Charcot-Marie-Tooth disease type X

Summary

Charcot-Marie-Tooth disease type X (MONDO:0018994) is a disease (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Europe)
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.6	Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type X
Mondo ID	MONDO:0018994
Orphanet	64747
DOID	DOID:0050542
SNOMED CT	230552007
UMLS	C4551551
MedGen	1637021
GARD	0012444
Is cancer (heuristic)	no

Also known as: CMTX · COWCK · X-linked hereditary motor and sensory neuropathy

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › Charcot-Marie-Tooth disease type X

Related subtypes (49): X-linked Opitz G/BBB syndrome, X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, Wiskott-Aldrich syndrome, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, exudative vitreoretinopathy 2, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked Emery-Dreifuss muscular dystrophy, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, spondyloepiphyseal dysplasia tarda, X-linked, X-linked cerebellar ataxia, adrenoleukodystrophy, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked cone-rod dystrophy, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

Subtypes (6): Charcot-Marie-Tooth disease X-linked dominant 6, Charcot-Marie-Tooth disease X-linked dominant 1, Charcot-Marie-Tooth disease X-linked recessive 2, Charcot-Marie-Tooth disease X-linked recessive 3, Charcot-Marie-Tooth disease X-linked recessive 4, Charcot-Marie-Tooth disease X-linked recessive 5

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1802194	NM_001939.3(DRP2):c.2159G>A (p.Arg720Gln)	DRP2	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
DPYSL2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

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
DPYSL2	HGNC:3014	ENSG00000092964	Q16555	Dihydropyrimidinase-related protein 2	clinvar
DRP2	HGNC:3032	ENSG00000102385	Q13474	Dystrophin-related protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPYSL2	Dihydropyrimidinase-related protein 2	Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration.
DRP2	Dystrophin-related protein 2	Required for normal myelination and for normal organization of the cytoplasm and the formation of Cajal bands in myelinating Schwann cells.

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)
DPYSL2	Other/Unknown	no		Amidohydro-rel, Metal-dep_hydrolase_composite, Hydantoinase/dihydroPyrase
DRP2	Transcription factor	no		Znf_ZZ, WW_dom, Spectrin_repeat

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
inferior vagus X ganglion	1
substantia nigra pars compacta	1
subthalamic nucleus	1
dorsal root ganglion	1
tibial nerve	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPYSL2	301	ubiquitous	marker	inferior vagus X ganglion, subthalamic nucleus, substantia nigra pars compacta
DRP2	151	broad	marker	trigeminal ganglion, tibial nerve, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPYSL2	2,980
DRP2	637

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DPYSL2	Q16555	15

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DRP2	Q13474	74.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
CRMPs in Sema3A signaling	1	317.2×	0.009	DPYSL2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.009	DRP2
Formation of the dystrophin-glycoprotein complex (DGC)	1	154.3×	0.009	DRP2
Recycling pathway of L1	1	112.0×	0.009	DPYSL2

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
synaptic signaling	1	766.0×	0.012	DRP2
nucleobase-containing compound metabolic process	1	263.3×	0.017	DPYSL2
synapse organization	1	140.4×	0.021	DRP2
cytoskeleton organization	1	66.3×	0.031	DPYSL2
central nervous system development	1	57.7×	0.031	DRP2
endocytosis	1	47.6×	0.031	DPYSL2
nervous system development	1	23.0×	0.055	DPYSL2
cell differentiation	1	14.6×	0.076	DPYSL2
signal transduction	1	8.0×	0.121	DPYSL2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DPYSL2	0	0
DRP2	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
DPYSL2	3	Binding:3

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	DPYSL2, DRP2

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)
DPYSL2	3	—
DRP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.