Oculopharyngeal muscular dystrophy

Summary

Oculopharyngeal muscular dystrophy (MONDO:0008116) is a disease caused by variants in PABPN1 and HNRNPA2B1, with 3 cohort genes and 11 clinical trials. Top therapeutic interventions include trehalose.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal genes: PABPN1 (GenCC Definitive), HNRNPA2B1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 5
• Phenotypes (HPO): 26
• Clinical trials: 11

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Point prevalence	>1 / 1000	167	Specific population	Validated
Point prevalence	1-9 / 100 000	1	France	Validated
Point prevalence	>1 / 1000	100	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0000602	Ophthalmoplegia	Very frequent (80-99%)
HP:0002015	Dysphagia	Very frequent (80-99%)
HP:0003198	Myopathy	Very frequent (80-99%)
HP:0003200	Ragged-red muscle fibers	Very frequent (80-99%)
HP:0003302	Spondylolisthesis	Very frequent (80-99%)
HP:0003805	Rimmed vacuoles	Very frequent (80-99%)
HP:0004303	Abnormal muscle fiber morphology	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0000183	Tongue muscle weakness	Frequent (30-79%)
HP:0001618	Dysphonia	Frequent (30-79%)
HP:0003325	Limb-girdle muscle weakness	Frequent (30-79%)
HP:0003327	Axial muscle weakness	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012473	Tongue atrophy	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0012548	Fatty replacement of skeletal muscle	Frequent (30-79%)
HP:0030319	Weakness of facial musculature	Frequent (30-79%)
HP:0032342	Reduced forced expiratory volume in one second	Frequent (30-79%)
HP:0034045	Angulated muscle fibers	Frequent (30-79%)
HP:0100304	Muscle fiber intranuclear inclusion bodies	Frequent (30-79%)
HP:6001011	Wet voice	Frequent (30-79%)
HP:0000298	Mask-like facies	Occasional (5-29%)
HP:0003236	Elevated circulating creatine kinase concentration	Occasional (5-29%)
HP:0010535	Sleep apnea	Very rare (<1-4%)
HP:0100543	Cognitive impairment	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculopharyngeal muscular dystrophy
Mondo ID	MONDO:0008116
MeSH	D039141
OMIM	164300
Orphanet	270
DOID	DOID:11719
ICD-11	1354386293
SNOMED CT	77097004
UMLS	C0270952
MedGen	75730
GARD	0007245
MedDRA	10052181
NORD	1523
Is cancer (heuristic)	no

Also known as: oculopharyngeal muscular dystrophy · OPMD

Data availability: 5 ClinVar variants · 4 GenCC gene-disease records · 3 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye adnexa disorder › myopathy of extraocular muscle › oculopharyngeal muscular dystrophy

Related subtypes (2): congenital fibrosis of extraocular muscles, orbital myositis

Subtypes (2): oculopharyngeal muscular dystrophy 1, oculopharyngeal muscular dystrophy 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323408	NM_004643.4(PABPN1):c.3GGC[12] (p.Ala11_Gly12insAlaAlaAlaAlaAla)	BCL2L2-PABPN1	Pathogenic	criteria provided, multiple submitters, no conflicts
279930	NM_004643.3(PABPN1):c.3GGC[10] (p.Ala9_Ala11dup)	BCL2L2-PABPN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
503634	NM_004643.3(PABPN1):c.3GGC[11] (p.Ala11_Gly12insAlaAlaAlaAla)	BCL2L2-PABPN1	Pathogenic	criteria provided, multiple submitters, no conflicts
803008	NM_004643.4(PABPN1):c.15_26dup (p.Ala11_Gly12insAlaAlaAlaAla)	BCL2L2-PABPN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2582731	NM_004643.4(PABPN1):c.74_76dup (p.Arg25_His26insArg)	BCL2L2-PABPN1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PABPN1	Definitive	Autosomal dominant	oculopharyngeal muscular dystrophy	5
HNRNPA2B1	Strong	Autosomal dominant	oculopharyngeal muscular dystrophy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HNRNPA2B1	Orphanet:52430	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
PABPN1	Orphanet:270	Oculopharyngeal muscular dystrophy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HNRNPA2B1	HGNC:5033	ENSG00000122566	P22626	Heterogeneous nuclear ribonucleoproteins A2/B1	gencc
PABPN1	HGNC:8565	ENSG00000100836	Q86U42	Polyadenylate-binding protein 2	gencc
BCL2L2-PABPN1	HGNC:42959	ENSG00000258643	Q92843	Bcl-2-like protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HNRNPA2B1	Heterogeneous nuclear ribonucleoproteins A2/B1	Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles.
PABPN1	Polyadenylate-binding protein 2	Involved in the 3’-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product.
BCL2L2-PABPN1	Bcl-2-like protein 2	Promotes cell survival.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HNRNPA2B1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, HnRNPA1/A2_C
PABPN1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
BCL2L2-PABPN1	Other/Unknown	no		Bcl2-like, Bcl2_BH4, Apop_reg_BclW

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of nasopharynx	1
tendon of biceps brachii	1
ventricular zone	1
left testis	1
right hemisphere of cerebellum	1
right testis	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HNRNPA2B1	295	ubiquitous	marker	epithelium of nasopharynx, tendon of biceps brachii, ventricular zone
PABPN1	259	ubiquitous	marker	right testis, left testis, right hemisphere of cerebellum
BCL2L2-PABPN1	134	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNRNPA2B1	5,996
PABPN1	2,799
BCL2L2-PABPN1	1,501

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HNRNPA2B1	P22626	13
BCL2L2-PABPN1	Q92843	5
PABPN1	Q86U42	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
mRNA Polyadenylation	2	87.8×	0.002	HNRNPA2B1, PABPN1
Inhibition of Host mRNA Processing and RNA Silencing	1	2855.0×	0.003	PABPN1
Dengue Virus-Host Interactions	2	45.7×	0.003	HNRNPA2B1, PABPN1
Z-decay: degradation of maternal mRNAs by zygotically expressed factors	1	475.8×	0.009	PABPN1
Processing of Intronless Pre-mRNAs	1	285.5×	0.013	PABPN1
Interleukin-12 family signaling	1	237.9×	0.013	HNRNPA2B1
Interleukin-12 signaling	1	203.9×	0.013	HNRNPA2B1
Nuclear RNA decay	1	154.3×	0.013	PABPN1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	150.3×	0.013	HNRNPA2B1
RNA Polymerase II Transcription Termination	1	109.8×	0.016	PABPN1
mRNA 3’-end processing	1	98.5×	0.017	PABPN1
mRNA Splicing	1	54.9×	0.027	HNRNPA2B1
Processing of Capped Intron-Containing Pre-mRNA	1	41.1×	0.034	HNRNPA2B1
Signaling by Interleukins	1	32.1×	0.040	HNRNPA2B1
mRNA Splicing - Major Pathway	1	27.3×	0.044	HNRNPA2B1
Metabolism of RNA	1	20.8×	0.051	HNRNPA2B1
Cytokine Signaling in Immune system	1	20.4×	0.051	HNRNPA2B1
Immune System	1	6.5×	0.148	HNRNPA2B1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of polynucleotide adenylyltransferase activity	1	5617.3×	0.004	PABPN1
miRNA transport	1	1872.4×	0.004	HNRNPA2B1
mRNA processing	2	52.5×	0.004	HNRNPA2B1, PABPN1
Sertoli cell proliferation	1	936.2×	0.005	BCL2L2-PABPN1
positive regulation of telomere maintenance via telomere lengthening	1	936.2×	0.005	HNRNPA2B1
DNA geometric change	1	702.2×	0.005	HNRNPA2B1
RNA transport	1	510.7×	0.006	HNRNPA2B1
primary miRNA processing	1	432.1×	0.007	HNRNPA2B1
release of cytochrome c from mitochondria	1	234.1×	0.010	BCL2L2-PABPN1
poly(A)+ mRNA export from nucleus	1	224.7×	0.010	PABPN1
extrinsic apoptotic signaling pathway in absence of ligand	1	156.0×	0.013	BCL2L2-PABPN1
intrinsic apoptotic signaling pathway in response to DNA damage	1	108.0×	0.018	BCL2L2-PABPN1
mRNA export from nucleus	1	98.5×	0.018	HNRNPA2B1
mRNA transport	1	87.8×	0.019	HNRNPA2B1
RNA processing	1	73.0×	0.021	PABPN1
muscle contraction	1	69.3×	0.021	PABPN1
MAPK cascade	1	51.1×	0.026	PABPN1
cellular response to lipopolysaccharide	1	32.7×	0.039	PABPN1
mRNA splicing, via spliceosome	1	30.5×	0.039	HNRNPA2B1
regulation of apoptotic process	1	27.8×	0.041	BCL2L2-PABPN1
positive regulation of apoptotic process	1	18.9×	0.057	BCL2L2-PABPN1
spermatogenesis	1	11.7×	0.084	BCL2L2-PABPN1
negative regulation of apoptotic process	1	11.6×	0.084	BCL2L2-PABPN1

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Trehalose	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BCL2L2-PABPN1	VENETOCLAX

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BCL2L2-PABPN1	6	4
HNRNPA2B1	0	0
PABPN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VENETOCLAX	4	BCL2L2-PABPN1
OBATOCLAX	3	BCL2L2-PABPN1
NAVITOCLAX	3	BCL2L2-PABPN1
GOSSYPOL	3	BCL2L2-PABPN1
EPIGALOCATECHIN GALLATE	3	BCL2L2-PABPN1
ABT 737	1	BCL2L2-PABPN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BCL2L2-PABPN1	41	Binding:41
HNRNPA2B1	12	Binding:12

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

6 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
VENETOCLAX	4	BCL2L2-PABPN1
OBATOCLAX	3	BCL2L2-PABPN1
NAVITOCLAX	3	BCL2L2-PABPN1
GOSSYPOL	3	BCL2L2-PABPN1
EPIGALOCATECHIN GALLATE	3	BCL2L2-PABPN1
ABT 737	1	BCL2L2-PABPN1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BCL2L2-PABPN1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	HNRNPA2B1, PABPN1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HNRNPA2B1	12	—
PABPN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06185673	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety and Clinical Activity of Intramuscular Doses of BB-301 Administered to Subjects With Oculopharyngeal Muscular Dystrophy With Dysphagia
NCT02015481	PHASE2	COMPLETED	Safety Tolerability and Efficacy Study of Cabaletta to Treat Oculopharyngeal Muscular Dystrophy (OPMD) Patients
NCT04226924	PHASE2	WITHDRAWN	Treatment of Oculopharyngeal Muscular Dystrophy With Trehalose
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT07118280	Not specified	RECRUITING	Oral Health, Saliva Viscosity and Composition in Oculo-Pharyngeal Muscular Dystrophy (OPMD)
NCT07146256	Not specified	RECRUITING	Natural History of Oculo-Pharyngeal Muscular Dystrophy (OPMD) - Israel National OPMD Registry
NCT02158156	Not specified	UNKNOWN	Effect of Aerobic Training in Patients With Oculopharyngeal Muscular Dystrophy
NCT02877784	Not specified	COMPLETED	Screening in Oculopharyngeal Muscular Dystrophy
NCT03161847	Not specified	WITHDRAWN	Natural History Study of Oculopharyngeal Muscular Dystrophy
NCT03874910	Not specified	UNKNOWN	Pathology Analysis of OPMD Patient Myotomies
NCT04009408	Not specified	UNKNOWN	Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TREHALOSE	3	2