Charcot-Marie-Tooth disease dominant intermediate B

Summary

Charcot-Marie-Tooth disease dominant intermediate B (MONDO:0011674) is a disease caused by DNM2 (GenCC Strong), with 7 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DNM2 (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 1,194

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		37	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease dominant intermediate B
Mondo ID	MONDO:0011674
OMIM	606482
Orphanet	100044
DOID	DOID:0110197
SNOMED CT	765745007
UMLS	C1847902
MedGen	338346
GARD	0012438
Is cancer (heuristic)	no

Also known as: Charcot-Marie-Tooth disease caused by mutation in DNM2 · Charcot-Marie-Tooth disease dominant intermediate type B · Charcot-Marie-Tooth disease, axonal type 2M · Charcot-Marie-Tooth disease, dominant intermediate B · Charcot-Marie-Tooth disease, dominant Intermediate type B · CMTDI1 · CMTDIB · DI-CMTB · DNM2 Charcot-Marie-Tooth disease · DNM2-related intermediate Charcot-Marie-Tooth neuropathy

Data availability: 1,194 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

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 B

Related subtypes (7): Charcot-Marie-Tooth Disease, axonal, type 2GG, Charcot-Marie-Tooth disease dominant intermediate D, Charcot-Marie-Tooth disease dominant intermediate C, Charcot-Marie-Tooth disease dominant intermediate E, Charcot-Marie-Tooth disease dominant intermediate F, autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain, Charcot-Marie-Tooth disease, dominant intermediate A

Subtypes (1): autosomal dominant Charcot-Marie-Tooth disease type 2M

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

600 retrieved; paginated sample, class counts are floors:

304 likely benign, 227 uncertain significance, 35 conflicting classifications of pathogenicity, 13 benign/likely benign, 11 benign, 4 likely pathogenic, 3 pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067936	NM_001005361.3(DNM2):c.1115T>C (p.Phe372Ser)	DNM2	Pathogenic	criteria provided, single submitter
158514	NM_001005361.3(DNM2):c.1565G>A (p.Arg522His)	DNM2	Pathogenic	reviewed by expert panel
158519	NM_001005361.3(DNM2):c.1862T>C (p.Leu621Pro)	DNM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158520	NM_001005361.3(DNM2):c.1880C>G (p.Pro627Arg)	DNM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
246295	NM_001005361.3(DNM2):c.1609G>A (p.Gly537Ser)	DNM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2281	NM_014874.4(MFN2):c.310C>T (p.Arg104Trp)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
158515	NM_001005361.3(DNM2):c.1567A>G (p.Arg523Gly)	DNM2	Likely pathogenic	reviewed by expert panel
1705621	NM_001005361.3(DNM2):c.1840G>A (p.Asp614Asn)	DNM2	Likely pathogenic	reviewed by expert panel
218920	NM_001005361.3(DNM2):c.1021G>A (p.Glu341Lys)	DNM2	Likely pathogenic	criteria provided, single submitter
246082	NM_001005361.3(DNM2):c.1678G>A (p.Glu560Lys)	DNM2	Likely pathogenic	reviewed by expert panel
1001108	NM_001005361.3(DNM2):c.2264C>T (p.Thr755Ile)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1005871	NM_001005361.3(DNM2):c.2074C>T (p.His692Tyr)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032513	NM_001005361.3(DNM2):c.1552A>C (p.Ile518Leu)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1040563	NM_001005361.3(DNM2):c.2523G>T (p.Gly841=)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1045441	NM_001005361.3(DNM2):c.1873G>A (p.Val625Ile)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1093753	NM_001005361.3(DNM2):c.1558-5C>A	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1256590	NM_001005361.3(DNM2):c.2292-7C>T	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133978	NM_001005361.3(DNM2):c.190G>A (p.Val64Ile)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133981	NM_001005361.3(DNM2):c.1912G>A (p.Ala638Thr)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1370640	NM_001005361.3(DNM2):c.2269C>T (p.Leu757Phe)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1418616	NM_001005361.3(DNM2):c.2278G>A (p.Ala760Thr)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1437218	NM_001005361.3(DNM2):c.2309G>A (p.Arg770Gln)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1438406	NM_001005361.3(DNM2):c.2465G>A (p.Ser822Asn)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1466536	NM_001005361.3(DNM2):c.676C>T (p.Pro226Ser)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1472768	NM_001005361.3(DNM2):c.2176T>C (p.Tyr726His)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1495890	NM_001005361.3(DNM2):c.2363C>T (p.Thr788Ile)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158518	NM_001005361.3(DNM2):c.1827C>T (p.Ser609=)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158522	NM_001005361.3(DNM2):c.2106G>C (p.Ser702=)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158524	NM_001005361.3(DNM2):c.235+12C>A	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
158528	NM_001005361.3(DNM2):c.822G>A (p.Thr274=)	DNM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 25 · 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
DNM2	Strong	Autosomal dominant	Charcot-Marie-Tooth disease dominant intermediate B	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNM2	Orphanet:100044	Autosomal dominant intermediate Charcot-Marie-Tooth disease type B
DNM2	Orphanet:169189	Autosomal dominant centronuclear myopathy
DNM2	Orphanet:228179	Autosomal dominant Charcot-Marie-Tooth disease type 2M
DNM2	Orphanet:363409	Fetal akinesia-cerebral and retinal hemorrhage syndrome
SCN9A	Orphanet:306577	Hereditary sodium channelopathy-related small fibers neuropathy
SCN9A	Orphanet:33069	Dravet syndrome
SCN9A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN9A	Orphanet:46348	Paroxysmal extreme pain disorder
SCN9A	Orphanet:88642	Congenital insensitivity to pain-anosmia-neuropathic arthropathy
SCN9A	Orphanet:90026	Primary erythromelalgia
SCN9A	Orphanet:970	Hereditary sensory and autonomic neuropathy type 2
ACP5	Orphanet:1855	Spondyloenchondrodysplasia
MFN2	Orphanet:2398	Multiple symmetric lipomatosis
MFN2	Orphanet:64751	Hereditary motor and sensory neuropathy type 5
MFN2	Orphanet:90118	Severe early-onset axonal neuropathy due to MFN2 deficiency
MFN2	Orphanet:90120	Hereditary motor and sensory neuropathy type 6
MFN2	Orphanet:99947	Autosomal dominant Charcot-Marie-Tooth disease type 2A2
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

7 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNM2	HGNC:2974	ENSG00000079805	P50570	Dynamin-2	gencc,clinvar
SCN9A	HGNC:10597	ENSG00000169432	Q15858	Sodium channel protein type 9 subunit alpha	clinvar
ACP5	HGNC:124	ENSG00000102575	P13686	Tartrate-resistant acid phosphatase type 5	clinvar
MFN2	HGNC:16877	ENSG00000116688	O95140	Mitofusin-2	clinvar
MIR638	HGNC:32894	ENSG00000207972		microRNA 638	clinvar
MIR6793	HGNC:50251	ENSG00000275640		microRNA 6793	clinvar
MPZ	HGNC:7225	ENSG00000158887	P25189	Myelin protein P0	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNM2	Dynamin-2	Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton.
SCN9A	Sodium channel protein type 9 subunit alpha	Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
ACP5	Tartrate-resistant acid phosphatase type 5	Involved in osteopontin/bone sialoprotein dephosphorylation.
MFN2	Mitofusin-2	Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.
MPZ	Myelin protein P0	Is an adhesion molecule necessary for normal myelination in the peripheral nervous system.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.43

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
Ion channel	1	15.9×	0.306
Antibody/Immunoglobulin	1	4.2×	0.541
Scaffold/PPI	1	2.5×	0.568
Enzyme (other)	1	1.7×	0.571
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNM2	Scaffold/PPI	no	3.6.5.5	Dynamin_stalk, Dynamin_GTPase, PH_domain
SCN9A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
ACP5	Enzyme (other)	yes	3.1.3.2	Calcineurin-like_PHP, Acid_PPase, Metallo-depent_PP-like
MFN2	Other/Unknown	no		Fzo/mitofusin_HR2, Mitofusin_fam, P-loop_NTPase
MIR638	Other/Unknown	no
MIR6793	Other/Unknown	no
MPZ	Antibody/Immunoglobulin	yes		Myelin_P0-rel, Ig_sub, Ig-like_dom

Expression context

Cohort genes with no expression data: 0.

5 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	2
granulocyte	1
metanephros cortex	1
mucosa of transverse colon	1
dorsal root ganglion	1
stromal cell of endometrium	1
periodontal ligament	1
right lung	1
upper lobe of left lung	1
apex of heart	1
cardiac ventricle	1
heart left ventricle	1
blood	1
monocyte	1
nucleus accumbens	1
adrenal tissue	1
bone marrow	1
kidney	1
olfactory bulb	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNM2	234	ubiquitous	marker	metanephros cortex, granulocyte, mucosa of transverse colon
SCN9A	187	ubiquitous	marker	sural nerve, dorsal root ganglion, stromal cell of endometrium
ACP5	233	broad	marker	periodontal ligament, upper lobe of left lung, right lung
MFN2	297	ubiquitous	marker	apex of heart, heart left ventricle, cardiac ventricle
MIR638	37		yes	blood, monocyte, nucleus accumbens
MIR6793	91		yes	kidney, bone marrow, adrenal tissue
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
DNM2	4,715
MFN2	3,853
ACP5	2,983
SCN9A	1,575
MPZ	25
MIR638	0
MIR6793	0

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN9A	Q15858	43
MFN2	O95140	3
ACP5	P13686	2
MPZ	P25189	2
DNM2	P50570	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NOSTRIN mediated eNOS trafficking	1	456.8×	0.024	DNM2
Miro GTPase Cycle	1	456.8×	0.024	MFN2
Vitamin B2 (riboflavin) metabolism	1	326.3×	0.024	ACP5
RHOT2 GTPase cycle	1	326.3×	0.024	MFN2
Formation of annular gap junctions	1	207.6×	0.024	DNM2
Mitophagy	1	207.6×	0.024	MFN2
Gap junction degradation	1	190.3×	0.024	DNM2
Nervous system development	2	17.2×	0.024	SCN9A, MPZ
Retrograde neurotrophin signalling	1	163.1×	0.024	DNM2
Interaction between L1 and Ankyrins	1	73.7×	0.036	SCN9A
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	73.7×	0.036	MPZ
PINK1-PRKN Mediated Mitophagy	1	71.4×	0.036	MFN2
Phase 0 - rapid depolarisation	1	69.2×	0.036	SCN9A
Sensory perception of taste	1	67.2×	0.036	SCN9A
Lysosome Vesicle Biogenesis	1	65.3×	0.036	DNM2
NGF-stimulated transcription	1	57.1×	0.036	DNM2
Selective autophagy	1	55.7×	0.036	MFN2
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	55.7×	0.036	SCN9A
Recycling pathway of L1	1	44.8×	0.042	DNM2
Golgi Associated Vesicle Biogenesis	1	40.1×	0.043	DNM2
Degradation of CDH1	1	39.4×	0.043	DNM2
Autophagy	1	29.7×	0.054	MFN2
Toll Like Receptor 4 (TLR4) Cascade	1	26.2×	0.059	DNM2
L1CAM interactions	1	24.0×	0.059	SCN9A
Macroautophagy	1	23.1×	0.059	MFN2
Developmental Biology	2	5.8×	0.059	SCN9A, MPZ
Cardiac conduction	1	21.8×	0.060	SCN9A
Sensory Perception	1	19.0×	0.066	SCN9A
MHC class II antigen presentation	1	17.8×	0.068	DNM2
Clathrin-mediated endocytosis	1	17.0×	0.069	DNM2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
action potential propagation	1	3370.4×	0.008	SCN9A
negative regulation of superoxide anion generation	1	1685.2×	0.008	ACP5
cell aggregation	1	1685.2×	0.008	MPZ
vesicle scission	1	1685.2×	0.008	DNM2
negative regulation of membrane tubulation	1	1685.2×	0.008	DNM2
actin filament bundle organization	1	1123.5×	0.009	DNM2
membrane tubulation	1	1123.5×	0.009	DNM2
synaptic vesicle budding from presynaptic endocytic zone membrane	1	674.1×	0.012	DNM2
type 2 mitophagy	1	674.1×	0.012	MFN2
detection of mechanical stimulus involved in sensory perception	1	561.7×	0.013	SCN9A
mitochondrial membrane organization	1	481.5×	0.013	MFN2
positive regulation of vascular associated smooth muscle cell apoptotic process	1	421.3×	0.014	MFN2
mitochondrion localization	1	337.0×	0.016	MFN2
transferrin transport	1	306.4×	0.016	DNM2
regulation of axon extension	1	259.3×	0.016	DNM2
negative regulation of macrophage cytokine production	1	240.7×	0.016	ACP5
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	224.7×	0.016	MPZ
post-Golgi vesicle-mediated transport	1	210.7×	0.016	DNM2
negative regulation of interleukin-12 production	1	210.7×	0.016	ACP5
protein localization to phagophore assembly site	1	198.3×	0.016	MFN2
negative regulation of nitric oxide biosynthetic process	1	198.3×	0.016	ACP5
protein polymerization	1	198.3×	0.016	DNM2
behavioral response to pain	1	177.4×	0.016	SCN9A
mitochondrial fusion	1	168.5×	0.016	MFN2
synaptic vesicle transport	1	168.5×	0.016	DNM2
detection of temperature stimulus involved in sensory perception of pain	1	168.5×	0.016	SCN9A
blastocyst formation	1	153.2×	0.016	MFN2
stress fiber assembly	1	153.2×	0.016	DNM2
camera-type eye morphogenesis	1	153.2×	0.016	MFN2
nitric oxide biosynthetic process	1	140.4×	0.016	ACP5

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 3 of 7 evidence-associated genes (43%) 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
SCN9A	IMIPRAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN9A	36	4
DNM2	0	0
ACP5	0	0
MFN2	0	0
MIR638	0	0
MIR6793	0	0
MPZ	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	SCN9A
SERTINDOLE	4	SCN9A
PIMOZIDE	4	SCN9A
NIFEDIPINE	4	SCN9A
DILTIAZEM	4	SCN9A
MIBEFRADIL	4	SCN9A
HALOPERIDOL	4	SCN9A
MEXILETINE	4	SCN9A
AMITRIPTYLINE	4	SCN9A
AMIODARONE	4	SCN9A
CHLORPROMAZINE	4	SCN9A
CARBAMAZEPINE	4	SCN9A
MEXILETINE HYDROCHLORIDE	4	SCN9A
CANNABIDIOL	4	SCN9A
SAFINAMIDE	4	SCN9A
LACOSAMIDE	4	SCN9A
TETRACAINE	4	SCN9A
LAMOTRIGINE	4	SCN9A
RILUZOLE	4	SCN9A
LIDOCAINE	4	SCN9A
TEDISAMIL	3	SCN9A
NITRENDIPINE	3	SCN9A
AJMALINE	3	SCN9A
RALFINAMIDE	3	SCN9A
VIXOTRIGINE	3	SCN9A
ELECLAZINE	3	SCN9A
TETRODOTOXIN	3	SCN9A
CIFENLINE	2	SCN9A
PF-05089771	2	SCN9A
PF-04531083	2	SCN9A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
SCN9A	428	Binding:395, Functional:29, ADMET:3, Toxicity:1
DNM2	15	Binding:15
MFN2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DNM2	3.6.5.5	dynamin GTPase
ACP5	3.1.3.2	acid phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN9A	428

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)
IMIPRAMINE	4	SCN9A
SERTINDOLE	4	SCN9A
PIMOZIDE	4	SCN9A
NIFEDIPINE	4	SCN9A
DILTIAZEM	4	SCN9A
MIBEFRADIL	4	SCN9A
HALOPERIDOL	4	SCN9A
MEXILETINE	4	SCN9A
AMITRIPTYLINE	4	SCN9A
AMIODARONE	4	SCN9A
CHLORPROMAZINE	4	SCN9A
CARBAMAZEPINE	4	SCN9A
MEXILETINE HYDROCHLORIDE	4	SCN9A
CANNABIDIOL	4	SCN9A
SAFINAMIDE	4	SCN9A
LACOSAMIDE	4	SCN9A
TETRACAINE	4	SCN9A
LAMOTRIGINE	4	SCN9A
RILUZOLE	4	SCN9A
LIDOCAINE	4	SCN9A
TEDISAMIL	3	SCN9A
NITRENDIPINE	3	SCN9A
AJMALINE	3	SCN9A
RALFINAMIDE	3	SCN9A
VIXOTRIGINE	3	SCN9A
ELECLAZINE	3	SCN9A
TETRODOTOXIN	3	SCN9A
CIFENLINE	2	SCN9A
PF-05089771	2	SCN9A
PF-04531083	2	SCN9A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN9A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ACP5, MPZ
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	DNM2, MFN2, MIR638, MIR6793

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNM2	15	—
ACP5	0	—
MFN2	3	—
MIR638	0	—
MIR6793	0	—
MPZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.