OPML1_NUTM2B_AS1
- Gene
- NUTM2B-AS1
- Disease
- OPML1
- Inheritance
- AD
- Classification
- Moderate
- Total Score
- 10
- Publications Reviewed
- 4
- Publication Span
- 5 years
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
A heterozygous CGG/CCG repeat expansion in overlapping noncoding exons of bidirectionally transcribed LOC642361/NUTM2B-AS1 is associated with autosomal dominant OPML1/LOC642361-NUTM2B-AS1-related oculopharyngeal myopathy spectrum. The original report identified the expansion in one Japanese OPML family with leukoencephalopathy, with segregation in affected relatives and absence in unaffected relatives and 1,000 controls. Subsequent independent reports identified OPDM-predominant cases from Chinese and Thai families, expanding the phenotype and showing variable or absent leukoencephalopathy. Patient-muscle studies showed rimmed vacuoles, p62-positive intranuclear inclusions, aggrephagy/RNA-binding protein accumulation, and mitochondrial abnormalities, supporting a repeat-mediated pathogenic mechanism.
Genetic evidence
Total: 7.5
| Singular Evidence | Probands | PMID:31332380 PMID:37923380 PMID:39308795 | 6 | PMID 31332380: one OPML family (F5305) with CGG/CCG expansion in LOC642361/NUTM2B-AS1; PMID 37923380: two unrelated Chinese OPDM cases with expansions >70 repeats among 26 unsolved OPDM cases; PMID 39308795: four Thai OPDM patients from three unrelated families with expansions >100 repeats/strong somatic instability. |
| Collective Evidence | Segregation | PMID:31332380 | 1.5 | PMID 31332380: In family F5305, RP-PCR confirmed the expansion in four affected individuals and absence in seven unaffected relatives, including three married-in controls; the expansion was absent in 1,000 controls. |
Experimental evidence
Total: 2.5
| Function | Biochemical function | PMID:38159879 | 0.5 | PMID 38159879: Patient muscle immunofluorescence showed aggrephagy pathway proteins p62, NBR1, and LC3B accumulated in intranuclear inclusions, suggesting the LOC642361/NUTM2B-AS1 CGG expansion may impair aggrephagic capacity. |
| Function | Protein interaction | PMID:38159879 | 0.5 | PMID 38159879: Patient muscle immunofluorescence showed RNA-binding proteins hnRNPA1, hnRNPA2B1, and MBNL1 accumulated in intranuclear inclusions, consistent with repeat-associated RNA-binding protein sequestration. |
| Function | Regulatory impact | PMID:38159879 | 0.5 | |
| Functional Alteration | Patient cells | PMID:38159879 | 1 | PMID 38159879: Patient muscle biopsies showed myopathic changes with rimmed vacuoles, p62-positive intranuclear inclusions, filamentous aggregates by electron microscopy, autophagic vacuoles, and swollen/disordered mitochondria. |
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.