CCT2

Summary

CCT2 (chaperonin containing TCP1 subunit 2, HGNC:1615) is a protein-coding gene on chromosome 12q15, encoding T-complex protein 1 subunit beta (P78371). Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10576 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leber congenital amaurosis (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 428 total
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1615
Approved symbol	CCT2
Name	chaperonin containing TCP1 subunit 2
Location	12q15
Locus type	gene with protein product
Status	Approved
Aliases	Cctb
Ensembl gene	ENSG00000166226
Ensembl biotype	protein_coding
OMIM	605139
Entrez	10576

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 protein_coding, 10 retained_intron, 1 nonsense_mediated_decay

ENST00000299300, ENST00000543146, ENST00000544368, ENST00000546850, ENST00000546859, ENST00000548787, ENST00000549933, ENST00000550010, ENST00000550455, ENST00000550638, ENST00000550653, ENST00000551620, ENST00000551899, ENST00000553169, ENST00000874955, ENST00000874956, ENST00000874957, ENST00000874958, ENST00000874959, ENST00000912673, ENST00000912674, ENST00000970547

RefSeq mRNA: 2 — MANE Select: NM_006431 NM_001198842, NM_006431

CCDS: CCDS55843, CCDS8991

Canonical transcript exons

ENST00000299300 — 16 exons

Exon	Start	End
ENSE00001101196	69597968	69598071
ENSE00001101202	69597156	69597275
ENSE00001101223	69597638	69597766
ENSE00002415709	69585459	69585524
ENSE00003466639	69601295	69601570
ENSE00003487294	69589485	69589687
ENSE00003494988	69586270	69586344
ENSE00003545750	69586753	69586818
ENSE00003552114	69587930	69588006
ENSE00003566680	69592059	69592159
ENSE00003620527	69599863	69600004
ENSE00003627744	69588150	69588262
ENSE00003644629	69598322	69598421
ENSE00003646646	69587505	69587616
ENSE00003656210	69593510	69593613
ENSE00003659903	69592976	69593103

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 166.5492 / max 25001.8005, expressed in 1824 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126725	155.8653	1823
126726	8.4892	1678
126728	0.6256	324
126729	0.4969	219
126736	0.4022	195
126724	0.2466	85
206793	0.1800	46
126730	0.1176	27
126737	0.1160	25
126727	0.0097	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.54	gold quality
male germ cell	CL:0000015	99.49	gold quality
epithelium of nasopharynx	UBERON:0001951	99.29	gold quality
nasopharynx	UBERON:0001728	99.27	gold quality
right testis	UBERON:0004534	99.27	gold quality
left testis	UBERON:0004533	99.25	gold quality
cortical plate	UBERON:0005343	99.24	gold quality
embryo	UBERON:0000922	99.23	gold quality
ganglionic eminence	UBERON:0004023	99.10	gold quality
ventricular zone	UBERON:0003053	99.02	gold quality
testis	UBERON:0000473	98.98	gold quality
endometrium epithelium	UBERON:0004811	98.97	gold quality
adult organism	UBERON:0007023	98.97	gold quality
gingival epithelium	UBERON:0001949	98.88	gold quality
bronchial epithelial cell	CL:0002328	98.81	gold quality
middle temporal gyrus	UBERON:0002771	98.79	gold quality
islet of Langerhans	UBERON:0000006	98.75	gold quality
gingiva	UBERON:0001828	98.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.72	gold quality
adrenal tissue	UBERON:0018303	98.60	gold quality
germinal epithelium of ovary	UBERON:0001304	98.59	gold quality
epithelium of bronchus	UBERON:0002031	98.59	gold quality
parietal pleura	UBERON:0002400	98.58	gold quality
bronchus	UBERON:0002185	98.51	gold quality
visceral pleura	UBERON:0002401	98.45	gold quality
pleura	UBERON:0000977	98.42	gold quality
trabecular bone tissue	UBERON:0002483	98.42	gold quality
esophagus squamous epithelium	UBERON:0006920	98.42	gold quality
colonic mucosa	UBERON:0000317	98.38	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.64
E-MTAB-9067	yes	21.53
E-HCAD-13	yes	19.99
E-CURD-112	yes	18.59
E-CURD-122	yes	18.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1

miRNA regulators (miRDB)

13 targeting CCT2, 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-3688-3P	99.97	72.02	2834
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-3684	96.90	67.51	293
HSA-MIR-4462	95.10	66.27	172
HSA-MIR-548AL	93.28	65.60	109
HSA-MIR-4445-3P	93.28	66.18	106
HSA-MIR-196B-3P	85.79	67.95	91

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 12)

• The chaperonin CCT is identified as a novel physiological substrate for p90 ribosomal S6 kinase (RSK) and p70 ribosomal S6 kinase (S6K). (PMID:19332537)
• PB2 associates with CCT2 as a monomer and the CCT binding site is located in a central region of the PB2 protein. (PMID:20573828)
• Destruction of the beta-tubulin:CCT-beta complex provokes Hsp90-dependent protein ubiquitination and degradation. (PMID:23190606)
• Increased expression of CCT2 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. (PMID:23782473)
• PDCD5 bound the apical domain of the CCTbeta subunit, projecting above the folding cavity without entering it. Like PDCD5, beta-tubulin also interacts with the CCTbeta apical domain, but a second site is found at the sensor loop deep within the folding cavity. (PMID:24375412)
• A role for the TRiC subunits TCP1 and CCT2, and potentially the entire TRiC complex, in breast cancer. (PMID:25704758)
• the novel LCA mutations in CCTbeta and the impact of chaperon disability by these mutations in cellular biology. (PMID:27645772)
• We applied whole-genome sequencing (WGS) on 9 trios where the probands are sporadically affected with the most severe form of the disorder and harbor no coding sequence variants affecting the function of known Hirschsprung disease (HSCR) genes. We found de novo protein-altering variants in three intolerant to change genes-CCT2, VASH1, and CYP26A1-for which a plausible link with the enteric nervous system (ENS) exists (PMID:29483666)
• we suggest that CCT2 correlates with Gli-1 expression and is an important determinant of survival in the colorectal cancer (CRC) patients. The results reveal that CCT2 can regulate the folding of Gli-1 in relation to hypoxia in CRC (PMID:31462707)
• Investigating Chaperonin-Containing TCP-1 subunit 2 as an essential component of the chaperonin complex for tumorigenesis. (PMID:31964905)
• CCT2 prevented beta-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer. (PMID:38165547)
• CCT2 Regulates ZEB1-Induced EMT Gene Transcription to Promote the Metastasis and Tumorigenesis of Papillary Thyroid Carcinoma. (PMID:39327245)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cct2	ENSDARG00000087206
danio_rerio	cct2	ENSDARG00000104674
mus_musculus	Cct2	ENSMUSG00000034024
rattus_norvegicus	Cct2	ENSRNOG00000021317
drosophila_melanogaster	CCT2	FBGN0030086
caenorhabditis_elegans		WBGENE00000378

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

T-complex protein 1 subunit beta — P78371 (reviewed: P78371)

Alternative names: CCT-beta, Chaperonin containing T-complex polypeptide 1 subunit 2

All UniProt accessions (4): P78371, F5GWF6, F8VQ14, V9HW96

UniProt curated annotations — full annotation on UniProt →

Function. Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia.

Subunit / interactions. Component of the chaperonin-containing T-complex (TRiC), a hexadecamer composed of two identical back-to-back stacked rings enclosing a protein folding chamber. Each ring is made up of eight different subunits: TCP1/CCT1, CCT2, CCT3, CCT4, CCT5, CCT6A/CCT6, CCT7, CCT8. Interacts with PACRG. Interacts with FLCN. Interacts with DLEC1. Interacts with SVEP1.

Subcellular location. Cytoplasm.

Similarity. Belongs to the TCP-1 chaperonin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P78371-1	1	yes
P78371-2	2

RefSeq proteins (2): NP_001185771, NP_006422* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002194	Chaperonin_TCP-1_CS	Conserved_site
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR012716	Chap_CCT_beta	Family
IPR017998	TCP-1	Family
IPR027409	GroEL-like_apical_dom_sf	Homologous_superfamily
IPR027410	TCP-1-like_intermed_sf	Homologous_superfamily
IPR027413	GROEL-like_equatorial_sf	Homologous_superfamily
IPR053374

Pfam: PF00118

Enzyme classification (BRENDA):

• EC 3.6.4.B10 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (87 total): strand 28, helix 19, binding site 17, modified residue 9, sequence conflict 6, turn 4, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

65 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7NVL	ELECTRON MICROSCOPY	2.5
8SH9	ELECTRON MICROSCOPY	2.7
8SHE	ELECTRON MICROSCOPY	2.8
8SHG	ELECTRON MICROSCOPY	2.8
8SHN	ELECTRON MICROSCOPY	2.8
7TTT	ELECTRON MICROSCOPY	2.9
8SG9	ELECTRON MICROSCOPY	2.9
8SGC	ELECTRON MICROSCOPY	2.9
8SGL	ELECTRON MICROSCOPY	2.9
8SHD	ELECTRON MICROSCOPY	2.9
8SHQ	ELECTRON MICROSCOPY	2.9
9NOQ	ELECTRON MICROSCOPY	2.9
9NRH	ELECTRON MICROSCOPY	2.9
7NVN	ELECTRON MICROSCOPY	3
7TRG	ELECTRON MICROSCOPY	3
8SG8	ELECTRON MICROSCOPY	3
8SHA	ELECTRON MICROSCOPY	3
8SHF	ELECTRON MICROSCOPY	3
8SHL	ELECTRON MICROSCOPY	3
8SHO	ELECTRON MICROSCOPY	3
8SHP	ELECTRON MICROSCOPY	3
8SHT	ELECTRON MICROSCOPY	3
9NPW	ELECTRON MICROSCOPY	3
9NQ1	ELECTRON MICROSCOPY	3
9NRG	ELECTRON MICROSCOPY	3
7NVM	ELECTRON MICROSCOPY	3.1
7X0A	ELECTRON MICROSCOPY	3.1
7X0S	ELECTRON MICROSCOPY	3.1
8HKI	ELECTRON MICROSCOPY	3.1
8I9U	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78371-F1	89.85	0.70

Antibody-complex structures (SAbDab): 4 — 7NVL, 7NVM, 7NVN, 7NVO

Functional residue map

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

Ligand- & substrate-binding residues (17): 100; 101; 168; 169; 410; 495; 495; 500; 500; 44; 44; 97 …

Post-translational modifications (10): 2, 3, 13, 60, 154, 181, 260, 261, 248, 1

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-389957	Prefoldin mediated transfer of substrate to CCT/TriC
R-HSA-389960	Formation of tubulin folding intermediates by CCT/TriC
R-HSA-390450	Folding of actin by CCT/TriC
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-5620922	BBSome-mediated cargo-targeting to cilium
R-HSA-6798695	Neutrophil degranulation
R-HSA-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-389958	Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding
R-HSA-390466	Chaperonin-mediated protein folding
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins
R-HSA-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane
R-HSA-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 321 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_SINGLE_FERTILIZATION, GOBP_CHROMOSOME_ORGANIZATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, MORF_SMC1L1, GOCC_SECRETORY_GRANULE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_HDAC1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MORF_UBE2N

GO Biological Process (8): protein folding (GO:0006457), binding of sperm to zona pellucida (GO:0007339), positive regulation of telomere maintenance via telomerase (GO:0032212), protein stabilization (GO:0050821), chaperone-mediated protein complex assembly (GO:0051131), scaRNA localization to Cajal body (GO:0090666), positive regulation of protein localization to Cajal body (GO:1904871), positive regulation of telomerase RNA localization to Cajal body (GO:1904874)

GO Molecular Function (9): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ubiquitin protein ligase binding (GO:0031625), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (11): zona pellucida receptor complex (GO:0002199), extracellular region (GO:0005576), cytosol (GO:0005829), chaperonin-containing T-complex (GO:0005832), microtubule (GO:0005874), azurophil granule lumen (GO:0035578), cell body (GO:0044297), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm head-tail coupling apparatus (GO:0120212), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	3
Chaperonin-mediated protein folding	3
RHOBTB GTPase Cycle	2
Cargo trafficking to the periciliary membrane	1
Innate Immune System	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Protein folding	1
Metabolism of proteins	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
ATP-dependent activity	2
cellular process	1
protein maturation	1
sperm-egg recognition	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
regulation of protein stability	1
protein-containing complex assembly	1
RNA localization to Cajal body	1
positive regulation of protein localization to nucleus	1
protein localization to Cajal body	1
regulation of protein localization to Cajal body	1
positive regulation of biological process	1
telomerase RNA localization to Cajal body	1
regulation of telomerase RNA localization to Cajal body	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ubiquitin-like protein ligase binding	1
molecular_function	1
protein folding	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
chaperonin-containing T-complex	1
protein-containing complex	1
cytoplasm	1
cytosol	1
protein folding chaperone complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

5262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCT2	CCT4	P50991	989
CCT2	CCT5	P48643	988
CCT2	CCT7	Q99832	986
CCT2	CCT3	P49368	986
CCT2	CCT8	P50990	984
CCT2	CCT6A	P40227	949
CCT2	TCP1	P17987	917
CCT2	CCT6B	Q92526	731
CCT2	HSPA8	P11142	643
CCT2	CCNE1	P24864	634
CCT2	HSPA5	P11021	578
CCT2	HSP90AB1	P08238	560
CCT2	LRRC10	Q5BKY1	544
CCT2	BEST3	Q8N1M1	539
CCT2	ZNF346	Q9UL40	506

IntAct

707 interactions, top by confidence:

A	B	Type	Score
IGBP1	PPP6C	psi-mi:“MI:0914”(association)	0.940
PPP6C	ANKRD28	psi-mi:“MI:0914”(association)	0.870
TCP1	CCT2	psi-mi:“MI:0915”(physical association)	0.860
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
WRAP53	DKC1	psi-mi:“MI:0914”(association)	0.830
CCT2	CCT4	psi-mi:“MI:0915”(physical association)	0.810
CCT2	CCT7	psi-mi:“MI:0915”(physical association)	0.800
TUBG1	TUBG1	psi-mi:“MI:2364”(proximity)	0.760
CCT5	CCT2	psi-mi:“MI:0915”(physical association)	0.740
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
CCT2	ZNRD2	psi-mi:“MI:0915”(physical association)	0.720
ZNRD2	CCT2	psi-mi:“MI:0915”(physical association)	0.720
WRAP53	TCP1	psi-mi:“MI:0914”(association)	0.690
AKAP8	HDAC3	psi-mi:“MI:0403”(colocalization)	0.650
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
TUBA1B	TXNDC9	psi-mi:“MI:0914”(association)	0.640
TUBB	PLD2	psi-mi:“MI:0914”(association)	0.640
ACTR3	ARPC2	psi-mi:“MI:0914”(association)	0.640
HDAC11	CLUH	psi-mi:“MI:0914”(association)	0.640
PPP2R2D	ENSA	psi-mi:“MI:0914”(association)	0.570
PPP2R2D	ENSA	psi-mi:“MI:2364”(proximity)	0.570
Cdc20	BUB1	psi-mi:“MI:0914”(association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
TSSK6	TCP1	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
MKKS	TCP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (1128): CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT2 (Two-hybrid), CCT2 (Affinity Capture-RNA), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-Western), CCT2 (Affinity Capture-Western), CCT2 (Affinity Capture-Western), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS)

ESM2 similar proteins: A3KN12, O88958, P21265, P21343, P30566, P36959, P38024, P50554, P50990, P54822, P61922, P78371, P80147, P80314, P80404, P82197, Q04447, Q0II59, Q259G4, Q2KIG0, Q3ZBF0, Q3ZBH0, Q3ZCI9, Q41141, Q4R4U1, Q4R5J0, Q4R5Y2, Q4R6F8, Q5E982, Q5R5F8, Q5RAP1, Q5XIM9, Q5ZMA6, Q64422, Q6EE31, Q6IA69, Q711T7, Q7XPW5, Q7ZV22, Q812E8

Diamond homologs: O00782, O04450, O15891, O24730, O24731, O24732, O24734, O24735, O26320, O26885, O28045, O28821, O30560, O30561, O57762, O74341, O77323, O93624, P28488, P39076, P39077, P39078, P40412, P40413, P42943, P46219, P47207, P47208, P47209, P48424, P48425, P48605, P48643, P49368, P50016, P50143, P50991, P50999, P53451, P54408

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
RPS6KA1	up-regulates	CCT2	phosphorylation
AKT1	unknown	CCT2	phosphorylation
RPS6KB1	unknown	CCT2	phosphorylation
AKT	unknown	CCT2	phosphorylation
RPS6K	up-regulates	CCT2	phosphorylation
CCT2	“form complex”	TRiC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 247 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
Formation of tubulin folding intermediates by CCT/TriC	11	29.3×	1e-11
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	11	28.2×	1e-11
Prefoldin mediated transfer of substrate to CCT/TriC	11	27.2×	1e-11
Chaperonin-mediated protein folding	12	22.7×	1e-11
BBSome-mediated cargo-targeting to cilium	7	21.9×	9e-07
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	20.5×	8e-06
Transport of connexons to the plasma membrane	6	20.5×	8e-06
Cargo trafficking to the periciliary membrane	13	20.3×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	8	28.6×	1e-07
microtubule-based process	5	24.2×	2e-04
mitotic spindle assembly checkpoint signaling	5	13.7×	2e-03
mitotic cell cycle	19	12.4×	1e-12
mitotic spindle organization	9	11.9×	1e-05
binding of sperm to zona pellucida	5	10.3×	8e-03
microtubule cytoskeleton organization	14	8.3×	5e-07
JNK cascade	6	8.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	229
Likely benign	165
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

1668 predictions. Top by Δscore:

Variant	Effect	Δscore
12:69585524:GGTG:G	donor_loss	1.0000
12:69585525:G:GC	donor_loss	1.0000
12:69585525:G:GG	donor_gain	1.0000
12:69585526:T:A	donor_loss	1.0000
12:69586266:TCA:T	acceptor_loss	1.0000
12:69586267:CAG:C	acceptor_loss	1.0000
12:69586268:A:AC	acceptor_loss	1.0000
12:69586268:A:AG	acceptor_gain	1.0000
12:69586269:G:GG	acceptor_gain	1.0000
12:69586269:GGC:G	acceptor_gain	1.0000
12:69586340:GTCTG:G	donor_gain	1.0000
12:69586342:CTGGT:C	donor_loss	1.0000
12:69586343:TGGTA:T	donor_loss	1.0000
12:69586345:G:GA	donor_loss	1.0000
12:69586345:G:GG	donor_gain	1.0000
12:69586346:TAAGC:T	donor_loss	1.0000
12:69586738:T:TA	acceptor_gain	1.0000
12:69586746:A:AG	acceptor_gain	1.0000
12:69586747:C:G	acceptor_gain	1.0000
12:69586751:A:AG	acceptor_gain	1.0000
12:69586751:AGACT:A	acceptor_loss	1.0000
12:69586752:G:GG	acceptor_gain	1.0000
12:69586752:GA:G	acceptor_gain	1.0000
12:69586752:GAC:G	acceptor_gain	1.0000
12:69586752:GACT:G	acceptor_gain	1.0000
12:69586752:GACTT:G	acceptor_gain	1.0000
12:69586814:GCATG:G	donor_gain	1.0000
12:69586816:ATGG:A	donor_loss	1.0000
12:69586819:G:GG	donor_gain	1.0000
12:69586819:GTAAG:G	donor_loss	1.0000

AlphaMissense

3510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:69587557:A:T	D66V	1.000
12:69587558:T:A	D66E	1.000
12:69587558:T:G	D66E	1.000
12:69587963:A:T	D97V	1.000
12:69587964:T:A	D97E	1.000
12:69587964:T:G	D97E	1.000
12:69589547:A:T	K170I	1.000
12:69593103:G:T	R293M	1.000
12:69586804:G:A	G44R	0.999
12:69586804:G:C	G44R	0.999
12:69586805:G:A	G44E	0.999
12:69586813:G:C	G47R	0.999
12:69587551:C:T	T64I	0.999
12:69587556:G:C	D66H	0.999
12:69587557:A:C	D66A	0.999
12:69587557:A:G	D66G	0.999
12:69587560:G:A	G67D	0.999
12:69587572:T:C	L71P	0.999
12:69587960:G:A	G96D	0.999
12:69587962:G:C	D97H	0.999
12:69587963:A:C	D97A	0.999
12:69587963:A:G	D97G	0.999
12:69587966:G:A	G98D	0.999
12:69587966:G:T	G98V	0.999
12:69588153:G:C	A113P	0.999
12:69589546:A:G	K170E	0.999
12:69589548:A:C	K170N	0.999
12:69589548:A:T	K170N	0.999
12:69592128:C:A	A240E	0.999
12:69592132:T:A	N241K	0.999

dbSNP variants (sampled 300 via entrez): RS1000082848 (12:69599442 C>G), RS1000452957 (12:69599123 G>C), RS1000470965 (12:69594031 G>A,C,T), RS1000669405 (12:69595206 GT>G,GTT), RS1001043671 (12:69600708 T>C), RS1001110119 (12:69584685 A>T), RS1001135404 (12:69588920 C>T), RS1001184906 (12:69591785 G>T), RS1001216086 (12:69591977 G>A), RS1001295115 (12:69585843 G>A,C), RS1001514101 (12:69601766 C>T), RS1001541521 (12:69584435 G>T), RS1001559503 (12:69600998 G>T), RS1001844365 (12:69585816 G>C), RS1002156218 (12:69592746 G>C)

Disease associations

OMIM: gene MIM:605139 | disease phenotypes: MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis	Strong	Autosomal recessive

Mondo (2): inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000175_26	Height	3.000000e-06
GCST006463_19	Urinary albumin excretion (no hypertensive medication)	4.000000e-09
GCST006586_32	Urinary albumin excretion	2.000000e-11
GCST007006_11	Logical memory (delayed recall) in normal cognition	4.000000e-07
GCST008794_36	Urinary albumin-to-creatinine ratio	2.000000e-13
GCST009640_43	Urinary albumin-to-creatinine ratio	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004285	albuminuria
EFO:0004874	memory performance
EFO:0007778	urinary albumin to creatinine ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725073 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

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

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.75	Kd	17.75	nM	CHEMBL3752910
7.75	ED50	17.75	nM	CHEMBL3752910
7.27	Kd	53.22	nM	CHEMBL5653589
7.27	ED50	53.22	nM	CHEMBL5653589
5.79	Kd	1619	nM	MOLIBRESIB
5.41	IC50	3860	nM	MOLIBRESIB

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148020: Binding affinity to human CCT2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0177	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148020: Binding affinity to human CCT2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0532	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179239: Binding affinity against CCT2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	1.6190	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, decreases expression, affects binding	4
Tobacco Smoke Pollution	affects expression, increases expression, increases metabolic processing	4
Resveratrol	affects cotreatment, increases expression, affects expression	2
Smoke	decreases expression	2
Particulate Matter	affects expression, increases reaction, decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
chlorophyllin	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	affects binding	1
cobaltous chloride	decreases expression	1
lead chloride	decreases expression	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
diphenylarsinic acid	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651062	Binding	Binding affinity to human CCT2 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)

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

Trial	Phase	Status	Title
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03913143	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT00749957	PHASE1/PHASE2	COMPLETED	Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
NCT01208389	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
NCT01496040	PHASE1/PHASE2	COMPLETED	Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65
NCT02781480	PHASE1/PHASE2	COMPLETED	Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)
NCT03913130	PHASE1/PHASE2	TERMINATED	Extension Study to Study PQ-110-001 (NCT03140969)
NCT03920007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D
NCT05203939	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
NCT05906953	PHASE1/PHASE2	RECRUITING	Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
NCT06088992	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02575430	Not specified	COMPLETED	Natural History Study in Inherited Retinal Disease Subjects Caused by Mutations in RPE65 or LRAT
NCT02714816	Not specified	COMPLETED	Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65
NCT02946879	Not specified	COMPLETED	Long-Term Follow-Up Gene Therapy Study for Leber Congenital Amaurosis OPTIRPE65 (Retinal Dystrophy Associated With Defects in RPE65)
NCT02970266	Not specified	COMPLETED	Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families.
NCT07026565	Not specified	NOT_YET_RECRUITING	Psychotherapy Group for Parents of Children With LCA
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study