MAGI1

Chr 3

membrane associated guanylate kinase, WW and PDZ domain containing 1

Also known as: AIP-3, AIP3, BAIAP1, BAP-1, BAP1, MAGI-1, MAGI-1b, Magi1d

NCBI Gene: 9223 ENSG00000151276 UniProt: Q96QZ7 OMIM: 602625

MAGI1 encodes a scaffolding protein that assembles multiprotein complexes at cell-cell junctions and couples actin fibers to junctions in endothelial cells. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.334), indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the membrane-associated guanylate kinase homologue (MAGUK) family. MAGUK proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. The product of this gene may play a role as scaffolding protein at cell-cell junctions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.33

Clinical Summary— MAGI1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.

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ClinVar Variants

140 VUS of 192 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.560

Z-score 6.16

OE 0.22 (0.15–0.33)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.36Z-score

OE missense 0.87 (0.82–0.93)

785 obs / 900.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.15–0.33)

0≤0.351.4

Missense OE?0.87 (0.82–0.93)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 16 / 72.7Missense obs/exp: 785 / 900.1Syn Z: -0.32

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

VUS140

Likely Benign9

Benign3

140

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	139	1	0	140
Likely Benign	1	5	0	3	9
Benign	0	2	0	1	3
Total	1	146	1	4	152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap MAGI1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →