Charcot-Marie-Tooth disease, axonal, type 2FF

disease

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Also known as Charcot-Marie-Tooth neuropathyCMT2FF

Summary

Charcot-Marie-Tooth disease, axonal, type 2FF (MONDO:0030433) is a disease caused by CADM3 (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

Causal gene: CADM3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 6
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease, axonal, type 2FF
Mondo ID	MONDO:0030433
OMIM	619519
UMLS	C5561981
MedGen	1794191
GARD	0025558
Is cancer (heuristic)	no

Also known as: Charcot-Marie-Tooth neuropathy · CMT2FF

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

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, axonal, type 2FF

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

6 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1268234	NM_001127173.3(CADM3):c.413A>G (p.Tyr138Cys)	CADM3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1710197	NM_001127173.3(CADM3):c.1000G>T (p.Gly334Cys)	CADM3	Uncertain significance	criteria provided, single submitter
1712342	NM_001127173.3(CADM3):c.383del	CADM3	Uncertain significance	criteria provided, single submitter
2439699	NM_001127173.3(CADM3):c.1061A>G (p.Tyr354Cys)	CADM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3897706	NM_001127173.3(CADM3):c.739G>A (p.Gly247Ser)	CADM3	Uncertain significance	criteria provided, single submitter
4292300	NM_001127173.3(CADM3):c.229+11A>G	CADM3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
CADM3	Strong	Autosomal dominant	Charcot-Marie-Tooth disease, axonal, type 2FF	3

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
CADM3	HGNC:17601	ENSG00000162706	Q8N126	Cell adhesion molecule 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CADM3	Cell adhesion molecule 3	Involved in cell-cell adhesion.

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)
CADM3	Antibody/Immunoglobulin	yes		Neurexin-like, Ig_sub2, Ig_sub

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CADM3	218	broad	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CADM3	1,131

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CADM3	Q8N126	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Nectin/Necl trans heterodimerization	1	1427.5×	0.004	CADM3
Adherens junctions interactions	1	248.3×	0.007	CADM3
Cell-cell junction organization	1	248.3×	0.007	CADM3
Cell junction organization	1	187.2×	0.007	CADM3
Cell-Cell communication	1	137.6×	0.007	CADM3

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
heterophilic cell-cell adhesion	1	337.0×	0.006	CADM3
homophilic cell-cell adhesion	1	140.4×	0.007	CADM3

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
CADM3	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	CADM3
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)
CADM3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03520751	PHASE1/PHASE2	NOT_YET_RECRUITING	Phase I/IIa Trial of scAAV1.tMCK.NTF3 for Treatment of CMT1A
NCT06845644	Not specified	RECRUITING	Longitudinal Quantitative Neuromuscular MRI in Neuropathic Patients

Cohort genes: CADM3