Miyoshi muscular dystrophy 1

Summary

Miyoshi muscular dystrophy 1 (MONDO:0024545) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 562

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Miyoshi muscular dystrophy 1
Mondo ID	MONDO:0024545
OMIM	254130
DOID	DOID:0070199
UMLS	C4551973
MedGen	1640757
GARD	0025425
Is cancer (heuristic)	no

Also known as: DYSF Miyoshi myopathy · Miyoshi myopathy caused by mutation in DYSF · MMD1

Data availability: 562 ClinVar variants · 18 cell lines.

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 › distal myopathy › Miyoshi myopathy › Miyoshi muscular dystrophy 1

Related subtypes (2): Miyoshi muscular dystrophy 2, Miyoshi muscular dystrophy 3

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

562 retrieved; paginated sample, class counts are floors:

177 likely pathogenic, 168 pathogenic, 67 pathogenic/likely pathogenic, 52 conflicting classifications of pathogenicity, 47 benign, 34 uncertain significance, 13 benign/likely benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070532	NM_001130987.2(DYSF):c.1258del (p.Ala420fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072386	NM_001130987.2(DYSF):c.4954del (p.Ser1652fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075046	NM_003494.4(DYSF):c.24T>G (p.Tyr8Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075368	NM_001130987.2(DYSF):c.3251dup (p.Glu1085fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075637	NM_001130987.2(DYSF):c.2605C>T (p.Gln869Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180848	NM_001130987.2(DYSF):c.4756-1G>A	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300184	NM_001130987.2(DYSF):c.3427del (p.Glu1143fs)	DYSF	Pathogenic	reviewed by expert panel
1300185	NM_001130987.2(DYSF):c.4989del (p.Glu1663fs)	DYSF	Pathogenic	reviewed by expert panel
1322807	NM_001130987.2(DYSF):c.923del (p.Glu308fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1322810	NM_001130987.2(DYSF):c.1985-1G>T	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1350474	NM_001130987.2(DYSF):c.6057dup (p.Leu2020fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1367528	NM_001130987.2(DYSF):c.5578A>T (p.Arg1860Ter)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1381552	NM_001130987.2(DYSF):c.3113dup (p.Glu1039fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1389207	NM_001130987.2(DYSF):c.5188C>T (p.Gln1730Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1402261	NM_001130987.2(DYSF):c.4254del (p.Ile1419fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1433815	NM_001130987.2(DYSF):c.2266C>T (p.Gln756Ter)	DYSF	Pathogenic	reviewed by expert panel
1448346	NM_001130987.2(DYSF):c.2955dup (p.Met986fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1454769	NM_001130987.2(DYSF):c.5025_5053dup (p.Thr1685delinsIleCysLeuTrpArgArgThrTer)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458148	NM_001130987.2(DYSF):c.4021C>T (p.Gln1341Ter)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
167021	NM_001130987.2(DYSF):c.2844G>C (p.Trp948Cys)	DYSF	Pathogenic	reviewed by expert panel
167025	NM_001130987.2(DYSF):c.3886C>T (p.Gln1296Ter)	DYSF	Pathogenic	reviewed by expert panel
167026	NM_001130987.2(DYSF):c.5383C>T (p.Gln1795Ter)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
167030	NM_001130987.2(DYSF):c.5642+1G>A	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1708551	NM_001130987.2(DYSF):c.2472C>A (p.Tyr824Ter)	DYSF	Pathogenic	criteria provided, single submitter
1708555	NM_001130987.2(DYSF):c.907_910del (p.Phe303fs)	DYSF	Pathogenic	no assertion criteria provided
1724499	NM_001130987.2(DYSF):c.4923C>A (p.Tyr1641Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1724791	NM_001130987.2(DYSF):c.2832G>A (p.Trp944Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1724930	NM_001130987.2(DYSF):c.1597del (p.Leu533fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1725487	NM_001130987.2(DYSF):c.561del (p.Gly188fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802250	NM_001130987.2(DYSF):c.5680_5681insC (p.Asp1894fs)	DYSF	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DYSF	Orphanet:178400	Distal myopathy with anterior tibial onset
DYSF	Orphanet:199329	Congenital myopathy, Paradas type
DYSF	Orphanet:268	Dysferlin-related limb-girdle muscular dystrophy R2
DYSF	Orphanet:45448	Miyoshi myopathy
PIP5K1C	Orphanet:137783	Lethal congenital contracture syndrome type 3

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DYSF	HGNC:3097	ENSG00000135636	O75923	Dysferlin	clinvar
PIP5K1C	HGNC:8996	ENSG00000186111	O60331	Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYSF	Dysferlin	Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion.
PIP5K1C	Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma	Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal trans…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYSF	Other/Unknown	no		C2_dom, Peroxin/Ferlin, Ferlin_A-domain
PIP5K1C	Kinase	yes	2.7.1.68	PInositol-4-P-4/5-kinase_core, PInositol-4/5-P-5/4-kinase, PInositol-4-P-4/5-kinase_C_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYSF	257	ubiquitous	marker	blood, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
PIP5K1C	279	ubiquitous	marker	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIP5K1C	1,853
DYSF	1,776

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYSF	O75923	11
PIP5K1C	O60331	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion	1	380.7×	0.014	PIP5K1C
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.014	PIP5K1C
Smooth Muscle Contraction	1	132.8×	0.014	DYSF
Synthesis of PIPs at the plasma membrane	1	105.7×	0.014	PIP5K1C
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.023	PIP5K1C
Clathrin-mediated endocytosis	1	42.6×	0.023	PIP5K1C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
monocyte activation involved in immune response	1	8426.0×	0.002	DYSF
adherens junction assembly	1	648.1×	0.007	PIP5K1C
macrophage activation involved in immune response	1	561.7×	0.007	DYSF
negative regulation of phagocytosis	1	495.6×	0.007	DYSF
synaptic vesicle exocytosis	1	383.0×	0.007	PIP5K1C
regulation of neurotransmitter secretion	1	383.0×	0.007	DYSF
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	351.1×	0.007	PIP5K1C
clathrin-dependent endocytosis	1	290.6×	0.007	PIP5K1C
membrane organization	1	255.3×	0.007	PIP5K1C
phosphatidylinositol phosphate biosynthetic process	1	240.7×	0.007	PIP5K1C
synaptic vesicle endocytosis	1	216.1×	0.007	PIP5K1C
phosphatidylinositol biosynthetic process	1	183.2×	0.007	PIP5K1C
neutrophil chemotaxis	1	142.8×	0.009	PIP5K1C
phagocytosis	1	120.4×	0.009	PIP5K1C
cell-cell adhesion	1	50.8×	0.021	PIP5K1C
actin cytoskeleton organization	1	39.6×	0.025	PIP5K1C

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PIP5K1C	PAZOPANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIP5K1C	10	4
DYSF	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PAZOPANIB	4	PIP5K1C
ENZASTAURIN	3	PIP5K1C
ALVOCIDIB	3	PIP5K1C
DOVITINIB	3	PIP5K1C
RUBOXISTAURIN	3	PIP5K1C
TG100-115	2	PIP5K1C
R-406	2	PIP5K1C
BIIB-091	2	PIP5K1C
GSK-461364	1	PIP5K1C
GSK-690693	1	PIP5K1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PIP5K1C	116	Binding:116

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIP5K1C	2.7.1.68	1-phosphatidylinositol-4-phosphate 5-kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PIP5K1C	116

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

10 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.

Compound	Max phase	Cohort target (bioactivity)
PAZOPANIB	4	PIP5K1C
ENZASTAURIN	3	PIP5K1C
ALVOCIDIB	3	PIP5K1C
DOVITINIB	3	PIP5K1C
RUBOXISTAURIN	3	PIP5K1C
TG100-115	2	PIP5K1C
R-406	2	PIP5K1C
BIIB-091	2	PIP5K1C
GSK-461364	1	PIP5K1C
GSK-690693	1	PIP5K1C

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PIP5K1C
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	DYSF

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)
DYSF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.