Myopathy, congenital, with respiratory insufficiency and bone fractures

Summary

Myopathy, congenital, with respiratory insufficiency and bone fractures (MONDO:0032936) is a disease caused by FXR1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FXR1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy, congenital, with respiratory insufficiency and bone fractures
Mondo ID	MONDO:0032936
OMIM	618822
DOID	DOID:0081343
UMLS	C5394189
MedGen	1718097
GARD	0025779
Is cancer (heuristic)	no

Also known as: MYORIBF

Data availability: 3 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 › congenital myopathy › myopathy, congenital, with respiratory insufficiency and bone fractures

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 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 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

3 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
828056	NM_005087.4(FXR1):c.1603+790_1603+793del	FXR1	Pathogenic	no assertion criteria provided
2582494	NM_005087.4(FXR1):c.28G>T (p.Gly10Cys)	FXR1	Uncertain significance	criteria provided, single submitter
729241	NM_005087.4(FXR1):c.52-7C>T	FXR1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
FXR1	Strong	Autosomal recessive	myopathy, congenital, with respiratory insufficiency and bone fractures	4

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
FXR1	HGNC:4023	ENSG00000114416	P51114	RNA-binding protein FXR1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FXR1	RNA-binding protein FXR1	mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis.

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
Complement	1	268.0×	0.004

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FXR1	Complement	yes		KH_dom, KH_dom_type_1, Agenet-like_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
gastrocnemius	1
hindlimb stylopod muscle	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FXR1	299	ubiquitous	marker	sperm, hindlimb stylopod muscle, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FXR1	4,128

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FXR1	P51114	3

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
Signaling by BRAF and RAF1 fusions	1	170.4×	0.006	FXR1

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
regulation of translation at presynapse, modulating synaptic transmission	1	5617.3×	0.002	FXR1
negative regulation of mRNA catabolic process	1	5617.3×	0.002	FXR1
nuclear pore localization	1	3370.4×	0.002	FXR1
regulation of circadian sleep/wake cycle, sleep	1	2407.4×	0.002	FXR1
positive regulation of miRNA-mediated gene silencing	1	2407.4×	0.002	FXR1
skeletal muscle organ development	1	2106.5×	0.002	FXR1
positive regulation of long-term neuronal synaptic plasticity	1	1872.4×	0.002	FXR1
nuclear pore complex assembly	1	1685.2×	0.002	FXR1
negative regulation of long-term synaptic potentiation	1	1296.3×	0.002	FXR1
membraneless organelle assembly	1	1123.5×	0.002	FXR1
animal organ development	1	732.7×	0.003	FXR1
mRNA destabilization	1	674.1×	0.003	FXR1
dentate gyrus development	1	624.1×	0.003	FXR1
positive regulation of Rho protein signal transduction	1	581.1×	0.003	FXR1
regulation of synaptic transmission, glutamatergic	1	510.7×	0.003	FXR1
regulation of mRNA stability	1	421.3×	0.004	FXR1
regulation of neurogenesis	1	401.2×	0.004	FXR1
mRNA transport	1	263.3×	0.005	FXR1
negative regulation of tumor necrosis factor production	1	251.5×	0.005	FXR1
positive regulation of translation	1	227.7×	0.005	FXR1
negative regulation of translation	1	195.9×	0.006	FXR1
muscle organ development	1	166.8×	0.007	FXR1
spermatid development	1	145.3×	0.007	FXR1
negative regulation of inflammatory response	1	137.0×	0.008	FXR1
apoptotic process	1	28.7×	0.035	FXR1

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
FXR1	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
FXR1	6	Binding:6

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	FXR1
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)
FXR1	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.