TBCB

Summary

TBCB (tubulin folding cofactor B, HGNC:1989) is a protein-coding gene on chromosome 19q13.12, encoding Tubulin-folding cofactor B (Q99426). Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer. It is a common-essential gene (DepMap: required in 97.2% of cancer cell lines).

Predicted to enable microtubule plus-end binding activity. Predicted to be involved in cytoplasmic microtubule organization. Located in cytosol.

Source: NCBI Gene 1155 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total
• Phenotypes (HPO): 36
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_001281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1989
Approved symbol	TBCB
Name	tubulin folding cofactor B
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	CG22, CKAPI
Ensembl gene	ENSG00000105254
Ensembl biotype	protein_coding
OMIM	601303
Entrez	1155

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000221855, ENST00000392178, ENST00000468156, ENST00000481742, ENST00000585746, ENST00000585910, ENST00000586868, ENST00000588385, ENST00000589308, ENST00000589624, ENST00000589996, ENST00000591296, ENST00000593075, ENST00000651435, ENST00000888742, ENST00000888743, ENST00000932775, ENST00000932776, ENST00000932777

RefSeq mRNA: 2 — MANE Select: NM_001281 NM_001281, NM_001300971

CCDS: CCDS12488, CCDS74344

Canonical transcript exons

ENST00000221855 — 6 exons

Exon	Start	End
ENSE00001151146	36115468	36115674
ENSE00003526770	36125451	36125523
ENSE00003662739	36121527	36121718
ENSE00003695439	36116041	36116184
ENSE00003695722	36120710	36120806
ENSE00003849507	36125668	36125941

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.2136 / max 454.6883, expressed in 1821 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175466	75.1603	1821
175465	2.0272	1067
175467	1.4510	900
175468	0.3637	161
175470	0.1722	18
175471	0.0245	8
175469	0.0148	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.28	gold quality
spinal cord	UBERON:0002240	99.23	gold quality
cortical plate	UBERON:0005343	99.18	gold quality
inferior vagus X ganglion	UBERON:0005363	99.12	gold quality
pons	UBERON:0000988	99.11	gold quality
prefrontal cortex	UBERON:0000451	99.00	gold quality
middle frontal gyrus	UBERON:0002702	98.90	gold quality
inferior olivary complex	UBERON:0002127	98.86	gold quality
hypothalamus	UBERON:0001898	98.85	gold quality
midbrain	UBERON:0001891	98.83	gold quality
substantia nigra	UBERON:0002038	98.83	gold quality
superior vestibular nucleus	UBERON:0007227	98.83	gold quality
medulla oblongata	UBERON:0001896	98.81	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.78	gold quality
amygdala	UBERON:0001876	98.74	gold quality
subthalamic nucleus	UBERON:0001906	98.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.72	gold quality
dorsal root ganglion	UBERON:0000044	98.66	gold quality
frontal cortex	UBERON:0001870	98.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.60	gold quality
frontal lobe	UBERON:0016525	98.60	gold quality
ventral tegmental area	UBERON:0002691	98.59	gold quality
postcentral gyrus	UBERON:0002581	98.57	gold quality
temporal lobe	UBERON:0001871	98.56	gold quality
Ammon’s horn	UBERON:0001954	98.56	gold quality
cingulate cortex	UBERON:0003027	98.55	gold quality
neocortex	UBERON:0001950	98.54	gold quality
cerebral cortex	UBERON:0000956	98.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.53	gold quality
ganglionic eminence	UBERON:0004023	98.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.02
E-GEOD-84465	yes	10.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TBCB, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6080	99.43	69.43	373
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-3139	96.68	66.77	652
HSA-MIR-28-5P	96.16	66.12	579
HSA-MIR-708-5P	96.16	66.12	576
HSA-MIR-6890-5P	92.89	65.83	442

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• These findings identified TCoB as the third cytoskeleton protein to be nitrated and suggest a previously undescribed mechanism, whereby growth factor signaling may coordinately integrate nitric oxide signaling in the regulation of microtubule dynamics. (PMID:18048340)
• TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into understanding of mechanisms controlling microtubule reorganization during microglial transition between phenotypes. (PMID:19038251)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Study demonstrates that, unlike its counterpart TBCE, TBCB only moderately destabilizes microtubules; neither TBCB abundance nor microtubule organization or densities are altered in giant axonal neuropathy mutant fibroblasts. (PMID:19168853)
• Overexpression of TBCB leads to the decreased localization of p150 to the microtubule network that might result in a functional modulation of this protein complex. (PMID:22777741)
• TBCB localizes at spindle and midzone microtubules during mitosis. (PMID:22940919)
• results support a role for MAP1 proteins in promoting efficient retrograde trafficking of HIV-1 by stimulating the formation of stable microtubules and mediating the association of HIV-1 cores with microtubules. (PMID:25505242)
• the role of the human TBCE and TBCB chaperones in alpha-tubulin-beta-tubulin dissociation, was investigated. (PMID:25908846)
• Our results showed that HILI suppresses microtubule polymerization and promotes cell proliferation, migration and invasion via TBCB for the first time, revealing a novel mechanism for HILI in tumorigenesis. (PMID:28393858)
• Data indicate a microRNA-1825/TBCB/TUBA4A pathway as a putative pathogenic cascade in both familial ALS (fALS) and both sporadic (sALS). (PMID:30030593)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbcb	ENSDARG00000068404
mus_musculus	Tbcb	ENSMUSG00000006095
rattus_norvegicus	Tbcb	ENSRNOG00000020781
drosophila_melanogaster	Tbcb	FBGN0034451

Protein

Protein identifiers

Tubulin-folding cofactor B — Q99426 (reviewed: Q99426)

Alternative names: Cytoskeleton-associated protein 1, Cytoskeleton-associated protein CKAPI, Tubulin-specific chaperone B

All UniProt accessions (7): Q99426, A0A494C0X0, K7EK42, K7EL99, K7EP07, K7EQH0, K7ER04

UniProt curated annotations — full annotation on UniProt →

Function. Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer. Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth.

Subunit / interactions. Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state. Cofactors B and E can form a heterodimer which binds to alpha-tubulin and enhances their ability to dissociate tubulin heterodimers. Interacts with GAN. Interacts with DCTN1.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Found in most tissues.

Post-translational modifications. Phosphorylation by PAK1 is required for normal function. Ubiquitinated in the presence of GAN which targets it for degradation by the proteasome. (Microbial infection) Glycosylated residues by S.typhimurium protein Ssek1: arginine GlcNAcylation promotes microtubule stability.

Similarity. Belongs to the TBCB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99426-1	1	yes
Q99426-2	2

RefSeq proteins (2): NP_001272, NP_001287900 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR000938	CAP-Gly_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036859	CAP-Gly_dom_sf	Homologous_superfamily
IPR045172	TBCB_Ubl	Domain

Pfam: PF01302, PF14560

UniProt features (12 total): modified residue 6, mutagenesis site 2, chain 1, domain 1, sequence conflict 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99426-F1	92.55	0.84

Functional residue map

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

Post-translational modifications (6): 1, 65, 98, 110, 128, 219

Mutagenesis-validated functional residues (2):

Position	Phenotype
128	reduced phosphorylation by pak1. reduced microtubule polymerization and loss of phosphorylation by pak1; when associated
65	reduced phosphorylation by pak1. reduced microtubule polymerization and loss of phosphorylation by pak1; when associated

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-389977	Post-chaperonin tubulin folding pathway
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 200 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, PAX4_01, GCM_NPM1, MORF_UBE2I, MATTIOLI_MGUS_VS_PCL, SP1_Q2_01, GCM_PPP1CC, GOBP_PROTEIN_MATURATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_PROTEIN_FOLDING, TGGNNNNNNKCCAR_UNKNOWN, GRUETZMANN_PANCREATIC_CANCER_UP, ZHAN_VARIABLE_EARLY_DIFFERENTIATION_GENES_DN

GO Biological Process (5): tubulin complex assembly (GO:0007021), post-chaperonin tubulin folding pathway (GO:0007023), nervous system development (GO:0007399), cell differentiation (GO:0030154), cytoplasmic microtubule organization (GO:0031122)

GO Molecular Function (3): alpha-tubulin binding (GO:0043014), microtubule plus-end binding (GO:0051010), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cell cortex (GO:0005938), microtubule cytoskeleton (GO:0015630), microtubule plus-end (GO:0035371), cytoskeleton (GO:0005856), microtubule (GO:0005874)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein folding	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
protein-containing complex assembly	1
tubulin complex assembly	1
system development	1
cellular developmental process	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
tubulin binding	1
microtubule binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cell periphery	1
cytoskeleton	1
microtubule end	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBCB	TBCD	Q9BTW9	776
TBCB	GAN	Q9H2C0	766
TBCB	A0A2R8Y809	A0A2R8Y809	735
TBCB	TBCE	Q15813	735
TBCB	TBCC	Q15814	731
TBCB	TBCA	O75347	667
TBCB	ARL2	P36404	620
TBCB	TUBB6	Q9BUF5	524
TBCB	ACTL7B	Q9Y614	523
TBCB	TBCEL	Q5QJ74	487
TBCB	TUBA4A	P05215	474
TBCB	ZNF704	Q6ZNC4	470
TBCB	TUBB8	Q3ZCM7	467
TBCB	TUBB2A	Q13885	460
TBCB	TUBB2B	Q9BVA1	449

IntAct

50 interactions, top by confidence:

A	B	Type	Score
TBCB	TUBA4A	psi-mi:“MI:0915”(physical association)	0.590
GAN	TBCB	psi-mi:“MI:0915”(physical association)	0.510
USP7	TBCB	psi-mi:“MI:0915”(physical association)	0.510
PAK1	TBCB	psi-mi:“MI:0915”(physical association)	0.370
TBCB	rep	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
MAP3K7	ACOT7	psi-mi:“MI:0914”(association)	0.350
ARAF		psi-mi:“MI:0914”(association)	0.350
RIPK4	TBCA	psi-mi:“MI:0914”(association)	0.350
PRKCZ	PGRMC1	psi-mi:“MI:0914”(association)	0.350
MYLK4	AP3D1	psi-mi:“MI:0914”(association)	0.350
NEK7	SUPT5H	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
TUBA1B	SLAIN2	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): ANXA6 (Co-fractionation), D2HGDH (Co-fractionation), HK2 (Co-fractionation), LGSN (Co-fractionation), PLBD2 (Co-fractionation), PPP1R14B (Co-fractionation), TBCB (Co-fractionation), TBCB (Co-fractionation), XPNPEP1 (Co-fractionation), TBCB (Affinity Capture-MS), TBCB (Proximity Label-MS), TBCB (Synthetic Lethality), TBCB (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TBCB (Affinity Capture-Western)

ESM2 similar proteins: A0A0E0SC50, A2X052, A6NHR9, B0F9L4, B5XFI8, C1BGZ8, C1BHN7, C1BXU5, C3KHF2, F1QWA8, O08658, O35099, O75165, P0CI65, P54729, P54731, P60670, P62869, P62870, Q05B17, Q15370, Q32PG3, Q3ZBQ1, Q4V8W7, Q5E951, Q5F3K4, Q5R8B7, Q5RAW8, Q5TZF3, Q67Z52, Q68FV8, Q6GL38, Q6P5D8, Q6PFM9, Q6ZGL4, Q7Z494, Q7ZWB2, Q8BH57, Q8TAF3, Q8TAT6

Diamond homologs: A0A287B8J2, B9EHT4, O08788, O42184, O42667, O55156, P28023, P30622, P33420, P35458, Q10235, Q14203, Q20728, Q54Z01, Q5E951, Q5R686, Q5U243, Q66HD5, Q6PCJ1, Q8CI96, Q8N3C7, Q922J3, Q96DZ5, Q99426, Q9D1E6, Q9JK25, Q9NQT8, Q9UDT6, Q9VJE5, Q9Z0H8, A1Z6J5, P13496, Q01397, Q15813, Q32KS0, Q5FVQ9, Q5RBD9, Q5U378, Q5U508, Q67Z52

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PAK1	up-regulates	TBCB	phosphorylation
CUL3	“down-regulates quantity”	TBCB	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1460 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36114335:TCA:T	donor_loss	1.0000
19:36114336:CAC:C	donor_loss	1.0000
19:36114337:A:AC	donor_gain	1.0000
19:36114337:ACT:A	donor_gain	1.0000
19:36114337:ACTC:A	donor_gain	1.0000
19:36114338:C:CT	donor_gain	1.0000
19:36114338:C:G	donor_loss	1.0000
19:36114338:CT:C	donor_gain	1.0000
19:36114338:CTC:C	donor_gain	1.0000
19:36114338:CTCC:C	donor_gain	1.0000
19:36114338:CTCCA:C	donor_gain	1.0000
19:36114345:T:TA	donor_gain	1.0000
19:36114413:C:CC	acceptor_gain	1.0000
19:36114709:TGTTA:T	acceptor_gain	1.0000
19:36114711:TTA:T	acceptor_gain	1.0000
19:36114712:TA:T	acceptor_gain	1.0000
19:36114713:AC:A	acceptor_loss	1.0000
19:36114714:C:CA	acceptor_loss	1.0000
19:36114714:C:CC	acceptor_gain	1.0000
19:36114801:T:A	donor_gain	1.0000
19:36115664:C:G	donor_gain	1.0000
19:36116039:A:AG	acceptor_gain	1.0000
19:36116040:G:GG	acceptor_gain	1.0000
19:36116040:GT:G	acceptor_gain	1.0000
19:36116137:G:GT	donor_gain	1.0000
19:36116185:G:GG	donor_gain	1.0000
19:36116190:G:GT	donor_gain	1.0000
19:36121524:CA:C	acceptor_loss	1.0000
19:36121525:A:AG	acceptor_gain	1.0000
19:36121525:A:C	acceptor_loss	1.0000

AlphaMissense

1590 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36125687:T:C	F214L	0.999
19:36125689:C:A	F214L	0.999
19:36125689:C:G	F214L	0.999
19:36121707:T:A	V179D	0.998
19:36125715:T:C	F223S	0.998
19:36125484:G:A	G194D	0.997
19:36125487:T:A	V195D	0.997
19:36125508:G:A	G202E	0.997
19:36125520:G:A	G206D	0.997
19:36125520:G:T	G206V	0.997
19:36125718:T:A	V224D	0.997
19:36115609:A:C	S17R	0.996
19:36115611:C:A	S17R	0.996
19:36115611:C:G	S17R	0.996
19:36115674:G:C	K38N	0.996
19:36115674:G:T	K38N	0.996
19:36121701:G:A	G177D	0.996
19:36125688:T:C	F214S	0.996
19:36125709:G:A	G221D	0.996
19:36116048:T:C	L41P	0.995
19:36116180:T:A	I85N	0.995
19:36116180:T:C	I85T	0.995
19:36120711:T:A	V87D	0.995
19:36121664:T:C	C165R	0.995
19:36125495:G:C	D198H	0.995
19:36125507:G:A	G202R	0.995
19:36125507:G:C	G202R	0.995
19:36125508:G:T	G202V	0.995
19:36125684:T:G	Y213D	0.995
19:36125688:T:G	F214C	0.995

dbSNP variants (sampled 300 via entrez): RS1000451021 (19:36115441 T>C,G), RS1000549581 (19:36116748 C>A), RS1000796666 (19:36119850 C>G), RS1000881102 (19:36120861 G>A,T), RS1001152552 (19:36115513 G>A,C), RS1001153486 (19:36126224 C>T), RS1001171651 (19:36114324 G>A,C), RS1001269753 (19:36115324 A>T), RS1001414183 (19:36124549 T>G), RS1001607736 (19:36115044 A>C,G), RS1001621464 (19:36120364 G>A,C,T), RS1001735943 (19:36120167 GTT>G), RS1001975079 (19:36115322 G>A), RS1002005439 (19:36119301 C>T), RS1002144307 (19:36124521 A>G)

Disease associations

OMIM: gene MIM:601303 | disease phenotypes: MIM:621382

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with behavioral abnormalities and childhood-onset spastic paraplegia (MONDO:0980706)

Orphanet (0):

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000002	Abnormality of body height
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000508	Ptosis
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001238	Slender finger
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001270	Motor delay
HP:0001271	Polyneuropathy
HP:0001765	Hammertoe
HP:0002007	Frontal bossing
HP:0003593	Infantile onset

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067314 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.50	Kd	3194	nM	CHEMBL5653589
5.48	ED50	3328	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149553: Binding affinity to human TBCB incubated for 45 mins by Kinobead based pull down assay	kd	3.1937	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sulforaphane	decreases expression, affects binding	2
Smoke	decreases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
microcystin RR	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Clozapine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Diuron	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects localization, decreases expression, affects cotreatment	1
Gallic Acid	decreases expression	1
Ivermectin	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression, affects cotreatment	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
CHEMBL5652595	Binding	Binding affinity to human TBCB incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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