TBCC

Summary

TBCC (tubulin folding cofactor C, HGNC:11580) is a protein-coding gene on chromosome 6p21.1, encoding Tubulin-specific chaperone C (Q15814). Tubulin-folding protein; involved in the final step of the tubulin folding pathway. It is a common-essential gene (DepMap: required in 95.4% of cancer cell lines).

Cofactor C 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.

Source: NCBI Gene 6903 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 95.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_003192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11580
Approved symbol	TBCC
Name	tubulin folding cofactor C
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	CFC
Ensembl gene	ENSG00000124659
Ensembl biotype	protein_coding
OMIM	602971
Entrez	6903

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372876

RefSeq mRNA: 1 — MANE Select: NM_003192 NM_003192

CCDS: CCDS4872

Canonical transcript exons

ENST00000372876 — 1 exons

Exon	Start	End
ENSE00001458875	42744498	42746103

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 97.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1517 / max 263.5303, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73631	21.9701	1818
73632	0.5973	326
73633	0.5843	288

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.44	gold quality
secondary oocyte	CL:0000655	96.29	gold quality
granulocyte	CL:0000094	94.07	gold quality
adult organism	UBERON:0007023	90.04	gold quality
blood	UBERON:0000178	89.17	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.12	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.41	silver quality
biceps brachii	UBERON:0001507	88.40	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.38	gold quality
mucosa of transverse colon	UBERON:0004991	88.28	gold quality
palpebral conjunctiva	UBERON:0001812	88.05	gold quality
islet of Langerhans	UBERON:0000006	87.50	gold quality
spleen	UBERON:0002106	87.39	gold quality
gastrocnemius	UBERON:0001388	87.29	gold quality
muscle of leg	UBERON:0001383	87.15	gold quality
superficial temporal artery	UBERON:0001614	87.08	silver quality
leukocyte	CL:0000738	87.02	gold quality
prefrontal cortex	UBERON:0000451	86.96	gold quality
endothelial cell	CL:0000115	86.84	gold quality
ganglionic eminence	UBERON:0004023	86.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.76	gold quality
mononuclear cell	CL:0000842	86.49	gold quality
monocyte	CL:0000576	86.41	gold quality
cortical plate	UBERON:0005343	86.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.03	gold quality
bone marrow	UBERON:0002371	85.84	gold quality
lymph node	UBERON:0000029	85.75	gold quality
endometrium epithelium	UBERON:0004811	85.64	gold quality
muscle organ	UBERON:0001630	85.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.27
E-MTAB-7052	no	195.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting TBCC, 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-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-3144-3P	98.15	67.34	677
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-509-3-5P	97.21	67.74	1517

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• functional overlap with retinitis pigmenosa 2 protein (PMID:11847227)
• Microtubule dynamicity was reduced in breast cancer cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC. TBCC had little effect on cell proliferation. (PMID:20384997)
• a testable model for TBCC N-terminal domain/tubulin recognition in which the highly charged N-terminus as well as residues from the three helices and the loops interact with the acidic hypervariable regions of tubulin monomers (PMID:22028797)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbcc	ENSDARG00000022918
mus_musculus	Tbcc	ENSMUSG00000036430
rattus_norvegicus	Tbcc	ENSRNOG00000048291
drosophila_melanogaster	Tbcc	FBGN0051961
caenorhabditis_elegans		WBGENE00044609

Protein

Protein identifiers

Tubulin-specific chaperone C — Q15814 (reviewed: Q15814)

Alternative names: Tubulin-folding cofactor C

All UniProt accessions (1): Q15814

UniProt curated annotations — full annotation on UniProt →

Function. Tubulin-folding protein; involved in the final 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.

Tissue specificity. Expressed in the retina. Expressed in the rod and cone photoreceptors, extending from the inner segments (IS), through the outer nuclear layer (ONL) and into the synapses in the outer plexiform layer (OPL). Strongly expressed to the photoreceptor connecting cilium at the tips of the IS (at protein level).

Similarity. Belongs to the TBCC family.

RefSeq proteins (1): NP_003183* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006599	CARP_motif	Domain
IPR012945	Tubulin-bd_cofactor_C_dom	Domain
IPR016098	CAP/MinC_C	Homologous_superfamily
IPR017901	C-CAP_CF_C-like	Domain
IPR027684	TBCC	Family
IPR031925	TBCC_N	Domain
IPR038397	TBCC_N_sf	Homologous_superfamily

Pfam: PF07986, PF16752

UniProt features (36 total): strand 13, helix 8, sequence variant 6, modified residue 3, region of interest 2, chain 1, domain 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9M1M	ELECTRON MICROSCOPY	2.21
9M1N	ELECTRON MICROSCOPY	2.24
2L3L	SOLUTION NMR
2YUH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15814-F1	82.09	0.52

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 (3): 1, 80, 168

Mutagenesis-validated functional residues (1):

Position	Phenotype
262	inhibits stimulation of tubulin gtpase activity.

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: 148 (showing top): RNGTGGGC_UNKNOWN, FXR_IR1_Q6, FREAC2_01, GCANCTGNY_MYOD_Q6, SP3_Q3, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, FOXO4_01, FOXO1_01, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_PROTEIN_MATURATION, IRF1_Q6, HFH8_01, HFH4_01

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

GO Molecular Function (4): GTPase activity (GO:0003924), tubulin binding (GO:0015631), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), cytoskeleton (GO:0005856), microtubule (GO:0005874), photoreceptor connecting cilium (GO:0032391)

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
cellular process	1
protein maturation	1
protein-containing complex assembly	1
tubulin complex assembly	1
ribonucleoside triphosphate phosphatase activity	1
cytoskeletal protein binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
ciliary transition zone	1
photoreceptor cell cilium	1

Protein interactions and networks

STRING

357 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBCC	ARL3	P36405	865
TBCC	TBCD	Q9BTW9	736
TBCC	TBCB	Q99426	731
TBCC	TBCA	O75347	690
TBCC	ARL2	P36404	624
TBCC	TBCEL	Q5QJ74	589
TBCC	A0A2R8Y809	A0A2R8Y809	576
TBCC	TBCE	Q15813	576
TBCC	TBCCD1	Q9NVR7	447
TBCC	RABGAP1L	Q5R372	408
TBCC	MKS1	Q9NXB0	402
TBCC	MTREX	P42285	349
TBCC	SKP1	P34991	348
TBCC	E5RI56	E5RI56	348
TBCC	A0A2R8YFB7	A0A2R8YFB7	347

IntAct

25 interactions, top by confidence:

A	B	Type	Score
COG3	COG7	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
CHAT	TBCC	psi-mi:“MI:0915”(physical association)	0.560
TBCC		psi-mi:“MI:0915”(physical association)	0.560
TBCC	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
TBCC	GSN	psi-mi:“MI:0915”(physical association)	0.560
TEAD1	RAD51	psi-mi:“MI:0914”(association)	0.560
COG3	TBCC	psi-mi:“MI:0914”(association)	0.530
Arl3	TBCC	psi-mi:“MI:0407”(direct interaction)	0.440
TBCC	NTM	psi-mi:“MI:0915”(physical association)	0.400
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
RCCD1	IFT56	psi-mi:“MI:0914”(association)	0.350
MMP14	BIN1	psi-mi:“MI:0914”(association)	0.350
MRPL52	MRPL33	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): TBCC (Affinity Capture-MS), TBCC (Affinity Capture-MS), TBCC (Affinity Capture-MS), TBCC (Affinity Capture-MS), TBCC (Affinity Capture-MS), NTM (Affinity Capture-MS), TBCC (Affinity Capture-MS), TBCC (Negative Genetic), TBCC (Negative Genetic), TBCC (Negative Genetic), TBCC (Affinity Capture-MS), TBCC (Co-fractionation), TBCC (Affinity Capture-MS), TBCC (Affinity Capture-MS), TBCC (Affinity Capture-RNA)

ESM2 similar proteins: A2VE39, D2HRF1, F1QC45, O00423, O13046, O65902, O75695, O75717, O81742, P09874, P11103, P18493, P26446, P27008, P31669, P59328, Q01518, Q15814, Q1MTD3, Q28FT4, Q29LW1, Q3SZE9, Q4KLT3, Q4R6F3, Q5R981, Q5RHR0, Q5U2Z5, Q5XI55, Q5ZHN4, Q5ZJM3, Q6GM65, Q6GQ76, Q7Z569, Q803R5, Q8AVX5, Q8K224, Q8N1G2, Q93VQ0, Q95K79, Q96BT7

Diamond homologs: Q15814, Q3SZE9, Q5R5J7, Q8VCN9, Q9SMR2, O75695, Q54PY1, Q5ZHN4, Q8AVX5, Q9EPK2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

149 predictions. Top by Δscore:

Variant	Effect	Δscore
6:42745334:T:TA	donor_gain	0.7300
6:42745420:CAGT:C	donor_gain	0.6200
6:42745279:A:AC	donor_gain	0.5900
6:42745280:C:CC	donor_gain	0.5900
6:42745359:G:T	donor_gain	0.5800
6:42745331:T:TA	donor_gain	0.5700
6:42745922:T:TA	donor_gain	0.5700
6:42745362:C:CT	donor_gain	0.5300
6:42745324:A:AC	donor_gain	0.5200
6:42745325:C:CC	donor_gain	0.5200
6:42745414:T:TA	donor_gain	0.5100
6:42745426:G:T	donor_gain	0.5100
6:42745275:T:TA	donor_gain	0.5000
6:42745421:A:C	donor_gain	0.4900
6:42745423:T:TA	donor_gain	0.4700
6:42745337:A:T	acceptor_gain	0.4600
6:42745419:ACAGT:A	donor_gain	0.4600
6:42745420:CAGTC:C	donor_gain	0.4600
6:42745429:CG:C	donor_gain	0.4600
6:42745419:A:AC	donor_gain	0.4500
6:42745420:C:CC	donor_gain	0.4500
6:42745859:T:TA	donor_gain	0.4500
6:42745293:G:C	donor_gain	0.4300
6:42745317:CGCAG:C	donor_gain	0.4300
6:42745958:T:TA	donor_gain	0.4300
6:42745352:G:C	donor_gain	0.4200
6:42745769:ACT:A	acceptor_gain	0.4200
6:42745150:TAA:T	donor_gain	0.4100
6:42745151:AAA:A	donor_gain	0.4100
6:42745336:C:CT	acceptor_gain	0.4100

AlphaMissense

2258 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:42745111:A:C	F321L	0.995
6:42745111:A:T	F321L	0.995
6:42745113:A:G	F321L	0.995
6:42745663:G:C	F137L	0.993
6:42745663:G:T	F137L	0.993
6:42745665:A:G	F137L	0.993
6:42745300:G:C	C258W	0.991
6:42745657:G:C	F139L	0.991
6:42745657:G:T	F139L	0.991
6:42745659:A:G	F139L	0.991
6:42745343:A:T	V244D	0.988
6:42745301:C:T	C258Y	0.987
6:42745114:A:C	D320E	0.984
6:42745114:A:T	D320E	0.984
6:42745427:A:T	V216D	0.984
6:42745361:C:T	G238D	0.983
6:42745302:A:G	C258R	0.982
6:42745290:G:T	R262S	0.980
6:42745289:C:G	R262P	0.979
6:42745292:A:G	L261P	0.979
6:42745432:G:C	C214W	0.979
6:42745116:C:G	D320H	0.978
6:42745131:A:G	W315R	0.978
6:42745131:A:T	W315R	0.978
6:42745222:G:C	C284W	0.978
6:42745077:A:G	W333R	0.977
6:42745077:A:T	W333R	0.977
6:42745451:A:G	L208S	0.976
6:42745115:T:G	D320A	0.975
6:42745400:A:G	L225P	0.975

dbSNP variants (sampled 300 via entrez): RS1000622268 (6:42744361 C>A,T), RS1000934969 (6:42744556 A>G), RS1001063165 (6:42746656 C>G,T), RS1001353028 (6:42747486 G>A), RS1002875511 (6:42747265 G>A,C), RS1003698161 (6:42746304 A>C), RS1005686959 (6:42746296 T>G), RS1005852162 (6:42747808 T>A,G), RS1005910721 (6:42744284 C>T), RS1006290521 (6:42744630 G>C), RS1007635736 (6:42746426 C>G,T), RS1007780579 (6:42746716 C>T), RS1007925539 (6:42744347 T>C), RS1007989593 (6:42747625 G>T), RS1008500119 (6:42744481 CCAAA>C)

Disease associations

OMIM: gene MIM:602971 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Irinotecan	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Emodin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ketoconazole	decreases expression	1
Rotenone	increases expression	1
Sarin	decreases expression, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Urethane	affects expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Metribolone	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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