MAGI3

protein-coding

membrane associated guanylate kinase, WW and PDZ domain containing 3, the group of PDZ domain containing|Membrane associated guanylate kinases

Gene summary

Predicted to enable GMP kinase activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within positive regulation of JUN kinase activity. Located in cell junction. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001142782.2

Inheritance

—

ClinVar variants

U:154B:7

Top phenotype

Fetal akinesia deformation sequence 1

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr1:113,390,515-113,685,923

External References & Databases

Ensembl (ENSG00000081026)

Transcript & Mutation Effects

hg38 • Region Span ~295.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAGI3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 149

not providedTotal: 3

Fetal akinesia deformation sequence 1Total: 1

Arthrogryposis multiplex congenitaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142782.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		2 clinvar	4
missense			148 clinvar	5 clinvar		153
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	154	5	2	161

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001142782.2	RefSeq	NP_001136254.1	21	MANE Select
ENST00000307546.14	Ensembl	ENSP00000304604.9	21	MANE Select
NM_152900.3	RefSeq	NP_690864.2	21	Standard
ENST00000369611.4	Ensembl	ENSP00000358624.4	21	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
magi3b	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

magi3b

Danio rerio

Structure: otolith

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Rap1 signaling pathway - Homo sapiens (human)

Biological Process

apoptotic process
signal transduction
viral process
intracellular signal transduction
GMP metabolic process

Molecular Function

guanylate kinase activity
protein binding
ATP binding
protein-containing complex scaffold activity

Cellular Component

nucleus
cytoplasm
plasma membrane
cell-cell junction
bicellular tight junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307546
Coding exons: 21
Length: 295175
Individuals with no LoFs: 125665
Homozygous LoFs: 0
Heterozygous LoFs: 83
Defined: 125748
p: 0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	595	778	0.765	0.0000385	9687
Missense (PolyPhen)		237	350.26	0.67665		4295
Synonymous	2.12	237	282	0.839	0.0000142	2862
Loss of Function	5.47	16	62.8	0.255	0.00000334	808

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0011	notable
Latino/Admixed American	0.00028	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00064	0.00062	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes. Cooperates with PTEN to modulate the kinase activity of AKT1. Its interaction with PTPRB and tyrosine phosphorylated proteins suggests that it may link receptor tyrosine phosphatase with its substrates at the plasma membrane. In polarized epithelial cells, involved in efficient trafficking of TGFA to the cell surface. Regulates the ability of LPAR2 to activate ERK and RhoA pathways. Regulates the JNK signaling cascade via its interaction with FZD4 and VANGL2. {ECO:0000269|PubMed:10748157}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.744
RVIS EVS: -0.93
RVIS percentile EVS: 9.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.589

Gene Damage Prediction

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