OPMD_PABPN1
- Gene
- PABPN1
- Disease
- OPMD
- Inheritance
- AD/AR
- Classification
- Definitive
- Total Score
- 15
- Publications Reviewed
- 5
- Publication Span
- 24.58 years
- Last Updated
- 08/14/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset myopathy characterized by ptosis, dysphagia, and proximal limb weakness. The curated locus is the short GCN/GCG repeat in exon 1 of PABPN1 (formerly PABP2), where expansions enlarge the N-terminal polyalanine tract and are associated with autosomal dominant and recessive OPMD. Uploaded genetic evidence supports pathogenic repeat expansions through large clinically characterized cohorts, founder/segregation haplotype data, and genotype–phenotype correlations including expansion-size and gene-dose effects.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:35112761 | 6 | Canary Islands cohort of 123 genetically diagnosed OPMD patients; 113/120 analyzed patients (94.2%) carried a heterozygous PABPN1 (GCN)15 expanded allele, with typical OPMD features including ptosis, dysphagia, and later proximal weakness. |
| Collective Evidence | Allele | PMID:28011929 PMID:9392020 | 2 | PMID 28011929: French cohort of 354 unrelated index cases showed pathogenic PABPN1 (GCN)11–17 alleles and a correlation between expansion size and age at diagnosis/severity, with homozygous patients more severely affected. PMID 9392020: linkage study supports the chromosome 14 OPMD locus but is gene/locus-mapping evidence, not repeat allele size-specific. |
| Collective Evidence | Segregation | PMID:11087766 | 1.5 | In 23 Bukhara Jewish patients from 8 unrelated families, all carried the PABP2/PABPN1 (GCG)9 mutation and shared a four-marker haplotype, supporting segregation of a shared founder mutation in this population. |
| Statistics | Case-control data | PMID:28011929 | 6 | French diagnostic cohort of 354 unrelated PABPN1 expansion-positive index cases characterized pathogenic (GCN)11–17 alleles; 200 control chromosomes had no (GCN)11 allele, supporting enrichment/rarity of expanded alleles in affected individuals versus controls. |
Experimental evidence
Total: 3
| Function | Biochemical function | PMID:9462747 | 0.5 | Gene-level, not repeat-locus-specific: PABP2/PABPN1 is a nuclear poly(A)-binding protein involved in mRNA polyadenylation; the paper proposed that expanded polyalanine PABP2 may accumulate as nuclear filament inclusions. |
| Function | Protein interaction | PMID:9462747 | 0.5 | |
| Function | Regulatory impact | PMID:9462747 | 0.5 | |
| Functional Alteration | Patient cells | PMID:9462747 | 1 | |
| Functional Alteration | Non-patient cells | PMID:9462747 | 0.5 |
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.