Oculopharyngodistal myopathy 1

Summary

Oculopharyngodistal myopathy 1 (MONDO:0020793) is a disease caused by LRP12 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LRP12 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oculopharyngodistal myopathy 1
Mondo ID	MONDO:0020793
OMIM	164310
DOID	DOID:0081297
UMLS	C5231388
MedGen	1684682
GARD	0015097
Is cancer (heuristic)	no

Also known as: faciooculolaryngopharyngeal myopathy with distal and respiratory involvement · oculopharyngodistal myopathy · oculopharyngodistal myopathy 1 · OPDM1

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record · 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 1

Related subtypes (4): 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

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
692233	NM_013437.5:c.-102CGG[(90_?)]	LRP12	Pathogenic	no assertion criteria provided
3067250	NM_013437.5(LRP12):c.2384T>C (p.Leu795Pro)	LRP12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3891591	NM_013437.5(LRP12):c.2000C>T (p.Ala667Val)	LRP12	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
LRP12	Strong	Autosomal dominant	oculopharyngodistal myopathy 1

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP12	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
LRP12	HGNC:31708	ENSG00000147650	Q9Y561	Low-density lipoprotein receptor-related protein 12	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP12	Low-density lipoprotein receptor-related protein 12	Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRP12	Other/Unknown	no		CUB_dom, LDrepeatLR_classA_rpt, LDLR_class-A_CS

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
cortical plate	1
ganglionic eminence	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP12	255	ubiquitous	marker	stromal cell of endometrium, cortical plate, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP12	920

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRP12	Q9Y561	63.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Metabolism of fat-soluble vitamins	1	380.7×	0.008	LRP12
Visual phototransduction	1	259.6×	0.008	LRP12
Retinoid metabolism and transport	1	248.3×	0.008	LRP12
Metabolism of vitamins and cofactors	1	116.5×	0.013	LRP12
Sensory Perception	1	95.2×	0.013	LRP12
Metabolism	1	11.6×	0.086	LRP12

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
lymphocyte migration into lymphoid organs	1	1872.4×	0.003	LRP12
integrin activation	1	1404.3×	0.003	LRP12
regulation of growth	1	936.2×	0.003	LRP12
neuron migration	1	133.8×	0.013	LRP12
neuron projection development	1	122.1×	0.013	LRP12
endocytosis	1	95.2×	0.014	LRP12
cell adhesion	1	37.5×	0.031	LRP12
signal transduction	1	16.1×	0.062	LRP12

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
LRP12	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	LRP12

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)
LRP12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.