Charcot-Marie-tooth disease, axonal, type 2JJ

Summary

Charcot-Marie-tooth disease, axonal, type 2JJ (MONDO:0976227) 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, axonal, type 2JJ
Mondo ID	MONDO:0976227
OMIM	621095
DOID	DOID:0051043
UMLS	C5975629
MedGen	1875159
GARD	0027433
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 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, axonal, type 2JJ

Related subtypes (23): Charcot-Marie-Tooth disease, Guadalajara neuronal type, Charcot-Marie-Tooth disease with ptosis and parkinsonism, Charcot-Marie-Tooth disease type 3, neuronopathy, distal hereditary motor, autosomal dominant 1, neuropathy, hereditary motor and sensory, type 6A, Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;, demyelinating hereditary motor and sensory neuropathy, intermediate Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease type X, Charcot-Marie-Tooth disease type 4, Charcot-Marie-Tooth disease type 1, Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1, Charcot-Marie-Tooth disease, axonal, type 2FF, Charcot-Marie-Tooth disease, axonal, Type 2HH, Charcot-Marie-Tooth disease, demyelinating, IIA 1I, Charcot-Marie-Tooth disease, demyelinating, IIA 1H, Charcot-Marie-Tooth disease, axonal, IIa 2II, Charcot-Marie-Tooth disease, demyelinating, type 1G, Charcot-Marie-Tooth disease, demyelinating, type 1J, Charcot-Marie-Tooth disease, axonal, type 2KK, Charcot-Marie-Tooth disease, axonal, type 2LL, charcot-marie-tooth disease, axonal, type 2MM

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 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3603261	BAG3, PRO209SER	BAG3	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 2 · 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
BAG3	Limited	Autosomal dominant	Charcot-Marie-tooth disease, axonal, type 2JJ	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BAG3	Orphanet:154	Familial isolated dilated cardiomyopathy
BAG3	Orphanet:199340	BAG3-related myofibrillar myopathy

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
BAG3	HGNC:939	ENSG00000151929	O95817	BAG family molecular chaperone regulator 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BAG3	BAG family molecular chaperone regulator 3	Co-chaperone and adapter protein that connects different classes of molecular chaperones including heat shock proteins 70 (HSP70s), e.g.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BAG3	Scaffold/PPI	no		WW_dom, BAG_domain, WW_dom_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
body of tongue	1
gastrocnemius	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BAG3	286	ubiquitous	marker	gastrocnemius, skeletal muscle tissue of rectus abdominis, body of tongue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BAG3	4,957

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BAG3	O95817	57.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cellular response to heat stress	1	393.8×	0.010	BAG3
Regulation of HSF1-mediated heat shock response	1	139.3×	0.014	BAG3
Cellular responses to stress	1	36.8×	0.032	BAG3
Cellular responses to stimuli	1	31.5×	0.032	BAG3

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
striated muscle cell apoptotic process	1	16852.0×	0.001	BAG3
negative regulation of striated muscle cell apoptotic process	1	5617.3×	0.001	BAG3
protein transport along microtubule	1	5617.3×	0.001	BAG3
chaperone-mediated autophagy	1	2808.7×	0.001	BAG3
aggresome assembly	1	2808.7×	0.001	BAG3
obsolete negative regulation of protein targeting to mitochondrion	1	2808.7×	0.001	BAG3
positive regulation of aggrephagy	1	2808.7×	0.001	BAG3
cellular response to unfolded protein	1	991.3×	0.003	BAG3
positive regulation of protein export from nucleus	1	802.5×	0.003	BAG3
muscle cell cellular homeostasis	1	648.1×	0.003	BAG3
spinal cord development	1	510.7×	0.004	BAG3
extrinsic apoptotic signaling pathway in absence of ligand	1	468.1×	0.004	BAG3
positive regulation of protein import into nucleus	1	421.3×	0.004	BAG3
extrinsic apoptotic signaling pathway via death domain receptors	1	401.2×	0.004	BAG3
cellular response to heat	1	343.9×	0.004	BAG3
autophagosome assembly	1	224.7×	0.005	BAG3
cellular response to mechanical stimulus	1	216.1×	0.005	BAG3
protein folding	1	103.4×	0.011	BAG3
protein stabilization	1	66.9×	0.016	BAG3
negative regulation of apoptotic process	1	34.8×	0.029	BAG3

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
BAG3	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
BAG3	8	Binding:8

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	BAG3

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)
BAG3	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.