dentin dysplasia, type IB

Summary

dentin dysplasia, type IB (MONDO:0700387) 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	dentin dysplasia, type IB
Mondo ID	MONDO:0700387
OMIM	621440
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 › dentin dysplasia type I › dentin dysplasia, type IB

Related subtypes (1): atypical dentin dysplasia due to SMOC2 deficiency

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
4538522	VPS4B, IVS7, C-G, +46	VPS4B	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VPS4B	Orphanet:99789	Dentin dysplasia type I

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
VPS4B	HGNC:10895	ENSG00000119541	O75351	Vacuolar protein sorting-associated protein 4B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VPS4B	Vacuolar protein sorting-associated protein 4B	Involved in late steps of the endosomal multivesicular bodies (MVB) pathway.

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)
VPS4B	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS

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
epithelium of esophagus	1
esophagus squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VPS4B	293	ubiquitous	marker	esophagus squamous epithelium, epithelium of esophagus, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VPS4B	1,743

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VPS4B	O75351	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Budding and maturation of HIV virion	1	407.9×	0.003	VPS4B
Endosomal Sorting Complex Required For Transport (ESCRT)	1	368.4×	0.003	VPS4B

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
protein depolymerization	1	16852.0×	0.001	VPS4B
late endosomal microautophagy	1	8426.0×	0.001	VPS4B
late endosome to lysosome transport via multivesicular body sorting pathway	1	8426.0×	0.001	VPS4B
negative regulation of exosomal secretion	1	4213.0×	0.002	VPS4B
obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	1	3370.4×	0.002	VPS4B
endosome to lysosome transport via multivesicular body sorting pathway	1	2808.7×	0.002	VPS4B
response to lipid	1	2407.4×	0.002	VPS4B
positive regulation of centriole elongation	1	2407.4×	0.002	VPS4B
ESCRT III complex disassembly	1	1685.2×	0.002	VPS4B
vacuole organization	1	1532.0×	0.002	VPS4B
establishment of blood-brain barrier	1	1404.3×	0.002	VPS4B
viral budding from plasma membrane	1	1296.3×	0.002	VPS4B
positive regulation of exosomal secretion	1	1123.5×	0.002	VPS4B
nuclear membrane reassembly	1	991.3×	0.002	VPS4B
viral budding via host ESCRT complex	1	802.5×	0.002	VPS4B
multivesicular body sorting pathway	1	802.5×	0.002	VPS4B
regulation of centrosome duplication	1	732.7×	0.002	VPS4B
cholesterol transport	1	732.7×	0.002	VPS4B
midbody abscission	1	732.7×	0.002	VPS4B
regulation of mitotic spindle assembly	1	732.7×	0.002	VPS4B
positive regulation of G2/M transition of mitotic cell cycle	1	601.9×	0.003	VPS4B
plasma membrane repair	1	581.1×	0.003	VPS4B
nucleus organization	1	561.7×	0.003	VPS4B
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	1	543.6×	0.003	VPS4B
multivesicular body assembly	1	526.6×	0.003	VPS4B
membrane fission	1	411.0×	0.003	VPS4B
mitotic metaphase chromosome alignment	1	383.0×	0.003	VPS4B
autophagosome maturation	1	351.1×	0.004	VPS4B
endosomal transport	1	244.2×	0.005	VPS4B
macroautophagy	1	240.7×	0.005	VPS4B

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
VPS4B	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
VPS4B	5	Binding:5

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	VPS4B

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)
VPS4B	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.