Charcot-Marie-Tooth disease type 2R

Summary

Charcot-Marie-Tooth disease type 2R (MONDO:0014208) is a disease caused by TRIM2 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TRIM2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 466
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 2R
Mondo ID	MONDO:0014208
OMIM	615490
Orphanet	397968
DOID	DOID:0110161
UMLS	C3809655
MedGen	815985
GARD	0012451
Is cancer (heuristic)	no

Also known as: Charcot-Marie-Tooth disease type 2 caused by mutation in TRIM2 · Charcot-Marie-Tooth disease type 2R · Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2R · Charcot-Marie-Tooth disease, axonal, type 2R · Charcot-Marie-Tooth disease, type 2R · CMT2R · TRIM2 Charcot-Marie-Tooth disease type 2

Data availability: 466 ClinVar variants · 4 GenCC gene-disease records.

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 2R

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 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, Charcot-Marie-Tooth disease type 2B5, 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

ClinVar germline variants

466 retrieved; paginated sample, class counts are floors:

231 uncertain significance, 217 likely benign, 8 benign, 5 conflicting classifications of pathogenicity, 3 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4734104	NM_015271.5(TRIM2):c.232_233dup (p.Pro79fs)	TRIM2	Pathogenic	criteria provided, single submitter
83303	NM_015271.5(TRIM2):c.761A>T (p.Glu254Val)	TRIM2	Pathogenic	no assertion criteria provided
83304	NM_015271.5(TRIM2):c.1781del (p.Lys594fs)	TRIM2	Pathogenic	no assertion criteria provided
243075	NM_015271.5(TRIM2):c.2000A>C (p.Asp667Ala)	TRIM2	Likely pathogenic	criteria provided, single submitter
4813761	NM_015271.5(TRIM2):c.1968dup (p.Val657fs)	TRIM2	Likely pathogenic	criteria provided, single submitter
1118482	NM_015271.5(TRIM2):c.282C>T (p.Ser94=)	TRIM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
474608	NM_015271.5(TRIM2):c.2197A>G (p.Ile733Val)	TRIM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
474620	NM_015271.5(TRIM2):c.1077C>T (p.Gly359=)	TRIM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
838972	NM_015271.5(TRIM2):c.2265G>A (p.Val755=)	TRIM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
859978	NM_015271.5(TRIM2):c.417G>A (p.Ala139=)	TRIM2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
474600	NC_000004.12:g.(?153204511)(153276150_?)del	LOC129993256	Uncertain significance	criteria provided, single submitter
1000483	NM_015271.5(TRIM2):c.583C>A (p.Gln195Lys)	TRIM2	Uncertain significance	criteria provided, single submitter
1010038	NM_015271.5(TRIM2):c.1196C>A (p.Pro399His)	TRIM2	Uncertain significance	criteria provided, single submitter
1018394	NM_015271.5(TRIM2):c.1565C>G (p.Ser522Cys)	TRIM2	Uncertain significance	criteria provided, single submitter
1030179	NM_015271.5(TRIM2):c.818A>G (p.Gln273Arg)	TRIM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035966	NM_015271.5(TRIM2):c.529C>G (p.Pro177Ala)	TRIM2	Uncertain significance	criteria provided, single submitter
1037263	NM_015271.5(TRIM2):c.1609G>A (p.Val537Met)	TRIM2	Uncertain significance	criteria provided, single submitter
1038417	NM_015271.5(TRIM2):c.511G>A (p.Gly171Arg)	TRIM2	Uncertain significance	criteria provided, single submitter
1041430	NM_015271.5(TRIM2):c.2132T>C (p.Ile711Thr)	TRIM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1046673	NM_015271.5(TRIM2):c.272G>T (p.Arg91Leu)	TRIM2	Uncertain significance	criteria provided, single submitter
1051668	NM_015271.5(TRIM2):c.1198G>A (p.Asp400Asn)	TRIM2	Uncertain significance	criteria provided, single submitter
1053003	NM_015271.5(TRIM2):c.416C>T (p.Ala139Val)	TRIM2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1177505	NM_015271.5(TRIM2):c.1663C>T (p.Arg555Cys)	TRIM2	Uncertain significance	criteria provided, single submitter
1331025	NM_015271.5(TRIM2):c.1903A>C (p.Ile635Leu)	TRIM2	Uncertain significance	criteria provided, single submitter
1348583	NM_015271.5(TRIM2):c.166C>T (p.Arg56Trp)	TRIM2	Uncertain significance	criteria provided, single submitter
1354347	NM_015271.5(TRIM2):c.1910C>T (p.Thr637Ile)	TRIM2	Uncertain significance	criteria provided, single submitter
1360611	NM_015271.5(TRIM2):c.662C>T (p.Thr221Ile)	TRIM2	Uncertain significance	criteria provided, single submitter
1364772	NM_015271.5(TRIM2):c.1391G>A (p.Arg464His)	TRIM2	Uncertain significance	criteria provided, single submitter
1367046	NM_015271.5(TRIM2):c.1897G>A (p.Gly633Arg)	TRIM2	Uncertain significance	criteria provided, single submitter
1367151	NM_015271.5(TRIM2):c.506C>T (p.Thr169Met)	TRIM2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
TRIM2	Strong	Autosomal recessive	Charcot-Marie-Tooth disease type 2R	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRIM2	Orphanet:397968	Charcot-Marie-Tooth disease type 2R

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
TRIM2	HGNC:15974	ENSG00000109654	Q9C040	Tripartite motif-containing protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIM2	Tripartite motif-containing protein 2	UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRIM2	Transcription factor	no		Znf_B-box, NHL_repeat, Filamin/ABP280_rpt

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
corpus callosum	1
dorsal motor nucleus of vagus nerve	1
inferior olivary complex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIM2	284	ubiquitous	marker	inferior olivary complex, dorsal motor nucleus of vagus nerve, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRIM2	1,275

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRIM2	Q9C040	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Interferon gamma signaling	1	125.5×	0.008	TRIM2

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
regulation of neuron apoptotic process	1	702.2×	0.006	TRIM2
cellular response to leukemia inhibitory factor	1	159.0×	0.012	TRIM2
protein polyubiquitination	1	115.4×	0.012	TRIM2
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.019	TRIM2

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
TRIM2	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	TRIM2

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)
TRIM2	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