TUBA4A

Summary

TUBA4A (tubulin alpha 4a, HGNC:12407) is a protein-coding gene on chromosome 2q35, encoding Tubulin alpha-4A chain (P68366). 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 encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7277 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 22 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 115 total — 18 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 75
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006000

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12407
Approved symbol	TUBA4A
Name	tubulin alpha 4a
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30169, H2-ALPHA
Ensembl gene	ENSG00000127824
Ensembl biotype	protein_coding
OMIM	191110
Entrez	7277

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000248437, ENST00000392088, ENST00000398989, ENST00000425551, ENST00000427737, ENST00000447205, ENST00000456818, ENST00000462806, ENST00000475683, ENST00000498660, ENST00000875456

RefSeq mRNA: 2 — MANE Select: NM_006000 NM_001278552, NM_006000

CCDS: CCDS2438, CCDS63131

Canonical transcript exons

ENST00000248437 — 4 exons

Exon	Start	End
ENSE00001842398	219253856	219253918
ENSE00003604371	219252008	219252230
ENSE00003681036	219251565	219251713
ENSE00003849934	219249710	219251323

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.7472 / max 1191.3186, expressed in 1752 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34054	65.0582	1740
34053	1.4879	628
34050	0.9098	438
34052	0.6093	336
34057	0.2006	75
34049	0.1851	82
34051	0.1220	49
34055	0.0974	44
34056	0.0273	15
34059	0.0266	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	99.53	gold quality
frontal pole	UBERON:0002795	99.46	gold quality
gingiva	UBERON:0001828	99.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.35	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.20	gold quality
upper arm skin	UBERON:0004263	99.17	gold quality
body of tongue	UBERON:0011876	99.13	gold quality
dorsal root ganglion	UBERON:0000044	99.09	gold quality
nipple	UBERON:0002030	99.09	gold quality
gastrocnemius	UBERON:0001388	99.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.01	gold quality
middle temporal gyrus	UBERON:0002771	98.98	gold quality
pons	UBERON:0000988	98.91	gold quality
tongue	UBERON:0001723	98.89	gold quality
pharyngeal mucosa	UBERON:0000355	98.88	gold quality
penis	UBERON:0000989	98.84	gold quality
superior vestibular nucleus	UBERON:0007227	98.82	gold quality
prefrontal cortex	UBERON:0000451	98.78	gold quality
skin of abdomen	UBERON:0001416	98.72	gold quality
skin of leg	UBERON:0001511	98.71	gold quality
zone of skin	UBERON:0000014	98.69	gold quality
oocyte	CL:0000023	98.62	gold quality
superior surface of tongue	UBERON:0007371	98.59	gold quality
skeletal muscle tissue	UBERON:0001134	98.53	gold quality
granulocyte	CL:0000094	98.49	gold quality
right frontal lobe	UBERON:0002810	98.43	gold quality
blood	UBERON:0000178	98.42	gold quality
islet of Langerhans	UBERON:0000006	98.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.39	gold quality
deltoid	UBERON:0001476	98.38	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	359.66
E-MTAB-8142	yes	47.88
E-CURD-122	yes	40.95
E-HCAD-4	yes	37.94
E-GEOD-135922	yes	28.05
E-MTAB-9221	yes	19.72
E-HCAD-11	yes	17.79
E-HCAD-10	yes	17.66
E-CURD-46	yes	10.37
E-MTAB-9801	yes	8.92
E-HCAD-1	yes	7.28
E-MTAB-6386	no	243.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA

miRNA regulators (miRDB)

32 targeting TUBA4A, 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-545-3P	99.95	70.74	2783
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-890	97.47	68.67	982
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-8083	95.93	67.55	694

Literature-anchored findings (GeneRIF, showing 22)

• increased levels in paclitaxel-resistant breast cancer cells (PMID:12054644)
• Some protein-protein interactions in rafts were disrupted in 3-nitrotyrosine-containing proteins, e.g. caveolin-1 was dissociated from a complex with flotillin-1 and alpha-tubulin. (PMID:15934946)
• Our results suggest that MIZIP might play an important role in mammalian cells by associating with tubulin and thus might provide a link between MCHR1 and tubulin functions. (PMID:16039987)
• These results provide the first characterisation of endogenously nitrated tubulin from human tumour samples. (PMID:16257120)
• Subunits of alphaB crystallin that exchange dynamically with the alphaB crystallin complex can interact with tubulin subunits to regulate the equilibrium between tubulin and microtubules. (PMID:20668689)
• The results suggested that cytoskeletal alterations in the amygdala determined by tubulin seem to be involved in the pathophysiology of drug addiction (PMID:20686780)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• TUBA4A is significantly increased in spermatazoa from men with azoospermia. (PMID:24268707)
• TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability (PMID:25374358)
• This study mutational screening revealed the presence of four novel heterozygous variants of TUBA4A mutation in four sporadic amyotrophic lateral sclerosis. (PMID:25893256)
• Data show that overexpression of the 14-3-3sigma isoform resulted in a disruption of the tubulin cytoskeleton mediated by binding Tau protein. (PMID:26103986)
• In conclusion, our current results did not find an association between TUBA4A and ALS in Chinese patients, and further studies will be required. (PMID:26465396)
• TUBA4A mutations are not associated with FTD. (PMID:26675813)
• alphaTubulin expression might be an independent prognostic factor for pancreatic cancer after surgical resection (PMID:27447976)
• Its mutations were seen in patients with ALS and frontotemporal dementia. (PMID:28069311)
• The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset. (PMID:28478440)
• The frequency of TUBA4A mutations suggests that TUBA4A is a rare cause of Amotrophic Lateral Sclerosis in Chinese patients. (PMID:29540513)
• Data indicate a microRNA-1825/TBCB/TUBA4A pathway as a putative pathogenic cascade in both familial ALS (fALS) and both sporadic (sALS). (PMID:30030593)
• Mice carrying a missense mutation in the Tuba4a gene, and a patient with a monoallelic double missense mutation in the TUBA4A gene displayed macrothrombocytopenia and structural abnormalities in the marginal band of platelets. (PMID:30760556)
• In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration. (PMID:36747013)
• A new genetic cause of spastic ataxia: the p.Glu415Lys variant in TUBA4A. (PMID:37418012)
• Novel TUBA4A variant causes congenital myopathy with focal myofibrillar disorganisation. (PMID:38413182)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tuba8l2	ENSDARG00000031164
mus_musculus	Tuba4a	ENSMUSG00000026202
rattus_norvegicus	Tuba4a	ENSRNOG00000003597

Paralogs (23): TUBG2 (ENSG00000037042), TUBE1 (ENSG00000074935), TUBA3D (ENSG00000075886), TUBB1 (ENSG00000101162), TUBB4A (ENSG00000104833), TUBD1 (ENSG00000108423), TUBA1B (ENSG00000123416), 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), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin alpha-4A chain — P68366 (reviewed: P68366)

Alternative names: Alpha-tubulin 1, Testis-specific alpha-tubulin, Tubulin H2-alpha, Tubulin alpha-1 chain

All UniProt accessions (6): P68366, C9JDL2, C9JDS9, C9JEV8, C9JJQ8, C9JQ00

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. Interacts with CFAP157.

Subcellular location. Cytoplasm. Cytoskeleton.

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. Although this tubulin does not encode a C-terminal tyrosine, a C-terminal tyrosine can be added post-translationally by the tubulin tyrosine ligase (TTL). It can then undergo a detyrosination cycle by the tubulin tyrosine carboxypeptidase (MATCAP1/KIAA0895L).

Disease relevance. Frontotemporal dementia and/or amyotrophic lateral sclerosis 9 (FTDALS9) [MIM:616208] An autosomal dominant neurodegenerative disorder characterized by adult onset of frontotemporal dementia or amyotrophic lateral sclerosis with upper and lower neuron involvement. Some patients manifest both frontotemporal dementia and amyotrophic lateral sclerosis. The disease is caused by variants affecting the gene represented in this entry. Congenital myopathy 26 (CMYO26) [MIM:621225] A form of congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness typically noticed at birth or during the neonatal period, and, in some cases, delayed motor development later in childhood. Specific pathological features are observed on muscle biopsy. CMYO26 is an autosomal dominant form characterized by limb muscle weakness and mild motor delay apparent from infancy, hyporeflexia, myopathic face with high-arched palate, and ophthalmoplegia in some patients. Skeletal muscle biopsy shows myopathic features with myofibrillar disorganization and rimmed vacuoles. The disease is caused by variants affecting the gene represented in this entry. Spastic ataxia 11, autosomal dominant (SPAX11) [MIM:621226] A form of spastic ataxia, a heterogeneous group of progressive neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. SPAX11 is an autosomal dominant, progressive form with age at onset usually in the first 2 decades. Brain imaging often shows cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry. Oocyte/zygote/embryo maturation arrest 23 (OZEMA23) [MIM:621231] A female infertility disorder characterized by oocyte maturation arrest at the oocyte, zygote, or embryo stage. Inheritance can be autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

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

Similarity. Belongs to the tubulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P68366-1	1	yes
P68366-2	2

RefSeq proteins (2): NP_001265481, NP_005991* (*=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 (47 total): sequence variant 29, binding site 9, modified residue 5, chain 1, short sequence motif 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P68366-F1	92.02	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.

Catalytic / active sites (1): 254

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

Post-translational modifications (5): 40, 48, 83, 432, 439

Function

Pathways and Gene Ontology

Reactome pathways

96 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
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-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-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-5620912	Anchoring of the basal body to the plasma membrane
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-8854518	AURKA Activation by TPX2
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

MSigDB gene sets: 463 (showing top): AP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, JAEGER_METASTASIS_DN, LFA1_Q6, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_317, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, AREB6_01, GOBP_NEUROGENESIS

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 (8): structural constituent of cytoskeleton (GO:0005200), GTP binding (GO:0005525), hydrolase activity (GO:0016787), protein kinase binding (GO:0019901), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), enzyme binding (GO:0019899)

GO Cellular Component (8): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), microtubule (GO:0005874), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Mitotic Prometaphase	2
Centrosome maturation	2
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	2
Assembly of the 9+0 primary cilium	2
Response to elevated platelet cytosolic Ca2+	1
Membrane Trafficking	1
Transport of connexons to the plasma membrane	1
Gap junction trafficking	1
Adaptive Immune System	1
Mitotic Anaphase	1
G2/M Transition	1
Cellular responses to stress	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Protein folding	1
L1CAM interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
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
kinase binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
protein binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

446 interactions, top by confidence:

A	B	Type	Score
DNAJB11	HSPA5	psi-mi:“MI:0914”(association)	0.830
TUBA4A	TCP11L2	psi-mi:“MI:0915”(physical association)	0.800
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
PRKAB1	PRKAB2	psi-mi:“MI:0914”(association)	0.740
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
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
MAP2K2	TUBA4A	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
SERPINF1	HSPA5	psi-mi:“MI:0914”(association)	0.620
TUBA1A	TUBA4A	psi-mi:“MI:0914”(association)	0.610
TBCB	TUBA4A	psi-mi:“MI:0915”(physical association)	0.590
APP	TUBA4A	psi-mi:“MI:0915”(physical association)	0.560
POC5	TUBA4A	psi-mi:“MI:0915”(physical association)	0.540
POC5	TUBA4A	psi-mi:“MI:0403”(colocalization)	0.540
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
CELA3A	POTEF	psi-mi:“MI:0914”(association)	0.530
ANTXR1	POTEF	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
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
ADAMTS4	MANBA	psi-mi:“MI:0914”(association)	0.530

BioGRID (672): TUBA4A (Affinity Capture-RNA), TUBA4A (Affinity Capture-RNA), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA4A (Affinity Capture-MS)

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

10 interactions.

A	Effect	B	Mechanism
NUMA1	up-regulates	TUBA4A	binding
TTL	down-regulates	TUBA4A	tyrosination
SYK	“up-regulates activity”	TUBA4A	phosphorylation
cabazitaxel	“down-regulates activity”	TUBA4A	“chemical inhibition”
“docetaxel anhydrous”	“down-regulates activity”	TUBA4A	“chemical inhibition”
“eribulin mesylate”	“down-regulates activity”	TUBA4A	“chemical inhibition”
paclitaxel	“down-regulates activity”	TUBA4A	“chemical inhibition”
“Elongator complex”	“up-regulates activity”	TUBA4A	acetylation
TUBA4A	up-regulates	Neuron_migration
ATAT1	“up-regulates quantity by stabilization”	TUBA4A	acetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 284 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
Activation of AMPK downstream of NMDARs	9	17.8×	9e-07
Post-chaperonin tubulin folding pathway	7	17.4×	2e-05
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	17.0×	6e-05
Transport of connexons to the plasma membrane	6	17.0×	6e-05
Gap junction trafficking and regulation	6	14.9×	1e-04
Gap junction trafficking	6	14.9×	1e-04
Formation of tubulin folding intermediates by CCT/TriC	6	13.2×	2e-04
Signaling by RAS mutants	6	13.2×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of peptidyl-serine phosphorylation	5	14.8×	6e-03
G1/S transition of mitotic cell cycle	12	9.3×	1e-05
cytoplasmic microtubule organization	7	9.3×	5e-03
microtubule cytoskeleton organization	11	5.2×	5e-03
protein phosphorylation	14	3.7×	9e-03
negative regulation of apoptotic process	22	3.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	6
Uncertain significance	32
Likely benign	43
Benign	12

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
180183	NM_006000.3(TUBA4A):c.959G>A (p.Arg320His)	Pathogenic
180184	NM_006000.3(TUBA4A):c.1220G>A (p.Trp407Ter)	Pathogenic
180187	NM_006000.3(TUBA4A):c.433A>C (p.Thr145Pro)	Pathogenic
3901247	L227F	Pathogenic
3901248	E415K	Pathogenic
3901249	NM_006000.3(TUBA4A):c.517C>T (p.Pro173Ser)	Pathogenic
3901250	NM_006000.3(TUBA4A):c.518C>G (p.Pro173Arg)	Pathogenic
3901251	NM_006000.3(TUBA4A):c.229G>A (p.Glu77Lys)	Pathogenic
3901252	NM_006000.3(TUBA4A):c.1040G>A (p.Cys347Tyr)	Pathogenic
3901253	NM_006000.3(TUBA4A):c.685C>T (p.Arg229Cys)	Pathogenic
3901254	NM_006000.3(TUBA4A):c.850G>A (p.Glu284Lys)	Pathogenic
3901255	NM_006000.3(TUBA4A):c.857T>C (p.Leu286Pro)	Pathogenic
3901256	NM_006000.3(TUBA4A):c.190del (p.Arg64fs)	Pathogenic
3901258	NM_006000.3(TUBA4A):c.907G>C (p.Val303Leu)	Pathogenic
3901259	E284G	Pathogenic
3901260	R339C	Pathogenic
3901261	TUBA4A, 2-BP DEL, NT1319	Pathogenic
583449	NC_000002.11:g.(?219135239)(220290732_?)del	Pathogenic
180182	NM_006000.3(TUBA4A):c.958C>T (p.Arg320Cys)	Likely pathogenic
180186	NM_006000.3(TUBA4A):c.1147G>A (p.Ala383Thr)	Likely pathogenic
3380962	NM_006000.3(TUBA4A):c.995_997delinsA (p.Ile332fs)	Likely pathogenic
818052	NM_006000.3(TUBA4A):c.761_762del (p.Glu254fs)	Likely pathogenic
986894	NM_006000.3(TUBA4A):c.225del (p.Ile75fs)	Likely pathogenic
996813	NM_006000.3(TUBA4A):c.1051_1055dup (p.Lys352fs)	Likely pathogenic

SpliceAI

1479 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219251319:TCAGA:T	acceptor_gain	1.0000
2:219251320:CAGA:C	acceptor_gain	1.0000
2:219251320:CAGAC:C	acceptor_gain	1.0000
2:219251322:GA:G	acceptor_gain	1.0000
2:219251324:C:CC	acceptor_gain	1.0000
2:219251559:TCTCA:T	donor_loss	1.0000
2:219251560:CTCA:C	donor_loss	1.0000
2:219251562:CACCA:C	donor_loss	1.0000
2:219251563:A:AC	donor_gain	1.0000
2:219251563:A:C	donor_loss	1.0000
2:219251564:C:CC	donor_gain	1.0000
2:219251564:C:CT	donor_loss	1.0000
2:219251564:CCAG:C	donor_gain	1.0000
2:219251709:CTCAT:C	acceptor_gain	1.0000
2:219251710:TCAT:T	acceptor_gain	1.0000
2:219251711:CAT:C	acceptor_gain	1.0000
2:219251711:CATC:C	acceptor_gain	1.0000
2:219251712:AT:A	acceptor_gain	1.0000
2:219251714:C:CA	acceptor_loss	1.0000
2:219251714:C:CC	acceptor_gain	1.0000
2:219251723:C:CT	acceptor_gain	1.0000
2:219251999:T:TA	donor_gain	1.0000
2:219252003:CTCAC:C	donor_loss	1.0000
2:219252004:TCACC:T	donor_loss	1.0000
2:219252227:CACG:C	acceptor_gain	1.0000
2:219252229:CG:C	acceptor_gain	1.0000
2:219253852:TCA:T	donor_loss	1.0000
2:219253853:CA:C	donor_loss	1.0000
2:219253854:A:AC	donor_gain	1.0000
2:219253854:A:T	donor_loss	1.0000

AlphaMissense

2952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219250408:C:G	D431H	1.000
2:219250416:A:G	L428P	1.000
2:219250434:C:G	R422P	1.000
2:219250435:G:T	R422S	1.000
2:219250438:C:G	A421P	1.000
2:219250445:G:C	F418L	1.000
2:219250445:G:T	F418L	1.000
2:219250446:A:C	F418C	1.000
2:219250446:A:G	F418S	1.000
2:219250447:A:G	F418L	1.000
2:219250461:A:G	M413T	1.000
2:219250465:C:G	G412R	1.000
2:219250480:A:G	W407R	1.000
2:219250480:A:T	W407R	1.000
2:219250483:G:C	H406D	1.000
2:219250487:A:C	F404L	1.000
2:219250487:A:T	F404L	1.000
2:219250488:A:C	F404C	1.000
2:219250488:A:G	F404S	1.000
2:219250489:A:G	F404L	1.000
2:219250489:A:T	F404I	1.000
2:219250493:C:A	R402S	1.000
2:219250493:C:G	R402S	1.000
2:219250494:C:A	R402M	1.000
2:219250494:C:G	R402T	1.000
2:219250509:A:G	L397P	1.000
2:219250512:T:A	D396V	1.000
2:219250514:G:C	F395L	1.000
2:219250514:G:T	F395L	1.000
2:219250516:A:G	F395L	1.000

dbSNP variants (sampled 300 via entrez): RS1001055240 (2:219252410 C>T), RS1001119991 (2:219255694 C>T), RS1001921760 (2:219252756 C>T), RS1001995199 (2:219253044 T>C), RS1003032999 (2:219255090 A>G), RS1003065583 (2:219254775 G>A), RS1003527769 (2:219250272 A>G), RS1003587852 (2:219253959 G>A,C,T), RS1003663122 (2:219254146 C>G), RS1003968493 (2:219250021 ACTC>A), RS1004000191 (2:219255584 T>G), RS1004599886 (2:219254691 C>T), RS1005457760 (2:219254425 C>T), RS1005497649 (2:219249706 A>T), RS1005798711 (2:219249979 G>A,C)

Disease associations

OMIM: gene MIM:191110 | disease phenotypes: MIM:612069, MIM:616208, MIM:621225, MIM:621226, MIM:621231, MIM:601419, MIM:615325

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 22	Strong	Autosomal dominant
spastic ataxia 11, autosomal dominant	Strong	Autosomal dominant
oocyte/zygote/embryo maturation arrest 23	Strong	Autosomal dominant
congenital myopathy	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 22	Moderate	AD
autosomal dominant macrothrombocytopenia	Limited	AD

Mondo (9): amyotrophic lateral sclerosis (MONDO:0004976), amyotrophic lateral sclerosis type 10 (MONDO:0012790), amyotrophic lateral sclerosis type 22 (MONDO:0014531), ptosis (MONDO:0000728), congenital myopathy 26 (MONDO:0979229), spastic ataxia 11, autosomal dominant (MONDO:0979230), oocyte/zygote/embryo maturation arrest 23 (MONDO:0979231), myofibrillar myopathy 1 (MONDO:0011076), congenital myopathy (MONDO:0019952)

Orphanet (4): Amyotrophic lateral sclerosis (Orphanet:803), Frontotemporal dementia with motor neuron disease (Orphanet:275872), Autosomal recessive limb-girdle muscular dystrophy type 2R (Orphanet:363543), Desminopathy (Orphanet:98909)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000009	Functional abnormality of the bladder
HP:0000218	High palate
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000649	Abnormality of visual evoked potentials
HP:0000708	Atypical behavior
HP:0000726	Dementia
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001310	Dysmetria
HP:0001315	Reduced tendon reflexes
HP:0001347	Hyperreflexia
HP:0001394	Cirrhosis
HP:0002015	Dysphagia
HP:0002064	Spastic gait
HP:0002075	Dysdiadochokinesis
HP:0002145	Frontotemporal dementia
HP:0002380	Fasciculations
HP:0002497	Spastic ataxia
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002650	Scoliosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000175_19	Height	1.000000e-06
GCST004616_133	Platelet distribution width	1.000000e-35
GCST90002401_424	Platelet distribution width	3.000000e-94
GCST90026412_16	Severe autoimmune type 2 diabetes	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D001763	Blepharoptosis	C11.338.204
C567429	Amyotrophic Lateral Sclerosis 10 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2070 (SINGLE PROTEIN), CHEMBL2095182 (PROTEIN COMPLEX GROUP), CHEMBL3832941 (PROTEIN FAMILY), CHEMBL6067579 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,613,690 (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
CHEMBL1232461	MOLIBRESIB	2	1,538
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
CHEMBL246600	COMBRETASTATIN	1

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Tubulins

ChEMBL bioactivities

1163 potent at pChembl≥5 of 1314 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
7.92	Kd	12.17	nM	CHEMBL3752910
7.92	ED50	12.17	nM	CHEMBL3752910
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

PubChem BioAssay actives

1091 with measured affinity, of 5785 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(Z)-1-[4-bromo-2-(4-fluorophenyl)-1-benzofuran-7-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1882651: Inhibition of tubulin polymerization (unknown origin) measured every 3 secs for 1 hr by spectroflourimetric analysis	ic50	0.0001	uM
(Z)-1-[4-bromo-2-(4-fluorophenyl)-1-benzofuran-7-yl]-3-[4-(trifluoromethoxy)phenyl]prop-2-en-1-one	1882651: Inhibition of tubulin polymerization (unknown origin) measured every 3 secs for 1 hr by spectroflourimetric analysis	ic50	0.0002	uM
Vinorelbine	1993632: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0003	uM
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide	270819: Inhibition of tubulin polymerization	ic50	0.0005	uM
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-(2-pyridin-2-ylethylamino)propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide	1896115: Binding affinity to tubulin (unknown origin)	ic50	0.0012	uM
(3Z,6Z)-3-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]-6-phenacylidenepiperazine-2,5-dione	1587857: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0014	uM
(3Z,6Z)-3-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]-6-[(2,5-difluorophenyl)methylidene]piperazine-2,5-dione	1587857: Inhibition of tubulin polymerization (unknown origin)	ic50	0.0026	uM
3-hydroxy-2-[N-[2-(methoxymethyl)-1-benzofuran-7-yl]-C-methylcarbonimidoyl]-5-phenylcyclohex-2-en-1-one	2034736: Displacement of fluorescent probe (R)-(+)-ethyl 5-amino2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-ylcarbamate from tubulin colchicine binding site (unknown origin) assessed as dissociation constant	kd	0.0030	uM
2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol	1862628: Inhibition of tubulin polymerization in human HeLa cells assessed as microtubule network polymerization after 30 mins by immunofluorescence analysis	ic50	0.0030	uM
Colchicine	2074087: Inhibition of microtubule polymerization in human K562 cells measured for 60 mins by fluorescence based analysis	ic50	0.0030	uM
(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione	1408257: Inhibition of tubulin polymerization in human MCF7 cells assessed as induction of mitotic arrest	ic50	0.0035	uM
tert-butyl (3R,4S,5S)-4-[[(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoate	1896110: Inhibition of tubulin (unknown origin) polymerization assessed as reduction in microtubule formation measured for 20 mins by spectrophotometric analysis	ic50	0.0042	uM
3-methoxy-6-[4-(3,4,5-trimethoxyphenyl)-1H-pyrazol-5-yl]benzene-1,2-diol	1929685: Inhibition of tubulin polymerization in human SH-SY5Y cells incubated for 24 hrs by SDS-PAGE based analysis	ic50	0.0054	uM
2-methoxy-5-[1-(3,4,5-trimethoxyphenyl)ethenyl]phenol	1862628: Inhibition of tubulin polymerization in human HeLa cells assessed as microtubule network polymerization after 30 mins by immunofluorescence analysis	ic50	0.0060	uM
(E)-1-[1-(4-chlorophenyl)-5-methyltriazol-4-yl]-3-(3,4-dimethoxyphenyl)prop-2-en-1-one	1689700: Inhibition of Tubulin in human RPMI-8226 cells incubated for 2 hrs by ELISA	ic50	0.0098	uM
N-(1,3-benzodioxol-5-yl)-5-[2-(3,5-dimethoxyphenoxy)-3-pyridinyl]-1H-1,2,4-triazol-3-amine	256882: Displacement of [3H]colchicine from tubulin	ki	0.0100	uM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[2-(pyridin-2-ylmethylamino)phenyl]-1,3-oxazol-2-amine	261214: Displacement of [3H]colchicine from tubulin at 65 nM	ic50	0.0100	uM
[(1S,2R,3S,5R,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] acetate	2126113: Displacement of fluorescent Maytansine probe from tubulin (unknown origin) assessed as dissociation constant by competitive binding based fluorescence anisotropy	kd	0.0110	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149676: Binding affinity to human TUBA4A incubated for 45 mins by Kinobead based pull down assay	kd	0.0122	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression	5
sulforaphane	affects binding, increases acetylation, increases expression	4
Tretinoin	decreases expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression, affects expression	3
Tobacco Smoke Pollution	increases expression, increases metabolic processing, affects expression, decreases acetylation	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
bisphenol A	decreases expression, increases expression	2
lead acetate	increases expression	2
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression	2
chloropicrin	increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Copper	affects binding, decreases expression, increases expression	2
Dactinomycin	increases expression, affects cotreatment, increases secretion	2
Doxorubicin	decreases expression, increases response to substance	2
Selenium	increases expression, increases abundance, affects binding	2
Selenomethionine	increases reaction, increases glutathionylation, increases abundance, affects binding	2
Silicon Dioxide	affects secretion, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
Acrylamide	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
marbostat-100	increases acetylation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1

ChEMBL screening assays

1695 unique, capped per target: 1654 binding, 35 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118606	Binding	Binding affinity to TUBA4A in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem
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

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B4H8	HeLa TUBA4A KO	Cancer cell line	Female
CVCL_D1ZI	Abcam A-549 TUBA4A KO	Cancer cell line	Male
CVCL_D2DI	Abcam HCT 116 TUBA4A KO	Cancer cell line	Male
CVCL_D2PC	Abcam THP-1 TUBA4A KO	Cancer cell line	Male
CVCL_TV14	HAP1 TUBA4A (-) 1	Cancer cell line	Male
CVCL_TV15	HAP1 TUBA4A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS