TUBA3C

Summary

TUBA3C (tubulin alpha 3c, HGNC:12408) is a protein-coding gene on chromosome 13q12.11, encoding Tubulin alpha-3C chain (P0DPH7). Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene is an alpha tubulin gene that encodes a protein 99% identical to the mouse testis-specific Tuba3 and Tuba7 gene products. This gene is located in the 13q11 region, which is associated with the genetic diseases Clouston hidrotic ectodermal dysplasia and Kabuki syndrome.

Source: NCBI Gene 7278 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006001

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12408
Approved symbol	TUBA3C
Name	tubulin alpha 3c
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Aliases	bA408E5.3
Ensembl gene	ENSG00000198033
Ensembl biotype	protein_coding
OMIM	602528
Entrez	7278

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000400113

RefSeq mRNA: 1 — MANE Select: NM_006001 NM_006001

CCDS: CCDS9284

Canonical transcript exons

ENST00000400113 — 5 exons

Exon	Start	End
ENSE00001382740	19181745	19181824
ENSE00001766741	19176927	19177607
ENSE00001883447	19173772	19174159
ENSE00003289479	19178246	19178394
ENSE00003416093	19179341	19179563

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 99.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.9019 / max 1060.0497, expressed in 68 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136305	1.8323	68
136306	0.0696	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.44	gold quality
left testis	UBERON:0004533	99.13	gold quality
adult organism	UBERON:0007023	98.76	gold quality
testis	UBERON:0000473	97.30	gold quality
oocyte	CL:0000023	94.18	gold quality
male germ cell	CL:0000015	94.08	gold quality
sperm	CL:0000019	93.80	gold quality
type B pancreatic cell	CL:0000169	92.08	silver quality
olfactory bulb	UBERON:0002264	91.95	silver quality
tendon of biceps brachii	UBERON:0008188	91.11	gold quality
triceps brachii	UBERON:0001509	90.42	silver quality
gluteal muscle	UBERON:0002000	89.91	silver quality
pons	UBERON:0000988	89.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.87	gold quality
gingival epithelium	UBERON:0001949	88.51	silver quality
dorsal plus ventral thalamus	UBERON:0001897	88.30	silver quality
vena cava	UBERON:0004087	88.27	gold quality
secondary oocyte	CL:0000655	88.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.10	silver quality
cerebellar vermis	UBERON:0004720	88.04	gold quality
heart right ventricle	UBERON:0002080	87.89	gold quality
subthalamic nucleus	UBERON:0001906	87.79	silver quality
medial globus pallidus	UBERON:0002477	87.79	gold quality
ventral tegmental area	UBERON:0002691	87.58	gold quality
deltoid	UBERON:0001476	87.35	silver quality
body of tongue	UBERON:0011876	87.30	gold quality
globus pallidus	UBERON:0001875	87.28	gold quality
myocardium	UBERON:0002349	87.11	silver quality
gingiva	UBERON:0001828	86.96	silver quality
substantia nigra pars compacta	UBERON:0001965	86.96	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	1616.22
E-ANND-3	yes	9.13

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• TUBA3C (and TUBA4A) are differentially expressed in individuals with poor sperm motility. (PMID:24268707)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tuba7l	ENSDARG00000104643
mus_musculus	Tuba3b	ENSMUSG00000067338
rattus_norvegicus	Tuba3b	ENSRNOG00000032967
drosophila_melanogaster	alphaTub84B	FBGN0003884
drosophila_melanogaster	alphaTub84D	FBGN0003885

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), TUBA4B (ENSG00000243910), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin alpha-3C chain — P0DPH7 (reviewed: P0DPH7)

Alternative names: Alpha-tubulin 2, Alpha-tubulin 3C, Tubulin alpha-2 chain

All UniProt accessions (2): P0DPH7, Q1ZYQ1

UniProt curated annotations — full annotation on UniProt →

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

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

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in testis.

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. Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly. Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability. Nitration of Tyr-450 is irreversible and interferes with normal dynein intracellular distribution. Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP1/KIAA0895L, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively. Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1. Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport. Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator. Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle. In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction.

Domain organisation. The MREC motif may be critical for tubulin autoregulation.

Similarity. Belongs to the tubulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P0DPH7-1	1	yes
P0DPH7-2	2

RefSeq proteins (1): NP_005992* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000217	Tubulin	Family
IPR002452	Alpha_tubulin	Family
IPR003008	Tubulin_FtsZ_GTPase	Domain
IPR008280	Tub_FtsZ_C	Homologous_superfamily
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

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (22 total): binding site 9, modified residue 4, sequence variant 3, chain 2, site 1, splice variant 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPH7-F1	92.26	0.83

Functional residue map

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

Catalytic / active sites (2): 450 (involved in polymerization); 254

Ligand- & substrate-binding residues (9): 179; 206; 228; 11; 71; 71; 140; 144; 145

Post-translational modifications (4): 40, 282, 439, 450

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: 201 (showing top): MORF_DNMT1, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, WANG_CLIM2_TARGETS_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MORF_RRM1, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, REACTOME_MEMBRANE_TRAFFICKING, MUELLER_PLURINET, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, BROWNE_HCMV_INFECTION_14HR_DN, MORF_BUB3, MORF_PRKDC

GO Biological Process (4): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), cytoskeleton organization (GO:0007010), microtubule-based process (GO:0007017)

GO Molecular Function (5): structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), nucleotide binding (GO:0000166)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule (GO:0005874), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), 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
microtubule-based process	1
cell cycle	1
mitotic nuclear division	1
organelle organization	1
cellular process	1
structural molecule activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBA3C	TUBB	P05218	886
TUBA3C	TUBB2A	Q13885	886
TUBA3C	TUBB6	Q9BUF5	810
TUBA3C	TUBB4A	P04350	808
TUBA3C	TUBA4A	P05215	807
TUBA3C	TUBB8	Q3ZCM7	807
TUBA3C	TUBB1	Q9H4B7	806
TUBA3C	TUBB4B	P05217	806
TUBA3C	TUBB2B	Q9BVA1	805
TUBA3C	TUBB3	Q13509	804
TUBA3C	ROBO3	Q96MS0	764
TUBA3C	HTATIP2	Q9BUP3	714
TUBA3C	HDAC6	Q9UBN7	512
TUBA3C	TUB	P50607	476
TUBA3C	EEF1A1	P04719	457

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A5A6J1, P02550, P02552, P05213, P05214, P06603, P06604, P06605, P08537, P09644, P0DPH7, P0DPH8, P18258, P18288, P30436, P34690, P36220, P41383, P52273, P68360, P68361, P68362, P68363, P68365, P68366, P68367, P68368, P68369, P68370, P68373, P81947, P81948, Q06331, Q28IX8, Q2HJ86, Q2XVP4, Q32KN8, Q3ZCJ7, Q4R538, Q52PV9

Diamond homologs: A0AAL4, A5A6J1, B9DGT7, B9DHQ0, O22347, O22348, O22349, P02550, P02552, P04105, P04106, P05213, P05214, P06603, P06604, P08537, P09204, P09205, P09243, P0DPH7, P0DPH8, P10872, P10873, P11139, P11237, P11480, P11481, P12543, P14640, P14641, P14642, P18258, P18288, P22275, P28268, P28287, P28752, P29511, P30436, P32255

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
“Elongator complex”	“up-regulates activity”	TUBA3C	acetylation
TUBA3C	up-regulates	Neuron_migration
ATAT1	“up-regulates quantity by stabilization”	TUBA3C	acetylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

677 predictions. Top by Δscore:

Variant	Effect	Δscore
13:19176922:CATA:C	donor_loss	1.0000
13:19176923:ATAC:A	donor_loss	1.0000
13:19176924:TA:T	donor_loss	1.0000
13:19176925:A:AT	donor_loss	1.0000
13:19176926:CCTT:C	donor_loss	1.0000
13:19178242:TTAC:T	donor_loss	1.0000
13:19178243:TACCA:T	donor_loss	1.0000
13:19178244:A:AC	donor_gain	1.0000
13:19178244:A:T	donor_loss	1.0000
13:19178244:AC:A	donor_gain	1.0000
13:19178245:C:CG	donor_loss	1.0000
13:19178245:C:CT	donor_gain	1.0000
13:19178245:CC:C	donor_gain	1.0000
13:19178245:CCA:C	donor_gain	1.0000
13:19178245:CCAG:C	donor_gain	1.0000
13:19178245:CCAGT:C	donor_gain	1.0000
13:19178390:TTCAT:T	acceptor_gain	1.0000
13:19178391:TCAT:T	acceptor_gain	1.0000
13:19178392:CAT:C	acceptor_gain	1.0000
13:19178392:CATC:C	acceptor_gain	1.0000
13:19178393:AT:A	acceptor_gain	1.0000
13:19178395:C:CC	acceptor_gain	1.0000
13:19179335:ACCT:A	donor_loss	1.0000
13:19179336:CCTA:C	donor_loss	1.0000
13:19179337:CTACC:C	donor_loss	1.0000
13:19179339:A:AC	donor_gain	1.0000
13:19179339:A:AT	donor_loss	1.0000
13:19179340:C:CC	donor_gain	1.0000
13:19179340:CCGA:C	donor_gain	1.0000
13:19179560:CACG:C	acceptor_gain	1.0000

AlphaMissense

2951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:19173925:C:G	D431H	1.000
13:19173933:A:G	L428P	1.000
13:19173951:C:G	R422P	1.000
13:19173952:G:T	R422S	1.000
13:19173955:C:G	A421P	1.000
13:19173963:A:G	F418S	1.000
13:19173978:A:G	M413T	1.000
13:19173997:A:G	W407R	1.000
13:19173997:A:T	W407R	1.000
13:19174000:G:C	H406D	1.000
13:19174004:A:C	F404L	1.000
13:19174004:A:T	F404L	1.000
13:19174005:A:C	F404C	1.000
13:19174005:A:G	F404S	1.000
13:19174006:A:G	F404L	1.000
13:19174006:A:T	F404I	1.000
13:19174008:G:T	A403D	1.000
13:19174011:C:G	R402P	1.000
13:19174026:A:G	L397P	1.000
13:19174031:G:C	F395L	1.000
13:19174031:G:T	F395L	1.000
13:19174033:A:G	F395L	1.000
13:19174054:A:G	W388R	1.000
13:19174054:A:T	W388R	1.000
13:19174076:G:C	N380K	1.000
13:19174076:G:T	N380K	1.000
13:19174155:C:T	G354D	1.000
13:19174156:C:G	G354R	1.000
13:19176927:C:A	K352N	1.000
13:19176927:C:G	K352N	1.000

dbSNP variants (sampled 300 via entrez): RS1000848087 (13:19180629 G>A), RS1000921526 (13:19180499 T>A), RS1001146126 (13:19183759 G>A), RS1001384262 (13:19180322 G>A), RS1001412838 (13:19175120 C>T), RS1002167667 (13:19180082 A>G), RS1002321348 (13:19183504 T>G), RS1002606855 (13:19183687 C>A), RS1002801947 (13:19183346 G>A), RS1002910509 (13:19177765 A>C), RS1002931479 (13:19181832 C>A,G,T), RS1003206306 (13:19182679 G>A), RS1003774795 (13:19179126 G>A), RS1004508846 (13:19182078 C>T), RS1004909390 (13:19173804 A>C,G)

Disease associations

OMIM: gene MIM:602528 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001526_5	Fasting blood insulin (BMI interaction)	3.000000e-24
GCST003560_2	Coronary artery aneurysm in Kawasaki disease	8.000000e-09
GCST003998_23	Joint mobility (Beighton score)	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007905	joint hypermobility measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2095182 (PROTEIN COMPLEX GROUP), CHEMBL3832941 (PROTEIN FAMILY), CHEMBL6067579 (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)

ChEMBL bioactivities

1159 potent at pChembl≥5 of 1310 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
7.64	IC50	23	nM	COMBRETASTATIN A4
7.62	EC50	24	nM	CHEMBL4250191
7.58	IC50	26	nM	PIRONETIN
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
7.40	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
7.16	IC50	70	nM	CHEMBL2369084
7.16	IC50	70	nM	VINBLASTINE

PubChem BioAssay actives

1088 with measured affinity, of 5775 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
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
(2R,3R)-3-ethyl-2-[(E,2R,3S,4R,5S)-2-hydroxy-4-methoxy-3,5-dimethylnon-7-enyl]-2,3-dihydropyran-6-one	1572465: Inhibition of tubulin alpha in human A2780 cells assessed as reduction in cell growth	ic50	0.0260	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
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
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-(1-diethoxyphosphorylethylcarbamoyl)-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
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-[[(1S)-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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression	2
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Demecolcine	decreases expression	1
Diclofenac	affects expression	1
Estradiol	increases expression, affects binding	1
Valproic Acid	increases methylation	1
Vincristine	decreases expression	1

ChEMBL screening assays

1686 unique, capped per target: 1645 binding, 35 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009021	Binding	Inhibition of tubulin polymerization in human MCF7 cells at 1 uM after 2 hrs by SDS-PAGE	A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus. — J Nat Prod
CHEMBL4146506	ADMET	Inhibition of tubulin polymerization in human HaCaT cells assessed as chromatin condensation at 1 uM after 24 hrs by Hoechst 33258 staining-based fluorescence microscopic analysis	Design, synthesis, and biological evaluation of novel combretastatin A-4 thio derivatives as microtubule targeting agents. — Eur J Med Chem
CHEMBL5056161	Functional	Inhibition of tubulin polymerization (unknown origin) assessed as fluorescence intensity measured for 90 mins by DAPI based microplate reader	Design, synthesis and biological evaluation of indole-based [1,2,4]triazolo[4,3-a] pyridine derivatives as novel microtubule polymerization inhibitors. — Eur J Med Chem

Clinical trials (associated diseases)

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