Isolated asymptomatic elevation of creatine phosphokinase

Summary

Isolated asymptomatic elevation of creatine phosphokinase (MONDO:0016103) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• Phenotypes (HPO): 3

Clinical features

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0003236	Elevated circulating creatine kinase concentration	Obligate (100%)
HP:0003198	Myopathy	Excluded (0%)
HP:0008331	Elevated creatine kinase after exercise	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated asymptomatic elevation of creatine phosphokinase
Mondo ID	MONDO:0016103
Orphanet	206599
DOID	DOID:0111338
NCIT	C148327
UMLS	C4751434
MedGen	1668524
GARD	0020356
Is cancer (heuristic)	no

Also known as: hyperCKmia · idiopathic asymptomatic hyperCKemia · isolated asymptomatic hyperCKemia · isolated hyperCKemia

Data availability: 1 GenCC gene-disease record · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › caveolinopathy › isolated asymptomatic elevation of creatine phosphokinase

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 4 · 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
DAG1	Limited	Autosomal dominant	isolated asymptomatic elevation of creatine phosphokinase	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DAG1	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
DAG1	Orphanet:280333	Alpha-dystroglycan-related limb-girdle muscular dystrophy R16
DAG1	Orphanet:370997	Muscle-eye-brain disease with bilateral multicystic leucodystrophy
DAG1	Orphanet:899	Walker-Warburg syndrome

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
DAG1	HGNC:2666	ENSG00000173402	Q14118	Dystroglycan 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DAG1	Dystroglycan 1	The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my…

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DAG1	Antibody/Immunoglobulin	yes		Cadg, DAG1_C, Ig-like_fold

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
dorsal root ganglion	1
olfactory bulb	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DAG1	299	ubiquitous	marker	olfactory bulb, trigeminal ganglion, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DAG1	2,301

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DAG1	Q14118	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	5710.0×	0.001	DAG1
Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2	1	3806.7×	0.001	DAG1
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	1	3806.7×	0.001	DAG1
DAG1 core M1 glycosylations	1	2855.0×	0.001	DAG1
DAG1 core M2 glycosylations	1	2284.0×	0.001	DAG1
DAG1 core M3 glycosylations	1	1903.3×	0.001	DAG1
Matriglycan biosynthesis on DAG1	1	815.7×	0.002	DAG1
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.004	DAG1
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.004	DAG1
Non-integrin membrane-ECM interactions	1	154.3×	0.007	DAG1
ECM proteoglycans	1	150.3×	0.007	DAG1
Regulation of expression of SLITs and ROBOs	1	69.2×	0.014	DAG1

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
muscle attachment	1	16852.0×	0.001	DAG1
nerve maturation	1	16852.0×	0.001	DAG1
calcium-dependent cell-matrix adhesion	1	8426.0×	0.001	DAG1
retrograde trans-synaptic signaling by trans-synaptic protein complex	1	5617.3×	0.002	DAG1
response to denervation involved in regulation of muscle adaptation	1	2407.4×	0.002	DAG1
morphogenesis of an epithelial sheet	1	1685.2×	0.002	DAG1
angiogenesis involved in wound healing	1	1685.2×	0.002	DAG1
branching involved in salivary gland morphogenesis	1	1404.3×	0.002	DAG1
microtubule anchoring	1	1296.3×	0.002	DAG1
axon regeneration	1	1123.5×	0.002	DAG1
commissural neuron axon guidance	1	991.3×	0.002	DAG1
nerve development	1	936.2×	0.002	DAG1
myelination in peripheral nervous system	1	887.0×	0.002	DAG1
skeletal muscle tissue regeneration	1	887.0×	0.002	DAG1
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	887.0×	0.002	DAG1
epithelial tube branching involved in lung morphogenesis	1	842.6×	0.002	DAG1
cellular response to cholesterol	1	842.6×	0.002	DAG1
positive regulation of myelination	1	766.0×	0.002	DAG1
positive regulation of cell-matrix adhesion	1	674.1×	0.002	DAG1
positive regulation of oligodendrocyte differentiation	1	674.1×	0.002	DAG1
membrane protein ectodomain proteolysis	1	648.1×	0.002	DAG1
positive regulation of Rac protein signal transduction	1	648.1×	0.002	DAG1
regulation of synapse organization	1	648.1×	0.002	DAG1
inhibitory synapse assembly	1	624.1×	0.002	DAG1
response to muscle activity	1	581.1×	0.003	DAG1
basement membrane organization	1	510.7×	0.003	DAG1
response to peptide hormone	1	391.9×	0.003	DAG1
heart morphogenesis	1	374.5×	0.004	DAG1
morphogenesis of an epithelium	1	343.9×	0.004	DAG1
negative regulation of MAPK cascade	1	300.9×	0.004	DAG1

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
DAG1	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
DAG1	4	Binding:4

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	DAG1
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)
DAG1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.