Congenital myopathy 20

Summary

Congenital myopathy 20 (MONDO:0957215) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myopathy 20
Mondo ID	MONDO:0957215
OMIM	620310
DOID	DOID:0081352
UMLS	C5830393
MedGen	1841029
GARD	0026789
Is cancer (heuristic)	no

Data availability: 24 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › congenital myopathy 20

Related subtypes (53): Ullrich congenital muscular dystrophy, congenital structural myopathy, Bethlem myopathy, MYH7-related skeletal myopathy, tubular aggregate myopathy, cylindrical spirals myopathy, congenital myopathy 7A, myosin storage, autosomal dominant, intellectual disability-myopathy-short stature-endocrine defect syndrome, myopathy, myosin storage, autosomal recessive, Bailey-Bloch congenital myopathy, fingerprint body myopathy, myopathy, proximal, and ophthalmoplegia, Compton-North congenital myopathy, MEGF10-related myopathy, fetal akinesia-cerebral and retinal hemorrhage syndrome, Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome, severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome, myopathy with hexagonally cross-linked tubular arrays, benign Samaritan congenital myopathy, congenital generalized hypercontractile muscle stiffness syndrome, hyaline body myopathy, centronuclear myopathy, reducing body myopathy, myopathy, congenital, with tremor, myopathy, congenital, progressive, with scoliosis, myopathy, congenital, with structured cores and z-line abnormalities, myopathy, congenital, with respiratory insufficiency and bone fractures, myopathy, congenital proximal, with minicore lesions, myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies, congenital myopathy with reduced type 2 muscle fibers, alpha-actinopathy, SELENON-related myopathy, TPM3-related myopathy, SCN4A-related myopathy, autosomal recessive, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, Batten-Turner congenital myopathy, TOR1AIP1-related myopathy, congenital myopathy 11, congenital myopathy 15, congenital myopathy 18, congenital myopathy 10b, mild variant, congenital myopathy 2b, severe infantile, autosomal recessive, congenital myopathy 2c, severe infantile, autosomal dominant, congenital myopathy 21 with early respiratory failure, congenital myopathy 22A, classic, congenital myopathy 22B, severe fetal, congenital myopathy 25, congenital myopathy 26, congenital myopathy 27, congenital myopathy 28 with rigid spine, congenital myopathy 29 with contractures

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

24 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 4 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
461938	NM_001036.6(RYR3):c.6698G>A (p.Arg2233Gln)	RYR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
531058	NM_001036.6(RYR3):c.6208A>G (p.Met2070Val)	RYR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
816850	NM_001036.6(RYR3):c.2000A>G (p.Asp667Gly)	RYR3	Conflicting classifications of pathogenicity	no assertion criteria provided
857441	NM_001036.6(RYR3):c.11G>C (p.Gly4Ala)	RYR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1053470	NM_001036.6(RYR3):c.161C>T (p.Ser54Leu)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2230857	NM_001036.6(RYR3):c.11758A>C (p.Lys3920Gln)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689904	NM_001036.6(RYR3):c.11914G>T (p.Asp3972Tyr)	RYR3	Uncertain significance	criteria provided, single submitter
2689905	NM_001036.6(RYR3):c.12785C>A (p.Thr4262Asn)	RYR3	Uncertain significance	criteria provided, single submitter
2921206	NM_001036.6(RYR3):c.4006G>C (p.Ala1336Pro)	RYR3	Uncertain significance	criteria provided, single submitter
3065468	NM_001036.6(RYR3):c.10063C>T (p.Arg3355Trp)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065469	NM_001036.6(RYR3):c.10495C>A (p.Leu3499Met)	RYR3	Uncertain significance	criteria provided, single submitter
3393137	NM_001036.6(RYR3):c.4298C>G (p.Thr1433Ser)	RYR3	Uncertain significance	criteria provided, single submitter
3577067	NM_001036.6(RYR3):c.2371A>T (p.Met791Leu)	RYR3	Uncertain significance	criteria provided, single submitter
3896973	NM_001036.6(RYR3):c.12406C>G (p.Leu4136Val)	RYR3	Uncertain significance	criteria provided, single submitter
4079947	NM_001036.6(RYR3):c.5677C>T (p.Arg1893Trp)	RYR3	Uncertain significance	criteria provided, single submitter
4293590	NM_001036.6(RYR3):c.10503-21C>T	RYR3	Uncertain significance	criteria provided, single submitter
575445	NM_001036.6(RYR3):c.12029G>A (p.Arg4010His)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
579688	NM_001036.6(RYR3):c.6835G>A (p.Val2279Met)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
653564	NM_001036.6(RYR3):c.11164+1G>A	RYR3	Uncertain significance	criteria provided, single submitter
655096	NM_001036.6(RYR3):c.8939G>T (p.Arg2980Leu)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
661221	NM_001036.6(RYR3):c.5837C>T (p.Thr1946Met)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
937338	NM_001036.6(RYR3):c.9727G>T (p.Asp3243Tyr)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
942721	NM_001036.6(RYR3):c.11146C>T (p.Leu3716Phe)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
992812	NM_001036.6(RYR3):c.7855A>G (p.Thr2619Ala)	RYR3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
RYR3	HGNC:10485	ENSG00000198838	Q15413	Ryanodine receptor 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RYR3	Ryanodine receptor 3	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RYR3	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom

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
diaphragm	1
right hemisphere of cerebellum	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RYR3	233	broad	marker	diaphragm, sural nerve, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RYR3	1,705

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RYR3	Q15413	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
Ion homeostasis	1	203.9×	0.016	RYR3
Stimuli-sensing channels	1	135.9×	0.016	RYR3
Cardiac conduction	1	108.8×	0.016	RYR3
Ion channel transport	1	96.0×	0.016	RYR3
Muscle contraction	1	77.2×	0.016	RYR3
Transport of small molecules	1	25.1×	0.040	RYR3

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 magnesium ion	1	2407.4×	0.002	RYR3
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	1685.2×	0.002	RYR3
cellular response to caffeine	1	1532.0×	0.002	RYR3
cellular response to ATP	1	887.0×	0.003	RYR3
striated muscle contraction	1	842.6×	0.003	RYR3
release of sequestered calcium ion into cytosol	1	343.9×	0.005	RYR3
protein homotetramerization	1	237.3×	0.006	RYR3
calcium ion transmembrane transport	1	210.7×	0.006	RYR3
cellular response to calcium ion	1	200.6×	0.006	RYR3
calcium ion transport	1	181.2×	0.006	RYR3
intracellular calcium ion homeostasis	1	145.3×	0.007	RYR3

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
RYR3	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
RYR3	2	Binding:2

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	1	RYR3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
RYR3	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.