Oculopharyngeal muscular dystrophy 1

Summary

Oculopharyngeal muscular dystrophy 1 (MONDO:0958176) is a disease caused by PABPN1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: PABPN1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oculopharyngeal muscular dystrophy 1
Mondo ID	MONDO:0958176
OMIM	164300
NCIT	C84942
GARD	0026954
Is cancer (heuristic)	no

Data availability: 29 ClinVar variants · 2 GenCC gene-disease records.

Disease family

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 › oculopharyngeal muscular dystrophy 1

Related subtypes (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

29 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 7 pathogenic, 5 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2444454	NM_145868.2(ANXA11):c.118_119delinsAT (p.Asp40Ile)	ANXA11	Pathogenic	criteria provided, single submitter
1323408	NM_004643.4(PABPN1):c.3GGC[12] (p.Ala11_Gly12insAlaAlaAlaAlaAla)	BCL2L2-PABPN1	Pathogenic	criteria provided, multiple submitters, no conflicts
2437738	NM_004643.4(PABPN1):c.21_26dup (p.Ala11_Gly12insAlaAla)	BCL2L2-PABPN1	Pathogenic	criteria provided, single submitter
279930	NM_004643.3(PABPN1):c.3GGC[10] (p.Ala9_Ala11dup)	BCL2L2-PABPN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3907692	NM_004643.4(PABPN1):c.3GGC[13] (p.Ala11_Gly12insAlaAlaAlaAlaAlaAla)	BCL2L2-PABPN1	Pathogenic	criteria provided, single submitter
503634	NM_004643.3(PABPN1):c.3GGC[11] (p.Ala11_Gly12insAlaAlaAlaAla)	BCL2L2-PABPN1	Pathogenic	criteria provided, multiple submitters, no conflicts
7367	NM_004643.4(PABPN1):c.3_23= (p.Met1_Ala8=)	BCL2L2-PABPN1	Pathogenic	no assertion criteria provided
987098	NM_004643.4(PABPN1):c.18_26dup (p.Ala11_Gly12insAlaAlaAla)	BCL2L2-PABPN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
978416	NM_004643.3:c.3GGC[(8_13)]	PABPN1	Pathogenic	no assertion criteria provided
4081574	NM_004643.4(PABPN1):c.9_26dup (p.Ala11_Gly12insAlaAlaAlaAlaAlaAla)	BCL2L2-PABPN1	Likely pathogenic	criteria provided, single submitter
1323406	NM_004643.4(PABPN1):c.24AGC[4] (p.Ala11_Gly12insAla)	BCL2L2-PABPN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1323407	NM_004643.4(PABPN1):c.3GGC[8] (p.Ala11_Gly12insAla)	BCL2L2-PABPN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1327685	NM_004643.4(PABPN1):c.31G>A (p.Ala11Thr)	BCL2L2-PABPN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2434543	NM_004643.4(PABPN1):c.26C>T (p.Ala9Val)	BCL2L2-PABPN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2434545	NM_004643.4(PABPN1):c.-1G>T	BCL2L2-PABPN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2434544	NM_004643.4(PABPN1):c.481A>G (p.Met161Val)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
2434546	NM_004643.4(PABPN1):c.242C>G (p.Pro81Arg)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
2434547	NM_004643.4(PABPN1):c.269C>T (p.Ser90Leu)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
2434549	NM_004643.4(PABPN1):c.37G>C (p.Ala13Pro)	BCL2L2-PABPN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434551	NM_004643.4(PABPN1):c.624_625dup (p.Ser209fs)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
281604	NM_004643.4(PABPN1):c.169C>T (p.Pro57Ser)	BCL2L2-PABPN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4079484	NM_004643.4(PABPN1):c.38C>T (p.Ala13Val)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
4079485	NM_004643.4(PABPN1):c.739A>G (p.Lys247Glu)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
4079486	NM_004643.4(PABPN1):c.186GGAGCCCGAGCC[3] (p.Glu71_Glu72insProGluProGlu)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
4079487	NM_004643.4(PABPN1):c.815A>G (p.Asn272Ser)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
4079488	NM_004643.4(PABPN1):c.287A>T (p.Gln96Leu)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
7368	NM_004643.4(PABPN1):c.35G>C (p.Gly12Ala)	BCL2L2-PABPN1	Uncertain significance	criteria provided, single submitter
2434548	NM_004643.4(PABPN1):c.3GGC[6] (p.Ala11del)	PABPN1	Uncertain significance	criteria provided, single submitter
2434550	NM_004643.4(PABPN1):c.198_203dup (p.Glu71_Glu72insProGlu)	PABPN1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PABPN1	Orphanet:270	Oculopharyngeal muscular dystrophy
ANXA11	Orphanet:803	Amyotrophic lateral sclerosis

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
PABPN1	HGNC:8565	ENSG00000100836	Q86U42	Polyadenylate-binding protein 2	gencc,clinvar
BCL2L2-PABPN1	HGNC:42959	ENSG00000258643	Q92843	Bcl-2-like protein 2	clinvar
ANXA11	HGNC:535	ENSG00000122359	P50995	Annexin A11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
ANXA11	Annexin A11	Binds specifically to calcyclin in a calcium-dependent manner.

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)
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
ANXA11	Other/Unknown	no		Annexin, ANX11, Annexin_repeat_CS

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
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
lower esophagus mucosa	1
mucosa of transverse colon	1
palpebral conjunctiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
ANXA11	300	ubiquitous	marker	lower esophagus mucosa, palpebral conjunctiva, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PABPN1	2,799
BCL2L2-PABPN1	1,501
ANXA11	1,344

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL2L2-PABPN1	Q92843	5
PABPN1	Q86U42	3
ANXA11	P50995	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Inhibition of Host mRNA Processing and RNA Silencing	1	5710.0×	0.001	PABPN1
Z-decay: degradation of maternal mRNAs by zygotically expressed factors	1	951.7×	0.004	PABPN1
Processing of Intronless Pre-mRNAs	1	571.0×	0.005	PABPN1
Nuclear RNA decay	1	308.6×	0.006	PABPN1
RNA Polymerase II Transcription Termination	1	219.6×	0.007	PABPN1
mRNA 3’-end processing	1	196.9×	0.007	PABPN1
mRNA Polyadenylation	1	87.8×	0.013	PABPN1
Dengue Virus-Host Interactions	1	45.7×	0.022	PABPN1

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×	0.003	PABPN1
cytokinetic process	1	1872.4×	0.005	ANXA11
Sertoli cell proliferation	1	936.2×	0.006	BCL2L2-PABPN1
release of cytochrome c from mitochondria	1	234.1×	0.016	BCL2L2-PABPN1
poly(A)+ mRNA export from nucleus	1	224.7×	0.016	PABPN1
extrinsic apoptotic signaling pathway in absence of ligand	1	156.0×	0.019	BCL2L2-PABPN1
intrinsic apoptotic signaling pathway in response to DNA damage	1	108.0×	0.021	BCL2L2-PABPN1
response to calcium ion	1	106.0×	0.021	ANXA11
phagocytosis	1	80.2×	0.023	ANXA11
RNA processing	1	73.0×	0.023	PABPN1
muscle contraction	1	69.3×	0.023	PABPN1
MAPK cascade	1	51.1×	0.029	PABPN1
cellular response to lipopolysaccharide	1	32.7×	0.042	PABPN1
regulation of apoptotic process	1	27.8×	0.045	BCL2L2-PABPN1
mRNA processing	1	26.2×	0.045	PABPN1
positive regulation of apoptotic process	1	18.9×	0.058	BCL2L2-PABPN1
spermatogenesis	1	11.7×	0.084	BCL2L2-PABPN1
negative regulation of apoptotic process	1	11.6×	0.084	BCL2L2-PABPN1

Therapeutics

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
PABPN1	0	0
ANXA11	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
ANXA11	7	Binding:7

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	PABPN1, ANXA11

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)
PABPN1	0	—
ANXA11	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.