Congenital myopathy 27

Summary

Congenital myopathy 27 (MONDO:0979897) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myopathy 27
Mondo ID	MONDO:0979897
OMIM	621343
DOID	DOID:0061258
Is cancer (heuristic)	no

Data availability: 3 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 27

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 20, congenital myopathy 21 with early respiratory failure, congenital myopathy 22A, classic, congenital myopathy 22B, severe fetal, congenital myopathy 25, congenital myopathy 26, 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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4087699	NM_016223.5(PACSIN3):c.609_610del (p.Lys203fs)	PACSIN3	Pathogenic	no assertion criteria provided
4087700	NM_016223.5(PACSIN3):c.592G>T (p.Glu198Ter)	PACSIN3	Pathogenic	no assertion criteria provided
4087701	NM_016223.5(PACSIN3):c.270_277del (p.Leu91fs)	PACSIN3	Pathogenic	no assertion criteria provided

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
PACSIN3	HGNC:8572	ENSG00000165912	Q9UKS6	Protein kinase C and casein kinase substrate in neurons protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PACSIN3	Protein kinase C and casein kinase substrate in neurons protein 3	Plays a role in endocytosis and regulates internalization of plasma membrane proteins.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PACSIN3	Scaffold/PPI	no		FCH_dom, SH3_domain, AH/BAR_dom_sf

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
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PACSIN3	216	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PACSIN3	1,572

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PACSIN3	Q9UKS6	87.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Clathrin-mediated endocytosis	1	85.2×	0.012	PACSIN3

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
negative regulation of calcium ion transport	1	1685.2×	0.002	PACSIN3
plasma membrane tubulation	1	1123.5×	0.002	PACSIN3
negative regulation of endocytosis	1	936.2×	0.002	PACSIN3
positive regulation of membrane protein ectodomain proteolysis	1	936.2×	0.002	PACSIN3
regulation of endocytosis	1	481.5×	0.003	PACSIN3
cytoskeleton organization	1	132.7×	0.009	PACSIN3
endocytosis	1	95.2×	0.011	PACSIN3

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
PACSIN3	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	PACSIN3

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)
PACSIN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.