TUBB3
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Also known as beta-4CFEOM3CFEOM3A
Summary
TUBB3 (tubulin beta 3 class III, HGNC:20772) is a protein-coding gene on chromosome 16q24.3, encoding Tubulin beta-3 chain (Q13509). Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers. In precision oncology, TUBB3 EXPRESSION confers sensitivity to Taxane Compound in Breast Cancer (CIViC Level B); 1 further curated variant–drug associations are listed below.
This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6.
Source: NCBI Gene 10381 — RefSeq curated summary.
At a glance
- Gene–disease (curated): TUBB3-related tubulinopathy (Definitive, ClinGen) — +4 more curated relationships
- GWAS associations: 11
- Clinical variants (ClinVar): 364 total — 16 pathogenic, 29 likely-pathogenic
- Phenotypes (HPO): 137
- Druggable target: yes — 21 molecules with ChEMBL bioactivity
- Precision-oncology evidence (CIViC): 2 curated variant–drug associations
- Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
- MANE Select transcript:
NM_006086
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:20772 |
| Approved symbol | TUBB3 |
| Name | tubulin beta 3 class III |
| Location | 16q24.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | beta-4, CFEOM3, CFEOM3A |
| Ensembl gene | ENSG00000258947 |
| Ensembl biotype | protein_coding |
| OMIM | 602661 |
| Entrez | 10381 |
Gene structure
Transcript identifiers
Ensembl transcripts: 16 — 7 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined
ENST00000315491, ENST00000553656, ENST00000553967, ENST00000554116, ENST00000554336, ENST00000554444, ENST00000554927, ENST00000555576, ENST00000555609, ENST00000555810, ENST00000556536, ENST00000556565, ENST00000557262, ENST00000557490, ENST00000680647, ENST00000680788
RefSeq mRNA: 2 — MANE Select: NM_006086
NM_001197181, NM_006086
CCDS: CCDS10988, CCDS56012
Canonical transcript exons
ENST00000315491 — 4 exons
| Exon | Start | End |
|---|---|---|
| ENSE00002473274 | 89923342 | 89923458 |
| ENSE00002847482 | 89934729 | 89936097 |
| ENSE00003458728 | 89932571 | 89932679 |
| ENSE00003568398 | 89933468 | 89933578 |
Expression profiles
Bgee: expression breadth ubiquitous, 144 present calls, max score 99.85.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.4477 / max 2006.2209, expressed in 1647 samples.
FANTOM5 promoters (4 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 155672 | 64.5336 | 1626 |
| 155671 | 2.2011 | 1074 |
| 155673 | 0.4684 | 193 |
| 155674 | 0.2446 | 124 |
Top tissues by expression
146 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| cortical plate | UBERON:0005343 | 99.85 | gold quality |
| ganglionic eminence | UBERON:0004023 | 99.73 | gold quality |
| embryo | UBERON:0000922 | 99.72 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 98.96 | gold quality |
| hypothalamus | UBERON:0001898 | 98.89 | gold quality |
| ventricular zone | UBERON:0003053 | 98.80 | gold quality |
| primary visual cortex | UBERON:0002436 | 98.54 | gold quality |
| prefrontal cortex | UBERON:0000451 | 98.43 | gold quality |
| frontal cortex | UBERON:0001870 | 98.42 | gold quality |
| frontal lobe | UBERON:0016525 | 98.42 | gold quality |
| right frontal lobe | UBERON:0002810 | 98.38 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 98.28 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 98.17 | gold quality |
| cerebral cortex | UBERON:0000956 | 98.08 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 98.04 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 97.97 | gold quality |
| cerebellum | UBERON:0002037 | 97.75 | gold quality |
| cerebellar cortex | UBERON:0002129 | 97.73 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 97.72 | gold quality |
| telencephalon | UBERON:0001893 | 97.21 | gold quality |
| temporal lobe | UBERON:0001871 | 97.16 | gold quality |
| brain | UBERON:0000955 | 97.12 | gold quality |
| amygdala | UBERON:0001876 | 97.12 | gold quality |
| substantia nigra | UBERON:0002038 | 97.01 | gold quality |
| Ammon’s horn | UBERON:0001954 | 96.61 | gold quality |
| nucleus accumbens | UBERON:0001882 | 96.30 | gold quality |
| caudate nucleus | UBERON:0001873 | 95.82 | gold quality |
| putamen | UBERON:0001874 | 95.76 | gold quality |
| pituitary gland | UBERON:0000007 | 94.34 | gold quality |
| adenohypophysis | UBERON:0002196 | 94.28 | gold quality |
Single-cell (SCXA)
Detected in 20 experiment(s), a significant marker in 19.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-11121 | yes | 4437.92 |
| E-HCAD-56 | yes | 4095.87 |
| E-GEOD-93593 | yes | 3018.25 |
| E-MTAB-10018 | yes | 2482.98 |
| E-MTAB-6911 | yes | 2417.41 |
| E-MTAB-10485 | yes | 2050.67 |
| E-HCAD-5 | yes | 1998.14 |
| E-GEOD-75140 | yes | 1363.85 |
| E-MTAB-8221 | yes | 1361.24 |
| E-MTAB-7407 | yes | 1293.13 |
| E-MTAB-9906 | yes | 1051.62 |
| E-GEOD-124472 | yes | 1014.79 |
| E-HCAD-10 | yes | 560.08 |
| E-GEOD-98556 | yes | 376.98 |
| E-HCAD-13 | yes | 27.14 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): AR, ASCL1, BHLHE23, CEBPB, EN1, FOS, HIF1A, HR, ID2, ID4, NKX2-6, NR4A1, NR4A2, RARB, REST, SCRT1, SNAI1, SOX10, SOX11, SOX17, SOX2, SOX9, SP1, SP3, TP53, TP63
miRNA regulators (miRDB)
15 targeting TUBB3, 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-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-4650-5P | 99.98 | 64.69 | 999 |
| HSA-MIR-6825-5P | 99.96 | 69.81 | 3431 |
| HSA-MIR-3660 | 99.68 | 67.33 | 1149 |
| HSA-MIR-4526 | 99.68 | 67.07 | 1136 |
| HSA-MIR-3120-3P | 99.54 | 70.28 | 2669 |
| HSA-MIR-6719-3P | 99.29 | 67.78 | 1387 |
| HSA-MIR-4477A | 98.83 | 69.75 | 2952 |
| HSA-MIR-6827-5P | 98.46 | 64.88 | 1256 |
| HSA-MIR-4660 | 97.79 | 67.44 | 1328 |
| HSA-MIR-509-3-5P | 97.21 | 67.74 | 1517 |
| HSA-MIR-509-5P | 97.21 | 67.90 | 1512 |
| HSA-MIR-424-3P | 97.20 | 65.86 | 385 |
Functional genomics
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
Literature-anchored findings (GeneRIF, showing 40)
- Patients with low beta-tubulin III levels had better response in the paclitaxel/carboplatin (PMID:12789263)
- Human brain and testis specific betaIII-tubulin diminishes microtubule assembly, and is able to confer weak resistance to paclitaxel when expressed at moderate levels in mammalian cells. (PMID:12905530)
- class III beta-tubulin has a role in paclitaxel resistance in ovarian cancer (PMID:15671559)
- high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy (PMID:16061864)
- useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy. (PMID:16675570)
- Deleterious post-translational modifications of beta 3 tubulin accumulate in a pathological protein fraction in Alzheimer dissease. (PMID:16816122)
- bTubIII has a role in progression of non-small cell lung cancer (PMID:17289895)
- Data suggest that aberrant expression and interactions of betaIII-tubulin and gamma-tubulin may be linked to malignant changes in glial cells. (PMID:17406983)
- study concludes that class III beta-tubulin is expressed in some cases of major primary brain tumour types except pilocytic astrocytoma; extent of class III beta-tubulin expression is variable (PMID:17543088)
- TUBB3 is expressed in most pancreatic ductal adenocarcinomas. Up-regulation of TUBB3 in PanIN lesions suggests that microtubule dysfunction is an early feature of this disease. (PMID:17714470)
- Methylation analysis of 3’ enhancer showed that it was free of methylation in 70% cells in A2780, while in less than 16% in both TC1 and HeLa cells, thereby suggesting that TUBB3 increase upon hypoxia is abolished through methylation of the 3’ enhancer. (PMID:18178340)
- In the midgestational human brain, betaIII-tubulin is not neuron specific because it is constitutively expressed in GFAP+/nestin+ presumptive fetal astrocytes (PMID:18379434)
- roles of cys124 & ser239 in function of betaIII tubulin; results indicate roles of these residues in colchicine binding & microtubule integrity are complex & residues at which betaIII differs from other isotypes keep betaIII in functional conformation (PMID:18435451)
- Epigenetic modification involved in aberrant expression of TUBB3 is associated with ovarian cancer (PMID:18497984)
- TUBB3 was analyzed in a panel of drug-sensitive and drug-resistant cell lines. (PMID:18645017)
- Study of expression of beta-III tubulin in human eye tissues during prenatal development (PMID:18946987)
- the level of tubulin beta 3 expression may predict survival in NSCLC patients receiving carboplatin and paclitaxel (PMID:18977553)
- Roles of tubulin beta 1,3 residues Ala428 and Thr429 in microtubule formation in vivo. (PMID:19074767)
- loss of TUBB3 protein may be induced by histone deacetylation in a subset of malignant melanomas, and may be associated with chemosensitivity to taxane (PMID:19122647)
- This is the first report documenting a preferential localization of beta(III)-tubulin in the invading epithelium of colorectal cancer. (PMID:19360438)
- This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
- betaIII-tubulin expression is augmented in prostate cancer by androgen ablation and that the expression of this beta-tubulin isoform is associated with the progression of prostate cancer to the castration-resistant state. (PMID:19690549)
- Class III beta-tubulin a potential candidate to distinguish small basal cell carcinoma non-neoplastic hair buds (PMID:19724850)
- This paper reviews the evidence base for betaIII tubulin expression as a prognostic and predictive biomarker inN on-small cell lung cancer (PMID:19828208)
- The immunostaining pattern of tubulin did not correlate with age, clinical stage, histological grade, depth of invasion of endometrial cancer. (PMID:19899405)
- determination of the expression of excision repair cross-complementation group 1 and class IIIbeta tubulin is useful to predict the effects of platinum-based anticancer drugs. (PMID:20021611)
- Work to define the TUBB3 syndromes establishes the requirement for a neuronal beta-tubulin isotype in axon guidance and normal brain development. (PMID:20074521)
- Over-expression of class III beta-tubulin is associated with resected non-small cell lung cancer. (PMID:20087230)
- A variety of neoplastic and non-neoplastic lymphoproliferative disorders exhibited characteristic TUBB3 expression patterns. (PMID:20220512)
- congenital fibrosis of extraocular muscle type 3 caused by TUBB3 R262C and D417N amino acid substitutions features abnormalities: subarachnoid CN3 hypoplasia, occasional abducens nerve hypoplasia, and subclinical optic nerve hypoplasia (PMID:20393110)
- betaIII tubulin expression is emerging as a valuable biomarker for taxane resistance in advanced disease, as well as offering prognostic information for outcomes among patients with earlier stage disease. (PMID:20403547)
- HER2 and TUBB3 status might be a good biomarker for determining the most appropriate therapeutic modality in extramammary Paget disease. (PMID:20534991)
- HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. (PMID:20587520)
- Mutations in the neuronal beta-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects. (PMID:20829227)
- In postoperative NSCLC patients who are receiving adjuvant chemotherapy, patients with high expression of beta-tubulin 3 tend to be resistant to taxane drugs. (PMID:20868593)
- Findings suggest a role for betaIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC. (PMID:21045157)
- The human melanocortin 1 receptor gene, has a highly complex and inefficient poly(A) site which is instrumental in allowing intergenic splicing between this locus and its immediate downstream neighbour tubulin-beta-III (TUBB3). (PMID:21071418)
- The expression of III beta-tubulin and MDR1 may play an important role in the development and progression of human non-small cell lung cancer. (PMID:21163067)
- High TUBB3 is associated with thymic epithelial tumors. (PMID:21289518)
- class III beta-tubulin expression in prechemotherapy effusions is associated with poor chemoresponse and shorter survival in serous ovarian carcinoma. (PMID:21315408)
Cross-species orthologs
2 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Tubb3 | ENSMUSG00000062380 |
| rattus_norvegicus | Tubb3 | ENSRNOG00000017209 |
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), TUBB (ENSG00000196230), TUBA3C (ENSG00000198033), TUBA4B (ENSG00000243910), TUBB8 (ENSG00000261456)
Protein
Protein identifiers
Tubulin beta-3 chain — Q13509 (reviewed: Q13509)
Alternative names: Tubulin beta-4 chain, Tubulin beta-III
All UniProt accessions (10): G3V2A3, G3V2N6, G3V2R8, G3V3J6, G3V3R4, G3V3W7, G3V4U2, G3V542, G3V5W4, Q13509
UniProt curated annotations — full annotation on UniProt →
Function. Tubulin is the major constituent of microtubules, protein filaments consisting 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, alpha-beta tubulin heterodimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. TUBB3 plays a critical role in proper axon guidance and maintenance. Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion. Plays a role in dorsal root ganglion axon projection towards the spinal cord.
Subunit / interactions. Heterodimer of alpha- and beta-tubulin. 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 gamma-tubulin; the interaction allows microtubules to nucleate from the gamma-tubulin ring complex (gTuRC). Interacts with UNC5C (via cytoplasmic domain); this interaction is decreased by NTN1/Netrin-1. Interacts with NLRP5/MATER at cytoskeleton microtubules. Interacts with DPYSL5. Interacts with CFAP61.
Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Growth cone. Lamellipodium. Filopodium.
Tissue specificity. Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues.
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. Fibrosis of extraocular muscles, congenital, 3A (CFEOM3A) [MIM:600638] A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases, the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy. The disease is caused by variants affecting the gene represented in this entry. Cortical dysplasia, complex, with other brain malformations 1 (CDCBM1) [MIM:614039] A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe intellectual disability, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved. The disease is caused by variants affecting the gene represented in this entry.
Domain organisation. The highly acidic C-terminal region may bind cations such as calcium. The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
Similarity. Belongs to the tubulin family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q13509-1 | 1 | yes |
| Q13509-2 | 2 |
RefSeq proteins (2): NP_001184110, NP_006077* (*=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 (90 total): helix 23, binding site 22, strand 19, sequence variant 12, turn 5, modified residue 3, chain 1, region of interest 1, short sequence motif 1, splice variant 1, compositionally biased region 1, sequence conflict 1
Structure
Experimental structures (PDB)
28 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6S8L | X-RAY DIFFRACTION | 1.8 |
| 7PJF | X-RAY DIFFRACTION | 1.86 |
| 9WD9 | ELECTRON MICROSCOPY | 2.26 |
| 9WD7 | ELECTRON MICROSCOPY | 2.34 |
| 9WDA | ELECTRON MICROSCOPY | 2.35 |
| 9WDB | ELECTRON MICROSCOPY | 2.39 |
| 22AK | ELECTRON MICROSCOPY | 2.41 |
| 22AJ | ELECTRON MICROSCOPY | 2.48 |
| 8VT7 | ELECTRON MICROSCOPY | 2.66 |
| 7Z6S | ELECTRON MICROSCOPY | 2.9 |
| 6WSL | ELECTRON MICROSCOPY | 3.1 |
| 7LXB | ELECTRON MICROSCOPY | 3.26 |
| 7M18 | ELECTRON MICROSCOPY | 3.38 |
| 6E7B | ELECTRON MICROSCOPY | 3.5 |
| 7SJ8 | ELECTRON MICROSCOPY | 3.6 |
| 9F3B | ELECTRON MICROSCOPY | 3.6 |
| 5IJ9 | ELECTRON MICROSCOPY | 3.7 |
| 5IJ0 | ELECTRON MICROSCOPY | 3.8 |
| 7SJ7 | ELECTRON MICROSCOPY | 3.8 |
| 7SJ9 | ELECTRON MICROSCOPY | 3.8 |
| 7SJA | ELECTRON MICROSCOPY | 3.8 |
| 7M20 | ELECTRON MICROSCOPY | 3.84 |
| 5JCO | ELECTRON MICROSCOPY | 4 |
| 9F3S | ELECTRON MICROSCOPY | 4.2 |
| 9F3H | ELECTRON MICROSCOPY | 4.3 |
| 9F3R | ELECTRON MICROSCOPY | 4.3 |
| 8VRJ | ELECTRON MICROSCOPY | 7.7 |
| 8VRK | ELECTRON MICROSCOPY | 8.5 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q13509-F1 | 91.55 | 0.82 |
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 (22): 69; 99; 138; 138; 142; 142; 143; 143; 144; 144; 177; 204 …
Post-translational modifications (3): 172, 438, 444
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: 557 (showing top):
WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, DAZARD_UV_RESPONSE_CLUSTER_G4, GOBP_NEUROGENESIS, REACTOME_MEMBRANE_TRAFFICKING, SMITH_TERT_TARGETS_DN, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, GOBP_MITOTIC_CELL_CYCLE, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, REACTOME_GAP_JUNCTION_ASSEMBLY, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES
GO Biological Process (8): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), axon guidance (GO:0007411), dorsal root ganglion development (GO:1990791), cytoskeleton organization (GO:0007010), microtubule-based process (GO:0007017), neuron differentiation (GO:0030182), netrin-activated signaling pathway (GO:0038007)
GO Molecular Function (8): GTPase activity (GO:0003924), structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), peptide binding (GO:0042277), metal ion binding (GO:0046872), netrin receptor binding (GO:1990890), nucleotide binding (GO:0000166), protein binding (GO:0005515)
GO Cellular Component (16): nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), lamellipodium (GO:0030027), filopodium (GO:0030175), axon (GO:0030424), dendrite (GO:0030425), growth cone (GO:0030426), neuronal cell body (GO:0043025), intercellular bridge (GO:0045171), extracellular exosome (GO:0070062), cell periphery (GO:0071944), mitotic spindle (GO:0072686), cytoskeleton (GO:0005856), cell projection (GO:0042995)
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 |
|---|---|
| cellular anatomical structure | 4 |
| cytoskeleton organization | 2 |
| cytoskeleton | 2 |
| binding | 2 |
| neuron projection | 2 |
| microtubule-based process | 1 |
| cell cycle | 1 |
| mitotic nuclear division | 1 |
| axonogenesis | 1 |
| neuron projection guidance | 1 |
| ganglion development | 1 |
| organelle organization | 1 |
| cellular process | 1 |
| cell differentiation | 1 |
| generation of neurons | 1 |
| cell surface receptor signaling pathway | 1 |
| ribonucleoside triphosphate phosphatase activity | 1 |
| structural molecule activity | 1 |
| guanyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| cation binding | 1 |
| signaling receptor binding | 1 |
| netrin-activated signaling pathway | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| intracellular membrane-bounded organelle | 1 |
| intracellular anatomical structure | 1 |
| microtubule cytoskeleton | 1 |
| polymeric cytoskeletal fiber | 1 |
| cell leading edge | 1 |
| plasma membrane bounded cell projection | 1 |
| actin-based cell projection | 1 |
| dendritic tree | 1 |
| site of polarized growth | 1 |
| distal axon | 1 |
| somatodendritic compartment | 1 |
| cell body | 1 |
| extracellular vesicle | 1 |
| spindle | 1 |
| intracellular membraneless organelle | 1 |
Protein interactions and networks
STRING
5826 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| TUBB3 | TUBA1B | P04687 | 943 |
| TUBB3 | KIF21A | Q7Z4S6 | 941 |
| TUBB3 | TUBA1C | Q9BQE3 | 858 |
| TUBB3 | TUBA4A | P05215 | 830 |
| TUBB3 | PHOX2A | O14813 | 815 |
| TUBB3 | TUBA8 | Q9NY65 | 805 |
| TUBB3 | TUBA3E | Q6PEY2 | 804 |
| TUBB3 | TUBAL3 | A6NHL2 | 804 |
| TUBB3 | TUBA3C | P0DPH7 | 804 |
| TUBB3 | TUBA1B | P04687 | 802 |
| TUBB3 | NES | P48681 | 734 |
| TUBB3 | MAP2 | P11137 | 713 |
| TUBB3 | GFAP | P14136 | 695 |
| TUBB3 | RBFOX3 | A6NFN3 | 638 |
| TUBB3 | PAX6 | P26367 | 636 |
IntAct
367 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| STAU1 | RPLP0 | psi-mi:“MI:0914”(association) | 0.750 |
| TUBA1A | TUBB3 | psi-mi:“MI:0914”(association) | 0.710 |
| CFTR | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.710 |
| CFTR | ESYT2 | psi-mi:“MI:0914”(association) | 0.710 |
| EFNB3 | DENND11 | psi-mi:“MI:0914”(association) | 0.640 |
| KLK5 | DENND11 | psi-mi:“MI:0914”(association) | 0.640 |
| EIF3F | EIF3CL | psi-mi:“MI:0914”(association) | 0.640 |
| SCN2B | EXOC5 | psi-mi:“MI:0914”(association) | 0.640 |
| TUBB | PLD2 | psi-mi:“MI:0914”(association) | 0.640 |
| VSIG1 | TTI1 | psi-mi:“MI:0914”(association) | 0.640 |
| TOMM22 | XRCC3 | psi-mi:“MI:0914”(association) | 0.640 |
| RAF1 | CALU | psi-mi:“MI:0914”(association) | 0.640 |
| TUBA1A | TUBA4A | psi-mi:“MI:0914”(association) | 0.610 |
| TUBB3 | POTEF | psi-mi:“MI:0914”(association) | 0.530 |
| MAPT | KIF2A | psi-mi:“MI:0914”(association) | 0.530 |
| FAM174A | BLTP3B | psi-mi:“MI:0914”(association) | 0.530 |
| BPNT1 | GTPBP10 | psi-mi:“MI:0914”(association) | 0.530 |
| TMEM108 | TCAF2 | psi-mi:“MI:0914”(association) | 0.530 |
| CD79A | METTL15 | psi-mi:“MI:0914”(association) | 0.530 |
| APLNR | METTL15 | psi-mi:“MI:0914”(association) | 0.530 |
| LAMP3 | METTL15 | psi-mi:“MI:0914”(association) | 0.530 |
| NPAS1 | DNAJB5 | psi-mi:“MI:0914”(association) | 0.530 |
| MAPK8IP1 | HOXC8 | psi-mi:“MI:0914”(association) | 0.530 |
| ADAMTS4 | MANBA | psi-mi:“MI:0914”(association) | 0.530 |
| PRG3 | ZNF324 | psi-mi:“MI:0914”(association) | 0.530 |
BioGRID (604): MTCL1 (Reconstituted Complex), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS)
ESM2 similar proteins: A2AQ07, P05304, P09207, P09652, P12411, P12458, P12460, P18025, P22012, P24637, P29513, P29514, P33630, P37392, P41385, P41742, P45960, P46263, P46264, P46265, P93176, Q00264, Q13509, Q2T9S0, Q2U2U3, Q40106, Q40665, Q41782, Q41783, Q41784, Q41785, Q43594, Q43695, Q43697, Q4QRB4, Q4WA70, Q5UBX3, Q60HC2, Q6VAF4, Q76FS3
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
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| NUMA1 | up-regulates | TUBB3 | binding |
| ixabepilone | “down-regulates activity” | TUBB3 | “chemical inhibition” |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 270 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 10 | 31.1× | 6e-11 |
| Transport of connexons to the plasma membrane | 10 | 31.1× | 6e-11 |
| Gap junction trafficking and regulation | 10 | 27.2× | 1e-10 |
| Gap junction trafficking | 10 | 27.2× | 1e-10 |
| Post-chaperonin tubulin folding pathway | 10 | 27.2× | 1e-10 |
| Formation of tubulin folding intermediates by CCT/TriC | 10 | 24.2× | 4e-10 |
| Activation of AMPK downstream of NMDARs | 11 | 23.9× | 9e-11 |
| RHO GTPases activate IQGAPs | 12 | 23.7× | 3e-11 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| microtubule-based process | 6 | 24.5× | 6e-05 |
| response to muscle stretch | 5 | 15.8× | 5e-03 |
| cytoplasmic microtubule organization | 7 | 9.9× | 3e-03 |
| microtubule cytoskeleton organization | 19 | 9.5× | 2e-10 |
| mitotic cell cycle | 13 | 7.2× | 3e-05 |
| cerebral cortex development | 8 | 6.8× | 7e-03 |
Disease & clinical
Cancer significance
Clinical variants and AI predictions
ClinVar
364 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 16 |
| Likely pathogenic | 29 |
| Uncertain significance | 147 |
| Likely benign | 97 |
| Benign | 29 |
Top pathogenic / likely-pathogenic (30)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1343012 | NM_006086.4(TUBB3):c.137G>A (p.Arg46Gln) | Pathogenic |
| 1708721 | NM_006086.4(TUBB3):c.683T>C (p.Leu228Pro) | Pathogenic |
| 219257 | NM_006086.4(TUBB3):c.1138C>T (p.Arg380Cys) | Pathogenic |
| 224784 | c.1228G>A | Pathogenic |
| 265354 | NM_006086.4(TUBB3):c.1172G>T (p.Arg391Leu) | Pathogenic |
| 2744601 | NM_006086.4(TUBB3):c.904G>T (p.Ala302Ser) | Pathogenic |
| 30272 | NM_006086.4(TUBB3):c.967A>G (p.Met323Val) | Pathogenic |
| 30274 | NM_006086.4(TUBB3):c.613G>A (p.Glu205Lys) | Pathogenic |
| 30275 | NM_006086.4(TUBB3):c.905C>T (p.Ala302Val) | Pathogenic |
| 421587 | NM_006086.4(TUBB3):c.845G>C (p.Arg282Pro) | Pathogenic |
| 6963 | NM_006086.4(TUBB3):c.784C>T (p.Arg262Cys) | Pathogenic |
| 6964 | NM_006086.4(TUBB3):c.904G>A (p.Ala302Thr) | Pathogenic |
| 6965 | NM_006086.4(TUBB3):c.1249G>C (p.Asp417His) | Pathogenic |
| 6966 | NM_006086.4(TUBB3):c.1249G>A (p.Asp417Asn) | Pathogenic |
| 6967 | NM_006086.4(TUBB3):c.1228G>A (p.Glu410Lys) | Pathogenic |
| 975630 | NM_006086.4(TUBB3):c.577G>A (p.Val193Met) | Pathogenic |
| 1027523 | NM_006086.4(TUBB3):c.1024G>A (p.Val342Met) | Likely pathogenic |
| 1218943 | NM_006086.4(TUBB3):c.728C>G (p.Pro243Arg) | Likely pathogenic |
| 1309208 | NM_006086.4(TUBB3):c.386G>A (p.Cys129Tyr) | Likely pathogenic |
| 1320071 | NM_006086.4(TUBB3):c.178G>T (p.Val60Leu) | Likely pathogenic |
| 1320230 | NM_006086.4(TUBB3):c.1139G>C (p.Arg380Pro) | Likely pathogenic |
| 1338328 | NM_006086.4(TUBB3):c.212G>C (p.Gly71Ala) | Likely pathogenic |
| 1679223 | NM_006086.4(TUBB3):c.929A>G (p.Tyr310Cys) | Likely pathogenic |
| 1701033 | NM_006086.4(TUBB3):c.535G>C (p.Val179Leu) | Likely pathogenic |
| 1708291 | NM_006086.4(TUBB3):c.817C>G (p.Leu273Val) | Likely pathogenic |
| 1710200 | NM_006086.4(TUBB3):c.313C>A (p.His105Asn) | Likely pathogenic |
| 1804227 | NM_006086.4(TUBB3):c.1172G>A (p.Arg391His) | Likely pathogenic |
| 219254 | NM_006086.4(TUBB3):c.185G>A (p.Arg62Gln) | Likely pathogenic |
| 2499586 | NM_006086.4(TUBB3):c.1138C>A (p.Arg380Ser) | Likely pathogenic |
| 2629824 | NM_006086.4(TUBB3):c.844C>G (p.Arg282Gly) | Likely pathogenic |
SpliceAI
956 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 16:89923454:CCAAG:C | donor_loss | 1.0000 |
| 16:89923455:CAAGG:C | donor_loss | 1.0000 |
| 16:89923458:GGTGA:G | donor_loss | 1.0000 |
| 16:89923459:G:A | donor_loss | 1.0000 |
| 16:89923460:T:A | donor_loss | 1.0000 |
| 16:89932562:T:TA | acceptor_gain | 1.0000 |
| 16:89932566:T:TA | acceptor_gain | 1.0000 |
| 16:89932569:A:AG | acceptor_gain | 1.0000 |
| 16:89932570:G:A | acceptor_loss | 1.0000 |
| 16:89932570:G:GA | acceptor_gain | 1.0000 |
| 16:89932570:G:GC | acceptor_gain | 1.0000 |
| 16:89932570:GT:G | acceptor_gain | 1.0000 |
| 16:89932570:GTT:G | acceptor_gain | 1.0000 |
| 16:89932570:GTTC:G | acceptor_gain | 1.0000 |
| 16:89932570:GTTCT:G | acceptor_gain | 1.0000 |
| 16:89932675:CTCTT:C | donor_gain | 1.0000 |
| 16:89932676:TCTT:T | donor_gain | 1.0000 |
| 16:89932677:CTT:C | donor_gain | 1.0000 |
| 16:89932678:TT:T | donor_gain | 1.0000 |
| 16:89932680:G:C | donor_loss | 1.0000 |
| 16:89932680:G:GG | donor_gain | 1.0000 |
| 16:89932680:GTG:G | donor_loss | 1.0000 |
| 16:89932681:T:G | donor_loss | 1.0000 |
| 16:89933464:TCA:T | acceptor_loss | 1.0000 |
| 16:89933464:TCAGC:T | acceptor_loss | 1.0000 |
| 16:89933465:CA:C | acceptor_loss | 1.0000 |
| 16:89933466:A:AG | acceptor_gain | 1.0000 |
| 16:89933466:AGCTC:A | acceptor_loss | 1.0000 |
| 16:89933467:G:GA | acceptor_gain | 1.0000 |
| 16:89933467:G:GC | acceptor_gain | 1.0000 |
AlphaMissense
3000 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 16:89923429:G:C | G10R | 1.000 |
| 16:89923429:G:T | G10C | 1.000 |
| 16:89923430:G:A | G10D | 1.000 |
| 16:89923430:G:T | G10V | 1.000 |
| 16:89923437:C:G | C12W | 1.000 |
| 16:89923438:G:C | G13R | 1.000 |
| 16:89923438:G:T | G13C | 1.000 |
| 16:89923439:G:A | G13D | 1.000 |
| 16:89923439:G:T | G13V | 1.000 |
| 16:89923443:C:A | N14K | 1.000 |
| 16:89923443:C:G | N14K | 1.000 |
| 16:89923450:G:A | G17R | 1.000 |
| 16:89923450:G:C | G17R | 1.000 |
| 16:89923450:G:T | G17W | 1.000 |
| 16:89923451:G:A | G17E | 1.000 |
| 16:89932574:T:A | W21R | 1.000 |
| 16:89932574:T:C | W21R | 1.000 |
| 16:89933483:C:A | P61H | 1.000 |
| 16:89933500:G:C | D67H | 1.000 |
| 16:89933501:A:C | D67A | 1.000 |
| 16:89933501:A:T | D67V | 1.000 |
| 16:89933504:T:C | L68P | 1.000 |
| 16:89933506:G:A | E69K | 1.000 |
| 16:89934741:C:A | A97D | 1.000 |
| 16:89934744:G:A | G98D | 1.000 |
| 16:89934748:C:A | N99K | 1.000 |
| 16:89934748:C:G | N99K | 1.000 |
| 16:89934751:C:A | N100K | 1.000 |
| 16:89934751:C:G | N100K | 1.000 |
| 16:89934752:T:A | W101R | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000149094 (16:89930610 G>A,C), RS1000345330 (16:89924193 T>C), RS1000459034 (16:89920287 C>A,T), RS1000459664 (16:89934589 T>C,G), RS1000640481 (16:89923574 G>C,T), RS1000708170 (16:89936221 G>C), RS1000718434 (16:89922940 G>A), RS1000770570 (16:89923198 C>A,G), RS1000847201 (16:89927389 A>T), RS1001045041 (16:89927318 G>C,T), RS1001098353 (16:89931730 G>T), RS1001155452 (16:89929733 C>T), RS1001285040 (16:89925592 T>C), RS1001302283 (16:89927190 C>T), RS1001312940 (16:89933932 C>T)
Disease associations
OMIM: gene MIM:602661 | disease phenotypes: MIM:108600, MIM:614039, MIM:607450, MIM:600638, MIM:135700, MIM:212720, MIM:607432
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement | Strong | Autosomal dominant |
| complex cortical dysplasia with other brain malformations 1 | Strong | Autosomal dominant |
| congenital fibrosis of extraocular muscles | Supportive | Autosomal dominant |
| tubulinopathy-associated dysgyria | Supportive | Autosomal dominant |
ClinGen Gene-Disease Validity (1)
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
| Disease | Classification | Inheritance |
|---|---|---|
| TUBB3-related tubulinopathy | Definitive | AD |
Mondo (13): spastic ataxia (MONDO:0017845), complex cortical dysplasia with other brain malformations 1 (MONDO:0013541), arrhythmogenic right ventricular dysplasia 8 (MONDO:0011831), fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement (MONDO:0010912), congenital fibrosis of extraocular muscles type 1 (MONDO:0021083), intellectual disability (MONDO:0001071), Martsolf syndrome 1 (MONDO:8000008), TUBB3-related tubulinopathy (MONDO:0100154), prostate cancer (MONDO:0008315), neurodevelopmental disorder (MONDO:0700092), congenital fibrosis of extraocular muscles (MONDO:0007614), lissencephaly spectrum disorders (MONDO:0018838), tubulinopathy-associated dysgyria (MONDO:0018763)
Orphanet (9): Spastic ataxia (Orphanet:316226), Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation (Orphanet:300570), Cataract-intellectual disability-hypogonadism syndrome (Orphanet:1387), Familial prostate cancer (Orphanet:1331), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Non-syndromic cerebral malformation (Orphanet:199633), Congenital fibrosis of extraocular muscles (Orphanet:45358), Lissencephaly (Orphanet:48471), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)
HPO phenotypes
137 total (30 of 137 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000044 | Hypogonadotropic hypogonadism |
| HP:0000218 | High palate |
| HP:0000252 | Microcephaly |
| HP:0000256 | Macrocephaly |
| HP:0000286 | Epicanthus |
| HP:0000347 | Micrognathia |
| HP:0000369 | Low-set ears |
| HP:0000407 | Sensorineural hearing impairment |
| HP:0000473 | Torticollis |
| HP:0000486 | Strabismus |
| HP:0000494 | Downslanted palpebral fissures |
| HP:0000496 | Abnormality of eye movement |
| HP:0000508 | Ptosis |
| HP:0000512 | Abnormal electroretinogram |
| HP:0000518 | Cataract |
| HP:0000539 | Abnormality of refraction |
| HP:0000542 | Impaired ocular adduction |
| HP:0000565 | Esotropia |
| HP:0000570 | Abnormal saccadic eye movements |
| HP:0000572 | Visual loss |
| HP:0000577 | Exotropia |
| HP:0000609 | Optic nerve hypoplasia |
| HP:0000616 | Miosis |
| HP:0000639 | Nystagmus |
| HP:0000646 | Amblyopia |
| HP:0000657 | Oculomotor apraxia |
| HP:0000712 | Emotional lability |
| HP:0000733 | Motor stereotypy |
| HP:0000736 | Short attention span |
GWAS associations
11 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST004703_1 | Obsessive-compulsive disorder or autism spectrum disorder | 7.000000e-07 |
| GCST005790_41 | Rosacea symptom severity | 1.000000e-07 |
| GCST006986_1 | Red vs. brown/black hair color | 4.000000e-08 |
| GCST006986_18 | Red vs. brown/black hair color | 3.000000e-103 |
| GCST008872_20 | Squamous cell carcinoma | 5.000000e-56 |
| GCST010148_22 | Cutaneous squamous cell carcinoma | 6.000000e-87 |
| GCST010304_52 | Cutaneous malignant melanoma | 2.000000e-08 |
| GCST010677_8 | Liver fibrogenesis (alpha smooth muscle actin levels) | 7.000000e-06 |
| GCST010703_280 | Brain morphology (MOSTest) | 2.000000e-15 |
| GCST90010427_19 | Left–right brain asymmetry | 6.000000e-15 |
| GCST90013421_18 | Left-handedness | 5.000000e-24 |
EFO canonical traits (6, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0009180 | rosacea severity measurement |
| EFO:0003924 | hair color |
| EFO:1001927 | cutaneous squamous cell carcinoma |
| EFO:0010576 | liver fibrosis measurement |
| EFO:0004346 | neuroimaging measurement |
| EFO:0009902 | handedness |
MeSH disease descriptors (9)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D008607 | Intellectual Disability | C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539 |
| D054082 | Lissencephaly | C10.500.507.450.499; C16.131.666.507.450.499 |
| D065886 | Neurodevelopmental Disorders | F03.625 |
| D011471 | Prostatic Neoplasms | C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750 |
| C564400 | Arrhythmogenic Right Ventricular Dysplasia, Familial, 8 (supp.) | |
| C567572 | Fibrosis Of Extraocular Muscles, Congenital, 3A, with or without Extraocular Involvement (supp.) | |
| C536028 | Martsolf syndrome (supp.) | |
| C564815 | Spastic Ataxia (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), CHEMBL2597 (SINGLE PROTEIN), CHEMBL3832942 (PROTEIN FAMILY), CHEMBL6066055 (PROTEIN-PROTEIN INTERACTION), 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 |
Clinical evidence (CIViC)
Drug × variant × indication: 2 predictive associations from 2 curated evidence items.
| Variant | Therapy | Indication | Effect | Level | CIViC |
|---|---|---|---|---|---|
| TUBB3 EXPRESSION | Taxane Compound | Breast Cancer | Sensitivity/Response | CIViC B | EID921 |
| TUBB3 EXPRESSION | Paclitaxel | Cancer | Resistance | CIViC D | EID920 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
4 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs2228478 | MC1R, TUBB3 | 3 | 2.25 | 1 | desipramine |
| rs4558416 | TUBB3 | 0.00 | 0 | ||
| rs4395073 | TUBB3 | 0.00 | 0 | ||
| rs2302898 | TUBB3 | 0.00 | 0 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: other protein — Tubulins
Most potent curated ligand interactions (1 total), top 1:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| combretastatin A4 | Inhibition | 8.24 | pIC50 |
ChEMBL bioactivities
1189 potent at pChembl≥5 of 1340 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
1116 with measured affinity, of 5940 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 |
| N-(5-methoxynaphthalen-2-yl)-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine | 1693360: Inhibition of beta3 Tubulin (unknown origin) expressed in human HeLa cell line assessed as inhibition of cell proliferation measured after 48 hrs by SRB method | 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 |
| Paclitaxel | 1693360: Inhibition of beta3 Tubulin (unknown origin) expressed in human HeLa cell line assessed as inhibition of cell proliferation measured after 48 hrs by SRB method | ic50 | 0.0077 | uM |
| N-(4-methoxyphenyl)-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine;hydrochloride | 769828: Inhibition of beta3 tubulin overexpressed in human HeLa cells after 48 hrs by SRB assay | ic50 | 0.0082 | uM |
| 4-N-(5-methoxynaphthalen-2-yl)-4-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine | 1693360: Inhibition of beta3 Tubulin (unknown origin) expressed in human HeLa cell line assessed as inhibition of cell proliferation measured after 48 hrs by SRB method | ic50 | 0.0096 | uM |
| N-(4-methoxyphenyl)-N,2-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine | 1693360: Inhibition of beta3 Tubulin (unknown origin) expressed in human HeLa cell line assessed as inhibition of cell proliferation measured after 48 hrs by SRB method | ic50 | 0.0096 | 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 |
| 4-N-(4-ethoxyphenyl)-4-N-methyl-9H-pyrimido[4,5-b]indole-2,4-diamine | 751509: Inhibition of beta-3 tubulin (unknown origin) transfected in human HeLa cells assessed as growth inhibition after 48 hrs by SRB assay | ic50 | 0.0188 | 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 |
| 4-N-(4-methoxyphenyl)-4-N-methyl-9H-pyrimido[4,5-b]indole-2,4-diamine | 751509: Inhibition of beta-3 tubulin (unknown origin) transfected in human HeLa cells assessed as growth inhibition after 48 hrs by SRB assay | ic50 | 0.0214 | 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,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine;hydrochloride | 769828: Inhibition of beta3 tubulin overexpressed in human HeLa cells after 48 hrs by SRB assay | ic50 | 0.0239 | 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 |
| (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-methoxynaphthalen-2-yl)-N-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine | 1693360: Inhibition of beta3 Tubulin (unknown origin) expressed in human HeLa cell line assessed as inhibition of cell proliferation measured after 48 hrs by SRB method | ic50 | 0.0430 | 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 |
| 4-N-ethyl-4-N-(4-methoxyphenyl)-9H-pyrimido[4,5-b]indole-2,4-diamine | 751509: Inhibition of beta-3 tubulin (unknown origin) transfected in human HeLa cells assessed as growth inhibition after 48 hrs by SRB assay | ic50 | 0.0455 | 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 |
CTD chemical–gene interactions
119 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Tretinoin | affects reaction, affects cotreatment, affects expression, affects binding, increases reaction (+2 more) | 8 |
| Valproic Acid | affects expression, decreases expression, increases expression, increases methylation | 7 |
| bisphenol A | decreases expression, decreases reaction, affects cotreatment, increases expression | 6 |
| sodium arsenite | increases expression, increases reaction, decreases expression, decreases reaction | 5 |
| Cyclosporine | decreases expression, increases expression | 5 |
| Benzo(a)pyrene | increases methylation, increases expression | 4 |
| Tobacco Smoke Pollution | affects expression, increases expression, increases metabolic processing | 4 |
| Cadmium Chloride | decreases reaction, increases abundance, increases palmitoylation, decreases expression, increases expression | 4 |
| Cadmium | decreases reaction, increases abundance, increases palmitoylation, increases expression | 3 |
| Estradiol | affects cotreatment, increases expression, decreases reaction | 3 |
| dinophysistoxin 1 | increases expression | 2 |
| chloropicrin | increases expression | 2 |
| (+)-JQ1 compound | increases expression | 2 |
| bisphenol AF | increases expression | 2 |
| Glyphosate | decreases expression, increases expression | 2 |
| Carbamazepine | affects expression, decreases expression | 2 |
| Diethylhexyl Phthalate | decreases expression, increases expression | 2 |
| Silicon Dioxide | affects secretion, increases expression | 2 |
| Smoke | increases abundance, decreases expression | 2 |
| Acrylamide | decreases expression | 2 |
| Particulate Matter | increases expression, decreases expression, decreases reaction | 2 |
| aristolochic acid I | increases expression | 1 |
| GSK-J4 | increases expression | 1 |
| 6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine | increases expression | 1 |
| bisphenol F | increases expression | 1 |
| ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate | affects cotreatment, affects expression | 1 |
| aminomethylphosphonic acid (AMPA) | decreases expression | 1 |
| beauvericin | affects cotreatment, increases expression | 1 |
| 2,4,6-tribromophenol | decreases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
ChEMBL screening assays
1781 unique, capped per target: 1741 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
5 cell lines: 5 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B1EC | Abcam HCT 116 TUBB3 KO | Cancer cell line | Male |
| CVCL_B2JY | Abcam HeLa TUBB3 KO | Cancer cell line | Female |
| CVCL_D1US | Abcam U-87MG TUBB3 KO | Cancer cell line | Male |
| CVCL_TV19 | HAP1 TUBB3 (-) 1 | Cancer cell line | Male |
| CVCL_TV20 | HAP1 TUBB3 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
301 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT05657860 | PHASE4 | COMPLETED | Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome |
| NCT05744479 | PHASE4 | RECRUITING | Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability |
| NCT06107829 | PHASE4 | WITHDRAWN | Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities |
| NCT06997198 | PHASE4 | NOT_YET_RECRUITING | Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities |
| NCT00029224 | PHASE4 | COMPLETED | Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions |
| NCT00035997 | PHASE4 | COMPLETED | Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis |
| NCT00063609 | PHASE4 | COMPLETED | The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy |
| NCT00103623 | PHASE4 | SUSPENDED | The Plenaxis® Experience Study |
| NCT00106392 | PHASE4 | COMPLETED | A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy |
| NCT00185029 | PHASE4 | UNKNOWN | MR-Lymphography and Lymph Node Staging in Prostate Cancer |
| NCT00199485 | PHASE4 | COMPLETED | Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer |
| NCT00219219 | PHASE4 | COMPLETED | Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases |
| NCT00219271 | PHASE4 | COMPLETED | Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer |
| NCT00237146 | PHASE4 | COMPLETED | Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy |
| NCT00242554 | PHASE4 | COMPLETED | Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases |
| NCT00280098 | PHASE4 | COMPLETED | Docetaxel in the Treatment of Hormone Refractory Prostate Cancer |
| NCT00293696 | PHASE4 | COMPLETED | Casodex/Zoladex Biomarkers in Localised Prostate Cancer |
| NCT00334139 | PHASE4 | COMPLETED | Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer |
| NCT00375765 | PHASE4 | COMPLETED | Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer |
| NCT00391690 | PHASE4 | COMPLETED | Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer |
| NCT00422708 | PHASE4 | COMPLETED | Local Anesthesia for Prostate Biopsy |
| NCT00526331 | PHASE4 | COMPLETED | Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy |
| NCT00590213 | PHASE4 | COMPLETED | Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX |
| NCT00629330 | PHASE4 | TERMINATED | Dissemination of Prostate Cancer Screening to PCP’s in African American Communities |
| NCT00771966 | PHASE4 | COMPLETED | Radical Prostatectomy and Perioperative Fluid Therapy |
| NCT00805701 | PHASE4 | COMPLETED | Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation |
| NCT00859027 | PHASE4 | COMPLETED | Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer |
| NCT00906269 | PHASE4 | UNKNOWN | Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer |
| NCT00953277 | PHASE4 | COMPLETED | Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer |
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Related Atlas pages
- Associated diseases: fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement, complex cortical dysplasia with other brain malformations 1, congenital fibrosis of extraocular muscles, tubulinopathy-associated dysgyria, TUBB3-related tubulinopathy, breast carcinoma, cancer
- Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Paclitaxel
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): arrhythmogenic right ventricular dysplasia 8, breast cancer, breast carcinoma, cancer, complex cortical dysplasia with other brain malformations 1, congenital fibrosis of extraocular muscles, congenital fibrosis of extraocular muscles type 1, cutaneous melanoma, fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement, lissencephaly spectrum disorders, Martsolf syndrome 1, spastic ataxia, squamous cell carcinoma, TUBB3-related tubulinopathy, tubulinopathy-associated dysgyria