TBCA

Summary

TBCA (tubulin folding cofactor A, HGNC:11579) is a protein-coding gene on chromosome 5q14.1, encoding Tubulin-specific chaperone A (O75347). Tubulin-folding protein; involved in the early step of the tubulin folding pathway. It is a common-essential gene (DepMap: required in 92.5% of cancer cell lines).

The product of this gene is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. This gene encodes chaperonin cofactor A. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6902 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 14 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 92.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_004607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11579
Approved symbol	TBCA
Name	tubulin folding cofactor A
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171530
Ensembl biotype	protein_coding
OMIM	610058
Entrez	6902

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000306388, ENST00000380377, ENST00000517679, ENST00000517881, ENST00000518218, ENST00000518338, ENST00000520039, ENST00000520361, ENST00000522370, ENST00000651106, ENST00000932727, ENST00000932728, ENST00000932729

RefSeq mRNA: 3 — MANE Select: NM_004607 NM_001297738, NM_001297740, NM_004607

CCDS: CCDS4040, CCDS75263, CCDS78024

Canonical transcript exons

ENST00000380377 — 4 exons

Exon	Start	End
ENSE00001484695	77776205	77776339
ENSE00002120354	77691166	77691498
ENSE00003510631	77693266	77693352
ENSE00003684976	77708242	77708347

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 194.6560 / max 2017.0104, expressed in 1828 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62193	116.5473	1827
62192	78.0838	1812
62194	0.0249	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	99.27	gold quality
left adrenal gland	UBERON:0001234	99.24	gold quality
left adrenal gland cortex	UBERON:0035825	99.23	gold quality
right adrenal gland	UBERON:0001233	99.22	gold quality
ganglionic eminence	UBERON:0004023	99.22	gold quality
cortical plate	UBERON:0005343	99.21	gold quality
adrenal tissue	UBERON:0018303	99.21	gold quality
ventricular zone	UBERON:0003053	99.06	gold quality
islet of Langerhans	UBERON:0000006	98.94	gold quality
left ovary	UBERON:0002119	98.94	gold quality
adenohypophysis	UBERON:0002196	98.93	gold quality
mucosa of stomach	UBERON:0001199	98.89	gold quality
popliteal artery	UBERON:0002250	98.80	gold quality
tibial artery	UBERON:0007610	98.80	gold quality
right ovary	UBERON:0002118	98.78	gold quality
right uterine tube	UBERON:0001302	98.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.72	gold quality
metanephros cortex	UBERON:0010533	98.72	gold quality
body of stomach	UBERON:0001161	98.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.71	gold quality
endocervix	UBERON:0000458	98.70	gold quality
right lung	UBERON:0002167	98.70	gold quality
left coronary artery	UBERON:0001626	98.66	gold quality
body of uterus	UBERON:0009853	98.66	gold quality
left uterine tube	UBERON:0001303	98.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.63	gold quality
lower esophagus mucosa	UBERON:0035834	98.62	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.59	gold quality
left lobe of thyroid gland	UBERON:0001120	98.56	gold quality
lower esophagus	UBERON:0013473	98.53	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	1597.85
E-ANND-3	yes	13.17
E-MTAB-10042	yes	8.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting TBCA, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-203B-5P	97.24	68.54	543
HSA-MIR-6718-5P	97.24	68.15	553
HSA-MIR-711	96.60	65.75	528
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• TBCA is essential for cell viability and its knockdown produces a decrease in the amount of soluble tubulin, modifications in microtubules and G1 cell cycle arrest. (PMID:15963512)
• overexpression of TBCA did not induce biocharacteristics that directly contrasted to those of TBCA knockdown (PMID:23740643)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbca	ENSDARG00000016754
mus_musculus	Tbca	ENSMUSG00000042043
rattus_norvegicus	Tbca	ENSRNOG00000048342
drosophila_melanogaster	Tbca	FBGN0039869
caenorhabditis_elegans	tbca-1	WBGENE00021475

Protein

Protein identifiers

Tubulin-specific chaperone A — O75347 (reviewed: O75347)

Alternative names: TCP1-chaperonin cofactor A, Tubulin-folding cofactor A

All UniProt accessions (8): O75347, A0A494C144, E5RHG6, E5RIW3, E5RIX8, E5RJD8, E5RJM1, Q6FGD7

UniProt curated annotations — full annotation on UniProt →

Function. Tubulin-folding protein; involved in the early step of the tubulin folding pathway.

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.

Subcellular location. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the TBCA family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75347-1	1	yes
O75347-2	2

RefSeq proteins (3): NP_001284667, NP_001284669, NP_004598* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004226	TBCA	Family
IPR036126	TBCA_sf	Homologous_superfamily

Pfam: PF02970

UniProt features (9 total): helix 5, initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1H7C	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75347-F1	94.29	0.94

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 (1): 2

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: 187 (showing top): MORF_MBD4, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MORF_RAD21, KYNG_DNA_DAMAGE_DN, PUJANA_CHEK2_PCC_NETWORK, MORF_SKP1A, GOBP_PROTEIN_MATURATION, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_NOT_BY_GAMMA_IN_WS, MORF_ATOX1, MORF_PPP6C, MORF_PPP2R4, GOBP_PROTEIN_FOLDING, SCHLOSSER_SERUM_RESPONSE_DN, KYNG_ENVIRONMENTAL_STRESS_RESPONSE_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP

GO Biological Process (3): protein folding (GO:0006457), tubulin complex assembly (GO:0007021), post-chaperonin tubulin folding pathway (GO:0007023)

GO Molecular Function (5): RNA binding (GO:0003723), tubulin binding (GO:0015631), beta-tubulin binding (GO:0048487), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (5): nucleolus (GO:0005730), cytoplasm (GO:0005737), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), cytoskeleton (GO:0005856)

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
intracellular membraneless organelle	2
cellular process	1
protein maturation	1
protein-containing complex assembly	1
tubulin complex assembly	1
nucleic acid binding	1
cytoskeletal protein binding	1
tubulin binding	1
protein binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1

Protein interactions and networks

STRING

1672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBCA	TBCC	Q15814	690
TBCA	TUBA4A	P05215	676
TBCA	TBCB	Q99426	667
TBCA	TUBB2A	Q13885	617
TBCA	TBCD	Q9BTW9	603
TBCA	TUBB	P05218	562
TBCA	A0A2R8Y809	A0A2R8Y809	536
TBCA	TBCE	Q15813	536
TBCA	PFDN1	O60925	517
TBCA	TBCEL	Q5QJ74	512
TBCA	TBC1D8B	Q0IIM8	440
TBCA	ARL2	P36404	436
TBCA	PFDN2	Q9UHV9	420
TBCA	HTT	P42858	368
TBCA	NARS2	Q96I59	364

IntAct

42 interactions, top by confidence:

A	B	Type	Score
	TBCA	psi-mi:“MI:0915”(physical association)	0.590
TBCA		psi-mi:“MI:0915”(physical association)	0.590
TERF2IP	TBCA	psi-mi:“MI:0915”(physical association)	0.510
ERBB3	TBCA	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
STAT1	KPNA6	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
CAV1	ACOT7	psi-mi:“MI:0914”(association)	0.350
TRIM24	DDTL	psi-mi:“MI:0914”(association)	0.350
RIPK4	TBCA	psi-mi:“MI:0914”(association)	0.350
TEK	LANCL1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
TUBB4B	TUBA1B	psi-mi:“MI:0914”(association)	0.350
TBCA	PLS1	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
CASP3	NACA	psi-mi:“MI:0914”(association)	0.350
GATA2	EFCAB5	psi-mi:“MI:0914”(association)	0.350
SMARCB1	KIF2A	psi-mi:“MI:2364”(proximity)	0.270
SMARCB1	FAM186A	psi-mi:“MI:2364”(proximity)	0.270
EPHA6	ARHGAP32	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (138): GDPGP1 (Co-fractionation), SEC31A (Co-fractionation), TBCA (Co-fractionation), TBCA (Co-fractionation), TBCA (Co-fractionation), TBCA (Co-fractionation), TBCA (Affinity Capture-MS), TBCA (Affinity Capture-MS), TBCA (Affinity Capture-RNA), TBCA (Affinity Capture-MS), FXN (Co-fractionation), LAP3 (Co-fractionation), LACTB2 (Co-fractionation), PMPCA (Co-fractionation), COA7 (Co-fractionation)

ESM2 similar proteins: A1A4P5, A1DGS2, A2R7Z2, B0BN18, O04350, O35685, O70591, O75347, O76031, P48427, P48428, P50502, P50503, P80584, Q07866, Q08851, Q08DB5, Q0VCY1, Q13190, Q15691, Q17QG2, Q3ZBD9, Q4SPU8, Q5D016, Q5R581, Q5R601, Q5R7N3, Q5R7Z5, Q5RF31, Q5U2U0, Q5ZLC7, Q5ZLF0, Q61166, Q63525, Q66HR2, Q66T82, Q68FJ8, Q6P848, Q6V291, Q8K1E0

Diamond homologs: O04350, O75347, P48427, P48428, P48606, P80584, P80585, Q6PEC1, Q75JC8, Q9Y703

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TBCA	“up-regulates quantity by stabilization”	Tubulin	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1405 predictions. Top by Δscore:

Variant	Effect	Δscore
5:77691494:TTTTC:T	acceptor_gain	1.0000
5:77691495:TTTC:T	acceptor_gain	1.0000
5:77691496:TTC:T	acceptor_gain	1.0000
5:77691497:TC:T	acceptor_gain	1.0000
5:77691498:CC:C	acceptor_gain	1.0000
5:77691498:CCTAA:C	acceptor_loss	1.0000
5:77691499:C:A	acceptor_loss	1.0000
5:77691499:C:CC	acceptor_gain	1.0000
5:77691500:T:A	acceptor_loss	1.0000
5:77691504:A:AC	acceptor_gain	1.0000
5:77693260:GCTTA:G	donor_loss	1.0000
5:77693261:CTTA:C	donor_loss	1.0000
5:77693262:TTA:T	donor_loss	1.0000
5:77693263:TACTA:T	donor_loss	1.0000
5:77693264:A:AC	donor_gain	1.0000
5:77693264:A:T	donor_loss	1.0000
5:77693265:C:CG	donor_gain	1.0000
5:77693265:CT:C	donor_gain	1.0000
5:77693265:CTA:C	donor_gain	1.0000
5:77693265:CTAG:C	donor_gain	1.0000
5:77693265:CTAGT:C	donor_gain	1.0000
5:77708237:TTTAC:T	donor_loss	1.0000
5:77708238:TTA:T	donor_loss	1.0000
5:77708239:TACCT:T	donor_loss	1.0000
5:77708240:A:T	donor_loss	1.0000
5:77708241:CCTG:C	donor_gain	1.0000
5:77708244:G:A	donor_gain	1.0000
5:77708343:CCAAC:C	acceptor_gain	1.0000
5:77708344:CAAC:C	acceptor_gain	1.0000
5:77708344:CAACC:C	acceptor_gain	1.0000

AlphaMissense

713 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:77693334:A:G	S60P	0.995
5:77693279:A:G	L78P	0.994
5:77693302:C:A	R70S	0.994
5:77693302:C:G	R70S	0.994
5:77693324:A:G	M63T	0.994
5:77708313:C:G	A30P	0.994
5:77693303:C:G	R70T	0.993
5:77776205:C:G	R18P	0.993
5:77708337:C:T	E22K	0.992
5:77693303:C:A	R70M	0.991
5:77693324:A:T	M63K	0.991
5:77776226:A:C	I11S	0.991
5:77776226:A:G	I11T	0.991
5:77708336:T:A	E22V	0.990
5:77693292:C:G	A74P	0.989
5:77693342:A:G	L57P	0.989
5:77708325:A:G	Y26H	0.989
5:77693311:G:C	C67W	0.988
5:77776237:T:A	R7S	0.987
5:77776237:T:G	R7S	0.987
5:77776211:A:T	V16E	0.986
5:77776226:A:T	I11N	0.986
5:77693324:A:C	M63R	0.983
5:77693337:C:T	E59K	0.983
5:77708336:T:G	E22A	0.983
5:77776238:C:G	R7T	0.981
5:77693313:A:G	C67R	0.980
5:77693312:C:T	C67Y	0.979
5:77708303:T:G	Q33P	0.979
5:77691455:G:T	A97E	0.978

dbSNP variants (sampled 300 via entrez): RS1000013429 (5:77754185 T>A,C), RS1000049539 (5:77705074 A>G), RS1000053839 (5:77725786 C>A), RS1000107723 (5:77738398 T>G), RS1000216783 (5:77777459 G>A), RS1000270452 (5:77733886 A>G), RS1000310659 (5:77698578 C>T), RS1000338434 (5:77702878 G>A,C,T), RS1000394883 (5:77691437 G>A), RS1000397896 (5:77696603 A>G), RS1000399349 (5:77777345 C>T), RS1000450998 (5:77735928 T>C), RS1000505439 (5:77731218 C>A,T), RS1000518055 (5:77758730 AG>A), RS1000537520 (5:77731511 A>T)

Disease associations

OMIM: gene MIM:610058 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004599_31	Mean platelet volume	2.000000e-10
GCST010796_5447	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_5448	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_5449	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST90000025_43	Appendicular lean mass	1.000000e-10
GCST90002395_452	Mean platelet volume	1.000000e-09
GCST90002395_453	Mean platelet volume	6.000000e-13
GCST90002401_164	Platelet distribution width	1.000000e-17
GCST90002401_165	Platelet distribution width	1.000000e-27
GCST90002402_774	Platelet count	1.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066315 (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
8.04	Kd	9.129	nM	CHEMBL5653589
8.04	ED50	9.129	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	2149552: Binding affinity to human TBCA incubated for 45 mins by Kinobead based pull down assay	kd	0.0091	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
microcystin RR	decreases expression	1
chloropicrin	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Phenobarbital	affects expression	1
Theophylline	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression	1
beta-Naphthoflavone	increases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL5652594	Binding	Binding affinity to human TBCA 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.