Charcot-Marie-Tooth disease type 2A2

Summary

Charcot-Marie-Tooth disease type 2A2 (MONDO:0012231) is a disease caused by MFN2 (GenCC Strong), with 3 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: MFN2 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 127
• Phenotypes (HPO): 45
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

45 HPO clinical features (Orphanet curated; top 45 by frequency):

HPO ID	Term	Frequency
HP:0001760	Abnormal foot morphology	Very frequent (80-99%)
HP:0003390	Sensory axonal neuropathy	Very frequent (80-99%)
HP:0003438	Absent Achilles reflex	Very frequent (80-99%)
HP:0003444	EMG: chronic denervation signs	Very frequent (80-99%)
HP:0003474	Somatic sensory dysfunction	Very frequent (80-99%)
HP:0009027	Foot dorsiflexor weakness	Very frequent (80-99%)
HP:0001155	Abnormality of the hand	Frequent (30-79%)
HP:0001761	Pes cavus	Frequent (30-79%)
HP:0002359	Frequent falls	Frequent (30-79%)
HP:0002378	Hand tremor	Frequent (30-79%)
HP:0002495	Impaired vibratory sensation	Frequent (30-79%)
HP:0002522	Areflexia of lower limbs	Frequent (30-79%)
HP:0002601	Paresis of extensor muscles of the big toe	Frequent (30-79%)
HP:0002936	Distal sensory impairment	Frequent (30-79%)
HP:0003394	Muscle spasm	Frequent (30-79%)
HP:0003551	Difficulty climbing stairs	Frequent (30-79%)
HP:0006460	Increased laxity of ankles	Frequent (30-79%)
HP:0007010	Poor fine motor coordination	Frequent (30-79%)
HP:0007328	Impaired pain sensation	Frequent (30-79%)
HP:0009046	Difficulty running	Frequent (30-79%)
HP:0009053	Distal lower limb muscle weakness	Frequent (30-79%)
HP:0010829	Impaired temperature sensition	Frequent (30-79%)
HP:0025238	Foot pain	Frequent (30-79%)
HP:0030237	Hand muscle weakness	Frequent (30-79%)
HP:0001371	Flexion contracture	Occasional (5-29%)
HP:0001605	Vocal cord paralysis	Occasional (5-29%)
HP:0001609	Hoarse voice	Occasional (5-29%)
HP:0001618	Dysphonia	Occasional (5-29%)
HP:0002143	Abnormality of the spinal cord	Occasional (5-29%)
HP:0002174	Postural tremor	Occasional (5-29%)
HP:0003376	Steppage gait	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0003731	Quadriceps muscle weakness	Occasional (5-29%)
HP:0006844	Absent patellar reflexes	Occasional (5-29%)
HP:0006915	Inability to walk by childhood/adolescence	Occasional (5-29%)
HP:0008944	Distal lower limb amyotrophy	Occasional (5-29%)
HP:0012452	Restless legs	Occasional (5-29%)
HP:0012513	Upper limb pain	Occasional (5-29%)
HP:0031108	Triceps weakness	Occasional (5-29%)
HP:0000238	Hydrocephalus	Very rare (<1-4%)
HP:0000407	Sensorineural hearing impairment	Very rare (<1-4%)
HP:0000648	Optic atrophy	Very rare (<1-4%)
HP:0000662	Nyctalopia	Very rare (<1-4%)
HP:0002650	Scoliosis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 2A2
Mondo ID	MONDO:0012231
MeSH	C563757
OMIM	609260
Orphanet	99947
DOID	DOID:0110155
ICD-11	1274363794
NCIT	C150646
SNOMED CT	764850002
UMLS	C4721887
MedGen	1648317
GARD	0016925
Is cancer (heuristic)	no

Also known as: Charcot-Marie-Tooth disease type 2 caused by mutation in MFN2 · Charcot-Marie-Tooth disease type 2A2A · Charcot-Marie-Tooth disease, axonal, type 2A2 · Charcot-Marie-Tooth disease, axonal, type 2A2A · CMT2A2 · CMT2A2A · hereditary motor and sensory neuropathy IIA2 · HMSN IIA2 · HMSN2A2 · MFN2 Charcot-Marie-Tooth disease type 2

Data availability: 127 ClinVar variants · 2 GenCC gene-disease records · 16 cell lines.

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 2 › Charcot-Marie-Tooth disease type 2A2

Related subtypes (37): Charcot-Marie-Tooth disease type 2A1, Charcot-Marie-Tooth disease type 2B, Charcot-Marie-Tooth disease type 2D, Charcot-Marie-Tooth disease type 2B1, Charcot-Marie-Tooth disease type 2B2, Charcot-Marie-Tooth disease axonal type 2C, Charcot-Marie-Tooth disease axonal type 2F, Charcot-Marie-Tooth disease type 2I, Charcot-Marie-Tooth disease type 2E, Charcot-Marie-Tooth disease axonal type 2H, Charcot-Marie-Tooth disease type 2J, Charcot-Marie-Tooth disease axonal type 2K, Charcot-Marie-Tooth disease axonal type 2L, giant axonal neuropathy 2, Charcot-Marie-Tooth disease axonal type 2N, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease axonal type 2P, Charcot-Marie-Tooth disease axonal type 2Q, Charcot-Marie-Tooth disease type 2R, Charcot-Marie-Tooth disease axonal type 2S, Charcot-Marie-Tooth disease axonal type 2U, Charcot-Marie-Tooth disease axonal type 2V, autosomal dominant Charcot-Marie-Tooth disease type 2W, Charcot-Marie-Tooth disease axonal type 2X, Charcot-Marie-Tooth disease type 2Y, Charcot-Marie-Tooth disease axonal type 2Z, Charcot-Marie-Tooth disease axonal type 2CC, autosomal dominant Charcot-Marie-Tooth disease type 2M, Charcot-Marie-Tooth disease type 2B5, autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation, autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation, autosomal dominant Charcot-Marie-Tooth disease type 2K, Charcot-Marie-Tooth disease, axonal, type 2EE, autosomal dominant charcot-marie-tooth disease type 2 due to DGAT2 mutation, Charcot-Marie-Tooth disease type 2T, MME-related autosomal dominant Charcot Marie Tooth disease type 2, Charcot-Marie-tooth disease, axonal, type 2DD

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

127 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 27 conflicting classifications of pathogenicity, 21 pathogenic/likely pathogenic, 20 likely pathogenic, 18 pathogenic, 5 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
545677	NM_000701.8(ATP1A1):c.143T>G (p.Leu48Arg)	ATP1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
545678	NM_000701.8(ATP1A1):c.1798C>G (p.Pro600Ala)	ATP1A1	Pathogenic	criteria provided, multiple submitters, no conflicts
545680	NM_000701.8(ATP1A1):c.1775T>C (p.Ile592Thr)	ATP1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39565	NM_018706.7(DHTKD1):c.1228C>T (p.Arg410Ter)	DHTKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
1193107	NM_014874.4(MFN2):c.382C>T (p.His128Tyr)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
155730	NM_014874.4(MFN2):c.775C>T (p.Arg259Cys)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
202171	NM_014874.4(MFN2):c.746C>T (p.Ser249Phe)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
214652	NM_014874.4(MFN2):c.314C>T (p.Thr105Met)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217161	NM_014874.4(MFN2):c.1126A>G (p.Met376Val)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217162	NM_014874.4(MFN2):c.2256C>A (p.Tyr752Ter)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
217163	NM_014874.4(MFN2):c.436C>T (p.Leu146Phe)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217164	NM_014874.4(MFN2):c.494A>G (p.His165Arg)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2268	NM_014874.4(MFN2):c.281G>A (p.Arg94Gln)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2269	NM_014874.4(MFN2):c.2219G>C (p.Trp740Ser)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2270	NM_014874.4(MFN2):c.227T>C (p.Leu76Pro)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2271	NM_014874.4(MFN2):c.839G>A (p.Arg280His)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2272	NM_014874.4(MFN2):c.751C>G (p.Pro251Ala)	MFN2	Pathogenic	criteria provided, single submitter
2273	NM_014874.4(MFN2):c.205G>T (p.Val69Phe)	MFN2	Pathogenic	no assertion criteria provided
2274	NM_014874.4(MFN2):c.1071G>C (p.Lys357Asn)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2275	NM_014874.4(MFN2):c.493C>G (p.His165Asp)	MFN2	Pathogenic	criteria provided, single submitter
2276	NM_014874.4(MFN2):c.280C>T (p.Arg94Trp)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2278	NM_014874.4(MFN2):c.1090C>T (p.Arg364Trp)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2280	NM_014874.4(MFN2):c.2119C>T (p.Arg707Trp)	MFN2	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
243057	NM_014874.4(MFN2):c.730G>T (p.Val244Leu)	MFN2	Pathogenic	criteria provided, single submitter
243066	NM_014874.4(MFN2):c.730G>A (p.Val244Met)	MFN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2431040	NM_014874.4(MFN2):c.705G>T (p.Gln235His)	MFN2	Pathogenic	no assertion criteria provided
245944	NM_014874.4(MFN2):c.1091G>A (p.Arg364Gln)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30738	NM_014874.4(MFN2):c.1085C>T (p.Thr362Met)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
476772	NM_014874.4(MFN2):c.326A>G (p.Lys109Arg)	MFN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 9 · 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
MFN2	Definitive	Autosomal recessive	Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
DHTKD1	Orphanet:329258	Autosomal dominant Charcot-Marie-Tooth disease type 2Q
DHTKD1	Orphanet:79154	2-aminoadipic 2-oxoadipic aciduria
ATP1A1	Orphanet:521414	Autosomal dominant Charcot-Marie-Tooth disease type 2DD
ATP1A1	Orphanet:564178	Primary hypomagnesemia-refractory seizures-intellectual disability syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MFN2	HGNC:16877	ENSG00000116688	O95140	Mitofusin-2	gencc,clinvar
DHTKD1	HGNC:23537	ENSG00000181192	Q96HY7	2-oxoadipate dehydrogenase complex component E1	clinvar
ATP1A1	HGNC:799	ENSG00000163399	P05023	Sodium/potassium-transporting ATPase subunit alpha-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MFN2	Mitofusin-2	Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.
DHTKD1	2-oxoadipate dehydrogenase complex component E1	2-oxoadipate dehydrogenase (E1a) component of the 2-oxoadipate dehydrogenase complex (OADHC).
ATP1A1	Sodium/potassium-transporting ATPase subunit alpha-1	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · 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
Enzyme (other)	1	4.0×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MFN2	Other/Unknown	no		Fzo/mitofusin_HR2, Mitofusin_fam, P-loop_NTPase
DHTKD1	Enzyme (other)	yes	1.2.1.105	DH_E1, Transketolase-like_Pyr-bd, 2oxoglutarate_DH_E1
ATP1A1	Transcription factor	no	7.2.2.3	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
cardiac ventricle	1
heart left ventricle	1
liver	1
right lobe of liver	1
secondary oocyte	1
left lobe of thyroid gland	1
renal medulla	1
right lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MFN2	297	ubiquitous	marker	apex of heart, heart left ventricle, cardiac ventricle
DHTKD1	270	ubiquitous	marker	liver, right lobe of liver, secondary oocyte
ATP1A1	305	ubiquitous	marker	renal medulla, right lobe of thyroid gland, left lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MFN2	3,853
ATP1A1	3,520
DHTKD1	2,099

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP1A1	P05023	13
DHTKD1	Q96HY7	8
MFN2	O95140	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
OADH complex synthesizes glutaryl-CoA from 2-OA	1	1268.9×	0.014	DHTKD1
Miro GTPase Cycle	1	761.3×	0.014	MFN2
RHOT2 GTPase cycle	1	543.8×	0.014	MFN2
Mitophagy	1	346.1×	0.017	MFN2
PINK1-PRKN Mediated Mitophagy	1	119.0×	0.039	MFN2
Selective autophagy	1	92.8×	0.041	MFN2
Ion transport by P-type ATPases	1	69.2×	0.042	ATP1A1
Ion homeostasis	1	68.0×	0.042	ATP1A1
Autophagy	1	49.4×	0.051	MFN2
Macroautophagy	1	38.5×	0.052	MFN2
Potential therapeutics for SARS	1	38.1×	0.052	ATP1A1
Cardiac conduction	1	36.2×	0.052	ATP1A1
Ion channel transport	1	32.0×	0.055	ATP1A1
Muscle contraction	1	25.7×	0.063	ATP1A1
Factors involved in megakaryocyte development and platelet production	1	22.1×	0.068	MFN2
SARS-CoV Infections	1	18.5×	0.076	ATP1A1
Hemostasis	1	12.0×	0.110	MFN2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	11.2×	0.111	MFN2
Viral Infection Pathways	1	10.3×	0.114	ATP1A1
Transport of small molecules	1	8.4×	0.127	ATP1A1
Infectious disease	1	8.3×	0.127	ATP1A1
Disease	1	4.4×	0.222	ATP1A1
Signal Transduction	1	3.4×	0.267	MFN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of glucocorticoid biosynthetic process	1	5617.3×	0.007	ATP1A1
positive regulation of striated muscle contraction	1	2808.7×	0.007	ATP1A1
negative regulation of heart contraction	1	1404.3×	0.007	ATP1A1
type 2 mitophagy	1	1123.5×	0.007	MFN2
establishment or maintenance of transmembrane electrochemical gradient	1	936.2×	0.007	ATP1A1
mitochondrial membrane organization	1	802.5×	0.007	MFN2
response to glycoside	1	802.5×	0.007	ATP1A1
positive regulation of heart contraction	1	702.2×	0.007	ATP1A1
positive regulation of vascular associated smooth muscle cell apoptotic process	1	702.2×	0.007	MFN2
mitochondrion localization	1	561.7×	0.007	MFN2
membrane repolarization during cardiac muscle cell action potential	1	561.7×	0.007	ATP1A1
osmosensory signaling pathway	1	510.7×	0.007	ATP1A1
cell communication by electrical coupling involved in cardiac conduction	1	468.1×	0.007	ATP1A1
relaxation of cardiac muscle	1	432.1×	0.007	ATP1A1
membrane repolarization	1	432.1×	0.007	ATP1A1
sodium ion export across plasma membrane	1	351.1×	0.007	ATP1A1
cellular response to steroid hormone stimulus	1	351.1×	0.007	ATP1A1
regulation of the force of heart contraction	1	330.4×	0.007	ATP1A1
intracellular potassium ion homeostasis	1	330.4×	0.007	ATP1A1
protein localization to phagophore assembly site	1	330.4×	0.007	MFN2
regulation of sodium ion transport	1	312.1×	0.007	ATP1A1
mitochondrial fusion	1	280.9×	0.007	MFN2
blastocyst formation	1	255.3×	0.007	MFN2
intracellular sodium ion homeostasis	1	255.3×	0.007	ATP1A1
camera-type eye morphogenesis	1	255.3×	0.007	MFN2
cardiac muscle cell action potential involved in contraction	1	234.1×	0.007	ATP1A1
negative regulation of Ras protein signal transduction	1	224.7×	0.007	MFN2
negative regulation of smooth muscle cell proliferation	1	208.1×	0.007	MFN2
obsolete protein targeting to mitochondrion	1	193.7×	0.008	MFN2
positive regulation of vascular associated smooth muscle cell proliferation	1	144.0×	0.010	MFN2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
ATP1A1	DIGOXIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP1A1	5	4
MFN2	0	0
DHTKD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIGOXIN	4	ATP1A1
OMEPRAZOLE	4	ATP1A1
DIGITOXIN	4	ATP1A1
LANSOPRAZOLE	4	ATP1A1
ROSTAFUROXIN	2	ATP1A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
ATP1A1	50	Binding:50
MFN2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DHTKD1	1.2.1.105	2-oxoglutarate dehydrogenase system
ATP1A1	7.2.2.3	P-type Na+ transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

5 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)
DIGOXIN	4	ATP1A1
OMEPRAZOLE	4	ATP1A1
DIGITOXIN	4	ATP1A1
LANSOPRAZOLE	4	ATP1A1
ROSTAFUROXIN	2	ATP1A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATP1A1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DHTKD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MFN2

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)
MFN2	3	—
DHTKD1	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