Myotonic dystrophy type 2

Summary

Myotonic dystrophy type 2 (MONDO:0011266) is a disease caused by CNBP (GenCC Definitive), with 1 cohort gene and 11 clinical trials. Top therapeutic interventions include linagliptin.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: CNBP (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 30
• Clinical trials: 11

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1	Europe	Validated
Point prevalence	1-9 / 100 000	1	Germany	Validated
Point prevalence	1-5 / 10 000	10	Finland	Validated
Point prevalence	1-9 / 1 000 000	0.17	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0000518	Cataract	Very frequent (80-99%)
HP:0002486	Myotonia	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0003326	Myalgia	Very frequent (80-99%)
HP:0003327	Axial muscle weakness	Very frequent (80-99%)
HP:0003701	Proximal muscle weakness	Very frequent (80-99%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0003552	Muscle stiffness	Frequent (30-79%)
HP:0004313	Decreased circulating antibody level	Frequent (30-79%)
HP:0005978	Type II diabetes mellitus	Frequent (30-79%)
HP:0007787	Posterior subcapsular cataract	Frequent (30-79%)
HP:0008189	Insulin insensitivity	Frequent (30-79%)
HP:0000026	Male hypogonadism	Occasional (5-29%)
HP:0000975	Hyperhidrosis	Occasional (5-29%)
HP:0001262	Excessive daytime somnolence	Occasional (5-29%)
HP:0001348	Brisk reflexes	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002870	Obstructive sleep apnea	Occasional (5-29%)
HP:0002926	Abnormality of thyroid physiology	Occasional (5-29%)
HP:0003077	Hyperlipidemia	Occasional (5-29%)
HP:0008981	Calf muscle hypertrophy	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0012452	Restless legs	Occasional (5-29%)
HP:0030319	Weakness of facial musculature	Occasional (5-29%)
HP:0031546	Cardiac conduction abnormality	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	myotonic dystrophy type 2
Mondo ID	MONDO:0011266
OMIM	602668
Orphanet	606
DOID	DOID:0050759
ICD-11	1005849639
NCIT	C84680
UMLS	C2931689
MedGen	419137
GARD	0009728
Is cancer (heuristic)	no

Also known as: CNBP myotonic dystrophy · DM2 · dystrophia myotonica type 2 · myotonic dystrophy 2 · myotonic dystrophy caused by mutation in CNBP · myotonic dystrophy type 2 · PROMM · proximal myotonic dystrophy · proximal myotonic myopathy · ricker disease · ricker syndrome

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

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › myotonic dystrophy › myotonic dystrophy type 2

Related subtypes (7): myotonic cataract, myotonic dystrophy type 1, congenital myotonic dystrophy, childhood-onset Steinert myotonic dystrophy, juvenile-onset Steinert myotonic dystrophy, adult-onset Steinert myotonic dystrophy, late-onset Steinert myotonic dystrophy

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 benign, 1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
17564	NM_003418.5(CNBP):c.-14-833_-14-806CCTG[(75_11000)]	CNBP	Pathogenic	no assertion criteria provided
2440154	NM_003418.5(CNBP):c.156C>A (p.Asp52Glu)	CNBP	Uncertain significance	criteria provided, single submitter
1217358	NM_003418.5(CNBP):c.156C>T (p.Asp52=)	CNBP	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CNBP	Definitive	Autosomal dominant	myotonic dystrophy type 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNBP	Orphanet:606	Proximal myotonic myopathy

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
CNBP	HGNC:13164	ENSG00000169714	P62633	CCHC-type zinc finger nucleic acid binding protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNBP	CCHC-type zinc finger nucleic acid binding protein	Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5’-GTGCGGTG-3’, and thereby mediates transcriptional repression.

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)
CNBP	Transcription factor	no		Znf_CCHC, Znf_CCHC_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
biceps brachii	1
diaphragm	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNBP	295	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, diaphragm, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNBP	562

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CNBP	P62633	71.09

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
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.011	CNBP

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
G-quadruplex DNA formation	1	16852.0×	5e-04	CNBP
positive regulation of cytoplasmic translation	1	991.3×	0.004	CNBP
cholesterol homeostasis	1	156.0×	0.017	CNBP
positive regulation of cell population proliferation	1	33.6×	0.048	CNBP
regulation of DNA-templated transcription	1	31.6×	0.048	CNBP
positive regulation of DNA-templated transcription	1	27.9×	0.048	CNBP
negative regulation of transcription by RNA polymerase II	1	17.7×	0.064	CNBP
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	CNBP

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
CNBP	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
CNBP	1	Binding:1

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	CNBP

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)
CNBP	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03051243	PHASE3	UNKNOWN	Safety and Efficiency of Linagliptin (Trajenta) in the Setting of Internal Medicine Department
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry
NCT02398786	Not specified	RECRUITING	Myotonic Dystrophy Family Registry
NCT05854433	Not specified	RECRUITING	Brain Structure and Clinical Endpoints in Myotonic Dystrophy Type 2
NCT06716931	Not specified	RECRUITING	Investigating Exercise in Myotonic Dystrophy Type 2 (DM2)
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.
NCT02729597	Not specified	COMPLETED	Tracking the Brain in Myotonic Dystrophies: a 5-year Longitudinal Follow-up Study
NCT03211923	Not specified	UNKNOWN	Muscle Relaxation in Myopathies With Positive Muscle Phenomena
NCT03603171	Not specified	COMPLETED	Clinical Outcome Measures in Myotonic Dystrophy Type 2
NCT03867435	Not specified	TERMINATED	Assessing Clinical Endpoints and Biomarkers in Myotonic Dystrophy Type-1 and Type 2 (ASCEND-DM)
NCT04907162	Not specified	COMPLETED	Musculoskeletal Nociceptive Pain in Participants With Neuromuscular Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LINAGLIPTIN	4	1
CHEMBL4747683	0	1