Familial idiopathic inflammatory myopathy

Summary

Familial idiopathic inflammatory myopathy (MONDO:0600024) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial idiopathic inflammatory myopathy
Mondo ID	MONDO:0600024
MeSH	C000598744
OMIM	160750
UMLS	C3888318
MedGen	854861
GARD	0026302
Is cancer (heuristic)	no

Also known as: familial idiopathic myositis

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › myositis disease › idiopathic inflammatory myopathy › familial idiopathic inflammatory myopathy

Related subtypes (1): acquired idiopathic inflammatory 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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1319979	NM_000070.3(CAPN3):c.452A>G (p.His151Arg)	CAPN3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CAPN3	Orphanet:267	Calpain-3-related limb-girdle muscular dystrophy R1
CAPN3	Orphanet:565909	Calpain-3-related limb-girdle muscular dystrophy D4

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
CAPN3	HGNC:1480	ENSG00000092529	P20807	Calpain-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAPN3	Calpain-3	Calcium-regulated non-lysosomal thiol-protease.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CAPN3	Protease	yes	3.4.22.54	Pept_cys_AS, Peptidase_C2_calpain_cat, 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
C1 segment of cervical spinal cord	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAPN3	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAPN3	1,977

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAPN3	P20807	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Degradation of the extracellular matrix	1	117.7×	0.016	CAPN3
Extracellular matrix organization	1	63.1×	0.016	CAPN3

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
calcium-dependent self proteolysis	1	16852.0×	0.002	CAPN3
positive regulation of satellite cell activation involved in skeletal muscle regeneration	1	8426.0×	0.002	CAPN3
cellular response to salt stress	1	4213.0×	0.002	CAPN3
G1 to G0 transition involved in cell differentiation	1	2808.7×	0.002	CAPN3
regulation of myoblast differentiation	1	2407.4×	0.002	CAPN3
negative regulation of protein sumoylation	1	1532.0×	0.002	CAPN3
self proteolysis	1	1532.0×	0.002	CAPN3
muscle structure development	1	1404.3×	0.002	CAPN3
myofibril assembly	1	1123.5×	0.003	CAPN3
positive regulation of proteolysis	1	802.5×	0.003	CAPN3
muscle cell cellular homeostasis	1	648.1×	0.004	CAPN3
protein localization to membrane	1	601.9×	0.004	CAPN3
response to muscle activity	1	581.1×	0.004	CAPN3
positive regulation of release of sequestered calcium ion into cytosol	1	495.6×	0.004	CAPN3
regulation of canonical NF-kappaB signal transduction	1	481.5×	0.004	CAPN3
sarcomere organization	1	383.0×	0.004	CAPN3
response to calcium ion	1	318.0×	0.005	CAPN3
protein destabilization	1	290.6×	0.005	CAPN3
protein catabolic process	1	237.3×	0.006	CAPN3
cellular response to calcium ion	1	200.6×	0.007	CAPN3
muscle organ development	1	166.8×	0.008	CAPN3
protein-containing complex assembly	1	113.9×	0.011	CAPN3
negative regulation of apoptotic process	1	34.8×	0.033	CAPN3
proteolysis	1	34.2×	0.033	CAPN3
negative regulation of DNA-templated transcription	1	31.6×	0.034	CAPN3
apoptotic process	1	28.7×	0.036	CAPN3
positive regulation of DNA-templated transcription	1	27.9×	0.036	CAPN3

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
CAPN3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAPN3	3.4.22.54, 3.4.22.56	calpain-3, caspase-3

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	CAPN3
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)
CAPN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.