Oculopharyngodistal myopathy

Summary

Oculopharyngodistal myopathy (MONDO:0025193) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• Phenotypes (HPO): 36

Clinical features

Signs & symptoms

Clinical features (HPO)

36 HPO clinical features (Orphanet curated; top 36 by frequency):

HPO ID	Term	Frequency
HP:0000301	Abnormality of facial musculature	Very frequent (80-99%)
HP:0000590	Progressive external ophthalmoplegia	Very frequent (80-99%)
HP:0000597	Ophthalmoparesis	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0007838	Progressive ptosis	Very frequent (80-99%)
HP:0008376	Nasal, dysarthic speech	Very frequent (80-99%)
HP:0030319	Weakness of facial musculature	Very frequent (80-99%)
HP:0000183	Tongue muscle weakness	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0001604	Vocal cord paresis	Frequent (30-79%)
HP:0002058	Myopathic facies	Frequent (30-79%)
HP:0002100	Recurrent aspiration pneumonia	Frequent (30-79%)
HP:0002705	High, narrow palate	Frequent (30-79%)
HP:0002747	Respiratory insufficiency due to muscle weakness	Frequent (30-79%)
HP:0007149	Distal upper limb amyotrophy	Frequent (30-79%)
HP:0008756	Bowing of the vocal cords	Frequent (30-79%)
HP:0008944	Distal lower limb amyotrophy	Frequent (30-79%)
HP:0009053	Distal lower limb muscle weakness	Frequent (30-79%)
HP:0009063	Progressive distal muscle weakness	Frequent (30-79%)
HP:0031162	Impaired oropharyngeal swallow response	Frequent (30-79%)
HP:0200136	Oral-pharyngeal dysphagia	Frequent (30-79%)
HP:0430015	Abnormal morphology of musculature of pharynx	Frequent (30-79%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0000408	Progressive sensorineural hearing impairment	Occasional (5-29%)
HP:0001284	Areflexia	Occasional (5-29%)
HP:0002091	Restrictive ventilatory defect	Occasional (5-29%)
HP:0002505	Loss of ambulation	Occasional (5-29%)
HP:0008959	Distal upper limb muscle weakness	Occasional (5-29%)
HP:0008963	Tibialis muscle weakness	Occasional (5-29%)
HP:0009027	Foot dorsiflexor weakness	Occasional (5-29%)
HP:0009073	Progressive proximal muscle weakness	Occasional (5-29%)
HP:0030192	Fatigable weakness of bulbar muscles	Occasional (5-29%)
HP:3000005	Abnormality of masseter muscle	Occasional (5-29%)
HP:0008997	Proximal muscle weakness in upper limbs	Very rare (<1-4%)
HP:0010550	Paraplegia	Very rare (<1-4%)
HP:3000010	Abnormality of orbicularis oris muscle	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculopharyngodistal myopathy
Mondo ID	MONDO:0025193
MeSH	C563508
OMIM	164310
Orphanet	98897
DOID	DOID:0081296
ICD-11	1493269618
SNOMED CT	763829004
UMLS	C1834014
MedGen	320250
GARD	0012592
Is cancer (heuristic)	no

Also known as: oculopharyngeal distal myopathy · oculopharyngodistal myopathy · OPDM

Data availability: 1 GenCC gene-disease record · 1 cell line.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › oculopharyngodistal myopathy

Related subtypes (12): facioscapulohumeral muscular dystrophy, congenital fibrosis of extraocular muscles, Bethlem myopathy, oculopharyngeal muscular dystrophy, X-linked myopathy with excessive autophagy, myopathy, myofibrillar, 9, with early respiratory failure, progressive scapulohumeroperoneal distal myopathy, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, myotonic dystrophy, Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy, childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome

Subtypes (5): oculopharyngodistal myopathy 1, oculopharyngodistal myopathy 3, oculopharyngodistal myopathy 2, oculopharyngodistal myopathy 4, oculopharyngodistal myopathy 5

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
GIPC1	Strong	Autosomal dominant	oculopharyngodistal myopathy 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GIPC1	Orphanet:98897	Oculopharyngodistal myopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GIPC1	HGNC:1226	ENSG00000123159	O14908	PDZ domain-containing protein GIPC1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GIPC1	PDZ domain-containing protein GIPC1	May be involved in G protein-linked signaling.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GIPC1	Scaffold/PPI	no		PDZ, GIPC1/2/3, PDZ_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
esophagus mucosa	1
lower esophagus mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GIPC1	292	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GIPC1	1,400

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GIPC1	O14908	81.92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 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
TGFBR3 regulates FGF2 signaling	1	3806.7×	0.001	GIPC1
TGFBR3 regulates TGF-beta signaling	1	1427.5×	0.001	GIPC1
FGFR1b ligand binding and activation	1	1268.9×	0.001	GIPC1
FGFR1c ligand binding and activation	1	761.3×	0.001	GIPC1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glutamate secretion	1	1685.2×	0.003	GIPC1
positive regulation of melanin biosynthetic process	1	1404.3×	0.003	GIPC1
cellular response to interleukin-7	1	1296.3×	0.003	GIPC1
positive regulation of transforming growth factor beta receptor signaling pathway	1	526.6×	0.004	GIPC1
presynaptic modulation of chemical synaptic transmission	1	455.5×	0.004	GIPC1
endothelial cell migration	1	411.0×	0.004	GIPC1
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	401.2×	0.004	GIPC1
positive regulation of cytokinesis	1	401.2×	0.004	GIPC1
protein targeting	1	366.4×	0.004	GIPC1
regulation of synaptic plasticity	1	259.3×	0.005	GIPC1
regulation of protein stability	1	125.8×	0.009	GIPC1
chemical synaptic transmission	1	77.3×	0.014	GIPC1
G protein-coupled receptor signaling pathway	1	36.2×	0.028	GIPC1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GIPC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	GIPC1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GIPC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.