TUBB2A

Summary

TUBB2A (tubulin beta 2A class IIa, HGNC:12412) is a protein-coding gene on chromosome 6p25.2, encoding Tubulin beta-2A chain (Q13885). Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. It is a common-essential gene (DepMap: required in 97.4% of cancer cell lines).

Microtubules, key participants in processes such as mitosis and intracellular transport, are composed of heterodimers of alpha- and beta-tubulins. The protein encoded by this gene is a beta-tubulin. Defects in this gene are associated with complex cortical dysplasia with other brain malformations-5. Two transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 7280 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tubulinopathy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 362 total — 10 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_001069

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12412
Approved symbol	TUBB2A
Name	tubulin beta 2A class IIa
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	dJ40E16.7
Ensembl gene	ENSG00000137267
Ensembl biotype	protein_coding
OMIM	615101
Entrez	7280

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 retained_intron, 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000333628, ENST00000489942, ENST00000679400, ENST00000679907, ENST00000680036, ENST00000680967, ENST00000940056

RefSeq mRNA: 2 — MANE Select: NM_001069 NM_001069, NM_001310315

CCDS: CCDS4484

Canonical transcript exons

ENST00000333628 — 4 exons

Exon	Start	End
ENSE00001484630	3153666	3154923
ENSE00003585737	3155625	3155735
ENSE00003596735	3157407	3157544
ENSE00003666774	3156044	3156152

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1222.4213 / max 6160.3868, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66762	1222.4213	1826
71453	79.2803	1789
66761	0.6997	313

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.98	gold quality
dorsal root ganglion	UBERON:0000044	99.98	gold quality
pons	UBERON:0000988	99.98	gold quality
frontal pole	UBERON:0002795	99.98	gold quality
substantia nigra pars compacta	UBERON:0001965	99.97	gold quality
superior vestibular nucleus	UBERON:0007227	99.96	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.96	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.95	gold quality
orbitofrontal cortex	UBERON:0004167	99.95	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.94	gold quality
paraflocculus	UBERON:0005351	99.94	gold quality
entorhinal cortex	UBERON:0002728	99.93	gold quality
parietal lobe	UBERON:0001872	99.92	gold quality
cerebellar vermis	UBERON:0004720	99.92	gold quality
postcentral gyrus	UBERON:0002581	99.91	gold quality
superior frontal gyrus	UBERON:0002661	99.90	gold quality
ventral tegmental area	UBERON:0002691	99.88	gold quality
middle temporal gyrus	UBERON:0002771	99.87	gold quality
CA1 field of hippocampus	UBERON:0003881	99.86	gold quality
trigeminal ganglion	UBERON:0001675	99.85	gold quality
medulla oblongata	UBERON:0001896	99.81	gold quality
cortical plate	UBERON:0005343	99.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.78	gold quality
hair follicle	UBERON:0002073	99.75	gold quality
middle frontal gyrus	UBERON:0002702	99.74	gold quality
adult organism	UBERON:0007023	99.73	gold quality
gingival epithelium	UBERON:0001949	99.70	gold quality
lateral globus pallidus	UBERON:0002476	99.68	gold quality
gingiva	UBERON:0001828	99.67	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1577.85
E-HCAD-35	yes	44.62
E-HCAD-5	yes	29.88
E-GEOD-135922	yes	19.34
E-HCAD-10	yes	16.02
E-MTAB-7316	yes	15.81
E-MTAB-5061	yes	14.06
E-GEOD-84465	yes	11.68
E-HCAD-25	yes	10.76
E-GEOD-81608	yes	10.15
E-GEOD-137537	yes	7.32
E-HCAD-9	yes	5.96
E-HCAD-31	yes	4.15
E-HCAD-56	no	2481.38
E-MTAB-9154	no	1831.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

19 targeting TUBB2A, 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-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-767-5P	99.95	70.85	993
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-591	96.29	68.16	611

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• Data show that connexin 43 (cx43) binds alpha-tubulin equally well as beta-tubulin, and that ZO-1 binds directly to Cx43. (PMID:12064592)
• lack of mutations in early stage lung cancer (PMID:12209967)
• Mutations of the beta-tubulin gene, which might be a contraindication for chemotherapy based on taxans, were very rare events in gastric cancer. (PMID:12861402)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• Data suggest that the increased betaII- and betaIII-tubulin contributed significantly to the resistance phenotype. (PMID:22180309)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Class II beta-tubulin may be very useful for immunohistochemical diagnosis of classical Hodgkin’s lymphoma. (PMID:22449234)
• This is the first study showing that paclitaxel neuropathy risk is influenced by polymorphisms regulating the expression of a beta-tubulin gene. (PMID:22718863)
• study associates mutations in TUBB2A with the spectrum of “tubulinopathy” phenotypes (PMID:24702957)
• TUBB2A missense mutation is associated with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay. (PMID:28840640)
• Consistent with the differential clinical and structural impact, TUBB2AA248V does not drastically affect TUBB2A binding to KIF1A, nor mitotic spindle bipolarity. Overall, our data demonstrate a pathogenic role of the p.D417N substitution that is different from previously reported TUBB2A mutations and expand the phenotypic spectrum associated with mutations in this gene. (PMID:29547997)
• 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)
• De novo mutations of TUBB2A cause infantile-onset epilepsy and developmental delay. (PMID:32203252)
• Defining the phenotypical spectrum associated with variants in TUBB2A. (PMID:32571897)
• Circular RNA circ_C16orf62 Suppresses Cell Growth in Gastric Cancer by miR-421/Tubulin beta-2A Chain (TUBB2A) Axis. (PMID:33006960)
• Using data from the 100,000 Genomes Project to resolve conflicting interpretations of a recurrent TUBB2A mutation. (PMID:33547136)
• Generation of an induced pluripotent stem cell line (DHMCi009-A) from an individual with TUBB2A tubulinopathy. (PMID:35930870)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tubb2	ENSDARG00000039522
mus_musculus	Tubb2a	ENSMUSG00000058672
rattus_norvegicus	Tubb2a	ENSRNOG00000017558
drosophila_melanogaster	betaTub85D	FBGN0003889

Paralogs (23): TUBG2 (ENSG00000037042), TUBE1 (ENSG00000074935), TUBA3D (ENSG00000075886), TUBB1 (ENSG00000101162), TUBB4A (ENSG00000104833), TUBD1 (ENSG00000108423), TUBA1B (ENSG00000123416), TUBA4A (ENSG00000127824), TUBG1 (ENSG00000131462), TUBB2B (ENSG00000137285), 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-2A chain — Q13885 (reviewed: Q13885)

Alternative names: Tubulin beta class IIa

All UniProt accessions (1): Q13885

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. Interacts with ZNRF1. Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. 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, where it represents 30% of all beta-tubulins.

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 5 (CDCBM5) [MIM:615763] A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include seizures, global developmental delay, and various brain malformations such as a diffuse simplified gyral pattern with reduced volume of white matter, globular basal ganglia, thin and dysmorphic corpus callosum, mild brainstem hypoplasia with a flat pons, mild cerebellar vermis hypoplasia, and mildly enlarged posterior fossa. The disease is caused by variants affecting the gene represented in this entry.

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 (2): NP_001060, NP_001297244 (=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 (54 total): helix 13, strand 10, binding site 9, modified residue 8, sequence variant 3, sequence conflict 3, cross-link 2, turn 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)
8V3O	X-RAY DIFFRACTION	2.3
8V3P	X-RAY DIFFRACTION	2.36
7NVN	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13885-F1	92.44	0.84

Antibody-complex structures (SAbDab): 1 — 7NVN

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 (10): 40, 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: 979 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GNF2_RTN1, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, LOPEZ_MESOTHELIOMA_SURVIVAL_DN, GOBP_EPITHELIUM_DEVELOPMENT, HONMA_DOCETAXEL_RESISTANCE, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, PAL_PRMT5_TARGETS_UP, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP

GO Biological Process (5): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), neuron migration (GO:0001764), cerebral cortex development (GO:0021987), microtubule-based process (GO:0007017)

GO Molecular Function (6): GTPase activity (GO:0003924), structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), intercellular bridge (GO:0045171), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686), extracellular vesicle (GO:1903561), 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
pallium development	1
anatomical structure development	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
structural molecule activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	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
extracellular vesicle	1
spindle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

4968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBB2A	TUBA1B	P04687	939
TUBB2A	TUBA1C	Q9BQE3	933
TUBB2A	TUBA4A	P05215	931
TUBB2A	TUBA8	Q9NY65	915
TUBB2A	TUBAL3	A6NHL2	887
TUBB2A	TUBA1B	P04687	887
TUBB2A	TUBA3E	Q6PEY2	886
TUBB2A	TUBA3C	P0DPH7	886
TUBB2A	WDR83OS	Q9Y284	750
TUBB2A	POTEF	A5A3E0	740
TUBB2A	SYT9	Q86SS6	711
TUBB2A	DYNC1I1	O14576	708
TUBB2A	KIF1A	Q12756	704
TUBB2A	ACTB	P02570	695
TUBB2A	KATNB1	Q9BVA0	688
TUBB2A	GAPDH	P00354	688

IntAct

195 interactions, top by confidence:

A	B	Type	Score
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TUBB2A	JUN	psi-mi:“MI:0915”(physical association)	0.670
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
TUBB2A	CASP6	psi-mi:“MI:0915”(physical association)	0.560
SYP	TUBB2A	psi-mi:“MI:0915”(physical association)	0.560
TUBB2A	BECN1	psi-mi:“MI:0915”(physical association)	0.560
TUBB2A	ZNF488	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
TUBB2A	TK1	psi-mi:“MI:0915”(physical association)	0.550
LRRK2	TUBB2A	psi-mi:“MI:0915”(physical association)	0.550
ILK	HAX1	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
TUBB2A	EML2	psi-mi:“MI:0914”(association)	0.530
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530

BioGRID (458): TUBB2A (Protein-peptide), TUBB2A (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB2A (Affinity Capture-MS), TUBB7P (Affinity Capture-MS), EML4 (Affinity Capture-MS), TBCD (Affinity Capture-MS), CCT6B (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), TTC5 (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: A2AQ07, A6NNZ2, O04386, O17449, O44388, P02554, P04350, P04690, P07436, P07437, P08841, P09203, P09206, P09207, P09244, P09652, P09653, P10876, P10878, P11482, P11833, P11857, P12456, P13602, P14643, P18241, P20365, P22852, P30883, P32882, P33188, P34108, P36221, P37832, P41352, P41387, P41937, P46265, P50261, P50262

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUMA1	up-regulates	TUBB2A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 230 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	29.0×	1e-08
Transport of connexons to the plasma membrane	8	29.0×	1e-08
Formation of tubulin folding intermediates by CCT/TriC	10	28.2×	6e-10
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	10	27.2×	6e-10
Gap junction trafficking and regulation	8	25.4×	3e-08
Gap junction trafficking	8	25.4×	3e-08
Post-chaperonin tubulin folding pathway	8	25.4×	3e-08
Removal of the Flap Intermediate from the C-strand	6	25.4×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of telomere maintenance via telomerase	6	22.8×	9e-05
positive regulation of telomere maintenance	5	13.2×	4e-03
cytoplasmic microtubule organization	7	12.5×	4e-04
autophagosome maturation	6	10.9×	2e-03
microtubule cytoskeleton organization	16	10.1×	8e-09
mitotic cell cycle	10	6.9×	5e-04
protein stabilization	13	4.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	19
Uncertain significance	125
Likely benign	158
Benign	20

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1182639	NM_001069.3(TUBB2A):c.1070C>T (p.Pro357Leu)	Pathogenic
127100	NM_001069.3(TUBB2A):c.741C>G (p.Asn247Lys)	Pathogenic
1369968	NM_001069.3(TUBB2A):c.296A>G (p.Asn99Ser)	Pathogenic
1386454	NM_001069.3(TUBB2A):c.365A>C (p.Lys122Thr)	Pathogenic
1453506	NM_001069.3(TUBB2A):c.615G>C (p.Glu205Asp)	Pathogenic
1455244	NC_000006.11:g.(?3157621)(3157697_?)del	Pathogenic
1459291	NM_001069.3(TUBB2A):c.941C>A (p.Ala314Asp)	Pathogenic
2857024	NM_001069.3(TUBB2A):c.767A>G (p.Asn256Ser)	Pathogenic
2982258	NM_001069.3(TUBB2A):c.1249G>A (p.Asp417Asn)	Pathogenic
4072027	NM_001069.3(TUBB2A):c.286G>A (p.Gly96Arg)	Pathogenic
1031017	NM_001069.3(TUBB2A):c.1073C>T (p.Pro358Leu)	Likely pathogenic
1065443	NM_001069.3(TUBB2A):c.1072C>A (p.Pro358Thr)	Likely pathogenic
1208720	NM_001069.3(TUBB2A):c.401A>T (p.Gln134Leu)	Likely pathogenic
1213605	NM_001069.3(TUBB2A):c.967A>C (p.Met323Leu)	Likely pathogenic
1253961	NM_001069.3(TUBB2A):c.518C>T (p.Pro173Leu)	Likely pathogenic
1685468	NM_001069.3(TUBB2A):c.148T>C (p.Tyr50His)	Likely pathogenic
1700177	NM_001069.3(TUBB2A):c.293G>T (p.Gly98Val)	Likely pathogenic
2028113	NM_001069.3(TUBB2A):c.1088T>G (p.Met363Arg)	Likely pathogenic
2430935	NM_001069.3(TUBB2A):c.935C>G (p.Thr312Arg)	Likely pathogenic
3026915	NM_001069.3(TUBB2A):c.391C>T (p.Gln131Ter)	Likely pathogenic
3363701	NM_001069.3(TUBB2A):c.518C>G (p.Pro173Arg)	Likely pathogenic
372880	NM_001069.3(TUBB2A):c.1240A>C (p.Asn414His)	Likely pathogenic
3778745	NM_001069.3(TUBB2A):c.620T>C (p.Leu207Pro)	Likely pathogenic
384308	NM_001069.3(TUBB2A):c.731G>C (p.Gly244Ala)	Likely pathogenic
3897572	NM_001069.3(TUBB2A):c.1204G>C (p.Gly402Arg)	Likely pathogenic
432097	NM_001069.3(TUBB2A):c.724T>C (p.Phe242Leu)	Likely pathogenic
624121	NM_001069.3(TUBB2A):c.1247A>G (p.Asn416Ser)	Likely pathogenic
800924	NM_001069.3(TUBB2A):c.1178C>T (p.Ala393Val)	Likely pathogenic
986830	NM_001069.3(TUBB2A):c.1228G>A (p.Glu410Lys)	Likely pathogenic

SpliceAI

858 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30722521:T:TA	acceptor_gain	1.0000
6:30722531:C:A	acceptor_gain	1.0000
6:30722532:G:A	acceptor_gain	1.0000
6:30722532:GGCA:G	acceptor_loss	1.0000
6:30722533:GCAG:G	acceptor_loss	1.0000
6:30722535:A:AG	acceptor_gain	1.0000
6:30722535:AG:A	acceptor_loss	1.0000
6:30722536:G:GA	acceptor_gain	1.0000
6:30722536:GT:G	acceptor_gain	1.0000
6:30722536:GTT:G	acceptor_gain	1.0000
6:30722536:GTTC:G	acceptor_gain	1.0000
6:30722645:GGTAA:G	donor_loss	1.0000
6:30722646:G:GG	donor_gain	1.0000
6:30722915:TAGGT:T	acceptor_loss	1.0000
6:30722916:A:AT	acceptor_loss	1.0000
6:30722917:G:A	acceptor_loss	1.0000
6:30723333:A:AG	acceptor_gain	1.0000
6:30723336:CCAG:C	acceptor_loss	1.0000
6:30723339:GGTCA:G	acceptor_gain	1.0000
6:3154919:CTGGC:C	acceptor_gain	1.0000
6:3154924:C:A	acceptor_loss	1.0000
6:3154925:T:G	acceptor_loss	1.0000
6:3155621:ATACC:A	donor_loss	1.0000
6:3155622:TA:T	donor_loss	1.0000
6:3155623:A:AC	donor_gain	1.0000
6:3155623:A:C	donor_loss	1.0000
6:3155624:C:CT	donor_gain	1.0000
6:3155624:CCGAA:C	donor_gain	1.0000
6:3155734:ACC:A	acceptor_loss	1.0000
6:3155736:C:CC	acceptor_gain	1.0000

AlphaMissense

2972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:3153937:A:G	Y422H	1.000
6:3153943:A:G	S420P	1.000
6:3153948:A:G	L418P	1.000
6:3153948:A:T	L418Q	1.000
6:3153951:T:A	D417V	1.000
6:3153951:T:C	D417G	1.000
6:3153951:T:G	D417A	1.000
6:3153952:C:G	D417H	1.000
6:3153969:G:T	A411D	1.000
6:3153970:C:G	A411P	1.000
6:3153977:G:C	F408L	1.000
6:3153977:G:T	F408L	1.000
6:3153978:A:C	F408C	1.000
6:3153978:A:G	F408S	1.000
6:3153979:A:G	F408L	1.000
6:3153982:C:T	E407K	1.000
6:3153990:T:A	D404V	1.000
6:3153991:C:G	D404H	1.000
6:3153992:C:A	M403I	1.000
6:3153992:C:G	M403I	1.000
6:3153992:C:T	M403I	1.000
6:3153993:A:G	M403T	1.000
6:3153996:C:A	G402V	1.000
6:3153996:C:T	G402D	1.000
6:3153997:C:A	G402C	1.000
6:3153997:C:G	G402R	1.000
6:3154012:A:G	W397R	1.000
6:3154012:A:T	W397R	1.000
6:3154015:G:C	H396D	1.000
6:3154019:G:C	F394L	1.000

dbSNP variants (sampled 300 via entrez): RS1000300382 (6:3157176 C>T), RS1000587148 (6:3156991 C>T), RS1001278609 (6:3157877 G>A), RS1001412724 (6:3155802 G>A,C), RS1001647929 (6:3158118 G>A), RS1001759317 (6:3156684 G>A), RS1002358681 (6:3157577 C>G,T), RS1002373326 (6:3158821 A>C), RS1003032383 (6:3153807 C>G), RS1003357053 (6:3159036 G>A), RS1003494353 (6:3153583 A>G), RS1004428801 (6:3153208 T>C), RS1005075801 (6:3153629 A>G), RS1005483483 (6:3157672 G>A), RS1005557724 (6:3153343 C>T)

Disease associations

OMIM: gene MIM:615101 | disease phenotypes: MIM:615763, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
complex cortical dysplasia with other brain malformations 5	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
tubulinopathy	Definitive	AD

Mondo (5): complex cortical dysplasia with other brain malformations 5 (MONDO:0014337), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), vascular dementia (MONDO:0004648), neurodevelopmental disorder (MONDO:0700092), tubulinopathy (MONDO:0100153)

Orphanet (2): Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001320	Cerebellar vermis hypoplasia
HP:0001344	Absent speech
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002365	Hypoplasia of the brainstem
HP:0002521	Hypsarrhythmia
HP:0002539	Cortical dysplasia
HP:0003593	Infantile onset
HP:0005445	Enlarged posterior fossa
HP:0009879	Simplified gyral pattern
HP:0010841	Multifocal epileptiform discharges
HP:0011344	Severe global developmental delay
HP:0012469	Infantile spasms
HP:0034295	Reduced cerebral white matter volume

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004621_90	Red cell distribution width	1.000000e-13
GCST90002390_149	Mean corpuscular hemoglobin	6.000000e-09
GCST90002396_317	Mean reticulocyte volume	5.000000e-09
GCST90002404_234	Red cell distribution width	2.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D065886	Neurodevelopmental Disorders	F03.625
C562568	Cerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095182 (PROTEIN COMPLEX GROUP), CHEMBL3797012 (SINGLE PROTEIN), CHEMBL3832942 (PROTEIN FAMILY), CHEMBL6066847 (PROTEIN-PROTEIN INTERACTION)

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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9501929	TUBB2A		0.00	0

ChEMBL bioactivities

1168 potent at pChembl≥5 of 1319 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
7.70	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
7.24	Kd	58	nM	COLCHICINE
7.22	Ki	60	nM	CHEMBL198522

PubChem BioAssay actives

1097 with measured affinity, of 5889 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
[(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
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-[[(1R)-1-diethoxyphosphoryl-2-(1H-indol-3-yl)ethyl]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	0.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, decreases expression, increases expression	7
Valproic Acid	affects expression, increases expression, increases methylation	5
methylmercuric chloride	increases expression, affects cotreatment	4
bisphenol A	decreases expression, increases expression, affects cotreatment	3
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression, increases expression	3
perfluorooctane sulfonic acid	affects expression, affects cotreatment, decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
Estradiol	affects cotreatment, increases expression, affects binding, increases reaction	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects expression, decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Antimycin A	decreases expression	2
Cisplatin	decreases expression, increases reaction, affects response to substance	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases metabolic processing	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
TL8-506	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	increases expression	1
testosterone undecanoate	increases expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1

ChEMBL screening assays

1758 unique, capped per target: 1718 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

2 cell lines: 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B3KA	Abcam HEK293T TUBB2A KO	Transformed cell line	Female
CVCL_C0JR	DHMCi009-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia
NCT04109963	PHASE2	UNKNOWN	Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
NCT05371639	PHASE2	UNKNOWN	Efficacy and Safety of Tian Ma Bian Chun Zhi Gan Tablets in Mild to Moderate Vascular Dementia
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00457769	PHASE1	UNKNOWN	Aricept to Improve Functional Tasks in Vascular Dementia
NCT03702543	PHASE1	UNKNOWN	Managing Vascular Dementia Risk Factors With SymTrend
NCT04567745	PHASE1	COMPLETED	Automated Retinal Image Analysis System (EyeQuant) for Computation of Vascular Biomarkers
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism