TUBB2B

Summary

TUBB2B (tubulin beta 2B class IIb, HGNC:30829) is a protein-coding gene on chromosome 6p25.2, encoding Tubulin beta-2B chain (Q9BVA1). Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

The protein encoded by this gene is a beta isoform of tubulin, which binds GTP and is a major component of microtubules. This gene is highly similar to TUBB2A and TUBB2C. Defects in this gene are a cause of asymmetric polymicrogyria.

Source: NCBI Gene 347733 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex cortical dysplasia with other brain malformations (Definitive, ClinGen) — +4 more curated relationships
• Clinical variants (ClinVar): 242 total — 21 pathogenic, 47 likely-pathogenic
• Phenotypes (HPO): 97
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_178012

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30829
Approved symbol	TUBB2B
Name	tubulin beta 2B class IIb
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC8685, DKFZp566F223, bA506K6.1
Ensembl gene	ENSG00000137285
Ensembl biotype	protein_coding
OMIM	612850
Entrez	347733

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 retained_intron, 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000259818, ENST00000473006, ENST00000680070, ENST00000681707, ENST00000681757

RefSeq mRNA: 1 — MANE Select: NM_178012 NM_178012

CCDS: CCDS4485

Canonical transcript exons

ENST00000259818 — 4 exons

Exon	Start	End
ENSE00001484585	3227487	3227653
ENSE00003257192	3224277	3225811
ENSE00003521939	3226561	3226669
ENSE00003640661	3226159	3226269

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.5822 / max 4759.1498, expressed in 936 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71460	87.1678	883
71461	0.3712	189
71459	0.0432	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.93	gold quality
ganglionic eminence	UBERON:0004023	99.90	gold quality
ventricular zone	UBERON:0003053	99.89	gold quality
embryo	UBERON:0000922	99.53	gold quality
spinal cord	UBERON:0002240	99.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.52	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.44	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.43	gold quality
substantia nigra pars compacta	UBERON:0001965	99.39	gold quality
superior vestibular nucleus	UBERON:0007227	99.38	gold quality
medulla oblongata	UBERON:0001896	99.37	gold quality
nucleus accumbens	UBERON:0001882	99.36	gold quality
substantia nigra	UBERON:0002038	99.34	gold quality
paraflocculus	UBERON:0005351	99.34	gold quality
midbrain	UBERON:0001891	99.31	gold quality
ventral tegmental area	UBERON:0002691	99.23	gold quality
middle frontal gyrus	UBERON:0002702	99.23	gold quality
putamen	UBERON:0001874	99.21	gold quality
caudate nucleus	UBERON:0001873	99.19	gold quality
hypothalamus	UBERON:0001898	99.19	gold quality
subthalamic nucleus	UBERON:0001906	99.15	gold quality
medial globus pallidus	UBERON:0002477	99.14	gold quality
globus pallidus	UBERON:0001875	99.13	gold quality
inferior olivary complex	UBERON:0002127	99.11	gold quality
amygdala	UBERON:0001876	99.10	gold quality
lateral globus pallidus	UBERON:0002476	99.06	gold quality
inferior vagus X ganglion	UBERON:0005363	98.97	gold quality
dorsal root ganglion	UBERON:0000044	98.85	gold quality
temporal lobe	UBERON:0001871	98.68	gold quality
right frontal lobe	UBERON:0002810	98.66	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	6540.12
E-MTAB-7407	yes	4123.30
E-MTAB-8221	yes	4115.92
E-MTAB-6701	yes	4115.19
E-MTAB-9906	yes	3034.84
E-HCAD-10	yes	2369.39
E-GEOD-124472	yes	1673.91
E-GEOD-98556	yes	841.14
E-GEOD-114530	yes	836.42
E-MTAB-9388	yes	811.11
E-GEOD-137537	yes	37.17
E-MTAB-7316	yes	30.28
E-HCAD-11	yes	29.63
E-GEOD-84465	yes	27.58
E-HCAD-25	yes	20.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting TUBB2B, 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-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4311	99.31	70.47	3041

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 21)

• The class II beta-tubulin isotype seems to be a promising predictive marker of docetaxel activity in the treatment of breast neoplasms. (PMID:12533264)
• The data suggest that the ratio of beta-tubulin classes II and V mRNA could be useful as a biomarker for NSCLC tumor differentiation and/or NSCLC aggressiveness. (PMID:18613117)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• TUBB2B is required for neuronal migration two disease-associated mutations lead to impaired formation of tubulin heterodimers. (PMID:19465910)
• Studies show that BFBTS bound and modified beta-tubulin at residue Cys12, forming beta-tubulin-SS-fluorobenzyl. (PMID:19996274)
• Three new TUBB2B mutations have been identified in three unrelated patients with a diffuse and rather symmetrical cortical abnormality. (PMID:22333901)
• Brain malformations are associated with mutations in the beta-tubulin gene TUBB2B, supporting its critical role in migration/organization and axon guidance processes. (PMID:22591407)
• Congenital fibrosis of the extraocular muscles and intellectual disability segregate with a heterozygous mutation in TUBB2B. (PMID:23001566)
• The TUBB2B and TUBA1 coding regions have been sequenced in patients with cortical malformations associated with these genes. (PMID:23361065)
• The association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B. (PMID:23495813)
• The present study confirms that mutations in tubulin genes are responsible for complex brain malformation. (PMID:24392928)
• off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development (PMID:26331477)
• At the cellular level, the p.Cys239Phe TUBB2B mutant leads to tubulin heterodimerization impairment, decreased ability to incorporate into the cytoskeleton, microtubule dynamics alteration, with an accelerated rate of depolymerization (PMID:26732629)
• CPAP regulates delivery of its bound beta-tubulin to define the size of microtubule-based cellular structures using a “clutch-like” mechanism. (PMID:27306797)
• The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects. (PMID:28013290)
• The results suggest that betaII-tubulin may facilitate cancer growth and metastasis and, to accomplish this, may not need to be in microtubule form. (PMID:30621030)
• the present study identified a novel significant association between the increased expression levels of MAPK10, TUBB2B and RASL11B, and neuroblastoma cells. (PMID:31432180)
• Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF-1 upregulation of TUBB2B beta-tubulin isoform. (PMID:33734457)
• A novel family illustrating the mild phenotypic spectrum of TUBB2B variants. (PMID:34592644)
• TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1. (PMID:36872411)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tubb2	ENSDARG00000039522
mus_musculus	Tubb2b	ENSMUSG00000045136
drosophila_melanogaster	betaTub85D	FBGN0003889

Paralogs (23): TUBG2 (ENSG00000037042), TUBE1 (ENSG00000074935), TUBA3D (ENSG00000075886), TUBB1 (ENSG00000101162), TUBB4A (ENSG00000104833), TUBD1 (ENSG00000108423), TUBA1B (ENSG00000123416), TUBA4A (ENSG00000127824), TUBG1 (ENSG00000131462), TUBB2A (ENSG00000137267), TUBA3E (ENSG00000152086), TUBA1A (ENSG00000167552), TUBA1C (ENSG00000167553), TUBB8B (ENSG00000173213), TUBB6 (ENSG00000176014), TUBAL3 (ENSG00000178462), TUBA8 (ENSG00000183785), TUBB4B (ENSG00000188229), TUBB (ENSG00000196230), TUBA3C (ENSG00000198033), TUBA4B (ENSG00000243910), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin beta-2B chain — Q9BVA1 (reviewed: Q9BVA1)

All UniProt accessions (2): Q9BVA1, A0A384MEE3

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. Plays a critical role in proper axon guidance in both central and peripheral axon tracts. Implicated in neuronal migration.

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.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. High expression in brain.

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. Cortical dysplasia, complex, with other brain malformations 7 (CDCBM7) [MIM:610031] A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. The disease is caused by variants affecting the gene represented in this entry. Defects in TUBB2B may be involved in cerebellar ataxia, intellectual disability, and dysequilibrium syndrome (CAMRQ).

Domain organisation. 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_821080* (*=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 (36 total): sequence variant 12, binding site 9, modified residue 9, cross-link 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9OX7	ELECTRON MICROSCOPY	2.69
7ZCW	ELECTRON MICROSCOPY	3.6
6E7C	ELECTRON MICROSCOPY	3.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVA1-F1	92.09	0.83

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 (11): 40, 55, 58, 58, 172, 285, 290, 318, 438, 58, 324

Function

Pathways and Gene Ontology

Reactome pathways

86 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-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
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-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-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-8955332	Carboxyterminal post-translational modifications of tubulin
R-HSA-9609690	HCMV Early Events
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9619483	Activation of AMPK downstream of NMDARs
R-HSA-9646399	Aggrephagy
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9668328	Sealing of the nuclear envelope (NE) by ESCRT-III
R-HSA-983189	Kinesins

MSigDB gene sets: 554 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MYAATNNNNNNNGGC_UNKNOWN, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, ZHAN_MULTIPLE_MYELOMA_MF_UP, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_AXON_GUIDANCE, REACTOME_MEMBRANE_TRAFFICKING, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT

GO Biological Process (10): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), neuron migration (GO:0001764), microtubule-based process (GO:0007017), cerebral cortex development (GO:0021987), modulation of chemical synaptic transmission (GO:0050804), positive regulation of axon guidance (GO:1902669), embryonic brain development (GO:1990403), cytoskeleton organization (GO:0007010), nervous system development (GO:0007399)

GO Molecular Function (7): GTPase activity (GO:0003924), structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), metal ion binding (GO:0046872), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), Schaffer collateral - CA1 synapse (GO:0098685), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Mitotic Prometaphase	2
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	2
Assembly of the 9+0 primary cilium	2
RHO GTPase Effectors	2
Golgi-to-ER retrograde transport	2
Membrane Trafficking	1
Transport of connexons to the plasma membrane	1
Gap junction trafficking	1
Adaptive Immune System	1
Mitotic Anaphase	1
Cellular responses to stress	1
Protein folding	1
L1CAM interactions	1
Signaling by Hedgehog	1
ER to Golgi Anterograde Transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	2
cytoskeleton	2
cellular anatomical structure	2
microtubule-based process	1
cell cycle	1
mitotic nuclear division	1
cell migration	1
generation of neurons	1
cellular process	1
pallium development	1
anatomical structure development	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
axon guidance	1
positive regulation of neuron projection development	1
regulation of axon guidance	1
embryonic organ development	1
organelle organization	1
system development	1
ribonucleoside triphosphate phosphatase activity	1
structural molecule activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
spindle	1
synapse	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

4250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBB2B	WDR83OS	Q9Y284	894
TUBB2B	TUBA1B	P04687	856
TUBB2B	TUBA1B	P04687	829
TUBB2B	TUBA1C	Q9BQE3	809
TUBB2B	TUBA8	Q9NY65	807
TUBB2B	TUBAL3	A6NHL2	806
TUBB2B	TUBA3E	Q6PEY2	806
TUBB2B	TUBA4A	P05215	805
TUBB2B	TUBA3C	P0DPH7	805
TUBB2B	FGD1	P98174	686
TUBB2B	KIF11	P52732	562
TUBB2B	KIF5C	O60282	555
TUBB2B	PACRG	Q96M98	509
TUBB2B	DYNC1H1	Q14204	482
TUBB2B	WDR62	O43379	475

IntAct

161 interactions, top by confidence:

A	B	Type	Score
PRDM14	CBFA2T2	psi-mi:“MI:0914”(association)	0.860
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RBKS	NSF	psi-mi:“MI:0914”(association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
TUBB2B	EML2	psi-mi:“MI:0914”(association)	0.530
TUBB2A	EML2	psi-mi:“MI:0914”(association)	0.530
GNB2	PFDN6	psi-mi:“MI:0914”(association)	0.530
RFFL	TUSC2	psi-mi:“MI:0914”(association)	0.530
P/V	IRS4	psi-mi:“MI:0914”(association)	0.530
TUBB2B	CACNA1A	psi-mi:“MI:0915”(physical association)	0.510
TUBB2B	MYO10	psi-mi:“MI:0407”(direct interaction)	0.440
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
PRDM7	TUBB2B	psi-mi:“MI:0915”(physical association)	0.400
DTNA	TUBB2B	psi-mi:“MI:0915”(physical association)	0.400
TUBB2B	DLG4	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	TUBB2B	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	BID	psi-mi:“MI:0915”(physical association)	0.370
C8orf33	TUBB2B	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	CDKN1A	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	CENPU	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	RGS2	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	RPL35	psi-mi:“MI:0915”(physical association)	0.370
TUBB2B	LRRK2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (325): TUBB2B (Affinity Capture-MS), TUBB2B (Affinity Capture-MS), TUBB2B (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), TBCD (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT6A (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), TSEN2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), EPHA4 (Affinity Capture-MS)

ESM2 similar proteins: O17449, O44388, O59837, P02554, P07437, P09203, P09244, P09652, P09653, P11833, P11857, P12456, P13602, P30883, P32882, P34108, P35394, P36221, P41937, P52275, P69893, P69895, P69897, P85108, P99024, Q13509, Q13885, Q17299, Q24560, Q27U48, Q2HJ81, Q2KJD0, Q2T9S0, Q3KRE8, Q4QRB4, Q4R5B3, Q5R943, Q60HC2, Q6B856, Q6GLE7

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 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	8	30.0×	2e-08
Transport of connexons to the plasma membrane	8	30.0×	2e-08
Gap junction trafficking and regulation	8	26.2×	4e-08
Gap junction trafficking	8	26.2×	4e-08
Post-chaperonin tubulin folding pathway	8	26.2×	4e-08
Activation of AMPK downstream of NMDARs	9	23.6×	2e-08
Formation of tubulin folding intermediates by CCT/TriC	8	23.3×	9e-08
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	8	22.5×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	6	28.1×	3e-05
canonical NF-kappaB signal transduction	7	14.2×	2e-04
microtubule cytoskeleton organization	13	8.8×	4e-06
negative regulation of translation	7	7.6×	6e-03
mitotic cell cycle	10	7.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	47
Uncertain significance	89
Likely benign	49
Benign	8

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1190491	NM_178012.5(TUBB2B):c.972G>C (p.Lys324Asn)	Pathogenic
1214258	NM_178012.5(TUBB2B):c.1138C>T (p.Arg380Cys)	Pathogenic
1695512	NM_178012.5(TUBB2B):c.730G>A (p.Gly244Ser)	Pathogenic
1708143	NM_178012.5(TUBB2B):c.776C>T (p.Pro259Leu)	Pathogenic
1720661	NM_178012.5(TUBB2B):c.287G>A (p.Gly96Glu)	Pathogenic
236255	NM_178012.5(TUBB2B):c.716G>T (p.Cys239Phe)	Pathogenic
2578313	NM_178012.5(TUBB2B):c.1171C>T (p.Arg391Cys)	Pathogenic
3342661	NM_178012.5(TUBB2B):c.632G>T (p.Cys211Phe)	Pathogenic
3777181	NM_178012.5(TUBB2B):c.1106G>T (p.Gly369Val)	Pathogenic
3780999	NM_178012.5(TUBB2B):c.844C>G (p.Arg282Gly)	Pathogenic
379922	NM_178012.5(TUBB2B):c.1189T>C (p.Trp397Arg)	Pathogenic
39720	NM_178012.5(TUBB2B):c.1249G>A (p.Asp417Asn)	Pathogenic
4086071	NM_178012.5(TUBB2B):c.4C>T (p.Arg2Cys)	Pathogenic
426	NM_178012.5(TUBB2B):c.514T>C (p.Ser172Pro)	Pathogenic
427	NM_178012.5(TUBB2B):c.683T>C (p.Leu228Pro)	Pathogenic
428	NM_178012.5(TUBB2B):c.793T>C (p.Phe265Leu)	Pathogenic
4282348	NM_178012.5(TUBB2B):c.832A>G (p.Ser278Gly)	Pathogenic
4526588	NM_178012.5(TUBB2B):c.795C>A (p.Phe265Leu)	Pathogenic
4740968	NM_178012.5(TUBB2B):c.1033A>T (p.Ile345Phe)	Pathogenic
800842	NM_178012.5(TUBB2B):c.4C>A (p.Arg2Ser)	Pathogenic
88897	NM_178012.5(TUBB2B):c.1261G>A (p.Glu421Lys)	Pathogenic
1048606	NM_178012.5(TUBB2B):c.1162A>C (p.Met388Leu)	Likely pathogenic
1193251	NM_178012.5(TUBB2B):c.953G>A (p.Arg318Gln)	Likely pathogenic
1336721	NM_178012.5(TUBB2B):c.5G>A (p.Arg2His)	Likely pathogenic
1337281	NM_178012.5(TUBB2B):c.673C>T (p.Leu225Phe)	Likely pathogenic
1519873	NM_178012.5(TUBB2B):c.904G>A (p.Ala302Thr)	Likely pathogenic
160177	NM_178012.5(TUBB2B):c.1139G>T (p.Arg380Leu)	Likely pathogenic
160187	NM_178012.5(TUBB2B):c.965C>T (p.Ser322Phe)	Likely pathogenic
1679255	NM_178012.5(TUBB2B):c.908G>A (p.Cys303Tyr)	Likely pathogenic
1686714	NM_178012.5(TUBB2B):c.893A>T (p.Asn298Ile)	Likely pathogenic

SpliceAI

418 predictions. Top by Δscore:

Variant	Effect	Δscore
6:3225807:CTGGC:C	acceptor_gain	1.0000
6:3225808:TGGC:T	acceptor_gain	1.0000
6:3225812:C:CC	acceptor_gain	1.0000
6:3225816:C:CT	acceptor_gain	1.0000
6:3225816:C:T	acceptor_gain	1.0000
6:3225817:A:T	acceptor_gain	1.0000
6:3226152:CACT:C	donor_loss	1.0000
6:3226153:ACTC:A	donor_loss	1.0000
6:3226154:CTCA:C	donor_loss	1.0000
6:3226155:TCAC:T	donor_loss	1.0000
6:3226156:CACCA:C	donor_loss	1.0000
6:3226157:A:AC	donor_gain	1.0000
6:3226157:A:AT	donor_loss	1.0000
6:3226158:C:CC	donor_gain	1.0000
6:3226158:CCAAA:C	donor_gain	1.0000
6:3226269:CCTG:C	acceptor_loss	1.0000
6:3226270:C:CC	acceptor_gain	1.0000
6:3226270:CTG:C	acceptor_loss	1.0000
6:3226271:T:A	acceptor_loss	1.0000
6:3225809:GGC:G	acceptor_gain	0.9900
6:3225810:GC:G	acceptor_gain	0.9900
6:3225811:CC:C	acceptor_gain	0.9900
6:3226151:GCAC:G	donor_loss	0.9900
6:3226265:GTTAC:G	acceptor_gain	0.9900
6:3226266:TTAC:T	acceptor_gain	0.9900
6:3226267:TAC:T	acceptor_gain	0.9900
6:3226268:AC:A	acceptor_gain	0.9900
6:3226269:CC:C	acceptor_gain	0.9900
6:3226273:C:CT	acceptor_gain	0.9900
6:3226555:GATTA:G	donor_loss	0.9900

AlphaMissense

2972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:3224825:A:G	Y422H	1.000
6:3224828:C:T	E421K	1.000
6:3224836:A:G	L418P	1.000
6:3224836:A:T	L418Q	1.000
6:3224839:T:A	D417V	1.000
6:3224839:T:C	D417G	1.000
6:3224839:T:G	D417A	1.000
6:3224840:C:G	D417H	1.000
6:3224857:G:T	A411D	1.000
6:3224858:C:G	A411P	1.000
6:3224865:G:C	F408L	1.000
6:3224865:G:T	F408L	1.000
6:3224866:A:C	F408C	1.000
6:3224866:A:G	F408S	1.000
6:3224867:A:G	F408L	1.000
6:3224870:C:T	E407K	1.000
6:3224879:C:G	D404H	1.000
6:3224880:C:A	M403I	1.000
6:3224880:C:G	M403I	1.000
6:3224880:C:T	M403I	1.000
6:3224881:A:C	M403R	1.000
6:3224881:A:G	M403T	1.000
6:3224884:C:A	G402V	1.000
6:3224884:C:T	G402D	1.000
6:3224885:C:A	G402C	1.000
6:3224885:C:G	G402R	1.000
6:3224898:C:A	W397C	1.000
6:3224898:C:G	W397C	1.000
6:3224900:A:G	W397R	1.000
6:3224900:A:T	W397R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004782 (6:3224635 C>A,G,T), RS1000376011 (6:3226895 G>A), RS1001147531 (6:3227016 G>T), RS1001178545 (6:3226880 C>T), RS1001652120 (6:3228136 C>A,G,T), RS1001955756 (6:3228434 G>C), RS1002156454 (6:3228295 G>A), RS1002866389 (6:3224592 A>G), RS1003734507 (6:3224251 A>G), RS1003788395 (6:3223962 G>A,C,T), RS1004073043 (6:3226874 G>T), RS1004579594 (6:3226538 G>T), RS1006146488 (6:3228051 T>C), RS1006573461 (6:3229030 G>A), RS1007082837 (6:3228841 G>C)

Disease associations

OMIM: gene MIM:612850 | disease phenotypes: MIM:610031, MIM:614039, MIM:607432

GenCC curated gene-disease

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations	Definitive	Autosomal dominant
complex cortical dysplasia with other brain malformations 7	Definitive	Autosomal dominant
congenital fibrosis of extraocular muscles	Supportive	Autosomal dominant
cerebellar ataxia, intellectual disability, and dysequilibrium	Supportive	Autosomal recessive
tubulinopathy-associated dysgyria	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations	Definitive	AD

Mondo (9): complex cortical dysplasia with other brain malformations 7 (MONDO:0012399), tubulinopathy (MONDO:0100153), complex cortical dysplasia with other brain malformations 1 (MONDO:0013541), bilateral perisylvian polymicrogyria (MONDO:0020340), lissencephaly spectrum disorders (MONDO:0018838), complex cortical dysplasia with other brain malformations (MONDO:0000904), congenital fibrosis of extraocular muscles (MONDO:0007614), cerebellar ataxia, intellectual disability, and dysequilibrium (MONDO:0009133), tubulinopathy-associated dysgyria (MONDO:0018763)

Orphanet (4): Polymicrogyria due to TUBB2B mutation (Orphanet:300573), Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation (Orphanet:300570), Bilateral perisylvian polymicrogyria (Orphanet:98889), Lissencephaly (Orphanet:48471)

HPO phenotypes

97 total (30 of 97 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000473	Torticollis
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000539	Abnormality of refraction
HP:0000542	Impaired ocular adduction
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000609	Optic nerve hypoplasia
HP:0000616	Miosis
HP:0000646	Amblyopia
HP:0000657	Oculomotor apraxia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001274	Agenesis of corpus callosum
HP:0001288	Gait disturbance

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
C535731	Dysequilibrium syndrome (supp.)
C580012	congenital fibrosis of the extraocular muscles (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095182 (PROTEIN COMPLEX GROUP), CHEMBL3832942 (PROTEIN FAMILY), CHEMBL6066847 (PROTEIN-PROTEIN INTERACTION), CHEMBL6067533 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,641,397 (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
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	29,245
CHEMBL246600	COMBRETASTATIN	1

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

ChEMBL bioactivities

1172 potent at pChembl≥5 of 1323 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
8.85	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
7.85	Kd	14.03	nM	CHEMBL5653589
7.85	ED50	14.03	nM	CHEMBL5653589
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

1099 with measured affinity, of 5891 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
(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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149679: Binding affinity to human TUBB2B incubated for 45 mins by Kinobead based pull down assay	kd	0.0140	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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	6
Cyclosporine	affects expression, decreases methylation, increases expression	4
Particulate Matter	affects cotreatment, increases abundance, increases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	2
perfluorooctane sulfonic acid	affects expression, affects cotreatment, decreases expression	2
Arsenic	decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases metabolic processing	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
cupric oxide	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
pentanal	increases expression	1
tamibarotene	increases expression	1
azoxystrobin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
2,4,3’,5’-tetramethoxystilbene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
thifluzamide	decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

1757 unique, capped per target: 1717 binding, 34 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009021	Binding	Inhibition of tubulin polymerization in human MCF7 cells at 1 uM after 2 hrs by SDS-PAGE	A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus. — J Nat Prod
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
CHEMBL5056161	Functional	Inhibition of tubulin polymerization (unknown origin) assessed as fluorescence intensity measured for 90 mins by DAPI based microplate reader	Design, synthesis and biological evaluation of indole-based [1,2,4]triazolo[4,3-a] pyridine derivatives as novel microtubule polymerization inhibitors. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1FV	Abcam HEK293 TUBB2B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies
NCT06366230	PHASE1/PHASE2	RECRUITING	Adding Urea to the Final Dialysis Fluid