Charcot-Marie-Tooth disease type 2B5

Summary

Charcot-Marie-Tooth disease type 2B5 (MONDO:0016454) 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
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 2B5
Mondo ID	MONDO:0016454
Orphanet	228374
ICD-11	1603286685
UMLS	C4749824
MedGen	1668955
GARD	0017153
Is cancer (heuristic)	no

Also known as: AR-CMT2B5 · autosomal recessive Charcot-Marie-Tooth disease type 2B5 · Charcot-Marie-Tooth disease type 2B5 · SEOAN due to NEFL deficiency · severe early-onset axonal neuropathy due to light neurofilament subunit deficiency · severe early-onset axonal neuropathy due to NEFL deficiency

Data availability: 1 GenCC gene-disease record.

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 2B5

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, Charcot-Marie-Tooth disease type 2A2, 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, 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
NEFL	Definitive	Autosomal dominant	Charcot-Marie-Tooth disease	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEFL	Orphanet:101085	Charcot-Marie-Tooth disease type 1F
NEFL	Orphanet:228374	Charcot-Marie-Tooth disease type 2B5
NEFL	Orphanet:99939	Autosomal dominant Charcot-Marie-Tooth disease type 2E

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
NEFL	HGNC:7739	ENSG00000277586	P07196	Neurofilament light polypeptide	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEFL	Neurofilament light polypeptide	Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEFL	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_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
dorsal root ganglion	1
lateral nuclear group of thalamus	1
pons	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEFL	214	broad	marker	dorsal root ganglion, pons, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NEFL	4,644

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NEFL	P07196	73.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Ras activation upon Ca2+ influx through NMDA receptor	1	571.0×	0.003	NEFL
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.003	NEFL
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.003	NEFL
Long-term potentiation	1	475.8×	0.003	NEFL
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.005	NEFL
RAF/MAP kinase cascade	1	61.1×	0.016	NEFL

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
intermediate filament polymerization or depolymerization	1	16852.0×	0.001	NEFL
response to sodium arsenite	1	8426.0×	0.001	NEFL
response to acrylamide	1	8426.0×	0.001	NEFL
neurofilament bundle assembly	1	5617.3×	0.001	NEFL
regulation of axon diameter	1	3370.4×	0.002	NEFL
peripheral nervous system axon regeneration	1	2106.5×	0.002	NEFL
neurofilament cytoskeleton organization	1	1685.2×	0.002	NEFL
retrograde axonal transport	1	1532.0×	0.002	NEFL
locomotion	1	1532.0×	0.002	NEFL
negative regulation of motor neuron apoptotic process	1	1532.0×	0.002	NEFL
axonal transport of mitochondrion	1	1404.3×	0.002	NEFL
response to corticosterone	1	1123.5×	0.002	NEFL
motor neuron apoptotic process	1	1123.5×	0.002	NEFL
protein polymerization	1	991.3×	0.002	NEFL
regulation of synapse maturation	1	936.2×	0.002	NEFL
postsynaptic modulation of chemical synaptic transmission	1	674.1×	0.003	NEFL
anterograde axonal transport	1	581.1×	0.003	NEFL
positive regulation of axonogenesis	1	581.1×	0.003	NEFL
spinal cord development	1	510.7×	0.003	NEFL
response to peptide hormone	1	391.9×	0.003	NEFL
neuromuscular process controlling balance	1	330.4×	0.004	NEFL
intermediate filament organization	1	240.7×	0.005	NEFL
hippocampus development	1	230.8×	0.005	NEFL
response to toxic substance	1	210.7×	0.005	NEFL
cerebral cortex development	1	205.5×	0.005	NEFL
axonogenesis	1	160.5×	0.006	NEFL
microtubule cytoskeleton organization	1	121.2×	0.008	NEFL

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
NEFL	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NEFL

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)
NEFL	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