Charcot-Marie-Tooth disease, dominant intermediate A

Summary

Charcot-Marie-Tooth disease, dominant intermediate A (MONDO:0957273) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease, dominant intermediate A
Mondo ID	MONDO:0957273
OMIM	620378
UMLS	C1847896
MedGen	376235
GARD	0026807
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

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 A

Related subtypes (7): Charcot-Marie-Tooth disease dominant intermediate B, 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

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3236643	NM_001377137.1(GBF1):c.556G>C (p.Val186Leu)	GBF1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
GBF1	HGNC:4181	ENSG00000107862	Q92538	Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GBF1	Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1	Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of acti…

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)
GBF1	Other/Unknown	no		Sec7_dom, ARM-type_fold, Sec7_C_sf

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
adenohypophysis	1
colonic epithelium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GBF1	259	ubiquitous	marker	colonic epithelium, ventricular zone, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GBF1	2,436

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GBF1	Q92538	71.42

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
Assembly and Release of Dengue Virus Virions	1	1427.5×	0.004	GBF1
VxPx cargo-targeting to cilium	1	519.1×	0.006	GBF1
trans-Golgi Network Vesicle Budding	1	253.8×	0.008	GBF1
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.011	GBF1
COPI-mediated anterograde transport	1	109.8×	0.011	GBF1
Dengue Virus-Host Interactions	1	45.7×	0.022	GBF1

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
cell activation involved in immune response	1	16852.0×	7e-04	GBF1
protein localization to endoplasmic reticulum tubular network	1	16852.0×	7e-04	GBF1
establishment of monopolar cell polarity	1	8426.0×	7e-04	GBF1
endoplasmic reticulum-Golgi intermediate compartment organization	1	8426.0×	7e-04	GBF1
Golgi disassembly	1	2808.7×	0.001	GBF1
COPI coating of Golgi vesicle	1	2407.4×	0.001	GBF1
protein localization to endoplasmic reticulum exit site	1	2106.5×	0.001	GBF1
reactive oxygen species biosynthetic process	1	1872.4×	0.001	GBF1
regulation of protein localization to cell surface	1	1685.2×	0.001	GBF1
post-Golgi vesicle-mediated transport	1	1053.2×	0.002	GBF1
Golgi to endosome transport	1	1053.2×	0.002	GBF1
regulation of ARF protein signal transduction	1	887.0×	0.002	GBF1
protein localization to Golgi apparatus	1	802.5×	0.002	GBF1
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	337.0×	0.005	GBF1
neutrophil chemotaxis	1	285.6×	0.005	GBF1
regulation of mitotic cell cycle	1	240.7×	0.006	GBF1
retrograde transport, endosome to Golgi	1	205.5×	0.006	GBF1
cellular response to virus	1	200.6×	0.006	GBF1
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.008	GBF1
Golgi organization	1	133.8×	0.008	GBF1
cilium assembly	1	73.6×	0.014	GBF1
protein transport	1	43.9×	0.023	GBF1

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
GBF1	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	GBF1

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)
GBF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.