autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation

Summary

autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation (MONDO:0018567) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation
Mondo ID	MONDO:0018567
Orphanet	435819
UMLS	C5569028
MedGen	1800451
GARD	0021815
Is cancer (heuristic)	no

Also known as: CMT2 due to TFG mutation

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 › motor peripheral neuropathy › hereditary motor and sensory neuropathy, Okinawa type › autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation

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: 7 · Orphanet: 5 · 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
TFG	Supportive	Autosomal dominant	autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFG	Orphanet:146	Differentiated thyroid carcinoma
TFG	Orphanet:209916	Extraskeletal myxoid chondrosarcoma
TFG	Orphanet:431329	Autosomal recessive spastic paraplegia type 57
TFG	Orphanet:435819	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation
TFG	Orphanet:90117	Hereditary motor and sensory neuropathy, Okinawa type

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
TFG	HGNC:11758	ENSG00000114354	Q92734	Protein TFG	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFG	Protein TFG	Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules.

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)
TFG	Other/Unknown	no		PB1_dom, TFG, PB1_TFG

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
gingival epithelium	1
jejunal mucosa	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFG	288	ubiquitous	marker	secondary oocyte, jejunal mucosa, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TFG	674

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TFG	Q92734	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Signaling by ALK in cancer	1	271.9×	0.023	TFG
COPII-mediated vesicle transport	1	163.1×	0.023	TFG
Signaling by ALK fusions and activated point mutants	1	150.3×	0.023	TFG
ER to Golgi Anterograde Transport	1	132.8×	0.023	TFG
Transport to the Golgi and subsequent modification	1	102.9×	0.023	TFG
Asparagine N-linked glycosylation	1	60.1×	0.030	TFG
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.030	TFG
Membrane Trafficking	1	37.1×	0.038	TFG
Vesicle-mediated transport	1	34.8×	0.038	TFG
Post-translational protein modification	1	19.2×	0.063	TFG
Disease	1	13.1×	0.081	TFG
Metabolism of proteins	1	12.4×	0.081	TFG

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
COPII vesicle coat assembly	1	702.2×	0.004	TFG
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.011	TFG
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.014	TFG

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TFG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TFG	2	Binding:2

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	TFG

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)
TFG	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.