Charcot-Marie-Tooth disease type 4B2

Summary

Charcot-Marie-Tooth disease type 4B2 (MONDO:0011475) is a disease caused by SBF2 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: SBF2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 211
• Phenotypes (HPO): 40
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001760	Abnormal foot morphology	Very frequent (80-99%)
HP:0002522	Areflexia of lower limbs	Very frequent (80-99%)
HP:0004336	Myelin outfoldings	Very frequent (80-99%)
HP:0007010	Poor fine motor coordination	Very frequent (80-99%)
HP:0007230	Decreased distal sensory nerve action potential	Very frequent (80-99%)
HP:0007340	Lower limb muscle weakness	Very frequent (80-99%)
HP:0008959	Distal upper limb muscle weakness	Very frequent (80-99%)
HP:0009053	Distal lower limb muscle weakness	Very frequent (80-99%)
HP:0000501	Glaucoma	Frequent (30-79%)
HP:0001605	Vocal cord paralysis	Frequent (30-79%)
HP:0001618	Dysphonia	Frequent (30-79%)
HP:0001761	Pes cavus	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002751	Kyphoscoliosis	Frequent (30-79%)
HP:0002936	Distal sensory impairment	Frequent (30-79%)
HP:0008994	Proximal muscle weakness in lower limbs	Frequent (30-79%)
HP:0012046	Areflexia of upper limbs	Frequent (30-79%)
HP:0000183	Tongue muscle weakness	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000557	Buphthalmos	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0001026	Penetrating foot ulcers	Occasional (5-29%)
HP:0001087	Developmental glaucoma	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001763	Pes planus	Occasional (5-29%)
HP:0002093	Respiratory insufficiency	Occasional (5-29%)
HP:0002540	Inability to walk	Occasional (5-29%)
HP:0002792	Reduced vital capacity	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0008997	Proximal muscle weakness in upper limbs	Occasional (5-29%)
HP:0012473	Tongue atrophy	Occasional (5-29%)
HP:0030051	Tip-toe gait	Occasional (5-29%)
HP:0030237	Hand muscle weakness	Occasional (5-29%)
HP:0030319	Weakness of facial musculature	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Charcot-Marie-Tooth disease type 4B2
Mondo ID	MONDO:0011475
MeSH	C535421
OMIM	604563
Orphanet	99956
DOID	DOID:0110190
ICD-11	393759720
SNOMED CT	715800000
UMLS	C1858278
MedGen	346869
GARD	0009200
Is cancer (heuristic)	no

Also known as: Charcot Marie Tooth disease type 4B2 · Charcot-Marie-Tooth disease type 4 caused by mutation in SBF2 · Charcot-Marie-Tooth disease type 4B2 · Charcot-Marie-Tooth disease, type 4B2 · CMT 4B2 · CMT4B2 · SBF2 Charcot-Marie-Tooth disease type 4

Data availability: 211 ClinVar variants · 5 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 4 › Charcot-Marie-Tooth disease type 4B2

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 4E, Charcot-Marie-Tooth disease type 4G, Charcot-Marie-Tooth disease type 4H, Charcot-Marie-Tooth disease type 4J, 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

211 retrieved; paginated sample, class counts are floors:

100 uncertain significance, 44 conflicting classifications of pathogenicity, 20 benign, 15 benign/likely benign, 11 likely benign, 10 likely pathogenic, 9 pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323552	NM_030962.4(SBF2):c.2055T>G (p.Tyr685Ter)	LOC101928008	Pathogenic	criteria provided, multiple submitters, no conflicts
1686137	NM_030962.4(SBF2):c.4877del (p.Pro1626fs)	SBF2	Pathogenic	criteria provided, single submitter
2909	NM_030962.4(SBF2):c.1088_1296+646del	SBF2	Pathogenic	no assertion criteria provided
2910	NM_030962.4(SBF2):c.2875C>T (p.Gln959Ter)	SBF2	Pathogenic	no assertion criteria provided
2911	NM_030962.4(SBF2):c.3586C>T (p.Arg1196Ter)	SBF2	Pathogenic	criteria provided, single submitter
2912	NM_030962.4(SBF2):c.1459C>T (p.Arg487Ter)	SBF2	Pathogenic	criteria provided, multiple submitters, no conflicts
3236699	NM_030962.4(SBF2):c.620G>T (p.Gly207Val)	SBF2	Pathogenic	criteria provided, single submitter
3239361	NM_030962.4(SBF2):c.1601-2A>G	SBF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3896982	NM_030962.4(SBF2):c.1024C>T (p.Arg342Ter)	SBF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
637855	NM_030962.4(SBF2):c.1066C>T (p.Arg356Ter)	SBF2	Pathogenic	criteria provided, multiple submitters, no conflicts
802656	NM_030962.4(SBF2):c.5203C>T (p.Gln1735Ter)	SBF2-AS1	Pathogenic	criteria provided, single submitter
2665001	NM_030962.4(SBF2):c.2329del (p.Trp777fs)	LOC101928008	Likely pathogenic	criteria provided, single submitter
1184512	NM_030962.4(SBF2):c.2215G>A (p.Glu739Lys)	SBF2	Likely pathogenic	no assertion criteria provided
2505355	NM_030962.4(SBF2):c.815dup (p.Ile273fs)	SBF2	Likely pathogenic	criteria provided, single submitter
3393149	NM_030962.4(SBF2):c.4444-1G>C	SBF2	Likely pathogenic	criteria provided, single submitter
3731532	NM_030962.4(SBF2):c.1902_1905dup (p.Pro636fs)	SBF2	Likely pathogenic	criteria provided, single submitter
3896983	NM_030962.4(SBF2):c.340_341dup (p.Val115fs)	SBF2	Likely pathogenic	criteria provided, single submitter
856411	NM_030962.4(SBF2):c.3653-1G>A	SBF2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
916834	NM_030962.4(SBF2):c.1395+1G>A	SBF2	Likely pathogenic	criteria provided, single submitter
930658	NM_030962.4(SBF2):c.4331_4332del (p.Lys1444fs)	SBF2	Likely pathogenic	criteria provided, single submitter
982777	NM_030962.4(SBF2):c.161G>A (p.Trp54Ter)	SBF2	Likely pathogenic	criteria provided, single submitter
194989	NM_030962.4(SBF2):c.2323G>A (p.Gly775Ser)	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
246062	NM_030962.4(SBF2):c.3290C>A (p.Thr1097Asn)	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306596	NM_030962.4(SBF2):c.2598G>A (p.Pro866=)	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306599	NM_030962.4(SBF2):c.2397A>G (p.Thr799=)	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306600	NM_030962.4(SBF2):c.2197C>G (p.Gln733Glu)	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
306601	NM_030962.4(SBF2):c.2100+7G>A	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
581159	NM_030962.4(SBF2):c.2081C>T (p.Ala694Val)	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881443	NM_030962.4(SBF2):c.2610+11A>G	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
883050	NM_030962.4(SBF2):c.1861-6T>C	LOC101928008	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SBF2	Definitive	Autosomal recessive	Charcot-Marie-Tooth disease type 4B2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SBF2	Orphanet:99956	Charcot-Marie-Tooth disease type 4B2

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SBF2	HGNC:2135	ENSG00000133812	Q86WG5	Myotubularin-related protein 13	gencc,clinvar
SBF2-AS1	HGNC:27438	ENSG00000246273		SBF2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SBF2	Myotubularin-related protein 13	Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Phosphatase	1	42.0×	0.047
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SBF2	Phosphatase	yes		cDENN_dom, PH_domain, GRAM
SBF2-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
colonic epithelium	1
epithelial cell of pancreas	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SBF2	257	ubiquitous	marker	epithelial cell of pancreas, colonic epithelium, calcaneal tendon
SBF2-AS1	165	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SBF2	994
SBF2-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SBF2	Q86WG5	73.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 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
Rab regulation of trafficking	1	368.4×	0.011	SBF2
PI Metabolism	1	356.9×	0.011	SBF2
Synthesis of PIPs at the plasma membrane	1	211.5×	0.011	SBF2
Phospholipid metabolism	1	200.3×	0.011	SBF2
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.015	SBF2
Membrane Trafficking	1	37.1×	0.036	SBF2
Vesicle-mediated transport	1	34.8×	0.036	SBF2
Metabolism of lipids	1	31.6×	0.036	SBF2
Metabolism	1	11.6×	0.086	SBF2

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
myelination	1	251.5×	0.008	SBF2
autophagy	1	110.1×	0.009	SBF2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SBF2	0	0
SBF2-AS1	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	1	SBF2
E	Difficult family or no structure, no drug	1	SBF2-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SBF2	0	—
SBF2-AS1	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