TUBB4B-related ciliopathy

Summary

TUBB4B-related ciliopathy (MONDO:1060115) is a disease caused by TUBB4B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TUBB4B (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	TUBB4B-related ciliopathy
Mondo ID	MONDO:1060115
GARD	0028151
Is cancer (heuristic)	no

Also known as: TUBB4B-related ciliopathy

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › TUBB4B-related ciliopathy

Related subtypes (35): Alstrom syndrome, Marden-Walker syndrome, nephronophthisis 1, Bardet-Biedl syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Jeune syndrome, Joubert syndrome, Meckel syndrome, retinal ciliopathy, oculocerebrodental syndrome, CEP290-related ciliopathy, IFT140-related recessive ciliopathy, BBS9-related ciliopathy, BBS10-related ciliopathy, CEP164-related ciliopathy, CFAP418-related ciliopathy, WDPCP-related ciliopathy, SDCCAG8-related ciliopathy, KIF7-related ciliopathy, Alsahan-Harris syndrome, OFD1-related ciliopathy, BBS7-related ciliopathy, BBS1-related ciliopathy, BBS4-related ciliopathy, BBS12-related ciliopathy, LZTFL1-related ciliopathy, BBS5-related ciliopathy, BBS2-related ciliopathy, TTC8-related ciliopathy, MKKS-related ciliopathy, ARL6-related ciliopathy, MKS1-related ciliopathy, INTU-related skeletal ciliopathy, ciliopathy-IFT74

Subtypes (1): Leber congenital amaurosis with early-onset deafness

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
TUBB4B	Strong	Autosomal dominant	TUBB4B-related ciliopathy	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBB4B	Orphanet:65	Leber congenital amaurosis

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
TUBB4B	HGNC:20771	ENSG00000188229	P68371	Tubulin beta-4B chain	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBB4B	Tubulin beta-4B chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

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)
TUBB4B	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase

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
bronchial epithelial cell	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBB4B	295	ubiquitous	marker	left testis, right testis, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB4B	1,158

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUBB4B	P68371	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 95. 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	543.8×	0.016	TUBB4B
Transport of connexons to the plasma membrane	1	543.8×	0.016	TUBB4B
Gap junction trafficking and regulation	1	475.8×	0.016	TUBB4B
Gap junction trafficking	1	475.8×	0.016	TUBB4B
Post-chaperonin tubulin folding pathway	1	475.8×	0.016	TUBB4B
Formation of tubulin folding intermediates by CCT/TriC	1	423.0×	0.016	TUBB4B
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	407.9×	0.016	TUBB4B
Prefoldin mediated transfer of substrate to CCT/TriC	1	393.8×	0.016	TUBB4B
Activation of AMPK downstream of NMDARs	1	380.7×	0.016	TUBB4B
RHO GTPases activate IQGAPs	1	346.1×	0.016	TUBB4B
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.016	TUBB4B
HCMV Infection	1	326.3×	0.016	TUBB4B
Chaperonin-mediated protein folding	1	300.5×	0.016	TUBB4B
Gap junction assembly	1	292.8×	0.016	TUBB4B
Nuclear Envelope (NE) Reassembly	1	292.8×	0.016	TUBB4B
Selective autophagy	1	278.5×	0.016	TUBB4B
Protein folding	1	259.6×	0.016	TUBB4B
Centrosome maturation	1	253.8×	0.016	TUBB4B
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.016	TUBB4B
Cargo trafficking to the periciliary membrane	1	248.3×	0.016	TUBB4B
Aggrephagy	1	248.3×	0.016	TUBB4B
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.016	TUBB4B
Recycling pathway of L1	1	223.9×	0.016	TUBB4B
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.016	TUBB4B
Post NMDA receptor activation events	1	203.9×	0.016	TUBB4B
Intraflagellar transport	1	200.3×	0.016	TUBB4B
Antimicrobial mechanism of IFN-stimulated genes	1	196.9×	0.016	TUBB4B
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.016	TUBB4B
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.016	TUBB4B
Signaling by Hedgehog	1	184.2×	0.016	TUBB4B

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
natural killer cell mediated cytotoxicity	1	432.1×	0.009	TUBB4B
mitotic cell cycle	1	133.8×	0.009	TUBB4B
microtubule cytoskeleton organization	1	121.2×	0.009	TUBB4B
flagellated sperm motility	1	117.0×	0.009	TUBB4B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TUBB4B	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB4B	22	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB4B
VINBLASTINE	4	TUBB4B
LEVOFLOXACIN ANHYDROUS	4	TUBB4B
DOCETAXEL	4	TUBB4B
NOSCAPINE	4	TUBB4B
VINBLASTINE SULFATE	4	TUBB4B
PACLITAXEL	4	TUBB4B
LEVOFLOXACIN	4	TUBB4B
VINORELBINE	4	TUBB4B
TIRBANIBULIN	4	TUBB4B
PODOFILOX	4	TUBB4B
VINCRISTINE	4	TUBB4B
DOCETAXEL ANHYDROUS	4	TUBB4B
PATUPILONE	3	TUBB4B
MOLIBRESIB	2	TUBB4B
ABT-751	2	TUBB4B
MAYTANSINE	2	TUBB4B
DOLASTATIN-10	2	TUBB4B
INDIBULIN	2	TUBB4B
PARBENDAZOLE	2	TUBB4B
NOCODAZOLE	2	TUBB4B
COMBRETASTATIN	1	TUBB4B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TUBB4B	1,769	Binding:1726, Functional:37, ADMET:6

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TUBB4B	1,769

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

22 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.

Compound	Max phase	Cohort target (bioactivity)
COLCHICINE	4	TUBB4B
VINBLASTINE	4	TUBB4B
LEVOFLOXACIN ANHYDROUS	4	TUBB4B
DOCETAXEL	4	TUBB4B
NOSCAPINE	4	TUBB4B
VINBLASTINE SULFATE	4	TUBB4B
PACLITAXEL	4	TUBB4B
LEVOFLOXACIN	4	TUBB4B
VINORELBINE	4	TUBB4B
TIRBANIBULIN	4	TUBB4B
PODOFILOX	4	TUBB4B
VINCRISTINE	4	TUBB4B
DOCETAXEL ANHYDROUS	4	TUBB4B
PATUPILONE	3	TUBB4B
MOLIBRESIB	2	TUBB4B
ABT-751	2	TUBB4B
MAYTANSINE	2	TUBB4B
DOLASTATIN-10	2	TUBB4B
INDIBULIN	2	TUBB4B
PARBENDAZOLE	2	TUBB4B
NOCODAZOLE	2	TUBB4B
COMBRETASTATIN	1	TUBB4B

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBB4B
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.