TUBA4B

Summary

TUBA4B (tubulin alpha 4b, HGNC:18637) is a protein-coding gene on chromosome 2q35, encoding Tubulin-like protein alpha-4B (Q9H853). Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed ofalpha- and beta-tubulin heterodimers.

Predicted to enable GTP binding activity; hydrolase activity; and metal ion binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in cytoskeleton organization and microtubule-based process. Predicted to be located in cytoplasm and microtubule.

Source: NCBI Gene 80086 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 3 total
• Druggable target: yes
• MANE Select transcript: NM_001355221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18637
Approved symbol	TUBA4B
Name	tubulin alpha 4b
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13940
Ensembl gene	ENSG00000243910
Ensembl biotype	protein_coding
Entrez	80086

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000473885, ENST00000485041, ENST00000490341, ENST00000713556

RefSeq mRNA: 1 — MANE Select: NM_001355221 NM_001355221

CCDS: CCDS86922

Canonical transcript exons

ENST00000490341 — 4 exons

Exon	Start	End
ENSE00002247466	219266521	219266566
ENSE00002283895	219270202	219270335
ENSE00002302786	219271166	219272197
ENSE00003775756	219253243	219253419

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 97.83.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.83	gold quality
epithelium of bronchus	UBERON:0002031	96.31	gold quality
bronchial epithelial cell	CL:0002328	95.74	gold quality
bronchus	UBERON:0002185	95.67	gold quality
oocyte	CL:0000023	95.04	gold quality
epithelium of nasopharynx	UBERON:0001951	94.05	gold quality
type B pancreatic cell	CL:0000169	92.05	gold quality
olfactory bulb	UBERON:0002264	91.68	gold quality
nasal cavity epithelium	UBERON:0005384	91.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.53	gold quality
secondary oocyte	CL:0000655	89.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.77	gold quality
diaphragm	UBERON:0001103	86.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.12	silver quality
fallopian tube	UBERON:0003889	82.94	gold quality
oviduct epithelium	UBERON:0004804	82.74	gold quality
gingival epithelium	UBERON:0001949	82.66	silver quality
gluteal muscle	UBERON:0002000	81.94	silver quality
hair follicle	UBERON:0002073	81.69	gold quality
nasal cavity mucosa	UBERON:0001826	80.52	gold quality
gingiva	UBERON:0001828	79.78	silver quality
trachea	UBERON:0003126	79.40	gold quality
upper arm skin	UBERON:0004263	76.65	silver quality
cervix squamous epithelium	UBERON:0006922	76.25	gold quality
caput epididymis	UBERON:0004358	75.65	gold quality
squamous epithelium	UBERON:0006914	75.12	silver quality
amniotic fluid	UBERON:0000173	74.69	gold quality
mucosa of urinary bladder	UBERON:0001259	74.40	gold quality
deltoid	UBERON:0001476	74.00	silver quality
biceps brachii	UBERON:0001507	73.82	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	26.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Low expression TUBA4B in NSCLC tissue. (PMID:27411923)
• The low expression of TUBA4B was significantly associated with poor overall survival, disease-free survival, and recurrence-free survival in cancer patients. (PMID:30157490)
• Low expression of lncRNA TUBA4B promotes proliferation and inhibits apoptosis of colorectal cancer cells via regulating P15 and P16 expressions. (PMID:32271419)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	tuba2	ENSDARG00000045014
caenorhabditis_elegans		WBGENE00003175

Paralogs (23): TUBG2 (ENSG00000037042), TUBE1 (ENSG00000074935), TUBA3D (ENSG00000075886), TUBB1 (ENSG00000101162), TUBB4A (ENSG00000104833), TUBD1 (ENSG00000108423), TUBA1B (ENSG00000123416), TUBA4A (ENSG00000127824), TUBG1 (ENSG00000131462), TUBB2A (ENSG00000137267), TUBB2B (ENSG00000137285), TUBA3E (ENSG00000152086), TUBA1A (ENSG00000167552), TUBA1C (ENSG00000167553), TUBB8B (ENSG00000173213), TUBB6 (ENSG00000176014), TUBAL3 (ENSG00000178462), TUBA8 (ENSG00000183785), TUBB4B (ENSG00000188229), TUBB (ENSG00000196230), TUBA3C (ENSG00000198033), TUBB3 (ENSG00000258947), TUBB8 (ENSG00000261456)

Protein

Protein identifiers

Tubulin-like protein alpha-4B — Q9H853 (reviewed: Q9H853)

Alternative names: Alpha-tubulin 4B

All UniProt accessions (2): Q9H853, A0AAA9YHK8

UniProt curated annotations — full annotation on UniProt →

Function. Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed ofalpha- and beta-tubulin heterodimers.

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.

Similarity. Belongs to the tubulin family.

RefSeq proteins (1): NP_001342150* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000217	Tubulin	Family
IPR002452	Alpha_tubulin	Family
IPR003008	Tubulin_FtsZ_GTPase	Domain
IPR036525	Tubulin/FtsZ_GTPase_sf	Homologous_superfamily

Pfam: PF00091

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (16 total): binding site 8, sequence conflict 3, compositionally biased region 2, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H853-F1	71.58	0.18

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): 193

Ligand- & substrate-binding residues (8): 118; 145; 167; 10; 10; 79; 83; 84

Function

Pathways and Gene Ontology

Reactome pathways

79 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-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-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
R-HSA-9833482	PKR-mediated signaling
R-HSA-109582	Hemostasis
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses

MSigDB gene sets: 148 (showing top): AP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, LFA1_Q6, AREB6_01, REACTOME_MEMBRANE_TRAFFICKING, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, MYOD_01, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MYCMAX_01, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, ARGGGTTAA_UNKNOWN, TGANTCA_AP1_C, NRF2_Q4

GO Biological Process (2): microtubule-based process (GO:0007017), cytoskeleton organization (GO:0007010)

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 (4): microtubule (GO:0005874), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Mitotic Prometaphase	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
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1
Protein folding	1
L1CAM interactions	1
ER to Golgi Anterograde Transport	1
M Phase	1
G2/M Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton	2
cellular process	1
organelle organization	1
structural molecule activity	1
cytoskeleton organization	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBA4B	NBEA	Q8NFP9	460
TUBA4B	C11orf16	Q9NQ32	431
TUBA4B	OR1M1	Q8NGA1	370
TUBA4B	TUBGCP2	Q9BSJ2	348
TUBA4B	OR2Z1	Q8NG97	294
TUBA4B	CLXN	Q9HAE3	277
TUBA4B	GARNL3	Q5VVW2	269
TUBA4B	TEKT1	Q969V4	268
TUBA4B	TMEM106A	Q96A25	265
TUBA4B	MYO9A	B2RTY4	247
TUBA4B	NACA2	Q9H009	246
TUBA4B	TUBGCP6	Q96RT7	225
TUBA4B	NOCT	Q9UK39	225
TUBA4B	TUBGCP4	Q9UGJ1	223
TUBA4B	TUBGCP3	Q96CW5	223
TUBA4B	CFAP65	Q6ZU64	223
TUBA4B	ZSCAN12	O43309	223

IntAct

19 interactions, top by confidence:

A	B	Type	Score
KATNAL1	CDK1	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
L	MYO1C	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
PRKY	METTL15	psi-mi:“MI:0914”(association)	0.350
ERBB2	DNM1L	psi-mi:“MI:0914”(association)	0.350
STAT3	IDH3B	psi-mi:“MI:0914”(association)	0.350
ATF3	TMEM223	psi-mi:“MI:0914”(association)	0.350
FOS	TMEM223	psi-mi:“MI:0914”(association)	0.350
GATA2	C11orf98	psi-mi:“MI:0914”(association)	0.350
CASP3	NACA	psi-mi:“MI:0914”(association)	0.350
FOS	C11orf98	psi-mi:“MI:0914”(association)	0.350
SLC38A1	XPOT	psi-mi:“MI:0914”(association)	0.350
IKBKG	TUBA4B	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0AAL4, A2AQ07, A6NHL2, P04688, P04689, P06606, P07304, P07436, P08070, P08841, P09207, P09643, P09645, P12460, P20364, P24633, P24634, P25862, P29502, P29514, P31017, P32255, P32256, P32925, P32928, P33624, P33631, P34475, P41385, P41386, P46264, P50260, P50719, P52274, P53371, P53372, P86221, P91910, P92120, Q39697

Diamond homologs: A0A644F0Y1, O49068, O93807, P18695, P23257, P23258, P23330, P25295, P32348, P34785, P34786, P34787, P38557, P38558, P40633, P42271, P53377, P53378, P54401, P54402, P54403, P54404, P54405, P83887, P83888, P90548, Q0VCD2, Q32KM1, Q39582, Q41807, Q41808, Q41874, Q4P235, Q55AR3, Q6DIM3, Q6FNU9, Q75A43, Q7Z9Z2, Q8HZV4, Q8J1R4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATAT1	“up-regulates quantity by stabilization”	TUBA4B	acetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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.

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	5	69.0×	4e-06
positive regulation of gene expression	6	8.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1107 predictions. Top by Δscore:

Variant	Effect	Δscore
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
2:219253855:C:CA	donor_loss	1.0000
2:219253855:C:CC	donor_gain	1.0000
2:219270332:GCTG:G	donor_gain	1.0000
2:219270342:A:T	donor_gain	1.0000
2:219253298:G:GT	donor_gain	0.9900
2:219253342:GGTGC:G	donor_gain	0.9900
2:219253854:AC:A	donor_gain	0.9900
2:219253855:CC:C	donor_gain	0.9900
2:219253855:CCA:C	donor_gain	0.9900
2:219253855:CCATG:C	donor_gain	0.9900
2:219270329:G:GT	donor_gain	0.9900
2:219270334:TGGT:T	donor_loss	0.9900
2:219270336:G:GA	donor_loss	0.9900
2:219270336:G:GG	donor_gain	0.9900
2:219270337:TGA:T	donor_loss	0.9900
2:219270338:GAG:G	donor_loss	0.9900
2:219253331:C:G	donor_gain	0.9800
2:219253343:GTGC:G	donor_gain	0.9800
2:219253344:TGCT:T	donor_gain	0.9800
2:219253345:GCTG:G	donor_gain	0.9800
2:219253855:CCAT:C	donor_gain	0.9800
2:219270341:G:GT	donor_gain	0.9800
2:219271165:GGCT:G	acceptor_gain	0.9800
2:219270228:G:C	acceptor_gain	0.9700
2:219271164:A:AG	acceptor_gain	0.9700
2:219271165:G:GG	acceptor_gain	0.9700

AlphaMissense

1576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219271193:T:C	F74L	0.842
2:219271195:C:A	F74L	0.842
2:219271195:C:G	F74L	0.842
2:219271295:T:C	F108L	0.837
2:219271297:C:A	F108L	0.837
2:219271297:C:G	F108L	0.837
2:219271520:T:C	F183L	0.791
2:219271522:T:A	F183L	0.791
2:219271522:T:G	F183L	0.791
2:219271394:T:C	F141L	0.769
2:219271396:C:A	F141L	0.769
2:219271396:C:G	F141L	0.769
2:219271202:T:C	F77L	0.752
2:219271204:C:A	F77L	0.752
2:219271204:C:G	F77L	0.752
2:219271553:T:C	F194L	0.714
2:219271555:C:A	F194L	0.714
2:219271555:C:G	F194L	0.714
2:219270219:T:C	F26L	0.689
2:219270221:C:A	F26L	0.689
2:219270221:C:G	F26L	0.689

dbSNP variants (sampled 300 via entrez): RS1000084278 (2:219257378 C>T), RS1000850288 (2:219268687 G>C), RS1000897360 (2:219265239 G>A), RS1000928012 (2:219265566 G>A), RS1000992129 (2:219263004 G>A), RS1001055240 (2:219252410 C>T), RS1001119991 (2:219255694 C>T), RS1001221202 (2:219264013 A>G), RS1001281208 (2:219269016 A>G), RS1001488455 (2:219257931 G>A), RS1001569636 (2:219270332 G>A), RS1001842617 (2:219271910 C>CT), RS1001855611 (2:219257743 G>A), RS1001899535 (2:219266762 G>T), RS1001921760 (2:219252756 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004616_133	Platelet distribution width	1.000000e-35
GCST006137_6	Serum folate levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295944 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression	4
Benzo(a)pyrene	increases expression	3
lasiocarpine	increases expression	1
1,6-hexamethylene diisocyanate	increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Fluorouracil	affects reaction, decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4270855	Binding	Binding affinity to tubulin beta-4B chain in human Hela cells lysates assessed as protein enrichment by measuring normalized heavy/light ratio at by nano-LC-ESIMS/MS analysis	Determination of Gymnemic Acid I as a Protein Biosynthesis Inhibitor Using Chemical Proteomics. — J Nat Prod

Clinical trials (associated diseases)

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