MAGEL2

MAGE family member L2, the group of MAGE family

Basic information

Region (hg38): 15:23643549-23647867

Previous symbols: [ "NDNL1" ]

Links

ENSG00000254585 ∙ NCBI:54551 ∙ OMIM:605283 ∙ HGNC:6814 ∙ Uniprot:Q9UJ55 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Schaaf-Yang syndrome (Strong), mode of inheritance: AD
• Schaaf-Yang syndrome (Definitive), mode of inheritance: AD
• Schaaf-Yang syndrome (Definitive), mode of inheritance: AD
• Schaaf-Yang syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schaaf-Yang syndrome (Prader-Willi-like syndrome)	AD	Endocrine	The condition has been described as including neonatal hyperinsulinemia hypoglycemia, and awareness may allow prompt management	Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	24076603; 25473036; 26365340; 27195816; 28281571

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAGEL2 gene.

• not_provided (1003 variants)
• Inborn_genetic_diseases (297 variants)
• MAGEL2-related_disorder (267 variants)
• Schaaf-Yang_syndrome (158 variants)
• not_specified (71 variants)
• Prader-Willi_syndrome (22 variants)
• Intellectual_disability (6 variants)
• Neurodevelopmental_disorder (2 variants)
• Prader-Willi-like_syndrome (2 variants)
• Developmental_disorder (2 variants)
• Multiple_joint_contractures (1 variants)
• Generalized_hypotonia (1 variants)
• Ventriculomegaly (1 variants)
• Autism_spectrum_disorder (1 variants)
• Neurodevelopmental_delay (1 variants)
• Ambiguous_genitalia (1 variants)
• See_cases (1 variants)
• Genetic_developmental_and_epileptic_encephalopathy (1 variants)
• Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAGEL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000019066.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			73	191	9	273
missense	2	4	739	117	4	866
nonsense	17	21	6			44
start loss		1				1
frameshift	24	33	5			62
splice donor/acceptor (+/-2bp)						0
Total	43	59	823	308	13

Highest pathogenic variant AF is 0.00001549108

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAGEL2	protein_coding	protein_coding	ENST00000532292	1	2485

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.563	399	369	1.08	0.0000209	4145
Missense in Polyphen		76	73.131	1.0392		861
Synonymous	-1.72	185	158	1.17	0.00000941	1352
Loss of Function	3.75	2	20.2	0.0992	0.00000112	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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-ARNTL/BMAL1 heterodimer. Significantly promotes the cytoplasmic accumulation of CLOCK (By similarity). {ECO:0000250|UniProtKB:Q9QZ04, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:23452853}.
• Pathway: Circadian rythm related genes;Prader-Willi and Angelman Syndrome (Consensus)

Essentials

• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: Arp2/3 complex-mediated actin nucleation;retrograde transport, endosome to Golgi;regulation of circadian rhythm;negative regulation of transcription, DNA-templated;rhythmic process;protein K63-linked ubiquitination
• Cellular component: nucleus;endosome;early endosome;cytosol;retromer complex
• Molecular function: ubiquitin-protein transferase activity;protein binding