Charcot-Marie-Tooth disease type 4J

Summary

Charcot-Marie-Tooth disease type 4J (MONDO:0012640) is a disease caused by FIG4 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FIG4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 112
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		18	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 4J
Mondo ID	MONDO:0012640
MeSH	C566984
OMIM	611228
Orphanet	139515
DOID	DOID:0110184
ICD-11	905681283
NCIT	C134954
SNOMED CT	720638000
UMLS	C1970011
MedGen	370808
GARD	0012443
Is cancer (heuristic)	no

Also known as: Charcot-Marie-Tooth disease type 4 caused by mutation in FIG4 · Charcot-Marie-Tooth disease, type 4J · CMT4J · FIG4 Charcot-Marie-Tooth disease type 4

Data availability: 112 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.

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 4 › Charcot-Marie-Tooth disease type 4J

Related subtypes (11): Charcot-Marie-Tooth disease type 4A, Charcot-Marie-Tooth disease type 4B1, Charcot-Marie-Tooth disease type 4D, Charcot-Marie-Tooth disease type 4C, Charcot-Marie-Tooth disease type 4B2, Charcot-Marie-Tooth disease type 4E, Charcot-Marie-Tooth disease type 4G, Charcot-Marie-Tooth disease type 4H, Charcot-Marie-Tooth disease type 4F, Charcot-Marie-Tooth disease type 4B3, Charcot-Marie-Tooth disease type 4K

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

112 retrieved; paginated sample, class counts are floors:

40 uncertain significance, 20 conflicting classifications of pathogenicity, 16 pathogenic, 12 benign, 10 benign/likely benign, 8 pathogenic/likely pathogenic, 5 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299662	NM_014845.6(FIG4):c.2174dup (p.Leu726fs)	FIG4	Pathogenic	criteria provided, single submitter
1721	NM_014845.6(FIG4):c.122T>C (p.Ile41Thr)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1722	NM_014845.6(FIG4):c.294del (p.Phe98fs)	FIG4	Pathogenic	criteria provided, single submitter
1723	NM_014845.6(FIG4):c.547C>T (p.Arg183Ter)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1724	NM_014845.6(FIG4):c.1043_1050del (p.Asp348fs)	FIG4	Pathogenic	criteria provided, single submitter
217228	NM_014845.6(FIG4):c.1141C>T (p.Arg381Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
2440262	NM_014845.6(FIG4):c.773C>G (p.Ser258Ter)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
246120	NM_014845.6(FIG4):c.2459+1G>A	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
254668	NM_014845.6(FIG4):c.759del (p.Phe254fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
355036	NM_014845.6(FIG4):c.262C>T (p.Arg88Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
355040	NM_014845.6(FIG4):c.1666dup (p.Thr556fs)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
419553	NM_014845.6(FIG4):c.1373dup (p.Leu458fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
420149	NM_014845.6(FIG4):c.737G>A (p.Trp246Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
447336	NM_014845.6(FIG4):c.2467C>T (p.Gln823Ter)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488991	NM_014845.6(FIG4):c.793C>T (p.Arg265Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
50995	NM_014845.6(FIG4):c.831_838del (p.Lys278fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
567685	NM_014845.6(FIG4):c.2386C>T (p.Gln796Ter)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
637085	NM_014845.6(FIG4):c.1149_1150delinsT (p.Lys383fs)	FIG4	Pathogenic	criteria provided, single submitter
637086	NM_014845.6(FIG4):c.1986dup (p.Lys663fs)	FIG4	Pathogenic	criteria provided, single submitter
637500	NM_014845.6(FIG4):c.2299dup (p.Glu767fs)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
637527	NM_014845.6(FIG4):c.1675A>T (p.Lys559Ter)	FIG4	Pathogenic	criteria provided, single submitter
637528	NM_014845.6(FIG4):c.877-2A>C	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
638361	NM_014845.6(FIG4):c.290-2A>G	FIG4	Pathogenic	criteria provided, single submitter
916868	NM_014845.6(FIG4):c.2247dup (p.Ser750fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
156016	NM_014845.6(FIG4):c.290-2A>T	FIG4	Likely pathogenic	criteria provided, single submitter
1710074	NM_014845.6(FIG4):c.446+2T>C	FIG4	Likely pathogenic	criteria provided, single submitter
3382272	NM_014845.6(FIG4):c.1389-2A>G	FIG4	Likely pathogenic	criteria provided, single submitter
3892147	NM_014845.6(FIG4):c.1150A>T (p.Arg384Ter)	FIG4	Likely pathogenic	criteria provided, single submitter
4074741	NM_014845.6(FIG4):c.1434+1G>T	FIG4	Likely pathogenic	criteria provided, single submitter
156015	NM_014845.6(FIG4):c.904G>A (p.Glu302Lys)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 4 · 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
FIG4	Definitive	Autosomal recessive	Charcot-Marie-Tooth disease type 4J	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FIG4	Orphanet:139515	Charcot-Marie-Tooth disease type 4J
FIG4	Orphanet:208441	Bilateral parasagittal parieto-occipital polymicrogyria
FIG4	Orphanet:3472	Yunis-Varon syndrome
FIG4	Orphanet:803	Amyotrophic lateral sclerosis

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
FIG4	HGNC:16873	ENSG00000112367	Q92562	Polyphosphoinositide phosphatase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FIG4	Polyphosphoinositide phosphatase	Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).

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)
FIG4	Other/Unknown	no		SAC_dom, Fig4-like

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
endothelial cell	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FIG4	295	ubiquitous	marker	middle temporal gyrus, endothelial cell, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FIG4	1,257

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FIG4	Q92562	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Synthesis of PIPs at the late endosome membrane	1	951.7×	0.002	FIG4
Synthesis of PIPs at the early endosome membrane	1	713.8×	0.002	FIG4
Synthesis of PIPs at the Golgi membrane	1	634.4×	0.002	FIG4

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
negative regulation of myelination	1	1872.4×	0.002	FIG4
myelin assembly	1	1872.4×	0.002	FIG4
vacuole organization	1	1532.0×	0.002	FIG4
pigmentation	1	702.2×	0.003	FIG4
phosphatidylinositol dephosphorylation	1	648.1×	0.003	FIG4
phosphatidylinositol biosynthetic process	1	366.4×	0.004	FIG4
neuron development	1	255.3×	0.005	FIG4
locomotory behavior	1	179.3×	0.006	FIG4
positive regulation of neuron projection development	1	137.0×	0.007	FIG4

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
FIG4	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	FIG4

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)
FIG4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07447557	PHASE1/PHASE2	NOT_YET_RECRUITING	Study of Intrathecal ELP-02 for Charcot-Marie-Tooth Disease Type 4J (CMT4J)