MPRIP

Chr 17

myosin phosphatase Rho interacting protein

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

NCBI Gene: 23164 ENSG00000133030 UniProt: Q6WCQ1 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

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

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.30

Clinical Summary— MPRIP

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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

157 VUS of 202 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 OE?0.18 (0.11–0.30)

0≤0.351.4

Missense OE?0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 56.2Missense obs/exp: 538 / 669.8Syn Z: 0.03

This gene — mechanism propensity

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

202 submitted variants in ClinVar

ClinVar

Classification Summary

VUS157

Likely Benign14

Benign5

Conflicting1

157

VUS

Likely Benign

Benign

Conflicting

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	156	1	0	157
Likely Benign	0	4	0	10	14
Benign	0	1	1	3	5
Conflicting	—				1
Total	0	161	2	13	177

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

View in ClinVar →

110 pathogenic / likely-pathogenic (of 121) ClinVar copy-number / structural variants overlap MPRIP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →