Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Summary

Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis (MONDO:0979249) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis
Mondo ID	MONDO:0979249
OMIM	620138
GARD	0028118
Is cancer (heuristic)	no

Data availability: 13 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 › myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Related subtypes (31): polyglucosan body myopathy, muscular atrophy, myopathy of extraocular muscle, acute quadriplegic myopathy, myofascial pain syndrome, myopathy with abnormal lipid metabolism, proximal myopathy with focal depletion of mitochondria, Brody myopathy, rippling muscle disease, myopathy due to myoadenylate deaminase deficiency, proximal myopathy with extrapyramidal signs, intermediate nemaline myopathy, hereditary inclusion-body myopathy, hereditary continuous muscle fiber activity, congenital myopathy, muscular dystrophy, metabolic myopathy, myositis disease, collagen 6-related myopathy, myopathy caused by variation in CRPPA, drug-induced myopathy, myopathy caused by variation in FKRP, myopathy caused by variation in FKTN, myopathy caused by variation in POMGNT1, myopathy caused by variation in POMGNT2, myopathy caused by variation in POMT1, myopathy caused by variation in POMT2, myopathy caused by variation in GMPPB, FHL1-related myopathy, myopathy, sarcoplasmic body, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2

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

13 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1801322	NM_001281747.2(MLIP):c.628C>T (p.Gln210Ter)	LOC126859697	Pathogenic	no assertion criteria provided
1801319	NM_001281747.2(MLIP):c.1739del (p.His580fs)	MLIP	Pathogenic	no assertion criteria provided
1801320	NM_001281747.2(MLIP):c.1832del (p.Phe611fs)	MLIP	Pathogenic	no assertion criteria provided
1801321	NM_001281747.2(MLIP):c.2443del (p.Ser815fs)	MLIP	Pathogenic	no assertion criteria provided
1801324	NM_001281747.2(MLIP):c.2530C>T (p.Arg844Ter)	MLIP	Pathogenic	criteria provided, single submitter
1801325	NM_001281747.2(MLIP):c.1825A>T (p.Lys609Ter)	MLIP	Pathogenic	criteria provided, single submitter
1801326	NM_001281747.2(MLIP):c.2273del (p.Leu758fs)	MLIP	Pathogenic	no assertion criteria provided
1801327	NM_001281747.2(MLIP):c.2284C>T (p.Gln762Ter)	MLIP	Pathogenic	no assertion criteria provided
4292502	NM_001281747.2(MLIP):c.645+2T>C	LOC126859697	Likely pathogenic	criteria provided, single submitter
3779873	NM_001281747.2(MLIP):c.1212del (p.Gly405_Val406insTer)	MLIP	Likely pathogenic	criteria provided, single submitter
3779874	NM_001281747.2(MLIP):c.2494_2497del (p.Val832fs)	MLIP	Likely pathogenic	criteria provided, single submitter
4292695	NM_001281747.2(MLIP):c.1905_1912del (p.Glu635fs)	MLIP	Likely pathogenic	criteria provided, single submitter
3363147	NM_001386795.1(DTNA):c.1651_1671del (p.Lys552_Arg558del)	DTNA	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DTNA	Orphanet:54260	Left ventricular noncompaction

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MLIP	HGNC:21355	ENSG00000146147	Q5VWP3	Muscular LMNA-interacting protein	clinvar
DTNA	HGNC:3057	ENSG00000134769	Q9Y4J8	Dystrobrevin alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MLIP	Muscular LMNA-interacting protein	Required for myoblast differentiation into myotubes, possibly acting as a transcriptional regulator of the myogenic program.
DTNA	Dystrobrevin alpha	May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MLIP	Other/Unknown	no		MLIP
DTNA	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1
C1 segment of cervical spinal cord	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MLIP	186	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
DTNA	266	ubiquitous	marker	medial globus pallidus, globus pallidus, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DTNA	1,738
MLIP	16

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DTNA	Q9Y4J8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MLIP	Q5VWP3	43.75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.003	DTNA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 cardiac muscle hypertrophy in response to stress	1	936.2×	0.006	MLIP
synaptic signaling	1	766.0×	0.006	DTNA
negative regulation of cardiac muscle hypertrophy	1	561.7×	0.006	MLIP
striated muscle contraction	1	421.3×	0.006	DTNA
neuromuscular synaptic transmission	1	300.9×	0.007	DTNA
chemical synaptic transmission	1	38.6×	0.040	DTNA
transcription by RNA polymerase II	1	35.3×	0.040	MLIP
negative regulation of transcription by RNA polymerase II	1	8.9×	0.130	MLIP
signal transduction	1	8.0×	0.130	DTNA
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	MLIP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
MLIP	0	0
DTNA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MLIP, DTNA

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MLIP	0	—
DTNA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.