TUBB

Summary

TUBB (tubulin beta class I, HGNC:20778) is a protein-coding gene on chromosome 6p21.33, encoding Tubulin beta chain (P07437). Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13.

Source: NCBI Gene 203068 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TUBB3-related tubulinopathy (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 24
• Clinical variants (ClinVar): 123 total — 9 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 68
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_178014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20778
Approved symbol	TUBB
Name	tubulin beta class I
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	OK/SW-cl.56, MGC16435, M40, Tubb5
Ensembl gene	ENSG00000196230
Ensembl biotype	protein_coding
OMIM	191130
Entrez	203068

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000327892, ENST00000330914, ENST00000396384, ENST00000396389, ENST00000680530, ENST00000681421, ENST00000681435, ENST00000940306, ENST00000940307, ENST00000940308, ENST00000940309

RefSeq mRNA: 6 — MANE Select: NM_178014 NM_001293212, NM_001293213, NM_001293214, NM_001293215, NM_001293216, NM_178014

CCDS: CCDS4687, CCDS78124

Canonical transcript exons

ENST00000327892 — 4 exons

Exon	Start	End
ENSE00001853302	30720352	30720563
ENSE00003650031	30722918	30723028
ENSE00003656975	30722537	30722645
ENSE00003841925	30723340	30725422

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6714 / max 146.3959, expressed in 1709 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66762	1222.4213	1826
66767	3.0472	1174
66764	2.5573	1262
66772	1.5609	884
66766	0.7773	508
66763	0.5235	309
66768	0.2052	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.92	gold quality
ganglionic eminence	UBERON:0004023	99.89	gold quality
ventricular zone	UBERON:0003053	99.84	gold quality
smooth muscle tissue	UBERON:0001135	99.56	gold quality
stromal cell of endometrium	CL:0002255	99.54	gold quality
vermiform appendix	UBERON:0001154	99.40	gold quality
ovary	UBERON:0000992	99.34	gold quality
islet of Langerhans	UBERON:0000006	99.33	gold quality
left ovary	UBERON:0002119	99.33	gold quality
placenta	UBERON:0001987	99.31	gold quality
right ovary	UBERON:0002118	99.31	gold quality
lymph node	UBERON:0000029	99.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.24	gold quality
body of uterus	UBERON:0009853	99.17	gold quality
myometrium	UBERON:0001296	99.13	gold quality
gall bladder	UBERON:0002110	99.06	gold quality
superior frontal gyrus	UBERON:0002661	99.05	gold quality
hypothalamus	UBERON:0001898	99.04	gold quality
left uterine tube	UBERON:0001303	99.03	gold quality
ectocervix	UBERON:0012249	99.01	gold quality
descending thoracic aorta	UBERON:0002345	99.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.98	gold quality
endocervix	UBERON:0000458	98.97	gold quality
right coronary artery	UBERON:0001625	98.97	gold quality
fallopian tube	UBERON:0003889	98.97	gold quality
lower esophagus	UBERON:0013473	98.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.97	gold quality
rectum	UBERON:0001052	98.93	gold quality
left coronary artery	UBERON:0001626	98.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.90	gold quality

Single-cell (SCXA)

Detected in 44 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	3159.88
E-MTAB-9543	yes	3068.81
E-CURD-79	yes	2140.44
E-GEOD-84465	yes	2032.86
E-MTAB-9435	yes	1763.78
E-CURD-126	yes	1752.42
E-GEOD-81547	yes	1675.99
E-MTAB-6379	yes	1046.69
E-MTAB-6701	yes	987.32
E-MTAB-10432	yes	979.18
E-GEOD-111727	yes	948.61
E-CURD-98	yes	937.05
E-MTAB-6653	yes	900.40
E-MTAB-10885	yes	713.49
E-MTAB-10283	yes	628.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

73 targeting TUBB, 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-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-1827	99.63	68.57	3265

Literature-anchored findings (GeneRIF, showing 32)

• Mutational analysis of the class I beta-tubulin gene in human breast cancer (PMID:12209587)
• the influence of beta-tubulin mutations in paclitaxel resistance in advanced non-small cell lung cancer (PMID:12826311)
• Review of studies comparing beta-tubulin mutations with antitubulin drug resistance. Throws doubts on earlier such correlation because of the existence of many pseudogenes for beta-tubulin. (PMID:15003198)
• TUBB exon 4 mutations and mismatch repair defects do not play a significant role in paclitaxel/cisplatin resistance (PMID:16095531)
• These data indicate that phosphorylation of tubulin by Cdk1 could be involved in the regulation of microtubule dynamics during mitosis. (PMID:16371510)
• cDNA subtraction revealed increased expression of alpha3-tubulin in the taxol-resistant cell line. (PMID:16380805)
• the dipole moments of each tubulin isotype may influence their functional characteristics within the cell, resulting in differences for MT assembly kinetics and stability (PMID:16941085)
• Nuclear matrix proteins such as mutant Pyst1 and nucleophosmin 1 were downregulated, whereas eIF6 and beta-tubulin were upregulated during cell differentiation in hepatocarcinoma cells. (PMID:17569113)
• Results suggest that glutamate198 in beta-tubulin is a critical determinant for microtubule stability and Taxol resistance. (PMID:17869412)
• Roles of tubulin beta 1,3 residues Ala428 and Thr429 in microtubule formation in vivo. (PMID:19074767)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• human tumor cells can acquire spontaneous mutations in beta1-tubulin that cause resistance to paclitaxel (PMID:20103599)
• Data show that knockdown of S100P led to downregulation of thioredoxin 1 and beta-tubulin and upregulation of RhoGDIA, all potential therapeutic targets in cancer. (PMID:21327297)
• This is the first cell-based evidence to support a beta-tubulin-binding site for peloruside A and laulimalide. (PMID:21653684)
• TQ induced a concentration- and time-dependent degradation of alpha/beta tubulin in both cancer cell types. (PMID:21881916)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Allele frequencies between a group of 191 ITP patients & controls showed no direct aetiological role for SNP (R307H), but it was associated with immunomodulatory treatment failure. (PMID:23157319)
• results provide insight into the functional repertoire of the tubulin gene family, specifically implicating TUBB5 in embryonic neurogenesis and microcephaly (PMID:23246003)
• Centaurin-alpha interacts with beta-tubulin and stabilizes microtubules. (PMID:23285209)
• Studies suggest that tubulin-interactive agents have the potential to play a significant role in the fight against cancer. (PMID:23818224)
• Citrullination of TUBB is associated with neoplasms. (PMID:24099319)
• mechanism of binding and stabilization of microtubules in mammalian cells can be effectively modeled in yeast and also having the advantage of lacking any beta-tubulin isotypes that can complicate interpretation of experiments in mammalian cells. (PMID:24161989)
• Data indicate that leucine-rich repeat kinase 2 (LRRK2) selectively interacts with three beta-tubulin isoforms: TUBB, TUBB4, and TUBB6. (PMID:24275654)
• Data suggest that, while lacking a stable structure, NFL-TBS.40-63 peptide (a peptide derived from light neurofilament protein) preferentially binds on a specific single site located near C-terminal end of beta-tubulin. (PMID:26016807)
• Data suggest a looser binding of the ligand in tubulin mutants. (PMID:26081685)
• Data show that tubulin phosphorylation and acetylation play important roles in the control of microtubule assembly and stability. (PMID:26165356)
• Mutations in either TUBB or MAPRE2 cause circumferential skin creases Kunze type. (PMID:26637975)
• Leucine point mutations viz. L215H, L217R, and L225M were reported for paclitaxel resistance in various cancers. In the current study, molecular mechanism of these resistance causing mutations in TUBB1 was explored using molecular docking, molecular dynamics simulation, binding energy estimation, free energy decomposition, principle component analysis and free energy landscape methods. (PMID:27233604)
• TUBB Variants Underlying Different Phenotypes Result in Altered Vesicle Trafficking and Microtubule Dynamics. (PMID:32085672)
• Competitive Microtubule Binding of PEX14 Coordinates Peroxisomal Protein Import and Motility. (PMID:33484719)
• Identification of two novel de novo TUBB variants in cases with brain malformations: case reports and literature review. (PMID:34211110)
• Dynamics of TUBB protein with five majorly occurring natural variants: a risk of cortical dysplasia. (PMID:36928665)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tubb5	ENSDARG00000037997
mus_musculus	Tubb5	ENSMUSG00000001525
rattus_norvegicus	Tubb5	ENSRNOG00000061216

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), TUBB4B (ENSG00000188229), TUBA3C (ENSG00000198033), TUBA4B (ENSG00000243910), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin beta chain — P07437 (reviewed: P07437)

Alternative names: Tubulin beta-5 chain

All UniProt accessions (4): P07437, Q5JP53, Q5ST81, Q5SU16

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. Heterodimer 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. Interacts with CIMAP3. Interacts with DIAPH1. Interacts with MX1. May interact with RNABP10. Interacts with CFAP157. Nascent tubulin polypeptide interacts (via beta-tubulin MREI motif) with TTC5/STRAP; this interaction results in tubulin mRNA-targeted degradation.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitously expressed with highest levels in spleen, thymus and immature 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 6 (CDCBM6) [MIM:615771] A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have microcephaly, ataxia, and severe delayed psychomotor development. Brain imaging shows variable malformations of cortical development, including white matter streaks, dysmorphic basal ganglia, corpus callosum abnormalities, brainstem and cerebellar hypoplasia, cortical dysplasia, polymicrogyria. The disease is caused by variants affecting the gene represented in this entry. Skin creases, congenital symmetric circumferential, 1 (CSCSC1) [MIM:156610] An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features. 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.

Induction. Autoregulated by feedback control of mRNA degradation. In excess of soluble tubulin, nascent beta-tubulin chain binds TTC5/STRAP cofactor through the MREI motif which triggers cotranslation degradation of tubulin mRNA.

Similarity. Belongs to the tubulin family.

RefSeq proteins (6): NP_001280141, NP_001280142, NP_001280143, NP_001280144, NP_001280145, NP_821133* (*=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 (89 total): helix 22, strand 18, modified residue 17, binding site 9, turn 7, sequence variant 5, sequence conflict 5, cross-link 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
3QNZ	X-RAY DIFFRACTION	2.2
3QO0	X-RAY DIFFRACTION	2.3
8BPO	ELECTRON MICROSCOPY	2.8
7TTT	ELECTRON MICROSCOPY	2.9
8V2J	ELECTRON MICROSCOPY	2.9
9COC	ELECTRON MICROSCOPY	2.9
7TRG	ELECTRON MICROSCOPY	3
7X0S	ELECTRON MICROSCOPY	3.1
9BP6	ELECTRON MICROSCOPY	3.1
9CMM	ELECTRON MICROSCOPY	3.1
9HQ4	ELECTRON MICROSCOPY	3.28
7TTN	ELECTRON MICROSCOPY	3.3
6I2I	ELECTRON MICROSCOPY	3.6
7TUB	ELECTRON MICROSCOPY	3.6
8T42	ELECTRON MICROSCOPY	3.6
8U3Z	ELECTRON MICROSCOPY	3.6
6QUS	ELECTRON MICROSCOPY	3.7
6QVE	ELECTRON MICROSCOPY	3.7
6QUY	ELECTRON MICROSCOPY	3.8
6QVJ	ELECTRON MICROSCOPY	3.8
5N5N	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07437-F1	92.18	0.85

Antibody-complex structures (SAbDab): 2 — 3QNZ, 3QO0

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 (19): 40, 55, 58, 58, 172, 285, 290, 318, 434, 438, 438, 439, 439, 441, 441, 442, 443, 58, 324

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
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-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-6798695	Neutrophil degranulation
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-5663205	Infectious disease
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 553 (showing top): GNF2_RTN1, GOBP_EPITHELIUM_DEVELOPMENT, HONMA_DOCETAXEL_RESISTANCE, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MATTIOLI_MGUS_VS_PCL, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN, PATIL_LIVER_CANCER, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (10): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), microtubule-based process (GO:0007017), cytoskeleton-dependent intracellular transport (GO:0030705), natural killer cell mediated cytotoxicity (GO:0042267), regulation of synapse organization (GO:0050807), spindle assembly (GO:0051225), cell division (GO:0051301), odontoblast differentiation (GO:0071895), cytoskeleton organization (GO:0007010)

GO Molecular Function (12): GTPase activity (GO:0003924), structural molecule activity (GO:0005198), structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), protein domain specific binding (GO:0019904), ubiquitin protein ligase binding (GO:0031625), GTPase activating protein binding (GO:0032794), MHC class I protein binding (GO:0042288), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (16): extracellular region (GO:0005576), nucleus (GO:0005634), nuclear envelope lumen (GO:0005641), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), protein-containing complex (GO:0032991), azurophil granule lumen (GO:0035578), cytoplasmic ribonucleoprotein granule (GO:0036464), cell body (GO:0044297), membrane raft (GO:0045121), intercellular bridge (GO:0045171), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Innate Immune System	1
SARS-CoV Infections	1
Immune System	1
Organelle biogenesis and maintenance	1
Disease	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoskeleton organization	2
cellular process	2
cytoskeleton	2
protein binding	2
binding	2
cytoplasm	2
microtubule-based process	1
cell cycle	1
mitotic nuclear division	1
intracellular transport	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
neuroepithelial cell differentiation	1
organelle organization	1
ribonucleoside triphosphate phosphatase activity	1
molecular_function	1
structural molecule activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ubiquitin-like protein ligase binding	1
MHC protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
organelle envelope lumen	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cellular_component	1
vacuolar lumen	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

487 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TUBB	NEDD8	psi-mi:“MI:0915”(physical association)	0.670
TUBB	SQSTM1	psi-mi:“MI:0915”(physical association)	0.670
APP	TUBB	psi-mi:“MI:0915”(physical association)	0.670
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
TUBB	PLD2	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
TJP1	ACTN4	psi-mi:“MI:0914”(association)	0.600
CALR	TUBB	psi-mi:“MI:0915”(physical association)	0.560
TUBB	DLST	psi-mi:“MI:0915”(physical association)	0.560
TUBB	NDUFV2	psi-mi:“MI:0915”(physical association)	0.560
TUBB	NEK7	psi-mi:“MI:0915”(physical association)	0.560
NEFL	TUBB	psi-mi:“MI:0915”(physical association)	0.560
TUBB	TFF2	psi-mi:“MI:0915”(physical association)	0.560
SOD1	TUBB	psi-mi:“MI:0915”(physical association)	0.560
TUBB	SNCA	psi-mi:“MI:0915”(physical association)	0.560
TUBB	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1025): TUBB (Affinity Capture-MS), TUBB (Affinity Capture-MS), TUBB (Affinity Capture-MS), TUBB (Two-hybrid), TUBB (Two-hybrid), MAGEA2B (Two-hybrid), TUBB (Affinity Capture-MS), TUBB (Affinity Capture-MS), TUBB (Reconstituted Complex), TUBB (Reconstituted Complex), TUBB (Affinity Capture-MS), TUBB (Affinity Capture-MS), TUBB (Affinity Capture-RNA), PHB2 (Co-fractionation), TUBB (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

11 interactions.

A	Effect	B	Mechanism
NUMA1	up-regulates	TUBB	binding
TUBB	down-regulates	SMAD2	binding
TUBB	down-regulates	SMAD3	binding
TUBB	“down-regulates activity”	SMAD2	binding
TUBB	“down-regulates activity”	SMAD3	binding
“Vincristine sulfate”	“down-regulates activity”	TUBB	“chemical inhibition”
“vincaleukoblastine sulfate”	“down-regulates activity”	TUBB	“chemical inhibition”
“vinorelbine L-tartrate”	“down-regulates activity”	TUBB	“chemical inhibition”
JAKMIP1	“up-regulates quantity by stabilization”	TUBB	binding
YAP1	“up-regulates quantity by expression”	TUBB	“transcriptional regulation”
YAP/TAZ	“up-regulates quantity by expression”	TUBB	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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	7	27.6×	4e-07
Transport of connexons to the plasma membrane	7	27.6×	4e-07
Gap junction trafficking and regulation	7	24.1×	8e-07
Gap junction trafficking	7	24.1×	8e-07
Post-chaperonin tubulin folding pathway	7	24.1×	8e-07
RHO GTPases activate IQGAPs	9	22.6×	6e-08
Activation of AMPK downstream of NMDARs	8	22.1×	3e-07
Formation of tubulin folding intermediates by CCT/TriC	7	21.4×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
amyloid fibril formation	7	24.4×	9e-06
Fc-gamma receptor signaling pathway involved in phagocytosis	5	20.3×	9e-04
cytoplasmic microtubule organization	8	15.9×	2e-05
protein destabilization	8	13.4×	5e-05
negative regulation of protein-containing complex assembly	5	13.2×	4e-03
intrinsic apoptotic signaling pathway	6	12.4×	1e-03
microtubule cytoskeleton organization	15	10.5×	2e-08
G1/S transition of mitotic cell cycle	8	9.3×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	23
Uncertain significance	52
Likely benign	12
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
127189	NM_178014.4(TUBB):c.895A>G (p.Met299Val)	Pathogenic
127191	NM_178014.4(TUBB):c.1201G>A (p.Glu401Lys)	Pathogenic
218925	NM_178014.4(TUBB):c.43C>A (p.Gln15Lys)	Pathogenic
218926	NM_178014.4(TUBB):c.665A>T (p.Tyr222Phe)	Pathogenic
2662647	NM_178014.4(TUBB):c.859C>T (p.Pro287Ser)	Pathogenic
3256783	NM_178014.4(TUBB):c.869C>T (p.Thr290Ile)	Pathogenic
3343929	NM_178014.4(TUBB):c.716G>C (p.Cys239Ser)	Pathogenic
4528358	NM_178014.4(TUBB):c.626A>G (p.Asp209Gly)	Pathogenic
977846	NM_178014.4(TUBB):c.1261G>A (p.Glu421Lys)	Pathogenic
1077126	NM_178014.4(TUBB):c.1081C>T (p.Leu361Phe)	Likely pathogenic
1172521	NM_178014.4(TUBB):c.316T>G (p.Tyr106Asp)	Likely pathogenic
1337305	NM_178014.4(TUBB):c.682C>A (p.Leu228Ile)	Likely pathogenic
1338518	NM_178014.4(TUBB):c.897G>A (p.Met299Ile)	Likely pathogenic
1339905	NM_178014.4(TUBB):c.917G>C (p.Arg306Pro)	Likely pathogenic
1685467	NM_178014.4(TUBB):c.45G>C (p.Gln15His)	Likely pathogenic
1709915	NM_178014.4(TUBB):c.670G>T (p.Asp224Tyr)	Likely pathogenic
2442458	NM_178014.4(TUBB):c.968T>C (p.Met323Thr)	Likely pathogenic
2443069	NM_178014.4(TUBB):c.260C>T (p.Pro87Leu)	Likely pathogenic
3256579	NM_178014.4(TUBB):c.670G>C (p.Asp224His)	Likely pathogenic
3256784	NM_178014.4(TUBB):c.91G>A (p.Asp31Asn)	Likely pathogenic
3343375	NM_178014.4(TUBB):c.202C>A (p.Leu68Ile)	Likely pathogenic
3600528	NM_178014.4(TUBB):c.245G>T (p.Gly82Val)	Likely pathogenic
373428	NM_178014.4(TUBB):c.322G>A (p.Glu108Lys)	Likely pathogenic
3764220	NM_178014.4(TUBB):c.680A>G (p.His227Arg)	Likely pathogenic
376764	NM_178014.4(TUBB):c.533C>G (p.Thr178Ser)	Likely pathogenic
3777398	NM_178014.4(TUBB):c.752G>T (p.Arg251Leu)	Likely pathogenic
392956	NM_178014.4(TUBB):c.682C>G (p.Leu228Val)	Likely pathogenic
426178	NM_178014.4(TUBB):c.1230G>T (p.Glu410Asp)	Likely pathogenic
545082	NM_178014.4(TUBB):c.647A>G (p.Lys216Arg)	Likely pathogenic
807517	NM_178014.4(TUBB):c.448C>T (p.Leu150Phe)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2961 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:30720534:G:C	G10R	1.000
6:30720535:G:A	G10D	1.000
6:30720535:G:T	G10V	1.000
6:30720542:T:G	C12W	1.000
6:30720543:G:C	G13R	1.000
6:30720544:G:A	G13D	1.000
6:30720544:G:T	G13V	1.000
6:30720548:C:A	N14K	1.000
6:30720548:C:G	N14K	1.000
6:30722540:T:A	W21R	1.000
6:30722540:T:C	W21R	1.000
6:30722950:G:C	D67H	1.000
6:30722951:A:T	D67V	1.000
6:30722954:T:C	L68P	1.000
6:30723348:G:A	G96R	1.000
6:30723348:G:C	G96R	1.000
6:30723348:G:T	G96W	1.000
6:30723349:G:A	G96E	1.000
6:30723355:G:A	G98D	1.000
6:30723359:C:A	N99K	1.000
6:30723359:C:G	N99K	1.000
6:30723362:C:A	N100K	1.000
6:30723362:C:G	N100K	1.000
6:30723363:T:A	W101R	1.000
6:30723363:T:C	W101R	1.000
6:30723364:G:C	W101S	1.000
6:30723365:G:C	W101C	1.000
6:30723365:G:T	W101C	1.000
6:30723367:C:A	A102D	1.000
6:30723371:A:C	K103N	1.000

dbSNP variants (sampled 300 via entrez): RS1000078102 (6:30719393 A>T), RS1000167465 (6:30721808 A>G), RS1000507617 (6:30723304 C>G), RS1000538751 (6:30722860 A>G), RS1000861472 (6:30725907 C>A), RS1001719194 (6:30721516 G>A,C,T), RS1002013820 (6:30722823 G>A), RS1002038200 (6:30719141 A>G), RS1002086642 (6:30721628 C>T), RS1002449516 (6:30722526 C>T), RS1002746118 (6:30721642 C>G,T), RS1005018813 (6:30720094 T>C), RS1005153319 (6:30720362 C>G,T), RS1005815530 (6:30725527 C>T), RS1006021642 (6:30721232 T>C)

Disease associations

OMIM: gene MIM:191130 | disease phenotypes: MIM:615771, MIM:156610, MIM:135700, MIM:607432

GenCC curated gene-disease

Disease	Classification	Inheritance
TUBB3-related tubulinopathy	Definitive	Autosomal dominant
multiple benign circumferential skin creases on limbs 1	Strong	Autosomal dominant
complex cortical dysplasia with other brain malformations 6	Strong	Autosomal dominant
multiple benign circumferential skin creases on limbs	Supportive	Autosomal dominant

Mondo (6): complex cortical dysplasia with other brain malformations 6 (MONDO:0014341), multiple benign circumferential skin creases on limbs 1 (MONDO:0020738), congenital fibrosis of extraocular muscles (MONDO:0007614), lissencephaly spectrum disorders (MONDO:0018838), TUBB3-related tubulinopathy (MONDO:0100154), multiple benign circumferential skin creases on limbs (MONDO:0007990)

Orphanet (2): Congenital fibrosis of extraocular muscles (Orphanet:45358), Lissencephaly (Orphanet:48471)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000045	Abnormal scrotum morphology
HP:0000046	Small scrotum
HP:0000047	Hypospadias
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000271	Abnormality of the face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000396	Overfolded helix
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000488	Retinopathy
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000629	Periorbital fullness
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000969	Edema

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_132	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_27	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_48	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST008533_1	Decreased fine motor function in Charcot-Marie-Tooth disease 1A (eating with utensils)	1.000000e-06
GCST008820_1	Handedness (non-right-handed vs right-handed)	3.000000e-08
GCST012228_102	Waist-hip index	3.000000e-08
GCST012230_301	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90010427_10	Left–right brain asymmetry	2.000000e-10
GCST90013421_14	Left-handedness	6.000000e-25

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010132	decreased fine motor function
EFO:0009902	handedness
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
C537575	Michelin tire baby syndrome (supp.)
C580012	congenital fibrosis of the extraocular muscles (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2095182 (PROTEIN COMPLEX GROUP), CHEMBL3832942 (PROTEIN FAMILY), CHEMBL3885647 (PROTEIN COMPLEX GROUP), CHEMBL5444 (SINGLE PROTEIN), 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: 1,641,397 (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
CHEMBL1232461	MOLIBRESIB	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

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
vinblastine	Inhibition	9.0	pIC50
eribulin	Inhibition	8.23	pIC50
paclitaxel	Inhibition	8.05	pEC50
colchicine	Inhibition	7.96	pIC50

ChEMBL bioactivities

1181 potent at pChembl≥5 of 1333 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
8.04	Kd	9.047	nM	CHEMBL5653589
8.04	ED50	9.047	nM	CHEMBL5653589
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

1108 with measured affinity, of 5941 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149678: Binding affinity to human TUBB incubated for 45 mins by Kinobead based pull down assay	kd	0.0090	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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment	6
bisphenol A	decreases expression, affects expression, affects cotreatment, increases methylation, increases expression	5
Tobacco Smoke Pollution	affects expression, decreases expression, increases metabolic processing	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
cobaltous chloride	increases expression, decreases expression	2
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression	2
chloropicrin	affects expression, decreases expression	2
Docetaxel	increases expression, decreases reaction, increases response to substance, decreases response to substance	2
Arsenic	affects methylation, affects binding, decreases activity, decreases reaction	2
Doxorubicin	affects cotreatment, increases expression, decreases expression	2
Quercetin	decreases expression	2
Tunicamycin	decreases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression, increases methylation	2
Thapsigargin	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
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
biochanin A	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
titanium dioxide	increases phosphorylation	1
withaferin A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
salinomycin	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1

ChEMBL screening assays

1780 unique, capped per target: 1740 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

Clinical trials (associated diseases)

1 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