Miyoshi muscular dystrophy 3

Summary

Miyoshi muscular dystrophy 3 (MONDO:0013222) is a disease caused by ANO5 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ANO5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 82
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		24	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0003323	Progressive muscle weakness	Very frequent (80-99%)
HP:0009053	Distal lower limb muscle weakness	Very frequent (80-99%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0002515	Waddling gait	Frequent (30-79%)
HP:0003552	Muscle stiffness	Frequent (30-79%)
HP:0009046	Difficulty running	Frequent (30-79%)
HP:0030234	Highly elevated creatine kinase	Frequent (30-79%)
HP:0003693	Distal amyotrophy	Occasional (5-29%)
HP:0003707	Calf muscle pseudohypertrophy	Occasional (5-29%)
HP:0008997	Proximal muscle weakness in upper limbs	Occasional (5-29%)
HP:0009073	Progressive proximal muscle weakness	Occasional (5-29%)
HP:0009049	Peroneal muscle atrophy	Excluded (0%)
HP:0003201	Rhabdomyolysis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Miyoshi muscular dystrophy 3
Mondo ID	MONDO:0013222
MeSH	C567645
OMIM	613319
Orphanet	399096
DOID	DOID:0070201
UMLS	C2750076
MedGen	413750
GARD	0017653
Is cancer (heuristic)	no

Also known as: distal anoctaminopathy · Miyoshi muscular dystrophy 3 · Miyoshi muscular dystrophy type 3 · MMD3

Data availability: 82 ClinVar variants · 1 GenCC gene-disease record.

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 3

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

82 retrieved; paginated sample, class counts are floors:

19 benign, 19 benign/likely benign, 13 pathogenic, 10 pathogenic/likely pathogenic, 7 likely pathogenic, 7 uncertain significance, 6 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029543	NM_213599.3(ANO5):c.2116C>T (p.Arg706Ter)	ANO5	Pathogenic	criteria provided, single submitter
1326848	NM_213599.3(ANO5):c.294+5G>A	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140553	NM_213599.3(ANO5):c.1733T>C (p.Phe578Ser)	ANO5	Pathogenic	reviewed by expert panel
194577	NM_213599.3(ANO5):c.1520del (p.Phe507fs)	ANO5	Pathogenic	criteria provided, multiple submitters, no conflicts
194805	NM_213599.3(ANO5):c.1898+1G>A	ANO5	Pathogenic	reviewed by expert panel
197402	NM_213599.3(ANO5):c.172C>T (p.Arg58Trp)	ANO5	Pathogenic	reviewed by expert panel
2163	NM_213599.3(ANO5):c.1295C>G (p.Ala432Gly)	ANO5	Pathogenic	reviewed by expert panel
2164	NM_213599.3(ANO5):c.191dup (p.Asn64fs)	ANO5	Pathogenic	reviewed by expert panel
2166	NM_213599.3(ANO5):c.2272C>T (p.Arg758Cys)	ANO5	Pathogenic	reviewed by expert panel
280322	NM_213599.3(ANO5):c.304_308del (p.Lys102fs)	ANO5	Pathogenic	reviewed by expert panel
282394	NM_213599.3(ANO5):c.1640G>A (p.Arg547Gln)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
285338	NM_213599.3(ANO5):c.2498T>A (p.Met833Lys)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
285669	NM_213599.3(ANO5):c.2004del (p.Leu669fs)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
285942	NM_213599.3(ANO5):c.1627dup (p.Met543fs)	ANO5	Pathogenic	criteria provided, multiple submitters, no conflicts
3599493	NM_213599.3(ANO5):c.846T>G (p.Tyr282Ter)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39276	NM_213599.3(ANO5):c.1407+5G>A	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
468825	NM_213599.3(ANO5):c.148C>T (p.Arg50Ter)	ANO5	Pathogenic	reviewed by expert panel
523571	NM_213599.3(ANO5):c.1965G>C (p.Trp655Cys)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
536726	NM_213599.3(ANO5):c.1120-1G>A	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
619026	NM_213599.3(ANO5):c.1158del (p.Phe386fs)	ANO5	Pathogenic	no assertion criteria provided
694040	NM_213599.3(ANO5):c.1359C>G (p.Tyr453Ter)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96688	NM_213599.3(ANO5):c.989dup (p.Leu330fs)	ANO5	Pathogenic	reviewed by expert panel
976689	NM_213599.3(ANO5):c.898dup (p.Ile300fs)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802145	NM_213599.3(ANO5):c.[1520del];[155A>G]		Likely pathogenic	criteria provided, single submitter
424764	NM_213599.2(ANO5):c.[155A>G];[191dupA]		Likely pathogenic	criteria provided, single submitter
2165	NM_213599.3(ANO5):c.692G>T (p.Gly231Val)	ANO5	Likely pathogenic	reviewed by expert panel
2572432	NM_213599.3(ANO5):c.2286C>G (p.Tyr762Ter)	ANO5	Likely pathogenic	criteria provided, single submitter
3383173	NM_213599.3(ANO5):c.1418_1421delinsGGACGACACCAGTGACGA (p.Val473fs)	ANO5	Likely pathogenic	criteria provided, single submitter
3599495	NM_213599.3(ANO5):c.2290_2293dup (p.Tyr765fs)	ANO5	Likely pathogenic	criteria provided, single submitter
3896778	NM_213599.3(ANO5):c.1777_1780del (p.Phe593fs)	ANO5	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · 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
ANO5	Strong	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2L	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANO5	Orphanet:206549	Anoctamin-5-related limb-girdle muscular dystrophy R12
ANO5	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
ANO5	Orphanet:399096	Distal anoctaminopathy
ANO5	Orphanet:53697	Gnathodiaphyseal dysplasia
ANO5	Orphanet:689021	Asymptomatic hyperCKemia-myalgia-rhabdomyolysis syndrome

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
ANO5	HGNC:27337	ENSG00000171714	Q75V66	Anoctamin-5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANO5	Anoctamin-5	Plays a role in plasma membrane repair in a process involving annexins.

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)
ANO5	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM

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
cardiac muscle of right atrium	1
left ventricle myocardium	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANO5	220	broad	marker	cardiac muscle of right atrium, left ventricle myocardium, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANO5	790

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANO5	Q75V66	82.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Induction of Cell-Cell Fusion	1	878.5×	0.013	ANO5
Late SARS-CoV-2 Infection Events	1	292.8×	0.016	ANO5
Regulation of clotting cascade	1	233.1×	0.016	ANO5
Stimuli-sensing channels	1	135.9×	0.020	ANO5
Ion channel transport	1	96.0×	0.023	ANO5
SARS-CoV-2 Infection	1	80.4×	0.023	ANO5
SARS-CoV Infections	1	55.4×	0.028	ANO5
Viral Infection Pathways	1	30.8×	0.044	ANO5
Transport of small molecules	1	25.1×	0.044	ANO5
Infectious disease	1	24.8×	0.044	ANO5
Disease	1	13.1×	0.076	ANO5

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
plasma membrane repair	1	581.1×	0.005	ANO5
chloride transmembrane transport	1	237.3×	0.005	ANO5
monoatomic ion transmembrane transport	1	208.1×	0.005	ANO5

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
ANO5	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	ANO5

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)
ANO5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.