RIPOR2

Chr 6ARAD

RHO family interacting cell polarization regulator 2

Also known as: C6orf32, DFNA21, DFNB104, DIFF40, DIFF48, FAM65B, MYONAP, PL48

NCBI Gene: 9750ENSG00000111913UniProt: Q9Y4F9

This gene encodes an atypical inhibitor of the small G protein RhoA. Inhibition of RhoA activity by the encoded protein mediates myoblast fusion and polarization of T cells and neutrophils. The encoded protein is a component of hair cell stereocilia that is essential for hearing. A splice site mutation in this gene results in hearing loss in human patients. [provided by RefSeq, Sep 2016]

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 104MIM #616515
AR
Deafness, autosomal dominant 21MIM #607017
AD
425
ClinVar variants
8
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RIPOR2
🧬
Gene-Disease Validity (ClinGen)
autosomal dominant nonsyndromic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 239 VUS of 425 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.923
Z-score 5.21
OE 0.19 (0.11–0.33)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.37Z-score
OE missense 0.72 (0.66–0.78)
400 obs / 557.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.11–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.66–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.84
0≤1.21.6
LoF obs/exp: 9 / 47.9Missense obs/exp: 400 / 557.3Syn Z: 1.86

ClinVar Variant Classifications

425 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS239
Likely Benign129
Benign41
Conflicting8
6
Pathogenic
2
Likely Pathogenic
239
VUS
129
Likely Benign
41
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
5
0
6
Likely Pathogenic
0
0
2
0
2
VUS
2
216
19
2
239
Likely Benign
0
6
66
57
129
Benign
0
10
24
7
41
Conflicting
—8
Total323211666425

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

View in ClinVar →

Protein Context — Lollipop Plot

RIPOR2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Deafness, autosomal recessive 104

MIM #616515

Molecular basis of disorder known

Autosomal recessive

Deafness, autosomal dominant 21

MIM #607017

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Ginsenoside F3 alleviates T cell exhaustion via RIPOR2-mediated immunometabolic reprogramming to potentiate anti-PD-1 therapy.
Jiang M et al.·Phytomedicine
2026
Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer.
Xu F et al.·Front Immunol
2022
RIPOR2 Expression Decreased by HPV-16 E6 and E7 Oncoproteins: An Opportunity in the Search for Prognostic Biomarkers in Cervical Cancer.
Olmedo-Nieva L et al.·Cells
2022
Exome sequencing identifies protein-coding variants associated with loneliness and social isolation.
Wang YX et al.·J Affect Disord
2025
RIPOR2: A new gene of non-syndromic cochleovestibular dysfunction, discrepancy between human pathology and animal models.
Morel G et al.·Clin Genet
2023Functional
Constructed competitive endogenous RNA network and patterns of immune infiltration revealing the prognostic signature for cervical cancer.
Luo L et al.·Epigenomics
2024
DNA methylation changes following narrative exposure therapy in a randomized controlled trial with female former child soldiers.
Carleial S et al.·Sci Rep
2021
Molecular crosstalk between MASLD and IVDD revealed through integrated biomarker discovery analysis.
Wang G et al.·Front Immunol
2026
Quantitative proteomics and phosphoproteomics reveal glucocorticoid stimulation of TLR and Rho GTPase signaling in neutrophil-like cells.
Cho H et al.·Genome Biol
2026
Single-Cell Sequencing Combined with RNA Sequencing Reveals the Role of Natural Killer Cells in Prognosis and Immunotherapy Response in Cervical Squamous Cell Carcinoma.
Lin J et al.·Crit Rev Immunol
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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