MPRIP

Chr 17

myosin phosphatase Rho interacting protein

Also known as: M-RIP, MRIP, RHOIP3, RIP3, p116Rip

NCBI Gene: 23164ENSG00000133030UniProt: Q6WCQ1

Enables cadherin binding activity. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
110
Pathogenic / LP
296
ClinVar variants
10
Pubs (1 yr)
1.8
Missense Z
0.30
LOEUF· LoF intolerant
Clinical Summary— MPRIP
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
110 Pathogenic / Likely Pathogenic· 164 VUS of 296 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.981
Z-score 5.71
OE 0.18 (0.11–0.30)
Highly constrained

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

Missense Constraint
1.81Z-score
OE missense 0.80 (0.75–0.86)
538 obs / 669.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.11–0.30)
0≤0.351.4
Missense OE0.80 (0.75–0.86)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 10 / 56.2Missense obs/exp: 538 / 669.8Syn Z: 0.03
LOF
DN
0.4884th %ile
GOF
0.5563th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.30

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

296 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic110
VUS164
Likely Benign16
Benign5
Conflicting1
110
Pathogenic
164
VUS
16
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
110
0
110
Likely Pathogenic
0
0
0
0
0
VUS
0
155
9
0
164
Likely Benign
0
4
2
10
16
Benign
0
0
2
3
5
Conflicting
—1
Total015912313296

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

View in ClinVar →

MPRIP · 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 →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Epithelioid Fibrous Histiocytoma Is on a Continuum With Superficial ALK -rearranged Myxoid Spindle Cell Neoplasm : A Clinicopathologic Series of 35 Cases Including Alternate RET and NTRK3 Fusions.
DeSimone MS et al.·Am J Surg Pathol
2024Cohort
Germline VWF/MPRIP and somatoplasm FGA variants synergically confer susceptibility to non-traumatic osteonecrosis of the femoral head.
Wang D et al.·Sci Rep
2023
Identification of molecular biomarkers associated with non-small-cell lung carcinoma (NSCLC) using whole-exome sequencing.
Singh V et al.·Cancer Biomark
2024
HVEM as a tumor-intrinsic regulator in non-small cell lung cancer: Suppression of metastasis via glycolysis inhibition and modulation of macrophage polarization.
Yao Y et al.·Pharmacol Res
2025
Structural Optimization of Next-Generation TRK Inhibitors against Acquired Drug Resistance Mutations for the Treatment of Solid Tumors.
Xu Z et al.·J Med Chem
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
MPRIP::PDGFRB Fusion Gene: A Rare Case Report of Adult Myeloid/Lymphoid Neoplasm With Eosinophilia and Tyrosine Kinase Gene Fusions.
Ukkahad T et al.·Case Rep Hematol
2025Open AccessCase report
Remarkable response to crizotinib in a patient with advanced lung adenocarcinoma harboring the MPRIP-ROS1 fusion gene: A case report.
Kishikawa Y et al.·Respir Med Case Rep
2025Open AccessCase report
Caspase-mediated cleavage of a scaffold protein, MPRIP, yields a truncated form that is involved in repetitive bleb formation.
Sakamaki K et al.·FEBS J
2025
LRRC8A anion channels modulate vascular reactivity via association with myosin phosphatase rho interacting protein.
Choi H et al.·FASEB J
2023
PIP2-Effector Protein MPRIP Regulates RNA Polymerase II Condensation and Transcription.
Balaban C et al.·Biomolecules
2023Open Access
Top 5 resultsSearch Europe PMC ↗

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