Oculopharyngodistal myopathy 2

Summary

Oculopharyngodistal myopathy 2 (MONDO:0030134) is a disease caused by GIPC1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GIPC1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oculopharyngodistal myopathy 2
Mondo ID	MONDO:0030134
OMIM	618940
DOID	DOID:0081298
UMLS	C5394548
MedGen	1718769
GARD	0016397
Is cancer (heuristic)	no

Also known as: OCULOPHARYNGODISTAL MYOPATHY 2 · oculopharyngodistal myopathy 2 · OPDM2

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

Disease family

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 › oculopharyngodistal myopathy 2

Related subtypes (4): oculopharyngodistal myopathy 1, oculopharyngodistal myopathy 3, 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

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
972742	NM_005716.4:c.-211GGC[(73_?)]	GIPC1	Pathogenic	no assertion criteria provided
3893120	NM_005716.4(GIPC1):c.916G>T (p.Glu306Ter)	GIPC1	Uncertain significance	criteria provided, single submitter

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,clinvar

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.