD
Support
Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities.
Schaaf-Yang syndrome
Autistic behavior
Support
Diagnosis of Schaaf-Yang syndrome in Korean children with developmental delay and hypotonia
Schaaf-Yang syndrome, DD
ASD or autistic features, epilepsy/seizures
Support
Pitfalls of trio-based exome sequencing: imprinted genes and parental mosaicism-MAGEL2 as an example.
Schaaf-Yang syndrome
DD
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ID
Support
MAGEL2-related disorders: A study and case series.
Schaaf-Yang syndrome
ASD, ADHD
Support
A nationwide survey of Schaaf-Yang syndrome in Japan
Schaaf-Yang syndrome
ASD
Support
A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes.
Schaaf-Yang syndrome
Features of Opitz trigonocephaly C syndrome, ID
Support
Neurocognitive and Neurobehavioral Phenotype of Youth with Schaaf-Yang Syndrome.
Schaaf-Yang syndrome
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Recent Recommendation
The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families.
Schaaf-Yang syndrome
DD, ID, ASD, epilepsy/seizures
Recent Recommendation
Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis.
AMC
Recent Recommendation
Schaaf-Yang syndrome overview: Report of 78 individuals.
Schaaf-Yang syndrome
ASD
Recent Recommendation
Loss of Magel2 impairs the development of hypothalamic Anorexigenic circuits.
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN578R002
frameshift_variant
c.1802del
p.Pro601GlnfsTer101
Unknown
Not maternal
GEN578R005
frameshift_variant
c.1996del
p.Gln666SerfsTer36
Familial
Paternal
Multiplex
GEN578R006
frameshift_variant
c.2118del
p.Leu708TrpfsTer7
De novo
Simplex
GEN578R007
frameshift_variant
c.1996dupC
p.Gln666ProfsTer47
De novo
Multiplex
GEN578R008
frameshift_variant
c.1996dupC
p.Gln666fs
Familial
Paternal
Extended multiplex
GEN578R011
frameshift_variant
c.1996dupC
p.Gln666fs
Familial
Paternal
Multiplex
GEN578R021
frameshift_variant
c.1996dup
p.Gln666ProfsTer47
Familial
Paternal
Extended multiplex
GEN578R023
frameshift_variant
c.1996dup
p.Gln666ProfsTer47
De novo
Simplex
GEN578R026
frameshift_variant
c.1996dup
p.Gln666ProfsTer47
Familial
Paternal
Simplex
GEN578R029a
complex_structural_alteration
Familial
Paternal
Multi-generational
GEN578R029b
complex_structural_alteration
Familial
Paternal
Multi-generational
GEN578R029c
complex_structural_alteration
Familial
Paternal
Multi-generational
GEN578R032
frameshift_variant
c.1996dup
p.Gln666ProfsTer47
Familial
Paternal
Simplex
GEN578R036
frameshift_variant
c.1996_1997insCA
p.Gln666ProfsTer37
Familial
Paternal
Simplex
GEN578R045
inframe_insertion
c.2170_2171insTCTTCTATAGACCGCAGGGGCTCCTCTAAAGAGCGCAGGACCTCCTCGAAGGAGCGCAGGGCC
p.Ser724delinsPhePheTyrArgProGlnGlyLeuLeuTer
Unknown
GEN578R049
frameshift_variant
c.3449_3450del
p.Phe1150TrpfsTer4
Familial
Paternal
Simplex
Common
No Common Variants Available
