Charcot-Marie-Tooth disease type 2I

Summary

Charcot-Marie-Tooth disease type 2I (MONDO:0011889) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 32
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 2I
Mondo ID	MONDO:0011889
OMIM	607677
Orphanet	99942
DOID	DOID:0110158
ICD-11	1858507973
SNOMED CT	717013009
UMLS	C3888087
MedGen	854756
GARD	0009197
Is cancer (heuristic)	no

Also known as: Charcot Marie Tooth disease type 2I · Charcot-Marie-Tooth disease, axonal, type 2I · Charcot-Marie-Tooth disease, type 2I · CMT 2I · CMT2I

Data availability: 32 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant intermediate Charcot-Marie-Tooth disease › Charcot-Marie-Tooth disease dominant intermediate D › Charcot-Marie-Tooth disease type 2I

Related subtypes (2): Charcot-Marie-Tooth disease type 1B, Charcot-Marie-Tooth disease type 2J

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

32 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 9 pathogenic, 9 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14182	NM_000530.6(MPZ):c.[266T>A;274G>A;486C>G]		Pathogenic	no assertion criteria provided
14170	NM_000530.8(MPZ):c.499G>C (p.Gly167Arg)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
14179	NM_000530.8(MPZ):c.242A>G (p.His81Arg)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
14181	NM_000530.8(MPZ):c.371C>T (p.Thr124Met)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
14185	NM_000530.8(MPZ):c.131C>T (p.Ser44Phe)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
14191	NM_000530.8(MPZ):c.434A>C (p.Tyr145Ser)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
3340162	NM_000530.8(MPZ):c.30del (p.Ser11fs)	MPZ	Pathogenic	criteria provided, single submitter
41017	NM_000530.8(MPZ):c.244T>C (p.Tyr82His)	MPZ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
462797	NM_000530.8(MPZ):c.397C>A (p.Pro133Thr)	MPZ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
531677	NM_000530.8(MPZ):c.434_437del (p.Tyr145fs)	MPZ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
549681	NM_000530.8(MPZ):c.245A>G (p.Tyr82Cys)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
637361	NM_000530.8(MPZ):c.421C>T (p.Gln141Ter)	MPZ	Pathogenic	criteria provided, single submitter
4687956	NM_000530.8(MPZ):c.660T>A (p.Tyr220Ter)	MPZ	Likely pathogenic	criteria provided, single submitter
578468	NM_000530.8(MPZ):c.397C>G (p.Pro133Ala)	MPZ	Likely pathogenic	criteria provided, multiple submitters, no conflicts
14193	NM_000530.8(MPZ):c.178G>C (p.Asp60His)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14194	NM_000530.8(MPZ):c.186C>G (p.Ile62Met)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216963	NM_000530.8(MPZ):c.451C>A (p.Pro151Thr)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
246524	NM_000530.8(MPZ):c.133C>T (p.Arg45Trp)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
447734	NM_000530.8(MPZ):c.703AAG[1] (p.Lys236del)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
462790	NM_000530.8(MPZ):c.103G>A (p.Asp35Asn)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
637323	NM_000530.8(MPZ):c.101C>T (p.Thr34Ile)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
637797	NM_000530.8(MPZ):c.316C>T (p.Arg106Cys)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
917380	NM_000530.8(MPZ):c.208C>A (p.Pro70Thr)	MPZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1211734	NM_000530.8(MPZ):c.312C>A (p.Asp104Glu)	MPZ	Uncertain significance	criteria provided, multiple submitters, no conflicts
2505530	NM_000530.8(MPZ):c.463G>A (p.Gly155Arg)	MPZ	Uncertain significance	criteria provided, multiple submitters, no conflicts
2627479	NM_000530.8(MPZ):c.597G>C (p.Lys199Asn)	MPZ	Uncertain significance	criteria provided, single submitter
2770145	NM_000530.8(MPZ):c.369C>T (p.Gly123=)	MPZ	Uncertain significance	criteria provided, multiple submitters, no conflicts
41026	NM_000530.8(MPZ):c.347A>G (p.Asn116Ser)	MPZ	Uncertain significance	criteria provided, multiple submitters, no conflicts
462799	NM_000530.8(MPZ):c.662C>T (p.Ala221Val)	MPZ	Uncertain significance	criteria provided, single submitter
637322	NM_000530.8(MPZ):c.59C>T (p.Ser20Phe)	MPZ	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 8 · 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
MPZ	Definitive	Autosomal dominant	Charcot-Marie-Tooth disease	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MPZ	Orphanet:100046	Autosomal dominant intermediate Charcot-Marie-Tooth disease type D
MPZ	Orphanet:101082	Charcot-Marie-Tooth disease type 1B
MPZ	Orphanet:3115	Roussy-Lévy syndrome
MPZ	Orphanet:324585	Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain
MPZ	Orphanet:538574	Palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome
MPZ	Orphanet:64748	Dejerine-Sottas syndrome
MPZ	Orphanet:99942	Autosomal dominant Charcot-Marie-Tooth disease type 2I
MPZ	Orphanet:99943	Autosomal dominant Charcot-Marie-Tooth disease type 2J

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
MPZ	HGNC:7225	ENSG00000158887	P25189	Myelin protein P0	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MPZ	Myelin protein P0	Is an adhesion molecule necessary for normal myelination in the peripheral nervous system.

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)
MPZ	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom

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
olfactory bulb	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MPZ	178	ubiquitous	marker	tibial nerve, sural nerve, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MPZ	25

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MPZ	P25189	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.008	MPZ
Nervous system development	1	42.9×	0.035	MPZ
Developmental Biology	1	14.5×	0.069	MPZ

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
cell aggregation	1	8426.0×	5e-04	MPZ
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	1123.5×	0.002	MPZ
myelination	1	251.5×	0.005	MPZ
chemical synaptic transmission	1	77.3×	0.013	MPZ

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
MPZ	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	1	MPZ
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)
MPZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease