Oculopharyngeal muscular dystrophy 2

Summary

Oculopharyngeal muscular dystrophy 2 (MONDO:0958195) is a disease caused by HNRNPA2B1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: HNRNPA2B1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oculopharyngeal muscular dystrophy 2
Mondo ID	MONDO:0958195
OMIM	620460
UMLS	C5830682
MedGen	1841318
GARD	0026969
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

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 2

Related subtypes (1): oculopharyngeal muscular dystrophy 1

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

7 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2574642	NM_002137.4(HNRNPA2B1):c.992del (p.Gly331fs)	HNRNPA2B1	Pathogenic	no assertion criteria provided
2574643	NM_002137.4(HNRNPA2B1):c.981del (p.Gly328fs)	HNRNPA2B1	Pathogenic	no assertion criteria provided
2574644	NM_002137.4(HNRNPA2B1):c.968del (p.Asn323fs)	HNRNPA2B1	Pathogenic	no assertion criteria provided
2574645	NM_002137.4(HNRNPA2B1):c.996_997dup (p.Gly333fs)	HNRNPA2B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3594491	NM_002137.4(HNRNPA2B1):c.770_772del (p.Tyr257_Gly258delinsCys)	HNRNPA2B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3644042	NM_002137.4(HNRNPA2B1):c.1000_1001dup (p.Tyr335fs)	HNRNPA2B1	Uncertain significance	criteria provided, single submitter
4292513	NM_002137.4(HNRNPA2B1):c.1019del (p.Arg340fs)	HNRNPA2B1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
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

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
HNRNPA2B1	HGNC:5033	ENSG00000122566	P22626	Heterogeneous nuclear ribonucleoproteins A2/B1	gencc,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.

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)
HNRNPA2B1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, HnRNPA1/A2_C

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
epithelium of nasopharynx	1
tendon of biceps brachii	1
ventricular zone	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNRNPA2B1	5,996

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HNRNPA2B1	P22626	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Interleukin-12 family signaling	1	475.8×	0.013	HNRNPA2B1
Interleukin-12 signaling	1	407.9×	0.013	HNRNPA2B1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.013	HNRNPA2B1
mRNA Splicing	1	109.8×	0.024	HNRNPA2B1
mRNA Polyadenylation	1	87.8×	0.024	HNRNPA2B1
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.024	HNRNPA2B1
Signaling by Interleukins	1	64.2×	0.027	HNRNPA2B1
mRNA Splicing - Major Pathway	1	54.6×	0.027	HNRNPA2B1
Dengue Virus-Host Interactions	1	45.7×	0.027	HNRNPA2B1
Metabolism of RNA	1	41.7×	0.027	HNRNPA2B1
Cytokine Signaling in Immune system	1	40.8×	0.027	HNRNPA2B1
Immune System	1	13.0×	0.077	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
miRNA transport	1	5617.3×	0.001	HNRNPA2B1
positive regulation of telomere maintenance via telomere lengthening	1	2808.7×	0.001	HNRNPA2B1
DNA geometric change	1	2106.5×	0.001	HNRNPA2B1
RNA transport	1	1532.0×	0.001	HNRNPA2B1
primary miRNA processing	1	1296.3×	0.001	HNRNPA2B1
mRNA export from nucleus	1	295.6×	0.005	HNRNPA2B1
mRNA transport	1	263.3×	0.005	HNRNPA2B1
mRNA splicing, via spliceosome	1	91.6×	0.012	HNRNPA2B1
mRNA processing	1	78.8×	0.013	HNRNPA2B1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HNRNPA2B1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
HNRNPA2B1	12	Binding:12

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	HNRNPA2B1

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)
HNRNPA2B1	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.