Curation OPDM4 RILPL1

Gene RILPL1

Disease OPDM4

Inheritance AD

Score

7.5 + 2.5 = 10 / 18

Genetic + experimental = total

Classification

Moderate

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 3

Publication Span 2.05 years

Publication Interval 2.05 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 7.5

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.