Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies

Summary

Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies (MONDO:0033548) is a disease caused by MYOD1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MYOD1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies
Mondo ID	MONDO:0033548
OMIM	618975
DOID	DOID:0081349
UMLS	C5436530
MedGen	1764743
GARD	0025807
Is cancer (heuristic)	no

Also known as: MYODRIF

Data availability: 7 ClinVar variants · 3 GenCC gene-disease records.

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 diaphragmatic defects, respiratory insufficiency, and dysmorphic facies

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, 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

7 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
631486	NM_002478.5(MYOD1):c.557dup (p.Arg188fs)	MYOD1	Pathogenic	criteria provided, single submitter
816937	NM_002478.5(MYOD1):c.188C>A (p.Ser63Ter)	MYOD1	Pathogenic	criteria provided, single submitter
976484	NM_002478.5(MYOD1):c.697G>T (p.Glu233Ter)	MYOD1	Pathogenic	no assertion criteria provided
3341452	NM_002478.5(MYOD1):c.468T>A (p.Tyr156Ter)	MYOD1	Likely pathogenic	criteria provided, single submitter
3764541	NM_002478.5(MYOD1):c.352G>T (p.Glu118Ter)	MYOD1	Likely pathogenic	criteria provided, single submitter
1210295	NM_002478.5(MYOD1):c.607C>G (p.Arg203Gly)	MYOD1	Uncertain significance	no assertion criteria provided
4079342	NM_002478.5(MYOD1):c.614A>G (p.Asn205Ser)	MYOD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
MYOD1	Strong	Autosomal recessive	myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYOD1	Orphanet:994	Fetal akinesia deformation sequence

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
MYOD1	HGNC:7611	ENSG00000129152	P15172	Myoblast determination protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYOD1	Myoblast determination protein 1	Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYOD1	Transcription factor	no		MyoD_N, bHLH_dom, Myf5

Expression context

Cohort genes with no expression data: 0.

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
gluteal muscle	1
skeletal muscle tissue of biceps brachii	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYOD1	51	tissue_specific	yes	triceps brachii, skeletal muscle tissue of biceps brachii, gluteal muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYOD1	3,624

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYOD1	P15172	62.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
TGFBR3 expression	1	456.8×	0.006	MYOD1
Myogenesis	1	380.7×	0.006	MYOD1
Signaling by TGFBR3	1	368.4×	0.006	MYOD1
Signaling by TGFB family members	1	115.3×	0.013	MYOD1
CHD1 and CHD2 subfamily	1	108.8×	0.013	MYOD1
Developmental Biology	1	14.5×	0.081	MYOD1
Signal Transduction	1	10.2×	0.098	MYOD1

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
myoblast fate determination	1	8426.0×	1e-03	MYOD1
negative regulation of myoblast proliferation	1	8426.0×	1e-03	MYOD1
positive regulation of skeletal muscle tissue regeneration	1	5617.3×	1e-03	MYOD1
skeletal muscle fiber adaptation	1	5617.3×	1e-03	MYOD1
positive regulation of snRNA transcription by RNA polymerase II	1	5617.3×	1e-03	MYOD1
cellular response to oxygen levels	1	4213.0×	0.001	MYOD1
myotube cell development	1	3370.4×	0.001	MYOD1
myotube differentiation involved in skeletal muscle regeneration	1	3370.4×	0.001	MYOD1
muscle cell fate commitment	1	2808.7×	0.001	MYOD1
positive regulation of skeletal muscle fiber development	1	2106.5×	0.001	MYOD1
positive regulation of muscle cell differentiation	1	1123.5×	0.002	MYOD1
positive regulation of myoblast fusion	1	1053.2×	0.002	MYOD1
cellular response to glucocorticoid stimulus	1	624.1×	0.003	MYOD1
myoblast fusion	1	601.9×	0.003	MYOD1
skeletal muscle fiber development	1	543.6×	0.003	MYOD1
cellular response to estradiol stimulus	1	411.0×	0.004	MYOD1
positive regulation of myoblast differentiation	1	366.4×	0.004	MYOD1
skeletal muscle cell differentiation	1	343.9×	0.004	MYOD1
skeletal muscle tissue development	1	290.6×	0.005	MYOD1
regulation of alternative mRNA splicing, via spliceosome	1	244.2×	0.006	MYOD1
regulation of RNA splicing	1	218.9×	0.006	MYOD1
cellular response to starvation	1	193.7×	0.006	MYOD1
muscle organ development	1	166.8×	0.007	MYOD1
cellular response to tumor necrosis factor	1	163.6×	0.007	MYOD1
transcription by RNA polymerase II	1	70.5×	0.015	MYOD1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.070	MYOD1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	MYOD1

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
MYOD1	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	MYOD1

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)
MYOD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.