Charcot-Marie-Tooth disease type 3

Summary

Charcot-Marie-Tooth disease type 3 (MONDO:0007790) is a disease caused by PMP22 (GenCC Strong), with 6 cohort genes. The dominant Reactome pathway is EGR2 and SOX10-mediated initiation of Schwann cell myelination (5 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PMP22 (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 111

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

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

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 3
Mondo ID	MONDO:0007790
OMIM	145900
Orphanet	64748
DOID	DOID:0050540
NCIT	C133087
SNOMED CT	111499002
UMLS	C0011195
MedGen	3710
GARD	0009204
NORD	1037
Is cancer (heuristic)	no

Also known as: Charcot-Marie-Tooth disease type 3 · Charcot-Marie-Tooth disease, type 3 · CMT3 · dejerine-sottas disease · Dejerine-Sottas neuropathy · Dejerine-Sottas Syndrome · Dejerine-Sottas syndrome · DSN · hereditary motor and sensory neuropathy 3 · hereditary motor and sensory neuropathy type 3 · hereditary motor and sensory neuropathy type III · HMSN 3 · HMSN III · HMSN3 · hypertrophic neuropathy of Dejerine-Sottas · hypertrophic neuropathy of infancy

Data availability: 111 ClinVar variants · 7 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › hereditary peripheral neuropathy › Charcot-Marie-Tooth disease › Charcot-Marie-Tooth disease type 3

Related subtypes (23): Charcot-Marie-Tooth disease, Guadalajara neuronal type, Charcot-Marie-Tooth disease with ptosis and parkinsonism, neuronopathy, distal hereditary motor, autosomal dominant 1, neuropathy, hereditary motor and sensory, type 6A, Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;, demyelinating hereditary motor and sensory neuropathy, intermediate Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease type X, Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 1, Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1, Charcot-Marie-Tooth disease, axonal, type 2FF, Charcot-Marie-Tooth disease, axonal, Type 2HH, Charcot-Marie-Tooth disease, demyelinating, IIA 1I, Charcot-Marie-Tooth disease, demyelinating, IIA 1H, Charcot-Marie-Tooth disease, axonal, IIa 2II, Charcot-Marie-Tooth disease, demyelinating, type 1G, Charcot-Marie-Tooth disease, demyelinating, type 1J, Charcot-Marie-tooth disease, axonal, type 2JJ, Charcot-Marie-Tooth disease, axonal, type 2KK, Charcot-Marie-Tooth disease, axonal, type 2LL, charcot-marie-tooth disease, axonal, type 2MM

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

111 retrieved; paginated sample, class counts are floors:

45 uncertain significance, 21 pathogenic, 14 conflicting classifications of pathogenicity, 11 pathogenic/likely pathogenic, 9 likely pathogenic, 7 benign/likely benign, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1525978	NM_000399.5(EGR2):c.1232A>G (p.Asp411Gly)	EGR2	Pathogenic	criteria provided, single submitter
16752	NM_000399.5(EGR2):c.1075C>T (p.Arg359Trp)	EGR2	Pathogenic	criteria provided, multiple submitters, no conflicts
16753	NM_000399.5(EGR2):c.1234G>A (p.Glu412Lys)	EGR2	Pathogenic	criteria provided, single submitter
1685761	NM_000399.5(EGR2):c.1152C>A (p.His384Gln)	EGR2	Pathogenic	criteria provided, single submitter
10451	NM_000166.6(GJB1):c.407T>C (p.Val136Ala)	GJB1	Pathogenic	no assertion criteria provided
14169	NM_000530.8(MPZ):c.188C>G (p.Ser63Cys)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
14170	NM_000530.8(MPZ):c.499G>C (p.Gly167Arg)	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
14191	NM_000530.8(MPZ):c.434A>C (p.Tyr145Ser)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
246122	NM_000530.8(MPZ):c.129_136del (p.Ser44fs)	MPZ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41014	NM_000530.8(MPZ):c.89T>C (p.Ile30Thr)	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
488548	NM_000530.8(MPZ):c.558del (p.Arg186fs)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
531694	NM_000530.8(MPZ):c.560_563dup (p.Ala189fs)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
577671	NM_000530.8(MPZ):c.411C>T (p.Gly137=)	MPZ	Pathogenic	criteria provided, multiple submitters, no conflicts
637350	NM_000530.8(MPZ):c.380G>A (p.Cys127Tyr)	MPZ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217238	NM_000304.4(PMP22):c.434del (p.Leu145fs)	PMP22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
234605	NM_000304.4(PMP22):c.447C>A (p.Ser149Arg)	PMP22	Pathogenic	criteria provided, multiple submitters, no conflicts
245805	NM_000304.4(PMP22):c.449G>A (p.Gly150Asp)	PMP22	Pathogenic	criteria provided, multiple submitters, no conflicts
384327	NM_000304.4(PMP22):c.448G>C (p.Gly150Arg)	PMP22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433198	NM_000304.4(PMP22):c.449G>T (p.Gly150Val)	PMP22	Pathogenic	criteria provided, multiple submitters, no conflicts
637384	NM_000304.4(PMP22):c.214T>C (p.Ser72Pro)	PMP22	Pathogenic	criteria provided, single submitter
637820	NM_000304.4(PMP22):c.298G>A (p.Gly100Arg)	PMP22	Pathogenic	criteria provided, single submitter
637822	NM_000304.4(PMP22):c.235T>C (p.Ser79Pro)	PMP22	Pathogenic	criteria provided, single submitter
637843	NM_000304.4(PMP22):c.215C>G (p.Ser72Trp)	PMP22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8434	NM_000304.4(PMP22):c.36C>A (p.His12Gln)	PMP22	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686102	NM_181882.3(PRX):c.1552_1558del (p.Pro518fs)	PRX	Pathogenic	criteria provided, single submitter
245870	NM_181882.3(PRX):c.1174C>T (p.Arg392Ter)	PRX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433553	NM_181882.3(PRX):c.1012del (p.Ala338fs)	PRX	Pathogenic	no assertion criteria provided
4794	NM_181882.3(PRX):c.3208C>T (p.Arg1070Ter)	PRX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 56 · Orphanet: 21 · 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
EGR2	Definitive	Autosomal recessive	Charcot-Marie-Tooth disease type 4E	10
MPZ	Definitive	Autosomal dominant	Charcot-Marie-Tooth disease	11
PMP22	Definitive	Autosomal dominant	Charcot-Marie-Tooth disease type 1A	21
PRDX6	Definitive	Autosomal recessive	Charcot-Marie-Tooth disease type 4	7
PRX	Definitive	Autosomal recessive	Charcot-Marie-Tooth disease type 4	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRX	Orphanet:64748	Dejerine-Sottas syndrome
PRX	Orphanet:99952	Charcot-Marie-Tooth disease type 4F
EGR2	Orphanet:101084	Charcot-Marie-Tooth disease type 1D
EGR2	Orphanet:64748	Dejerine-Sottas syndrome
EGR2	Orphanet:99951	Charcot-Marie-Tooth disease type 4E
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
PMP22	Orphanet:101081	Charcot-Marie-Tooth disease type 1A
PMP22	Orphanet:3115	Roussy-Lévy syndrome
PMP22	Orphanet:640	Hereditary neuropathy with liability to pressure palsies
PMP22	Orphanet:64748	Dejerine-Sottas syndrome
PMP22	Orphanet:90658	Charcot-Marie-Tooth disease type 1E
PMP22	Orphanet:98916	Acute inflammatory demyelinating polyradiculoneuropathy
GJB1	Orphanet:101075	X-linked Charcot-Marie-Tooth disease type 1
GJB1	Orphanet:1175	X-linked progressive cerebellar ataxia

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRX	HGNC:13797	ENSG00000105227	Q9BXM0	Periaxin	gencc,clinvar
PRDX6	HGNC:16753	ENSG00000117592	P30041	Peroxiredoxin-6	gencc,clinvar
EGR2	HGNC:3239	ENSG00000122877	P11161	E3 SUMO-protein ligase EGR2	gencc,clinvar
MPZ	HGNC:7225	ENSG00000158887	P25189	Myelin protein P0	gencc,clinvar
PMP22	HGNC:9118	ENSG00000109099	Q01453	Peripheral myelin protein 22	gencc,clinvar
GJB1	HGNC:4283	ENSG00000169562	P08034	Gap junction beta-1 protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRX	Periaxin	Scaffolding protein that functions as part of a dystroglycan complex in Schwann cells, and as part of EZR and AHNAK-containing complexes in eye lens fiber cells.
PRDX6	Peroxiredoxin-6	Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.
EGR2	E3 SUMO-protein ligase EGR2	Sequence-specific DNA-binding transcription factor.
MPZ	Myelin protein P0	Is an adhesion molecule necessary for normal myelination in the peripheral nervous system.
PMP22	Peripheral myelin protein 22	Might be involved in growth regulation, and in myelinization in the peripheral nervous system.
GJB1	Gap junction beta-1 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Protein-family classification

Druggable: 2 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.33

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	4.9×	0.674
Scaffold/PPI	1	2.9×	0.674
Enzyme (other)	1	2.0×	0.674
Transcription factor	1	1.4×	0.674
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRX	Scaffold/PPI	no		PDZ, PDZ_sf, Myelin_sheath_structural
PRDX6	Enzyme (other)	yes	1.11.1.27	AhpC/TSA, Thioredoxin_domain, Peroxiredoxin_C
EGR2	Transcription factor	no		Znf_C2H2_type, EGR_N, Znf_C2H2_sf
MPZ	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom
PMP22	Other/Unknown	no		PMP22, PMP22/EMP/MP20/Claudin, PMP22_EMP_MP20
GJB1	Other/Unknown	no		Connexin, Connexin32, Connexin_N

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
olfactory bulb	3
sural nerve	2
trigeminal ganglion	2
tibial nerve	2
corpus epididymis	1
gastrocnemius	1
mucosa of stomach	1
gall bladder	1
granulocyte	1
dorsal root ganglion	1
C1 segment of cervical spinal cord	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRX	258	ubiquitous	marker	olfactory bulb, trigeminal ganglion, sural nerve
PRDX6	295	ubiquitous	marker	corpus epididymis, gastrocnemius, mucosa of stomach
EGR2	143	ubiquitous	marker	gall bladder, tibial nerve, granulocyte
MPZ	178	ubiquitous	marker	tibial nerve, sural nerve, olfactory bulb
PMP22	294	ubiquitous	marker	olfactory bulb, trigeminal ganglion, dorsal root ganglion
GJB1	207	broad	marker	right lobe of liver, C1 segment of cervical spinal cord, liver

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRDX6	4,106
EGR2	3,269
PRX	1,569
GJB1	1,494
PMP22	647
MPZ	25

Intra-cohort edges

A	B	Sources
EGR2	GJB1	string_interaction
EGR2	PMP22	string_interaction
EGR2	PRX	string_interaction
GJB1	PMP22	string_interaction
GJB1	PRX	string_interaction
MPZ	PMP22	biogrid_interaction
PMP22	PRX	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GJB1	P08034	15
PRDX6	P30041	3
MPZ	P25189	2
PRX	Q9BXM0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PMP22	Q01453	89.87
EGR2	P11161	49.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 6 evidence-associated genes (6 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 6 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	5	307.0×	7e-12	PRX, EGR2, MPZ, PMP22, GJB1
Oligomerization of connexins into connexons	1	634.4×	0.006	GJB1
Transport of connexins along the secretory pathway	1	634.4×	0.006	GJB1
Detoxification of Reactive Oxygen Species	1	50.1×	0.038	PRDX6
Gap junction assembly	1	48.8×	0.038	GJB1
NGF-stimulated transcription	1	47.6×	0.038	EGR2
Transcriptional regulation of white adipocyte differentiation	1	21.6×	0.071	EGR2
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	15.2×	0.088	EGR2
Nervous system development	1	7.2×	0.161	MPZ
Neutrophil degranulation	1	3.9×	0.257	PRDX6
Developmental Biology	1	2.4×	0.350	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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peripheral nervous system development	2	193.7×	0.002	EGR2, PMP22
rhombomere 3 structural organization	1	2808.7×	0.003	EGR2
rhombomere 3 formation	1	2808.7×	0.003	EGR2
rhombomere 5 structural organization	1	2808.7×	0.003	EGR2
rhombomere 5 formation	1	2808.7×	0.003	EGR2
myelination	2	83.8×	0.003	EGR2, MPZ
rhythmic behavior	1	1404.3×	0.004	EGR2
positive regulation of Schwann cell differentiation	1	1404.3×	0.004	EGR2
cell aggregation	1	1404.3×	0.004	MPZ
brain segmentation	1	936.2×	0.005	EGR2
axon ensheathment	1	468.1×	0.008	PRX
Schwann cell differentiation	1	401.2×	0.008	EGR2
gap junction assembly	1	351.1×	0.008	GJB1
facial nerve structural organization	1	312.1×	0.008	EGR2
myelin assembly	1	312.1×	0.008	PMP22
cellular oxidant detoxification	1	312.1×	0.008	PRDX6
chemical synaptic transmission	2	25.8×	0.008	MPZ, PMP22
bleb assembly	1	255.3×	0.009	PMP22
peripheral nervous system myelin maintenance	1	255.3×	0.009	PRX
regulation of ossification	1	200.6×	0.011	EGR2
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	187.2×	0.011	MPZ
glycerophospholipid catabolic process	1	175.5×	0.012	PRDX6
positive regulation of myelination	1	127.7×	0.015	EGR2
motor neuron axon guidance	1	117.0×	0.016	EGR2
hydrogen peroxide catabolic process	1	112.3×	0.016	PRDX6
aorta development	1	93.6×	0.018	EGR2
positive regulation of mRNA splicing, via spliceosome	1	90.6×	0.018	PRDX6
protein export from nucleus	1	85.1×	0.019	EGR2
skeletal muscle cell differentiation	1	57.3×	0.026	EGR2
cell redox homeostasis	1	57.3×	0.026	PRDX6

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 3 of 6 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PMP22	PROGESTERONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PMP22	213	4
PRX	0	0
PRDX6	0	0
EGR2	0	0
MPZ	0	0
GJB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PROGESTERONE	4	PMP22
CLOTRIMAZOLE	4	PMP22
OXAPROZIN	4	PMP22
SALMETEROL XINAFOATE	4	PMP22
AMIODARONE HYDROCHLORIDE	4	PMP22
TRIHEXYPHENIDYL HYDROCHLORIDE	4	PMP22
AMOXAPINE	4	PMP22
RALOXIFENE HYDROCHLORIDE	4	PMP22
IDARUBICIN	4	PMP22
OXYBUTYNIN CHLORIDE	4	PMP22
PINACIDIL ANHYDROUS	4	PMP22
NICARDIPINE HYDROCHLORIDE	4	PMP22
PILOCARPINE HYDROCHLORIDE	4	PMP22
PROTRIPTYLINE HYDROCHLORIDE	4	PMP22
BENZTROPINE MESYLATE	4	PMP22
BUSPIRONE HYDROCHLORIDE	4	PMP22
DOBUTAMINE HYDROCHLORIDE	4	PMP22
PROMAZINE HYDROCHLORIDE	4	PMP22
DICYCLOMINE HYDROCHLORIDE	4	PMP22
GUANFACINE HYDROCHLORIDE	4	PMP22
HYDROCORTISONE SODIUM SUCCINATE	4	PMP22
BROMOCRIPTINE MESYLATE	4	PMP22
DIHYDROERGOTAMINE MESYLATE	4	PMP22
DOXAZOSIN MESYLATE	4	PMP22
CYCLOBENZAPRINE HYDROCHLORIDE	4	PMP22
DEXBROMPHENIRAMINE MALEATE	4	PMP22
CLOMIPRAMINE HYDROCHLORIDE	4	PMP22
CHLORMEZANONE	4	PMP22
PROMETHAZINE HYDROCHLORIDE	4	PMP22
CITALOPRAM HYDROBROMIDE	4	PMP22

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRDX6	15	Binding:15
PMP22	1	Functional:1
GJB1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRDX6	1.11.1.27, 2.3.1.23, 3.1.1.4	glutathione-dependent peroxiredoxin, 1-acylglycerophosphocholine O-acyltransferase, phospholipase A2

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
PROGESTERONE	4	PMP22
CLOTRIMAZOLE	4	PMP22
OXAPROZIN	4	PMP22
SALMETEROL XINAFOATE	4	PMP22
AMIODARONE HYDROCHLORIDE	4	PMP22
TRIHEXYPHENIDYL HYDROCHLORIDE	4	PMP22
AMOXAPINE	4	PMP22
RALOXIFENE HYDROCHLORIDE	4	PMP22
IDARUBICIN	4	PMP22
OXYBUTYNIN CHLORIDE	4	PMP22
PINACIDIL ANHYDROUS	4	PMP22
NICARDIPINE HYDROCHLORIDE	4	PMP22
PILOCARPINE HYDROCHLORIDE	4	PMP22
PROTRIPTYLINE HYDROCHLORIDE	4	PMP22
BENZTROPINE MESYLATE	4	PMP22
BUSPIRONE HYDROCHLORIDE	4	PMP22
DOBUTAMINE HYDROCHLORIDE	4	PMP22
PROMAZINE HYDROCHLORIDE	4	PMP22
DICYCLOMINE HYDROCHLORIDE	4	PMP22
GUANFACINE HYDROCHLORIDE	4	PMP22
HYDROCORTISONE SODIUM SUCCINATE	4	PMP22
BROMOCRIPTINE MESYLATE	4	PMP22
DIHYDROERGOTAMINE MESYLATE	4	PMP22
DOXAZOSIN MESYLATE	4	PMP22
CYCLOBENZAPRINE HYDROCHLORIDE	4	PMP22
DEXBROMPHENIRAMINE MALEATE	4	PMP22
CLOMIPRAMINE HYDROCHLORIDE	4	PMP22
CHLORMEZANONE	4	PMP22
PROMETHAZINE HYDROCHLORIDE	4	PMP22
CITALOPRAM HYDROBROMIDE	4	PMP22

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PMP22
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	PRDX6, MPZ
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	PRX, EGR2, GJB1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GJB1	1	PMP22
PRX	0	—
PRDX6	15	—
EGR2	0	—
MPZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.