Finnish upper limb-onset distal myopathy

Summary

Finnish upper limb-onset distal myopathy (MONDO:0012410) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0002312	Clumsiness	Frequent (30-79%)
HP:0002936	Distal sensory impairment	Frequent (30-79%)
HP:0003376	Steppage gait	Frequent (30-79%)
HP:0003458	EMG: myopathic abnormalities	Frequent (30-79%)
HP:0003805	Rimmed vacuoles	Frequent (30-79%)
HP:0008180	Mildly elevated creatine kinase	Frequent (30-79%)
HP:0008954	Intrinsic hand muscle atrophy	Frequent (30-79%)
HP:0009005	Weakness of the intrinsic hand muscles	Frequent (30-79%)
HP:0009031	Amyotrophy of ankle musculature	Frequent (30-79%)
HP:0009063	Progressive distal muscle weakness	Frequent (30-79%)
HP:0009473	Joint contracture of the hand	Frequent (30-79%)
HP:0012548	Fatty replacement of skeletal muscle	Frequent (30-79%)
HP:0001171	Split hand	Occasional (5-29%)
HP:0009073	Progressive proximal muscle weakness	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Finnish upper limb-onset distal myopathy
Mondo ID	MONDO:0012410
OMIM	610099
Orphanet	399086
DOID	DOID:0111189
SNOMED CT	763718009
UMLS	C1864706
MedGen	400595
GARD	0017652
Is cancer (heuristic)	no

Also known as: distal myopathy type 3 · MPD3 · myopathy, distal, 3

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant distal myopathy › Finnish upper limb-onset distal myopathy

Related subtypes (14): tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure, distal myopathy, Welander type, myofibrillar myopathy 2, myofibrillar myopathy 3, myofibrillar myopathy 4, distal myopathy with posterior leg and anterior hand involvement, distal myopathy, Tateyama type, adult-onset distal myopathy due to VCP mutation, KLHL9-related early-onset distal myopathy, distal myopathy with vocal cord weakness, TARDBP-related predominantly upper-limb distal myopathy, asymetric thumb-handgrip weakness-distal myopathy, calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy

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
2575312	NM_031157.4(HNRNPA1):c.1064-63_*4+37del	HNRNPA1	Pathogenic	no assertion criteria provided
2432495	NM_031157.4(HNRNPA1):c.959A>G (p.Asn320Ser)	HNRNPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HNRNPA1	Orphanet:399086	HNRNPA1-related adult-onset distal myopathy
HNRNPA1	Orphanet:52430	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
HNRNPA1	Orphanet:803	Amyotrophic lateral sclerosis

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
HNRNPA1	HGNC:5031	ENSG00000135486	P09651	Heterogeneous nuclear ribonucleoprotein A1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HNRNPA1	Heterogeneous nuclear ribonucleoprotein A1	Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection.

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)
HNRNPA1	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
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HNRNPA1	295	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNRNPA1	6,616

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HNRNPA1	P09651	73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
FGFR2 alternative splicing	1	423.0×	0.015	HNRNPA1
Signaling by FGFR2	1	407.9×	0.015	HNRNPA1
Signaling by FGFR	1	346.1×	0.015	HNRNPA1
SARS-CoV-1 modulates host translation machinery	1	308.6×	0.015	HNRNPA1
SARS-CoV-1-host interactions	1	175.7×	0.020	HNRNPA1
SARS-CoV-1 Infection	1	142.8×	0.021	HNRNPA1
mRNA Splicing	1	109.8×	0.023	HNRNPA1
mRNA Polyadenylation	1	87.8×	0.024	HNRNPA1
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.024	HNRNPA1
SARS-CoV Infections	1	55.4×	0.029	HNRNPA1
mRNA Splicing - Major Pathway	1	54.6×	0.029	HNRNPA1
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.029	HNRNPA1
Dengue Virus-Host Interactions	1	45.7×	0.030	HNRNPA1
Metabolism of RNA	1	41.7×	0.031	HNRNPA1
Viral Infection Pathways	1	30.8×	0.039	HNRNPA1
Infectious disease	1	24.8×	0.045	HNRNPA1
Disease	1	13.1×	0.081	HNRNPA1
Signal Transduction	1	10.2×	0.098	HNRNPA1

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
cellular response to sodium arsenite	1	3370.4×	0.002	HNRNPA1
import into nucleus	1	2407.4×	0.002	HNRNPA1
nuclear export	1	1532.0×	0.003	HNRNPA1
RNA export from nucleus	1	936.2×	0.003	HNRNPA1
negative regulation of telomere maintenance via telomerase	1	732.7×	0.003	HNRNPA1
positive regulation of telomere maintenance via telomerase	1	732.7×	0.003	HNRNPA1
alternative mRNA splicing, via spliceosome	1	674.1×	0.003	HNRNPA1
cellular response to glucose starvation	1	337.0×	0.004	HNRNPA1
mRNA transport	1	263.3×	0.005	HNRNPA1
regulation of alternative mRNA splicing, via spliceosome	1	244.2×	0.005	HNRNPA1
regulation of RNA splicing	1	218.9×	0.005	HNRNPA1
mRNA splicing, via spliceosome	1	91.6×	0.011	HNRNPA1

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
HNRNPA1	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
HNRNPA1	7	Binding:7

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	HNRNPA1

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)
HNRNPA1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.