OPMD is a late-onset neuromuscular disease, characterized by ptosis, dysphagia, and general facial weakness^1,2,3. Proximal limb weakness commonly develops later in the disease course⁴.

Prevalence

1 100,000

1/100,000 (population specific)⁵. Frequency of (GCN)11 alleles is 1-2% of North America/Europe/Japan⁶. Disease is significantly enriched in individuals of Jewish Bukharian descent⁴. Disease is found worldwide, in more than 30 countries⁶.

Age of Onset

Typical: 40-59⁷; Range: 20-79⁸.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr14:23790681-23790712

hg38 chr14:23321472-23321503

t2t chr14:17522488-17522519

Details

Disease is caused by a GCN polyalanine expansion in the first exon of PABPN1. Most known patients have (GCG)+, but GCN (any polyalanine) may be pathogenic⁶. This locus is heterozygous in ~90% of cases (autosomal dominant inheritance), while expansions are biallelic in ~10% of cases (consistent with autosomal recessive inheritance). Disease is generally more severe in cases with two expanded alleles. Age of onset is inverse to allele size, while penetrance and severity increase with allele size⁶. Mild, late-onset disease can occur in individuals with a (GCN)10(GCN)11 genotype, suggesting variable penetrance⁹. The definition of this locus differs in the literature with prior work counting exact GCG motifs for a benign size of (GCG)6¹⁰, while later resources count GCNs (any alanine codon), widening the region by 4 motifs to a benign size of (GCN)10^6,2. STRchive is using the GCN definition.

Mechanism

GoF/LoF

Polyalanine expansions leading to cellular toxicity (loss of function) as well as abnormal aggregation and inefficient protein degradation, which may impact mRNA processing⁶.

Detection

Flanking PCR with fragment analysis has accurately detected expansions [@pmid:27980005]. Heterozygous expansions have been sized by Sanger sequencing. Biallelic expanded variants were assessed using short-read sequencing or PCR fragment analysis.

Year

1998¹⁰

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

GCN

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GCN

Pathogenic (gene)

CNG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

1omim:164300

Repeat expansion disorders.

Zhongbo,Chen, Huw R,Morris, James,Polke, Nicholas W,Wood, Sonia,Gandhi, Mina,Ryten, Henry,Houlden, Arianna,Tucci

Practical neurology · 2025-05-15

pmid:39349043

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

The genetic and clinical characteristics of oculopharyngeal muscular dystrophy patients in Israel.

Merav,Ben-David, Lior,Greenbaum, Vera,Nikitn, Alex,Zvulunov, Hagit,Charas, Naama,Divon, Tali,Barkan, Odelia,Chorin, Haike,Reznik-Wolf, Ofira,Zloto, Limor,Benyamini, Shahar,Shelly, Amir,Dori

Orphanet journal of rare diseases · 2026-05-19

pmid:42157275

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

Oculopharyngeal Muscular Dystrophy

Capucine,Trollet, Alexis,Boulinguiez, Fanny,Roth, Tanya,Stojkovic, Gillian,Butler-Browne, Teresinha,Evangelista, Jean,Lacau St Guily, Pascale,Richard

GeneReviews® · 1993-01-01

genereviews:NBK1126

Choked: A Case Report of Oculopharyngeal Muscular Dystrophy Mimicking Hypothyroidism From the Philippines.

Jerome M,Infante, Belinda Lioba,Nepomuceno

Cureus · 2023-06-27

pmid:37519616

Clinical and genetic features of a large homogeneous cohort of oculopharyngeal muscular dystrophy patients from the Canary Islands.

Jorge,Alonso-Pérez, Juan Carlos,de León Hernández, Helena,Pérez-Pérez, María Dolores,Mendoza-Grimón, Antonio José,Gutierrez-Martinez, Ioanna,Hadjigeorgiou, Fernando,Montón-Álvarez, Lidia,González-Quereda, Alicia,Alonso-Jimenez, Xavier,Suárez-Calvet, Jordi,Díaz-Manera

European journal of neurology · 2022-02-03

pmid:35112761

Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy.

Pascale,Richard, Capucine,Trollet, Tanya,Stojkovic, Alix,de Becdelievre, Sophie,Perie, Jean,Pouget, Bruno,Eymard

Neurology · 2016-12-23

pmid:28011929

Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy.

B,Brais, J P,Bouchard, Y G,Xie, D L,Rochefort, N,Chrétien, F M,Tomé, R G,Lafrenière, J M,Rommens, E,Uyama, O,Nohira, S,Blumen, A D,Korczyn, P,Heutink, J,Mathieu, A,Duranceau, F,Codère, M,Fardeau, G A,Rouleau

Nature genetics · 1998-02-01

pmid:9462747

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.

Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak

International journal of molecular sciences · 2026-05-13

pmid:42196324

The genetic and clinical characteristics of oculopharyngeal muscular dystrophy patients in Israel.

Merav,Ben-David, Lior,Greenbaum, Vera,Nikitn, Alex,Zvulunov, Hagit,Charas, Naama,Divon, Tali,Barkan, Odelia,Chorin, Haike,Reznik-Wolf, Ofira,Zloto, Limor,Benyamini, Shahar,Shelly, Amir,Dori

Orphanet journal of rare diseases · 2026-05-19

pmid:42157275

Evaluation of Epidermal Growth Factor Receptor and Its Inducible Feedback Inhibitor Leucine Rich Repeats and Immunoglobulin Like Domains 1 as Prognostic Marker in Oral Cancer.

Deepika,Verma, S S,Chauhan, Joginder,Kumar, Mohit,Arora, Qulsum,Akhtar, Lokesh,Kadian, Prerna,Jain, Vivek,Nayyar, Ajoy,Roychaudhury, Deepika,Mishra, Alok,Thakar, Riyaz A,Mir

Molecular carcinogenesis · 2026-03-01

pmid:41764774

Recurrent Pneumonia in a Patient With Oculopharyngeal Muscular Dystrophy (OPMD) due to GCN Expansion in the

Claudia,Mañana Valdés, Miguel,Arias Guillén, Germán,Moris de la Tassa

Open respiratory archives · 2026-01-15

pmid:41676387

Oculopharyngeal muscular dystrophy (OPMD) associated alanine expansion impairs the function of the nuclear polyadenosine RNA binding protein PABPN1 as revealed by proximity labeling and comparative proteomics.

Allison T,Mezzell, Yu,Zhang, Alexandra M,Perez, Katherine E,Vest

PLoS genetics · 2026-01-26

pmid:41587185

Feasibility of long-read sequencing to identify molecular alterations in an Indonesian cohort of locally advanced to advanced nasopharyngeal cancer.

,Handoko, Marlinda,Adham, Lisnawati,Rachmadi, Demak Lumban,Tobing, ,Asmarinah, ,Fadilah, Wei,Dai, Anne Wing Mui,Lee, Soehartati A,Gondhowiardjo

Scientific reports · 2025-07-01

pmid:40594369

Polyalanine Expansion in PABPN1 Alters the Structure and Dynamics of Its Nuclear Aggregates in Differentiated Muscle Cells.

Sander D,Mallon, Erik,Bos, Vahid,Sheikhhassani, Milad,Shademan, Lenard M,Voortman, Alireza,Mashaghi, Thomas H,Sharp, Vered,Raz

FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025-06-30

pmid:40552959

ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation.

Jana,Key, Luis-Enrique,Almaguer-Mederos, Arvind Reddy,Kandi, Nesli-Ece,Sen, Suzana,Gispert, Gabriele,Köpf, David,Meierhofer, Georg,Auburger

Neurobiology of disease · 2025-04-11

pmid:40220918

Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.

Alexis,Boulinguiez, Jamila,Dhiab, Barbara,Crisol, Laura,Muraine, Ludovic,Gaut, Corentin,Rouxel, Justine,Flaire, Hadidja-Rose,Mouigni, Mégane,Lemaitre, Benoit,Giroux, Lucie,Audoux, Benjamin,SaintPierre, Arnaud,Ferry, Vincent,Mouly, Gillian,Butler-Browne, Elisa,Negroni, Alberto,Malerba, Capucine,Trollet

Journal of cachexia, sarcopenia and muscle · 2024-08-07

pmid:39113268

Locus OPMD PABPN1

Disease

Locus

Alleles

gnomAD

References

Additional Literature