TUBB4B

Summary

TUBB4B (tubulin beta 4B class IVb, HGNC:20771) is a protein-coding gene on chromosome 9q34.3, encoding Tubulin beta-4B chain (P68371). Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. It is a selective cancer dependency (DepMap: 26.9% of cell lines).

Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in axonemal microtubule; intercellular bridge; and mitotic spindle. Implicated in Leber congenital amaurosis with early-onset deafness.

Source: NCBI Gene 10383 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TUBB4B-related ciliopathy (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 168 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 26.9% of screened cell lines
• MANE Select transcript: NM_006088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20771
Approved symbol	TUBB4B
Name	tubulin beta 4B class IVb
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	Beta2
Ensembl gene	ENSG00000188229
Ensembl biotype	protein_coding
OMIM	602660
Entrez	10383

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000340384, ENST00000604929, ENST00000938213, ENST00000938214, ENST00000938215

RefSeq mRNA: 1 — MANE Select: NM_006088 NM_006088

CCDS: CCDS7039

Canonical transcript exons

ENST00000340384 — 4 exons

Exon	Start	End
ENSE00001275234	137241287	137241417
ENSE00001418634	137242496	137243707
ENSE00002401408	137241911	137242021
ENSE00003598655	137241721	137241829

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 535.9003 / max 5481.7606, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99678	534.4925	1828
99680	1.4079	887

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.87	gold quality
right testis	UBERON:0004534	99.87	gold quality
bronchial epithelial cell	CL:0002328	99.82	gold quality
right uterine tube	UBERON:0001302	99.82	gold quality
epithelium of bronchus	UBERON:0002031	99.82	gold quality
bronchus	UBERON:0002185	99.75	gold quality
dorsal root ganglion	UBERON:0000044	99.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.57	gold quality
endometrium epithelium	UBERON:0004811	99.49	gold quality
substantia nigra pars compacta	UBERON:0001965	99.47	gold quality
ileal mucosa	UBERON:0000331	99.45	gold quality
orbitofrontal cortex	UBERON:0004167	99.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.40	gold quality
superior vestibular nucleus	UBERON:0007227	99.38	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.35	gold quality
postcentral gyrus	UBERON:0002581	99.34	gold quality
cervix squamous epithelium	UBERON:0006922	99.34	gold quality
entorhinal cortex	UBERON:0002728	99.32	gold quality
mucosa of transverse colon	UBERON:0004991	99.32	gold quality
pons	UBERON:0000988	99.31	gold quality
gingiva	UBERON:0001828	99.26	gold quality
parietal lobe	UBERON:0001872	99.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.26	gold quality
testis	UBERON:0000473	99.25	gold quality
gingival epithelium	UBERON:0001949	99.22	gold quality
superior frontal gyrus	UBERON:0002661	99.19	gold quality
adult organism	UBERON:0007023	99.19	gold quality
upper leg skin	UBERON:0004262	99.17	gold quality
caput epididymis	UBERON:0004358	99.14	gold quality
heart left ventricle	UBERON:0002084	99.08	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	4873.53
E-GEOD-134144	yes	2648.26
E-GEOD-124263	yes	2504.63
E-MTAB-7051	yes	2466.15
E-MTAB-8894	yes	2030.29
E-HCAD-56	yes	1718.19
E-MTAB-10290	yes	1384.01
E-MTAB-8142	yes	1317.09
E-HCAD-6	yes	1248.27
E-HCAD-13	yes	903.21
E-MTAB-6108	yes	659.80
E-CURD-114	yes	61.60
E-HCAD-10	yes	38.47
E-HCAD-1	yes	28.98
E-HCAD-5	yes	17.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting TUBB4B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-3138	98.41	67.53	744

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• transformation may lead to localization of beta(II)-tubulin in cell nuclei, serving an as yet unknown function, and that nuclear beta(II) may be a useful marker for detection of tumor cells (PMID:12037579)
• Normal and tumor breast tissues, before chemotherapy or radiation treatment, have broad distributions of beta-tubulin isotypes; furthermore, beta class II tubulin predominates in most breast tissues. (PMID:12927047)
• nuclear beta(II)-tubulin can modulate Notch signaling through interaction with notch1 receptor intracellular domain in cancer cells (PMID:15548702)
• Annexin II and beta(2)-tubulin down-regulation is important in nasopharyngeal carcinoma formation and may represent potential targets for further investigations. (PMID:18384219)
• Studies show that BFBTS bound and modified beta-tubulin at residue Cys12, forming beta-tubulin-SS-fluorobenzyl. (PMID:19996274)
• Data suggest that increased expression of hnRNP A1, Ezrin, tubulin beta-2C and Annexin A1 in SLNMM indicate a significantly elevated early colorectal cancer metastasis. (PMID:20872967)
• The results od this study found that betaI-tubulin protein expression was decreased in the anterior cingulate cortex and increased in the dorsolateral prefrontal cortex, but not changed in superior temporal gyrus or hippocampus in schizophrenia. (PMID:22264600)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• TUBB3 and TUBB4 are necessary for the transport and proper localization of N-cadherin within the plasma membrane. (PMID:28648944)
• The authors identified TUBB4B mutations as the cause of a previously unreported autosomal-dominant syndrome manifesting as early-onset and severe photoreceptor and cochlear cell loss. (PMID:29198720)
• The authors uncovered that decomposition of microtubules associated with the decrease of TUBB4B protein observed during epithelial-mesenchymal transition of colon cancer cells is critical for the regulation of cell polarization and control of vimentin localization and function. (PMID:31375012)
• TUBB4B gene mutation in Leber phenotype of congenital amaurosis syndrome associated with early-onset deafness. (PMID:35240325)
• P300 reduces TUBB4B expression to facilitate the biological process of migration and invasion of non-small cell lung cancer cells. (PMID:38636368)
• Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules. (PMID:38662826)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tubb2b	ENSDARG00000098591
mus_musculus	Tubb4b	ENSMUSG00000036752
rattus_norvegicus	Tubb4b	ENSRNOG00000010170
drosophila_melanogaster	betaTub56D	FBGN0284243
caenorhabditis_elegans		WBGENE00006538

Paralogs (23): TUBG2 (ENSG00000037042), TUBE1 (ENSG00000074935), TUBA3D (ENSG00000075886), TUBB1 (ENSG00000101162), TUBB4A (ENSG00000104833), TUBD1 (ENSG00000108423), TUBA1B (ENSG00000123416), TUBA4A (ENSG00000127824), TUBG1 (ENSG00000131462), TUBB2A (ENSG00000137267), TUBB2B (ENSG00000137285), TUBA3E (ENSG00000152086), TUBA1A (ENSG00000167552), TUBA1C (ENSG00000167553), TUBB8B (ENSG00000173213), TUBB6 (ENSG00000176014), TUBAL3 (ENSG00000178462), TUBA8 (ENSG00000183785), TUBB (ENSG00000196230), TUBA3C (ENSG00000198033), TUBA4B (ENSG00000243910), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin beta-4B chain — P68371 (reviewed: P68371)

Alternative names: Tubulin beta-2 chain, Tubulin beta-2C chain

All UniProt accessions (1): P68371

UniProt curated annotations — full annotation on UniProt →

Function. Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.

Subunit / interactions. Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Component of sperm flagellar doublet microtubules.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Ubiquitous.

Post-translational modifications. Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group. Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Glutamylation is also involved in cilia motility. Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally. Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.

Disease relevance. Leber congenital amaurosis with early-onset deafness (LCAEOD) [MIM:617879] An autosomal dominant disease characterized by severe retinal degeneration and sensorineural hearing loss. Symptoms occur within the first decade of life. Onset at birth is observed in some patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The highly acidic C-terminal region may bind cations such as calcium. The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.

Similarity. Belongs to the tubulin family.

RefSeq proteins (1): NP_006079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000217	Tubulin	Family
IPR002453	Beta_tubulin	Family
IPR003008	Tubulin_FtsZ_GTPase	Domain
IPR008280	Tub_FtsZ_C	Homologous_superfamily
IPR013838	Beta-tubulin_BS	Binding_site
IPR017975	Tubulin_CS	Conserved_site
IPR018316	Tubulin/FtsZ_2-layer-sand-dom	Domain
IPR023123	Tubulin_C	Homologous_superfamily
IPR036525	Tubulin/FtsZ_GTPase_sf	Homologous_superfamily
IPR037103	Tubulin/FtsZ-like_C	Homologous_superfamily

Pfam: PF00091, PF03953

UniProt features (60 total): helix 23, strand 15, binding site 9, modified residue 4, turn 3, sequence variant 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8SH7	ELECTRON MICROSCOPY	2.8
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1
7UN1	ELECTRON MICROSCOPY	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P68371-F1	92.36	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 144; 204; 226; 11; 69; 69; 138; 142; 143

Post-translational modifications (4): 55, 58, 172, 438

Function

Pathways and Gene Ontology

Reactome pathways

95 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-190840	Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane
R-HSA-190861	Gap junction assembly
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-389957	Prefoldin mediated transfer of substrate to CCT/TriC
R-HSA-389960	Formation of tubulin folding intermediates by CCT/TriC
R-HSA-389977	Post-chaperonin tubulin folding pathway
R-HSA-437239	Recycling pathway of L1
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5620920	Cargo trafficking to the periciliary membrane
R-HSA-5620924	Intraflagellar transport
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6798695	Neutrophil degranulation
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

MSigDB gene sets: 465 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, DAZARD_UV_RESPONSE_CLUSTER_G4, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, REACTOME_MEMBRANE_TRAFFICKING, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY

GO Biological Process (5): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), flagellated sperm motility (GO:0030317), natural killer cell mediated cytotoxicity (GO:0042267), microtubule-based process (GO:0007017)

GO Molecular Function (9): double-stranded RNA binding (GO:0003725), GTPase activity (GO:0003924), structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), MHC class I protein binding (GO:0042288), metal ion binding (GO:0046872), obsolete unfolded protein binding (GO:0051082), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (17): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), microtubule (GO:0005874), axonemal microtubule (GO:0005879), microtubule cytoskeleton (GO:0015630), azurophil granule lumen (GO:0035578), sperm flagellum (GO:0036126), intercellular bridge (GO:0045171), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686), extracellular vesicle (GO:1903561), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	3
Mitotic Prometaphase	2
Centrosome maturation	2
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	2
Membrane Trafficking	1
Transport of connexons to the plasma membrane	1
Gap junction trafficking	1
Adaptive Immune System	1
Mitotic Anaphase	1
G2/M Transition	1
Cellular responses to stress	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Protein folding	1
L1CAM interactions	1
Signaling by Hedgehog	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoskeleton organization	2
cytoskeleton	2
microtubule-based process	1
cell cycle	1
mitotic nuclear division	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
cellular process	1
RNA binding	1
ribonucleoside triphosphate phosphatase activity	1
structural molecule activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
MHC protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoplasmic microtubule	1
axoneme	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
9+2 motile cilium	1
extracellular vesicle	1
spindle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1
intraciliary transport particle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

410 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
CCT2	PPP6C	psi-mi:“MI:0914”(association)	0.640
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
MAP2K2	BAG2	psi-mi:“MI:0914”(association)	0.530
ARL2	TUBB4A	psi-mi:“MI:0914”(association)	0.530
CCT6A	TXNDC9	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ZMYM2	HDAC3	psi-mi:“MI:0914”(association)	0.480
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
TUBB4B	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
Tubb4b	MGST3	psi-mi:“MI:0915”(physical association)	0.400
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
TERF1	TUBB4B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (748): TUBB4B (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), TUBB4B (Reconstituted Complex), TUBB4B (Affinity Capture-MS), TUBB4B (Affinity Capture-MS), PHB2 (Co-fractionation), RPL10A (Co-fractionation), TUBB4B (Co-fractionation), TUBB4B (Co-fractionation), TUBB4B (Co-fractionation), TUBB4B (Co-fractionation)

ESM2 similar proteins: A6NNZ2, P02554, P04350, P07437, P09206, P09244, P09652, P11833, P11857, P14643, P18025, P30156, P61857, P61858, P68371, P69893, P69895, P69897, P83130, P99024, Q08115, Q13509, Q24560, Q27U48, Q2HJ81, Q2KJD0, Q2T9S0, Q3MHM5, Q3ZBU7, Q3ZCM7, Q4QRB4, Q4R4X8, Q5R943, Q60HC2, Q6GLE7, Q6P9T8, Q6VAF4, Q767L7, Q7JJU6, Q7KQL5

Diamond homologs: A0A644F0Y1, O04386, O17449, O49068, O93807, P04690, P05220, P07437, P10653, P10875, P10876, P10878, P11482, P11833, P12456, P14140, P14643, P18695, P20365, P22012, P22013, P22852, P23257, P23258, P23330, P25295, P31863, P32348, P32882, P32925, P34475, P34785, P34786, P34787, P38557, P38558, P40633, P40904, P41741, P42271

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUMA1	up-regulates	TUBB4B	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 250 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	10	32.0×	3e-11
Transport of connexons to the plasma membrane	10	32.0×	3e-11
Gap junction trafficking and regulation	10	28.0×	9e-11
Gap junction trafficking	10	28.0×	9e-11
Post-chaperonin tubulin folding pathway	9	25.2×	2e-09
Formation of tubulin folding intermediates by CCT/TriC	10	24.9×	3e-10
Activation of AMPK downstream of NMDARs	11	24.6×	5e-11
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	10	24.0×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance via telomerase	5	17.3×	1e-03
negative regulation of telomere maintenance via telomerase	5	17.3×	1e-03
protein refolding	5	14.7×	2e-03
cytoplasmic microtubule organization	8	13.0×	4e-05
positive regulation of telomere maintenance	5	12.0×	4e-03
insulin-like growth factor receptor signaling pathway	5	11.7×	5e-03
extrinsic apoptotic signaling pathway via death domain receptors	6	11.4×	2e-03
intrinsic apoptotic signaling pathway	6	10.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

168 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	27
Likely benign	110
Benign	16

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1806624	NM_006088.6(TUBB4B):c.776C>T (p.Pro259Leu)	Pathogenic
3366296	NM_006088.6(TUBB4B):c.775C>T (p.Pro259Ser)	Pathogenic
1488406	NM_006088.6(TUBB4B):c.76G>C (p.Asp26His)	Likely pathogenic
4830016	NM_006088.6(TUBB4B):c.1229A>T (p.Glu410Val)	Likely pathogenic

SpliceAI

235 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137241416:AG:A	donor_gain	1.0000
9:137241417:GG:G	donor_gain	1.0000
9:137241418:G:GA	donor_loss	1.0000
9:137241418:G:GG	donor_gain	1.0000
9:137241826:ACCGG:A	donor_loss	1.0000
9:137241827:CCGGT:C	donor_loss	1.0000
9:137241828:CGGT:C	donor_loss	1.0000
9:137241829:GGT:G	donor_loss	1.0000
9:137241830:G:GG	donor_gain	1.0000
9:137241830:GTG:G	donor_loss	1.0000
9:137241905:CCGCA:C	acceptor_loss	1.0000
9:137241908:CAGGC:C	acceptor_loss	1.0000
9:137241909:A:AC	acceptor_loss	1.0000
9:137241909:A:AG	acceptor_gain	1.0000
9:137241909:AGGC:A	acceptor_gain	1.0000
9:137241909:AGGCG:A	acceptor_gain	1.0000
9:137241910:G:GG	acceptor_gain	1.0000
9:137241910:GGCG:G	acceptor_gain	1.0000
9:137241910:GGCGG:G	acceptor_gain	1.0000
9:137242022:G:GG	donor_gain	1.0000
9:137242023:T:A	donor_loss	1.0000
9:137242490:TCACA:T	acceptor_loss	1.0000
9:137242494:A:T	acceptor_loss	1.0000
9:137242495:G:GA	acceptor_loss	1.0000
9:137241413:CCAAG:C	donor_gain	0.9900
9:137241414:CAAG:C	donor_gain	0.9900
9:137241415:AAG:A	donor_gain	0.9900
9:137241719:A:AG	acceptor_gain	0.9900
9:137241720:G:GG	acceptor_gain	0.9900
9:137241813:C:CG	donor_gain	0.9900

AlphaMissense

2966 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137241388:G:A	G10R	1.000
9:137241388:G:C	G10R	1.000
9:137241388:G:T	G10W	1.000
9:137241389:G:A	G10E	1.000
9:137241389:G:T	G10V	1.000
9:137241395:G:A	C12Y	1.000
9:137241396:C:G	C12W	1.000
9:137241397:G:C	G13R	1.000
9:137241397:G:T	G13C	1.000
9:137241398:G:A	G13D	1.000
9:137241398:G:T	G13V	1.000
9:137241402:C:A	N14K	1.000
9:137241402:C:G	N14K	1.000
9:137241409:G:C	G17R	1.000
9:137241724:T:A	W21R	1.000
9:137241724:T:C	W21R	1.000
9:137241943:G:C	D67H	1.000
9:137241944:A:C	D67A	1.000
9:137241944:A:T	D67V	1.000
9:137241947:T:A	L68Q	1.000
9:137241947:T:C	L68P	1.000
9:137241949:G:A	E69K	1.000
9:137242504:G:C	G96R	1.000
9:137242508:C:A	A97D	1.000
9:137242510:G:T	G98W	1.000
9:137242511:G:A	G98E	1.000
9:137242515:C:A	N99K	1.000
9:137242515:C:G	N99K	1.000
9:137242518:C:A	N100K	1.000
9:137242518:C:G	N100K	1.000

dbSNP variants (sampled 300 via entrez): RS1000115299 (9:137239658 A>G), RS1000179624 (9:137240683 G>A), RS1000442972 (9:137239433 G>A,C), RS1001153927 (9:137243959 G>C), RS1002038108 (9:137241137 T>A,C), RS1002451365 (9:137240948 A>C,T), RS1003119611 (9:137241701 C>A,T), RS1003382822 (9:137241275 A>C,G), RS1003390162 (9:137240307 A>C,T), RS1003578473 (9:137244176 A>G), RS1003631124 (9:137240458 C>T), RS1004221423 (9:137241405 A>C,G), RS1004527863 (9:137240874 C>G,T), RS1004964322 (9:137244088 C>T), RS1005215368 (9:137242393 T>A,G)

Disease associations

OMIM: gene MIM:602660 | disease phenotypes: MIM:617879

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis with early-onset deafness	Strong	Autosomal dominant
TUBB4B-related ciliopathy	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
TUBB4B-related ciliopathy	Definitive	AD

Mondo (2): Leber congenital amaurosis with early-onset deafness (MONDO:0060650), TUBB4B-related ciliopathy (MONDO:1060115)

Orphanet (0):

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000563	Keratoconus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000729	Autistic behavior
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001483	Eye poking
HP:0002084	Encephalocele
HP:0002269	Abnormality of neuronal migration
HP:0003577	Congenital onset
HP:0004374	Hemiplegia/hemiparesis
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007814	Retinal pigment epithelial mottling
HP:0008499	High hypermetropia
HP:0011463	Childhood onset
HP:0012426	Optic disc drusen

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1848 (SINGLE PROTEIN), CHEMBL2095182 (PROTEIN COMPLEX GROUP), CHEMBL3832942 (PROTEIN FAMILY), CHEMBL6066847 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,613,690 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL107	COLCHICINE	4	93,932
CHEMBL159	VINBLASTINE	4	412,636
CHEMBL33	LEVOFLOXACIN ANHYDROUS	4	43,403
CHEMBL3545252	DOCETAXEL	4	1,009
CHEMBL364713	NOSCAPINE	4	14,987
CHEMBL378544	VINBLASTINE SULFATE	4	32,829
CHEMBL428647	PACLITAXEL	4	332,542
CHEMBL5315124	LEVOFLOXACIN	4	189
CHEMBL553025	VINORELBINE	4	142,159
CHEMBL571546	TIRBANIBULIN	4	1,192
CHEMBL61	PODOFILOX	4	37,640
CHEMBL90555	VINCRISTINE	4	268,031
CHEMBL92	DOCETAXEL ANHYDROUS	4	196,686
CHEMBL94657	PATUPILONE	3	14,934
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL20684	ABT-751	2	2,238
CHEMBL292702	MAYTANSINE	2	9,300
CHEMBL39541	DOLASTATIN-10	2	1,380
CHEMBL49642	INDIBULIN	2	963
CHEMBL528271	PARBENDAZOLE	2	6,102
CHEMBL9514	NOCODAZOLE	2
CHEMBL246600	COMBRETASTATIN	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Tubulins

ChEMBL bioactivities

1174 potent at pChembl≥5 of 1325 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.26	IC50	0.0551	nM	CHEMBL5194719
9.75	IC50	0.176	nM	CHEMBL5203711
9.51	IC50	0.308	nM	VINORELBINE
9.30	IC50	0.5	nM	DOLASTATIN-10
8.92	IC50	1.2	nM	CHEMBL5169466
8.92	Kd	1.201	nM	CHEMBL5653589
8.92	ED50	1.201	nM	CHEMBL5653589
8.85	IC50	1.4	nM	CHEMBL4575066
8.74	IC50	1.8	nM	PATUPILONE
8.59	IC50	2.6	nM	CHEMBL2024544
8.52	Ki	3	nM	COMBRETASTATIN A4
8.52	IC50	3	nM	COMBRETASTATIN A4
8.52	IC50	3	nM	DOLASTATIN-10
8.52	Kd	3	nM	CHEMBL5410715
8.52	IC50	3	nM	COLCHICINE
8.46	IC50	3.5	nM	PATUPILONE
8.38	IC50	4.2	nM	CHEMBL5197739
8.27	IC50	5.4	nM	CHEMBL5280519
8.22	IC50	6	nM	CHEMBL498271
8.05	EC50	9	nM	COMBRETASTATIN A4
8.01	EC50	9.8	nM	COMBRETASTATIN A4
8.01	IC50	9.77	nM	CHEMBL4778826
8.00	Ki	10	nM	CHEMBL381852
8.00	IC50	10	nM	CHEMBL204241
7.96	Kd	11	nM	CHEMBL5611905
7.89	IC50	12.9	nM	COMBRETASTATIN A4
7.85	Kd	14	nM	MAYTANSINE
7.70	IC50	20	nM	CHEMBL2369093
7.70	Ki	20	nM	CHEMBL369927
7.70	IC50	20	nM	CHEMBL5183440
7.70	Kd	20	nM	CHEMBL5613121
7.67	Kd	21.5	nM	CHEMBL4797381
7.64	IC50	23	nM	COMBRETASTATIN A4
7.62	EC50	24	nM	CHEMBL4250191
7.60	IC50	25	nM	CHEMBL552462
7.52	IC50	30	nM	CHEMBL381122
7.52	IC50	30	nM	COMBRETASTATIN A4
7.52	IC50	30	nM	CHEMBL203062
7.52	IC50	30	nM	CHEMBL204710
7.51	EC50	31	nM	PACLITAXEL
7.43	Kd	36.9	nM	CHEMBL4756812
7.40	EC50	40	nM	CHEMBL1688184
7.35	EC50	45	nM	CHEMBL4239716
7.34	IC50	46	nM	CHEMBL374257
7.33	Kd	47	nM	CHEMBL5542101
7.30	Ki	50	nM	CHEMBL196966
7.30	EC50	50	nM	CHEMBL1688183
7.30	EC50	50	nM	CHEMBL1688189
7.29	Kd	51	nM	CHEMBL5614306
7.28	EC50	53	nM	CHEMBL4241638

PubChem BioAssay actives

1102 with measured affinity, of 5924 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(Z)-1-[4-bromo-2-(4-fluorophenyl)-1-benzofuran-7-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1882651: Inhibition of tubulin polymerization (unknown origin) measured every 3 secs for 1 hr by spectroflourimetric analysis	ic50	0.0001	uM
(Z)-1-[4-bromo-2-(4-fluorophenyl)-1-benzofuran-7-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one	1882651: Inhibition of tubulin polymerization (unknown origin) measured every 3 secs for 1 hr by spectroflourimetric analysis	ic50	0.0002	uM
Vinorelbine	1993632: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0003	uM
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide	270819: Inhibition of tubulin polymerization	ic50	0.0005	uM
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-(2-pyridin-2-ylethylamino)propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide	1896115: Binding affinity to tubulin (unknown origin)	ic50	0.0012	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149681: Binding affinity to human TUBB4B incubated for 45 mins by Kinobead based pull down assay	kd	0.0012	uM
(3Z,6Z)-3-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]-6-phenacylidenepiperazine-2,5-dione	1587857: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0014	uM
(3Z,6Z)-3-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]-6-[(2,5-difluorophenyl)methylidene]piperazine-2,5-dione	1587857: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0026	uM
3-hydroxy-2-[N-[2-(methoxymethyl)-1-benzofuran-7-yl]-C-methylcarbonimidoyl]-5-phenylcyclohex-2-en-1-one	2034736: Displacement of fluorescent probe (R)-(+)-ethyl 5-amino2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-ylcarbamate from tubulin colchicine binding site (unknown origin) assessed as dissociation constant	kd	0.0030	uM
2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol	1862628: Inhibition of tubulin polymerization in human HeLa cells assessed as microtubule network polymerization after 30 mins by immunofluorescence analysis	ic50	0.0030	uM
Colchicine	2074087: Inhibition of microtubule polymerization in human K562 cells measured for 60 mins by fluorescence based analysis	ic50	0.0030	uM
(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione	1408257: Inhibition of tubulin polymerization in human MCF7 cells assessed as induction of mitotic arrest	ic50	0.0035	uM
tert-butyl (3R,4S,5S)-4-[[(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoate	1896110: Inhibition of tubulin (unknown origin) polymerization assessed as reduction in microtubule formation measured for 20 mins by spectrophotometric analysis	ic50	0.0042	uM
3-methoxy-6-[4-(3,4,5-trimethoxyphenyl)-1H-pyrazol-5-yl]benzene-1,2-diol	1929685: Inhibition of tubulin polymerization in human SH-SY5Y cells incubated for 24 hrs by SDS-PAGE based analysis	ic50	0.0054	uM
2-methoxy-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]phenol	1862628: Inhibition of tubulin polymerization in human HeLa cells assessed as microtubule network polymerization after 30 mins by immunofluorescence analysis	ic50	0.0060	uM
(E)-1-[1-(4-chlorophenyl)-5-methyltriazol-4-yl]-3-(3,4-dimethoxyphenyl)prop-2-en-1-one	1689700: Inhibition of Tubulin in human RPMI-8226 cells incubated for 2 hrs by ELISA	ic50	0.0098	uM
N-(1,3-benzodioxol-5-yl)-5-[2-(3,5-dimethoxyphenoxy)-3-pyridinyl]-1H-1,2,4-triazol-3-amine	256882: Displacement of [3H]colchicine from tubulin	ki	0.0100	uM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[2-(pyridin-2-ylmethylamino)phenyl]-1,3-oxazol-2-amine	261214: Displacement of [3H]colchicine from tubulin at 65 nM	ic50	0.0100	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] acetate	2126113: Displacement of fluorescent Maytansine probe from tubulin (unknown origin) assessed as dissociation constant by competitive binding based fluorescence anisotropy	kd	0.0110	uM
[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[acetyl(methyl)amino]propanoate	2126113: Displacement of fluorescent Maytansine probe from tubulin (unknown origin) assessed as dissociation constant by competitive binding based fluorescence anisotropy	kd	0.0140	uM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[2-(3,5-dimethoxyphenoxy)-3-pyridinyl]-1H-1,2,4-triazol-3-amine	256882: Displacement of [3H]colchicine from tubulin	ki	0.0200	uM
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-(1-diethoxyphosphorylhexylcarbamoyl)-12-ethyl-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate	214333: The compound tested for the inhibition of tubulin polymerization.	ic50	0.0200	uM
(E)-3-[5-[(2-cyanoquinolin-4-yl)-methylamino]-2-methoxyphenyl]-N-hydroxyprop-2-enamide	1862628: Inhibition of tubulin polymerization in human HeLa cells assessed as microtubule network polymerization after 30 mins by immunofluorescence analysis	ic50	0.0200	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] hept-6-ynoate	2126113: Displacement of fluorescent Maytansine probe from tubulin (unknown origin) assessed as dissociation constant by competitive binding based fluorescence anisotropy	kd	0.0200	uM
(3S)-3-[(5R)-6-[[1-(4-fluorophenyl)triazol-4-yl]methyl]-4-methoxy-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6,7-dimethoxy-3H-2-benzofuran-1-one	1675128: Binding affinity to CM5 chip immobilized beta tubulin (unknown origin) assessed as thermodynamic constants by SPR assay	kd	0.0215	uM
N-(4-methoxyphenyl)-N,5-dimethylfuro[2,3-d]pyrimidin-4-amine	1635267: Induction of microtubule depolymerization in human A10 cells incubated for 18 hrs by indirect immunofluorescence analysis	ec50	0.0240	uM
[4-amino-2-(4-methoxyanilino)-1,3-thiazol-5-yl]-(3,4-dimethoxyphenyl)methanone	1674862: Binding affinity to beta tubulin in HEK293 cells assessed as disruption of microtubule polymerization by ITDRF-CETSA assay	ic50	0.0250	uM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[2-(pyridin-3-ylmethylamino)-3-pyridinyl]-1,3,4-oxadiazol-2-amine	261214: Displacement of [3H]colchicine from tubulin at 65 nM	ic50	0.0300	uM
N-(1,3-benzodioxol-5-yl)-5-[2-(pyridin-4-ylmethylamino)-3-pyridinyl]-1,3,4-oxadiazol-2-amine	261214: Displacement of [3H]colchicine from tubulin at 65 nM	ic50	0.0300	uM
N-(1,3-benzodioxol-5-yl)-5-[2-(pyridin-2-ylmethylamino)-3-pyridinyl]-1,3,4-oxadiazol-2-amine	261214: Displacement of [3H]colchicine from tubulin at 65 nM	ic50	0.0300	uM
Paclitaxel	260235: Effect on induction of mitotic arrest by phosphohistone H3 (pH3) assay	ec50	0.0310	uM
(3S)-3-[(5R)-9-bromo-6-[[1-(4-bromophenyl)triazol-4-yl]methyl]-4-methoxy-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6,7-dimethoxy-3H-2-benzofuran-1-one	1675128: Binding affinity to CM5 chip immobilized beta tubulin (unknown origin) assessed as thermodynamic constants by SPR assay	kd	0.0369	uM
6-(3-chloro-6,11,11-trioxobenzo[b][1,4]benzothiazepin-5-yl)-N-hydroxyhexanamide	580932: Inhibition of HDAC activity in human NB4 cells assessed as acetylated tubulin after 24 hrs by Western blot analysis	ec50	0.0400	uM
N,5-dimethyl-N-(4-methylsulfanylphenyl)furo[2,3-d]pyrimidin-4-amine	1635267: Induction of microtubule depolymerization in human A10 cells incubated for 18 hrs by indirect immunofluorescence analysis	ec50	0.0450	uM
[7-(3-hydroxyprop-1-ynyl)-6-methoxy-2H-indazol-3-yl]-(3,4,5-trimethoxyphenyl)methanone	280080: Displacement of [3H]colchicine from tubulin in MCF7 cells	ic50	0.0460	uM
(3S,10R,13E,16S)-10-[(3-chloro-4-methoxyphenyl)methyl]-6,6-dimethyl-3-(2-methylpropyl)-16-[(1S)-1-[(2R,3S)-3-phenyloxiran-2-yl]ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone	2061859: Binding affinity to tubulin (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.0470	uM
N-hydroxy-6-(3-methoxy-6,11,11-trioxobenzo[b][1,4]benzothiazepin-5-yl)hexanamide	580932: Inhibition of HDAC activity in human NB4 cells assessed as acetylated tubulin after 24 hrs by Western blot analysis	ec50	0.0500	uM
N-hydroxy-6-(6,11,11-trioxobenzo[b][1,4]benzothiazepin-5-yl)hexanamide	580932: Inhibition of HDAC activity in human NB4 cells assessed as acetylated tubulin after 24 hrs by Western blot analysis	ec50	0.0500	uM
5-[2-(3,5-dimethoxyphenoxy)-3-pyridinyl]-N-(3-methoxyphenyl)-1H-1,2,4-triazol-3-amine	256882: Displacement of [3H]colchicine from tubulin	ki	0.0500	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] benzoate	2126113: Displacement of fluorescent Maytansine probe from tubulin (unknown origin) assessed as dissociation constant by competitive binding based fluorescence anisotropy	kd	0.0510	uM
N-ethyl-N-(4-methoxyphenyl)-5-methylfuro[2,3-d]pyrimidin-4-amine	1635267: Induction of microtubule depolymerization in human A10 cells incubated for 18 hrs by indirect immunofluorescence analysis	ec50	0.0530	uM
3-[3-(1,3-benzodioxol-5-ylamino)-1H-1,2,4-triazol-5-yl]-N-(3,5-dimethoxyphenyl)pyridin-2-amine	256882: Displacement of [3H]colchicine from tubulin	ki	0.0600	uM
Vinblastine	214333: The compound tested for the inhibition of tubulin polymerization.	ic50	0.0700	uM
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-[(1-diethoxyphosphoryl-2-phenylethyl)carbamoyl]-12-ethyl-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate	214333: The compound tested for the inhibition of tubulin polymerization.	ic50	0.0700	uM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[3-(pyridin-2-ylmethylamino)thiophen-2-yl]-1,3,4-oxadiazol-2-amine	261214: Displacement of [3H]colchicine from tubulin at 65 nM	ic50	0.0750	uM
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-[[(1S)-1-diethoxyphosphorylethyl]carbamoyl]-12-ethyl-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraene-13-carboxylate	214333: The compound tested for the inhibition of tubulin polymerization.	ic50	0.0800	uM
4-methoxy-2-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]thiophene	1267532: Inhibition of Tubulin polymerization in human HeLa cells assessed as decrease in dynamic tyrosinated microtubules after 2 hrs by microplate reader analysis	ec50	0.0810	uM
N-[2-[[(E)-(2,4-dihydroxyphenyl)methylideneamino]carbamoyl]phenyl]furan-2-carboxamide	1882654: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0876	uM
N-hydroxy-6-(3-methoxy-6-oxobenzo[b][1,4]benzoxazepin-5-yl)hexanamide	580932: Inhibition of HDAC activity in human NB4 cells assessed as acetylated tubulin after 24 hrs by Western blot analysis	ec50	0.0900	uM
N-(3,5-dimethoxyphenyl)-3-[3-(3-methoxyanilino)-1H-1,2,4-triazol-5-yl]pyridin-2-amine	256882: Displacement of [3H]colchicine from tubulin	ki	0.1000	uM

CTD chemical–gene interactions

86 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression, increases metabolic processing	6
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
sulforaphane	increases expression, affects binding	2
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression	2
chloropicrin	affects expression, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression	2
Silicon Dioxide	affects secretion, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tunicamycin	decreases expression	2
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
beauvericin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
hexamethylene bisacetamide	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
ochratoxin A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
lead chloride	increases expression	1
cupric chloride	increases expression	1
resorcinol	increases expression	1
dibenzo(a,l)pyrene	increases expression	1
diallyl trisulfide	decreases expression	1
phenethyl isothiocyanate	affects binding	1
chromium hexavalent ion	decreases expression, increases abundance	1

ChEMBL screening assays

1769 unique, capped per target: 1726 binding, 37 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4155367	Binding	Binding affinity to tubulin beta-4B in human A549 cells at 0.15 mM after 4 hrs by HPLC-MS based pull down assay relative to control	Synthesis, cytotoxic evaluation and target identification of thieno[2,3-d]pyrimidine derivatives with a dithiocarbamate side chain at C2 position. — Eur J Med Chem
CHEMBL873499	Functional	Inhibitory activity against tubulin using tubulin polymerization assay	Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 7- and 5-, 6-, 8-positions. — Bioorg Med Chem Lett
CHEMBL4146506	ADMET	Inhibition of tubulin polymerization in human HaCaT cells assessed as chromatin condensation at 1 uM after 24 hrs by Hoechst 33258 staining-based fluorescence microscopic analysis	Design, synthesis, and biological evaluation of novel combretastatin A-4 thio derivatives as microtubule targeting agents. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3KB	Abcam HEK293T TUBB4B KO	Transformed cell line	Female
CVCL_TV21	HAP1 TUBB4B (-) 1	Cancer cell line	Male
CVCL_TV22	HAP1 TUBB4B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.