MAGI2

membrane associated guanylate kinase, WW and PDZ domain containing 2, the group of PDZ domain containing|Membrane associated guanylate kinases

Basic information

Region (hg38): 7:78017055-79453667

Links

ENSG00000187391 ∙ NCBI:9863 ∙ OMIM:606382 ∙ HGNC:18957 ∙ Uniprot:Q86UL8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephrotic syndrome 15 (Limited), mode of inheritance: AR
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• nephrotic syndrome 15 (Strong), mode of inheritance: AR
• epilepsy (Refuted Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome 15	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	27932480
Renal transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAGI2 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAGI2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	59	10	79
missense			123	7	1	131
nonsense			2			2
start loss						0
frameshift	1	1	2			4
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)						0
splice region			1	8	2	11
non coding			2	39	70	111
Total	1	1	141	106	81

Variants in MAGI2

This is a list of pathogenic ClinVar variants found in the MAGI2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-78019216-C-T			Likely benign (Feb 24, 2020)
7-78019249-C-G			Likely benign (Mar 17, 2021)
7-78019326-C-T		not specified	Uncertain significance (Oct 27, 2023)
7-78019330-C-T		not specified • Nephrotic syndrome 15 • MAGI2-related disorder	Likely benign (Nov 21, 2023)
7-78019354-G-C		not specified • Nephrotic syndrome 15	Benign (Jul 15, 2024)
7-78019378-C-T			Likely benign (Apr 18, 2023)
7-78019385-GGCCCCGGCGCGACGGCGGCCTTGCGCGCCGGGGC-G		Nephrotic syndrome 15	Uncertain significance (May 22, 2022)
7-78019409-C-A			Uncertain significance (Dec 06, 2023)
7-78019414-C-G		not specified	Benign (Jan 31, 2024)
7-78019424-C-T		not specified	Uncertain significance (Aug 02, 2023)
7-78019428-G-C		Nephrotic syndrome 15 • not specified	Uncertain significance (Mar 30, 2024)
7-78019451-C-T			Uncertain significance (May 18, 2022)
7-78019462-A-G			Likely benign (May 07, 2022)
7-78019467-C-T			Likely benign (Jan 13, 2024)
7-78019476-C-A			Uncertain significance (Nov 02, 2021)
7-78019491-C-T		not specified	Uncertain significance (Dec 16, 2023)
7-78019493-C-T		not specified	Uncertain significance (Apr 07, 2022)
7-78019494-T-TGCC			Uncertain significance (Mar 23, 2022)
7-78019494-T-TGCCGCC		not specified	Likely benign (Jul 19, 2013)
7-78019500-C-T			Uncertain significance (Apr 17, 2022)
7-78019509-G-A		not specified	Uncertain significance (Jun 09, 2022)
7-78019514-G-T		not specified	Uncertain significance (Aug 04, 2023)
7-78019521-C-G		not specified	Uncertain significance (Mar 29, 2024)
7-78019529-G-A		not specified	Uncertain significance (Jul 12, 2023)
7-78019533-C-A		not specified	Uncertain significance (Jun 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAGI2	protein_coding	protein_coding	ENST00000354212	22	1436498

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000566	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.81	632	774	0.816	0.0000407	9486
Missense in Polyphen		206	361.15	0.57039		4158
Synonymous	0.255	291	297	0.981	0.0000163	2937
Loss of Function	6.18	9	61.2	0.147	0.00000344	716

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.000303	0.000298
East Asian	0.0000548	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000807	0.0000791
Middle Eastern	0.0000548	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to act as scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. {ECO:0000269|PubMed:10760291}.
• Pathway: Rap1 signaling pathway - Homo sapiens (human);Pathways Affected in Adenoid Cystic Carcinoma;Nephrin family interactions;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.392
• rvis_EVS: -2.08
• rvis_percentile_EVS: 1.6

Haploinsufficiency Scores

• pHI: 0.979
• hipred: Y
• hipred_score: 0.655
• ghis: 0.606

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.783

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Magi2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; renal/urinary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: magi2a
• Affected structure: pronephric glomerulus
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: positive regulation of receptor internalization;planar cell polarity pathway involved in axis elongation;signal transduction;negative regulation of cell population proliferation;positive regulation of neuron projection development;negative regulation of cell migration;positive regulation of phosphoprotein phosphatase activity;negative regulation of activin receptor signaling pathway;nerve growth factor signaling pathway;receptor clustering;protein heterooligomerization;negative regulation of protein kinase B signaling;SMAD protein signal transduction;mitotic cell cycle arrest;glomerular visceral epithelial cell development;neuroligin clustering involved in postsynaptic membrane assembly;cellular response to nerve growth factor stimulus;positive regulation of synaptic vesicle clustering
• Cellular component: nucleus;cytoplasm;late endosome;plasma membrane;cell-cell junction;bicellular tight junction;postsynaptic density;dendrite;protein-containing complex;slit diaphragm;synapse;perinuclear region of cytoplasm
• Molecular function: protein binding;phosphatase binding;receptor signaling complex scaffold activity;beta-1 adrenergic receptor binding;SMAD binding;type II activin receptor binding