MPRIP

Chr 17

myosin phosphatase Rho interacting protein

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

NCBI Gene: 23164ENSG00000133030UniProt: Q6WCQ1OMIM: 612935

The protein targets myosin phosphatase to the actin cytoskeleton and is required for regulation of the actin cytoskeleton by RhoA and ROCK1. Mutations cause autosomal dominant neurodevelopmental disorder with hypotonia and variable intellectual disability. This gene is highly constrained against loss-of-function variants (pLI = 0.98), indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.30
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.
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ClinVar Variants
110 unique Pathogenic / Likely Pathogenic· 165 VUS of 323 total submissions
Explore recent and relevant literature in Research Assistant →

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
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

323 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic110
VUS165
Likely Benign16
Benign5
Conflicting1
110
Pathogenic
165
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
156
9
0
165
Likely Benign
0
4
2
10
16
Benign
0
1
1
3
5
Conflicting
—1
Total016112213297

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

View in ClinVar →

Protein Context — Lollipop Plot

MPRIP · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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
Central Nervous System-Infecting Pathogens Escherichia coli and Cryptococcus neoformans Exploit the Host Pdlim2 for Intracellular Traversal and Exocytosis in the Blood-Brain Barrier.
Li Z et al.·Infect Immun
2021
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
Next Generation Proteomic Pipeline for Chromosome-Based Proteomic Research Using NeXtProt and GENCODE Databases.
Hwang H et al.·J Proteome Res
2017
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