OPDM4_RILPL1
- Gene
- RILPL1
- Disease
- OPDM4
- Inheritance
- AD
- Classification
- Moderate
- Total Score
- 10
- Publications Reviewed
- 3
- Publication Span
- 2.05 years
- Last Updated
- 08/14/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
A CGG/GGC repeat expansion in the 5′ UTR/promoter region of RILPL1 is associated with autosomal dominant oculopharyngodistal myopathy type 4 (OPDM4). Uploaded sources report RILPL1 expansions in multiple affected individuals, including cohort-level evidence of 11 OPDM4 individuals, with pathogenic repeat sizes around 135–197 repeats and much smaller repeat ranges in controls. Supporting evidence includes linkage/co-segregation in OPDM4 families, patient muscle pathology with rimmed vacuoles and p62-positive intranuclear inclusions, repeat-containing RNA foci with RNA-binding protein/p62 co-localization, and polyG/p62 co-localization in patient muscle. Regulatory studies show locus methylation/transcriptional context and bidirectional transcription across the repeat, but no consistent change in RILPL1 mRNA or protein levels in OPDM4 muscle.
Genetic evidence
Total: 7.5
| Singular Evidence | Probands | PMID:37923380 | 6 | In a 94-case Chinese OPDM cohort, 11 individuals were reported with RILPL1 CGG/GGC repeat expansions (OPDM4) after screening known OPDM repeat loci; the paper provides cohort-level support rather than detailed new RILPL1 proband descriptions. |
| Collective Evidence | Segregation | PMID:35700120 | 1.5 | Parametric linkage analysis in Family 1 mapped disease to 12q24.3 with a maximum LOD score of 2.4007; RILPL1 GGC expansion was identified within the linked interval, tracked with affected relatives, and shared haplotype data supported a founder effect across families. |
Experimental evidence
Total: 2.5
| Function | Protein interaction | PMID:35148830 | 1 | In OPDM4 patient muscle, immunofluorescence showed glycine/polyG signal co-localized with p62 in intranuclear inclusions, consistent with repeat-associated polyG protein aggregation; the paper also notes gene-level RILPL1/RAB10 interaction biology. |
| Function | Regulatory impact | PMID:35700120 | 0.5 | Targeted methylation showed hypermethylation at the RILPL1 locus in unaffected ultralong expansion carriers, while OPDM4 patient muscle showed no significant RILPL1 mRNA or protein change; CAGE-seq and strand-specific RNA-seq supported alternative/antisense TSSs and bidirectional transcription across the repeat locus. |
| Functional Alteration | Patient cells | PMID:35148830 | 1 | Patient muscle biopsies showed rimmed vacuoles and intranuclear filamentous inclusions; RNA FISH/immunofluorescence showed expanded RILPL1 RNA foci co-localized with MBNL1 and p62 in intranuclear inclusions in OPDM4 muscle but not control muscle. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.