CCT3

Summary

CCT3 (chaperonin containing TCP1 subunit 3, HGNC:1616) is a protein-coding gene on chromosome 1q22, encoding T-complex protein 1 subunit gamma (P49368). 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 100.0% 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. Alternate transcriptional splice variants have been characterized for this gene. In addition, a pseudogene of this gene has been found on chromosome 8.

Source: NCBI Gene 7203 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 105 total — 2 pathogenic
• Phenotypes (HPO): 48
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_005998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1616
Approved symbol	CCT3
Name	chaperonin containing TCP1 subunit 3
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	Cctg
Ensembl gene	ENSG00000163468
Ensembl biotype	protein_coding
OMIM	600114
Entrez	7203

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 28 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000295688, ENST00000368256, ENST00000368258, ENST00000368259, ENST00000368261, ENST00000368262, ENST00000413555, ENST00000415548, ENST00000446905, ENST00000463132, ENST00000472765, ENST00000478640, ENST00000489870, ENST00000490221, ENST00000496684, ENST00000533194, ENST00000898516, ENST00000898517, ENST00000940011, ENST00000940012, ENST00000940013, ENST00000940014, ENST00000940015, ENST00000940016, ENST00000940017, ENST00000940018, ENST00000940019, ENST00000940020, ENST00000940021, ENST00000940022, ENST00000954292, ENST00000954293, ENST00000954294, ENST00000954295, ENST00000954296

RefSeq mRNA: 2 — MANE Select: NM_005998 NM_001008800, NM_005998

CCDS: CCDS1140, CCDS30888

Canonical transcript exons

ENST00000295688 — 14 exons

Exon	Start	End
ENSE00002187055	156338154	156338292
ENSE00003338881	156308968	156309303
ENSE00003484734	156312041	156312221
ENSE00003495557	156310558	156310689
ENSE00003515605	156324972	156325089
ENSE00003542036	156318868	156319017
ENSE00003542154	156317166	156317247
ENSE00003558856	156335827	156335888
ENSE00003613771	156310950	156311195
ENSE00003614402	156334868	156334918
ENSE00003648585	156320839	156321025
ENSE00003649963	156317415	156317547
ENSE00003658732	156334713	156334775
ENSE00003660813	156333547	156333643

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 171.8317 / max 1873.8678, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15106	162.6054	1824
15105	7.8230	1646
15103	1.0751	637
15104	0.3282	137

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.45	gold quality
embryo	UBERON:0000922	98.97	gold quality
cortical plate	UBERON:0005343	98.95	gold quality
islet of Langerhans	UBERON:0000006	98.85	gold quality
adrenal tissue	UBERON:0018303	98.78	gold quality
ventricular zone	UBERON:0003053	98.77	gold quality
ganglionic eminence	UBERON:0004023	98.75	gold quality
right adrenal gland	UBERON:0001233	98.54	gold quality
smooth muscle tissue	UBERON:0001135	98.52	gold quality
right testis	UBERON:0004534	98.47	gold quality
left testis	UBERON:0004533	98.38	gold quality
right adrenal gland cortex	UBERON:0035827	98.36	gold quality
left adrenal gland	UBERON:0001234	98.32	gold quality
adrenal gland	UBERON:0002369	98.27	gold quality
left adrenal gland cortex	UBERON:0035825	98.23	gold quality
adrenal cortex	UBERON:0001235	98.20	gold quality
vermiform appendix	UBERON:0001154	98.03	gold quality
gingival epithelium	UBERON:0001949	98.03	gold quality
testis	UBERON:0000473	98.02	gold quality
lymph node	UBERON:0000029	98.00	gold quality
cartilage tissue	UBERON:0002418	98.00	gold quality
rectum	UBERON:0001052	97.98	gold quality
epithelium of nasopharynx	UBERON:0001951	97.97	gold quality
endometrium epithelium	UBERON:0004811	97.97	gold quality
nasopharynx	UBERON:0001728	97.96	gold quality
gingiva	UBERON:0001828	97.96	gold quality
adult organism	UBERON:0007023	97.96	gold quality
caecum	UBERON:0001153	97.92	gold quality
stromal cell of endometrium	CL:0002255	97.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.74	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	455.34
E-MTAB-9067	yes	21.76
E-GEOD-110499	no	1482.29
E-MTAB-10596	no	1019.83
E-GEOD-86618	no	864.06
E-GEOD-93593	no	4.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

26 targeting CCT3, 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-4697-3P	99.89	67.09	1123
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-152-5P	96.42	66.59	960
HSA-MIR-664A-5P	95.84	64.93	949

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 18)

• Among ten hepatocellular carcinoma cases with amplicon 1q21-q22, significant gene expression level of JTB, SHC1, CCT3 and COPA in the tumors than the paired adjacent non-malignant liver tissues. (PMID:12586295)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Our results implicate a novel cell signaling loop in HCt116 cells involving p53 and TCP1-gamma phosphorylation, which may be related to regulation and action of centrosomes. (PMID:22399500)
• Expression of S100A9 and CCTgamma was significantly elevated in liver tissue of patients with cholangiocarcinoma compared with controls. (PMID:23868055)
• Overexpression of CCT3 in the nuclei of cancerous cells is associated with hepatocellular carcinoma progression. CCT3 may be a target that affects the activation of STAT3 in HCC. (PMID:26229401)
• Suggest that CCT3 is indispensible for hepatocellular carcinoma cell proliferation, and provides a potential drug target for treatment of HCC. (PMID:26739059)
• CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer. (PMID:31501420)
• Data suggest that circCCT3 circular RNA plays an oncogenic role in colorectal cancer (CRC) metastasis through miR-613/vascular endothelial growth factor A (VEGFA) and Wnt signaling. (PMID:31859543)
• High expression of chaperonin-containing TCP1 subunit 3 may induce dismal prognosis in multiple myeloma. (PMID:31902948)
• CCT3 suppression prompts apoptotic machinery through oxidative stress and energy deprivation in breast and prostate cancers. (PMID:33508424)
• Identification of CCT3 as a prognostic factor and correlates with cell survival and invasion of head and neck squamous cell carcinoma. (PMID:34505628)
• Chaperonin containing TCP1 subunit 3 (CCT3) promotes cisplatin resistance of lung adenocarcinoma cells through targeting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. (PMID:34612768)
• Upregulation of CCT3 promotes cervical cancer progression through FN1. (PMID:34651664)
• Upregulation of CCT3 predicts poor prognosis and promotes cell proliferation via inhibition of ferroptosis and activation of AKT signaling in lung adenocarcinoma. (PMID:35773623)
• Integrated analyzes identify CCT3 as a modulator to shape immunosuppressive tumor microenvironment in lung adenocarcinoma. (PMID:36918801)
• m[6]A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression. (PMID:37092305)
• Circular RNA CCT3 is a unique molecular marker in bladder cancer. (PMID:37833621)
• Dysfunction of CCT3-associated network signals for the critical state during progression of hepatocellular carcinoma. (PMID:38360074)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cct3	ENSDARG00000016173
mus_musculus	Cct3	ENSMUSG00000001416
rattus_norvegicus	Cct3	ENSRNOG00000019090
drosophila_melanogaster	CCT3	FBGN0015019
caenorhabditis_elegans		WBGENE00018782

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

T-complex protein 1 subunit gamma — P49368 (reviewed: P49368)

Alternative names: CCT-gamma, Chaperonin containing T-complex polypeptide 1 subunit 3, hTRiC5

All UniProt accessions (10): B4DUR8, E9PM09, E9PQ35, E9PRC8, E9PRM9, E9PRN0, P49368, Q5SZW8, Q5SZX6, Q5SZX9

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 DNAAF4. Interacts with DLEC1.

Subcellular location. Cytoplasm.

Disease relevance. Neurodevelopmental disorder with speech or visual impairment and brain hypomyelination (NEDSVH) [MIM:621034] An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and brain abnormalities including hypomyelination, cerebellar atrophy, and optic nerve atrophy. Some patients have severe visual impairment, dystonic movements, and seizures. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TCP-1 chaperonin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49368-1	1	yes
P49368-2	2

RefSeq proteins (2): NP_001008800, NP_005989* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002194	Chaperonin_TCP-1_CS	Conserved_site
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR012719	Chap_CCT_gamma	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
IPR054827	TCP-1-like	Family

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 (101 total): strand 32, helix 22, binding site 20, modified residue 10, cross-link 4, sequence variant 3, turn 3, region of interest 2, sequence conflict 2, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

66 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-P49368-F1	89.23	0.67

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 (20): 96; 96; 97; 162; 163; 411; 411; 482; 482; 483; 497; 497 …

Post-translational modifications (14): 1, 11, 170, 222, 243, 244, 247, 252, 430, 459, 15, 248, 249, 381

Disulfide bonds (1): 366–372

Function

Pathways and Gene Ontology

Reactome pathways

13 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-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-1852241	Organelle biogenesis and maintenance
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

MSigDB gene sets: 291 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_SINGLE_FERTILIZATION, GOBP_CHROMOSOME_ORGANIZATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, TGCGCANK_UNKNOWN, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MATTIOLI_MGUS_VS_PCL, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (6): 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), 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): RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), 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 (8): zona pellucida receptor complex (GO:0002199), cytosol (GO:0005829), chaperonin-containing T-complex (GO:0005832), cytoskeleton (GO:0005856), microtubule (GO:0005874), cell body (GO:0044297), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	3
Chaperonin-mediated protein folding	3
Cargo trafficking to the periciliary membrane	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	3
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
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
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	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
intracellular membraneless organelle	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCT3	CCT4	P50991	989
CCT3	CCT5	P48643	988
CCT3	CCT2	P78371	986
CCT3	CCT7	Q99832	985
CCT3	CCT6A	P40227	982
CCT3	CCT8	P50990	978
CCT3	TCP1	P17987	965
CCT3	CCT6B	Q92526	719
CCT3	PFDN1	O60925	607
CCT3	EEF1G	P26641	592
CCT3	HSPD1	P10809	576
CCT3	HSPA4	P34932	556
CCT3	TOP2A	P11388	515
CCT3	ELOB	Q15370	490
CCT3	HSF1	Q00613	466

IntAct

614 interactions, top by confidence:

A	B	Type	Score
IGBP1	PPP6C	psi-mi:“MI:0914”(association)	0.940
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
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
CCT3	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	CCT3	psi-mi:“MI:0915”(physical association)	0.720
WRAP53	TCP1	psi-mi:“MI:0914”(association)	0.690
WRAP53	CCT6A	psi-mi:“MI:0914”(association)	0.640
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
TUBA1B	TXNDC9	psi-mi:“MI:0914”(association)	0.640
ACTR3	ARPC2	psi-mi:“MI:0914”(association)	0.640
DCAF12L2	CETN3	psi-mi:“MI:0914”(association)	0.640
HDAC11	CLUH	psi-mi:“MI:0914”(association)	0.640
STAT3	CCT3	psi-mi:“MI:0407”(direct interaction)	0.590
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
EED	CCT3	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
PTK6	TCP1	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
PPP2R2D	TCP1	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530

BioGRID (995): CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), MIPOL1 (Two-hybrid), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT3 (Affinity Capture-MS)

ESM2 similar proteins: A2RVK7, A2X0Q3, A6QLJ3, O00442, O23617, O81147, O81852, P0CT46, P31754, P37142, P48605, P49080, P49368, P80318, Q01415, Q06265, Q14181, Q2HJ88, Q2KHU3, Q3SWZ4, Q3T0K2, Q4QR75, Q4R3J0, Q4R963, Q5NVF9, Q5R6J8, Q5R7P3, Q5RCW2, Q5RGJ5, Q5XJQ5, Q69LE7, Q6P502, Q6STH5, Q6YXZ7, Q7YRA3, Q84T68, Q8C3X4, Q8GZQ3, Q8K1R3, Q8N442

Diamond homologs: O00782, O04450, O15891, O24730, O24731, O24732, O24734, O24735, O26320, O26885, O28045, O28821, O30560, O30561, O57762, O74341, O93624, P12613, P17987, P18279, P28480, P28488, P28769, P39077, P40412, P40413, P41988, P42943, P46219, P47208, P47209, P48424, P48425, P48605, P48643, P49368, P50016, P50143, P50991, P50999

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CCT3	“form complex”	TRiC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 261 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	8	20.6×	4e-07
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	8	19.9×	4e-07
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	19.9×	1e-05
Transport of connexons to the plasma membrane	6	19.9×	1e-05
Prefoldin mediated transfer of substrate to CCT/TriC	8	19.2×	4e-07
Chaperonin-mediated protein folding	10	18.3×	9e-08
Gap junction trafficking and regulation	6	17.4×	2e-05
Gap junction trafficking	6	17.4×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
microtubule-based process	5	23.6×	5e-04
positive regulation of telomere maintenance via telomerase	5	17.4×	1e-03
chaperone-mediated protein complex assembly	5	16.7×	2e-03
mitotic cell cycle	17	10.8×	5e-10
mitotic spindle organization	8	10.3×	4e-04
microtubule cytoskeleton organization	16	9.2×	1e-08
non-motile cilium assembly	6	8.3×	7e-03
JNK cascade	6	7.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	65
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3544400	NM_005998.5(CCT3):c.1186del (p.Gln396fs)	Pathogenic
3778716	NM_005998.5(CCT3):c.791dup (p.Thr265fs)	Pathogenic

SpliceAI

2448 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156309300:CCGT:C	acceptor_gain	1.0000
1:156309301:CGT:C	acceptor_gain	1.0000
1:156309301:CGTC:C	acceptor_gain	1.0000
1:156309304:C:CC	acceptor_gain	1.0000
1:156309304:C:T	acceptor_loss	1.0000
1:156310553:CTTA:C	donor_loss	1.0000
1:156310554:TTA:T	donor_loss	1.0000
1:156310555:TA:T	donor_loss	1.0000
1:156310556:A:AC	donor_gain	1.0000
1:156310557:C:CC	donor_gain	1.0000
1:156310557:C:CT	donor_loss	1.0000
1:156310685:TTGGC:T	acceptor_gain	1.0000
1:156310686:TGGC:T	acceptor_gain	1.0000
1:156310687:GGC:G	acceptor_gain	1.0000
1:156310687:GGCCT:G	acceptor_loss	1.0000
1:156310688:GC:G	acceptor_gain	1.0000
1:156310689:CC:C	acceptor_gain	1.0000
1:156310690:C:CC	acceptor_gain	1.0000
1:156310690:CTGCA:C	acceptor_loss	1.0000
1:156310691:T:G	acceptor_loss	1.0000
1:156310693:C:CT	acceptor_gain	1.0000
1:156310694:A:T	acceptor_gain	1.0000
1:156310695:A:AC	acceptor_gain	1.0000
1:156310695:A:C	acceptor_gain	1.0000
1:156310696:T:C	acceptor_gain	1.0000
1:156310696:T:TC	acceptor_gain	1.0000
1:156310702:C:CT	acceptor_gain	1.0000
1:156310703:A:T	acceptor_gain	1.0000
1:156312038:CA:C	donor_loss	1.0000
1:156312039:A:AC	donor_gain	1.0000

AlphaMissense

3595 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156333571:C:A	G94W	1.000
1:156333621:G:T	A77D	1.000
1:156334720:A:G	L67P	1.000
1:156334720:A:T	L67H	1.000
1:156309284:C:G	R518P	0.999
1:156310565:G:T	A509E	0.999
1:156310566:C:G	A509P	0.999
1:156310954:A:G	L466P	0.999
1:156310999:A:G	L451P	0.999
1:156311179:A:G	L391P	0.999
1:156311185:C:G	R389P	0.999
1:156312066:C:G	R377P	0.999
1:156317175:C:G	R322P	0.999
1:156317199:C:G	R314T	0.999
1:156317241:G:T	A300D	0.999
1:156320913:C:G	A179P	0.999
1:156333570:C:A	G94V	0.999
1:156333570:C:T	G94E	0.999
1:156333571:C:G	G94R	0.999
1:156333571:C:T	G94R	0.999
1:156333597:C:G	R85P	0.999
1:156333599:G:C	S84R	0.999
1:156333599:G:T	S84R	0.999
1:156333601:T:G	S84R	0.999
1:156333622:C:G	A77P	0.999
1:156333624:G:T	A76E	0.999
1:156334717:C:G	R68P	0.999
1:156334727:C:G	A65P	0.999
1:156334732:C:A	G63V	0.999
1:156334732:C:T	G63D	0.999

dbSNP variants (sampled 300 via entrez): RS1000039263 (1:156322999 A>T), RS1000111108 (1:156322492 C>G,T), RS1000349819 (1:156309879 A>C), RS1000378015 (1:156326527 G>A), RS1000413523 (1:156322719 C>A,T), RS1000455773 (1:156332282 G>C), RS1000499632 (1:156326826 C>T), RS1000574926 (1:156327064 A>C), RS1000712347 (1:156338433 A>G), RS1000713126 (1:156321171 A>G), RS1000732826 (1:156332695 C>A,G,T), RS1000743269 (1:156338555 G>A,T), RS1000884098 (1:156314802 G>A,C), RS1000928027 (1:156315675 T>C), RS1001104492 (1:156332400 T>C)

Disease associations

OMIM: gene MIM:600114 | disease phenotypes: MIM:621034

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant
neurodevelopmental disorder with speech or visual impairment and brain hypomyelination	Moderate	Autosomal dominant

Mondo (2): neurodevelopmental disorder with speech or visual impairment and brain hypomyelination (MONDO:0976125), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000505	Visual impairment
HP:0000609	Optic nerve hypoplasia
HP:0000648	Optic atrophy
HP:0000657	Oculomotor apraxia
HP:0000666	Horizontal nystagmus
HP:0000711	Restlessness
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000954	Single transverse palmar crease
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001344	Absent speech
HP:0001385	Hip dysplasia
HP:0001508	Failure to thrive
HP:0001642	Pulmonic stenosis
HP:0001655	Patent foramen ovale
HP:0002015	Dysphagia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0002376	Developmental regression
HP:0002719	Recurrent infections
HP:0002835	Aspiration

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000582_7	Mean corpuscular hemoglobin concentration	3.000000e-09
GCST001521_7	Subcutaneous adipose tissue	9.000000e-06
GCST002390_1	Glycated hemoglobin levels	1.000000e-23
GCST005996_41	Red blood cell count	3.000000e-15
GCST006011_21	Mean corpuscular volume	4.000000e-26
GCST009524_10	Household income (MTAG)	7.000000e-10
GCST011122_30	Walking pace	6.000000e-10
GCST90002379_7	Basophil count	6.000000e-11
GCST90002404_429	Red cell distribution width	1.000000e-11
GCST90002404_430	Red cell distribution width	8.000000e-15

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004541	HbA1c measurement
EFO:0004305	erythrocyte count
EFO:0009695	household income
EFO:0005090	basophil count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066171 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12138564	CCT3		0.00	0

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.19	Kd	64.37	nM	CHEMBL3752910
7.19	ED50	64.37	nM	CHEMBL3752910
7.05	Kd	89.98	nM	CHEMBL5653589
7.05	ED50	89.98	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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	2148021: Binding affinity to human CCT3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0644	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148021: Binding affinity to human CCT3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
bisphenol A	decreases expression	3
Air Pollutants	affects expression, increases abundance, increases expression	2
Atrazine	increases expression, decreases expression	2
Ivermectin	affects cotreatment, increases expression, decreases expression	2
Ozone	decreases expression, affects expression, increases abundance, affects cotreatment	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
cinobufagin	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
cadmium acetate	decreases expression	1
coumarin	increases phosphorylation	1
triphenyltin	decreases expression	1
cupric oxide	decreases expression	1
artenimol	affects binding	1
methacrylaldehyde	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
tributyltinisothiocyanate	decreases expression	1
CD 437	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651063	Binding	Binding affinity to human CCT3 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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice