MPP7

Chr 10

MAGUK p55 scaffold protein 7

NCBI Gene: 143098ENSG00000150054UniProt: Q13112

The protein encoded by this gene is a member of the p55 Stardust family of membrane-associated guanylate kinase proteins that establishes epithelial cell polarity by forming complexes with DLG1 and facilitating tight junction formation. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), suggesting mutations would likely cause severe developmental disorders. However, no definitive human disease associations have been established for this gene based on the available data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
14
P/LP submissions
0%
P/LP missense
0.94
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— MPP7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 90 VUS of 130 total submissions
Explore recent and relevant literature in Research Assistant →
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.82
OE 0.66 (0.47–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.90Z-score
OE missense 0.86 (0.77–0.95)
266 obs / 310.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.47–0.94)
0≤0.351.4
Missense OE0.86 (0.77–0.95)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 22 / 33.3Missense obs/exp: 266 / 310.7Syn Z: 0.01
DN
0.7327th %ile
GOF
0.6735th %ile
LOF
0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

130 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS90
Likely Benign4
Benign1
13
Pathogenic
1
Likely Pathogenic
90
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
83
7
0
90
Likely Benign
0
2
0
2
4
Benign
0
0
1
0
1
Total085222109

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

View in ClinVar →

Protein Context — Lollipop Plot

MPP7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients