CCT8

Summary

CCT8 (chaperonin containing TCP1 subunit 8, HGNC:1623) is a protein-coding gene on chromosome 21q21.3, encoding T-complex protein 1 subunit theta (P50990). 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 98.9% of cancer cell lines).

This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1.

Source: NCBI Gene 10694 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 93 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_006585

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1623
Approved symbol	CCT8
Name	chaperonin containing TCP1 subunit 8
Location	21q21.3
Locus type	gene with protein product
Status	Approved
Aliases	Cctq, PRED71
Ensembl gene	ENSG00000156261
Ensembl biotype	protein_coding
OMIM	617786
Entrez	10694

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000286788, ENST00000431234, ENST00000432178, ENST00000470450, ENST00000475205, ENST00000480359, ENST00000481059, ENST00000484403, ENST00000494296, ENST00000496121, ENST00000540844, ENST00000626972, ENST00000852626, ENST00000852627, ENST00000852628, ENST00000852629, ENST00000852630, ENST00000936253, ENST00000936254, ENST00000936255, ENST00000936256, ENST00000936257, ENST00000960004, ENST00000960005, ENST00000960006

RefSeq mRNA: 4 — MANE Select: NM_006585 NM_001282907, NM_001282908, NM_001282909, NM_006585

CCDS: CCDS33528, CCDS68181

Canonical transcript exons

ENST00000286788 — 15 exons

Exon	Start	End
ENSE00001504993	29073531	29073648
ENSE00003525940	29060541	29060660
ENSE00003573058	29056326	29056552
ENSE00003598993	29069423	29069502
ENSE00003644939	29070247	29070337
ENSE00004283619	29067556	29067705
ENSE00004283620	29064968	29065105
ENSE00004283621	29066891	29067071
ENSE00004283622	29063352	29063530
ENSE00004283623	29062128	29062243
ENSE00004283624	29066716	29066777
ENSE00004283625	29061253	29061417
ENSE00004283626	29062490	29062556
ENSE00004283627	29061496	29061567
ENSE00004283628	29062328	29062415

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 144.5411 / max 2820.5614, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190069	143.9133	1826
190067	0.6278	301

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.44	gold quality
secondary oocyte	CL:0000655	99.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.34	gold quality
cortical plate	UBERON:0005343	99.33	gold quality
epithelium of nasopharynx	UBERON:0001951	99.31	gold quality
nasopharynx	UBERON:0001728	99.30	gold quality
embryo	UBERON:0000922	99.16	gold quality
ganglionic eminence	UBERON:0004023	99.13	gold quality
endothelial cell	CL:0000115	99.12	gold quality
germinal epithelium of ovary	UBERON:0001304	98.98	gold quality
adrenal tissue	UBERON:0018303	98.92	gold quality
choroid plexus epithelium	UBERON:0003911	98.89	gold quality
ventricular zone	UBERON:0003053	98.87	gold quality
cartilage tissue	UBERON:0002418	98.86	gold quality
islet of Langerhans	UBERON:0000006	98.74	gold quality
parietal pleura	UBERON:0002400	98.55	gold quality
right adrenal gland	UBERON:0001233	98.53	gold quality
pleura	UBERON:0000977	98.44	gold quality
visceral pleura	UBERON:0002401	98.42	gold quality
lymph node	UBERON:0000029	98.41	gold quality
tongue squamous epithelium	UBERON:0006919	98.41	gold quality
right adrenal gland cortex	UBERON:0035827	98.39	gold quality
body of pancreas	UBERON:0001150	98.38	gold quality
adrenal gland	UBERON:0002369	98.36	gold quality
left adrenal gland	UBERON:0001234	98.34	gold quality
gluteal muscle	UBERON:0002000	98.33	gold quality
trabecular bone tissue	UBERON:0002483	98.31	gold quality
adrenal cortex	UBERON:0001235	98.30	gold quality
pancreas	UBERON:0001264	98.28	gold quality
saphenous vein	UBERON:0007318	98.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	14.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELK1, ELK3, ELK4

miRNA regulators (miRDB)

22 targeting CCT8, 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-4795-3P	100.00	74.62	4024
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-618	97.62	67.46	861
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-125A-3P	97.04	66.92	902

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• showed that high CCT8 protein expression might be related to poor outcome of glioma (PMID:26304164)
• data suggest that the GRP94/CCT8/c-Jun/EMT signaling cascade might be a new therapeutic target for HCC (PMID:26718209)
• Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington’s disease. (PMID:27892468)
• Study demonstrated that CCT8 expression is widely upregulated in esophageal squamous cell carcinoma (ESCC), and enhanced the migration and invasion of ESCC cells, indicating that ectopic CCT8 expression contributes to the highly aggressive nature of ESCC probably by increasing alpha-actin and beta-tubulin expression. (PMID:29620162)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cct8	ENSDARG00000008243
mus_musculus	Cct8	ENSMUSG00000025613
rattus_norvegicus	Cct8	ENSRNOG00000001592
drosophila_melanogaster	CCT8	FBGN0284436
caenorhabditis_elegans		WBGENE00021934

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

T-complex protein 1 subunit theta — P50990 (reviewed: P50990)

Alternative names: CCT-theta, Chaperonin containing T-complex polypeptide 1 subunit 8, Renal carcinoma antigen NY-REN-15

All UniProt accessions (3): P50990, H7C2U0, H7C4C8

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 synaptic plasticity regulator PANTS.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cilium basal body.

Disease relevance. De novo genetic variants in nearly every subunit of the TRiC complex, including CCT8, have been found in individuals with a broad spectrum of brain malformations, and clinical phenotypes ranging from mild to severe epilepsy, developmental delay, intellectual disability, ataxia, and other features of cerebral malfunction.

Similarity. Belongs to the TCP-1 chaperonin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P50990-1	1	yes
P50990-2	2
P50990-3	3

RefSeq proteins (4): NP_001269836, NP_001269837, NP_001269838, NP_006576* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002194	Chaperonin_TCP-1_CS	Conserved_site
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR012721	Chap_CCT_theta	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

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 28, helix 23, binding site 20, modified residue 12, cross-link 6, turn 3, splice variant 2, sequence variant 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 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-P50990-F1	87.85	0.58

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): 102; 102; 103; 169; 170; 170; 171; 171; 412; 412; 499; 499 …

Post-translational modifications (18): 2, 23, 30, 162, 213, 269, 317, 318, 400, 466, 505, 537, 224, 254, 260, 459, 534, 539

Function

Pathways and Gene Ontology

Reactome pathways

16 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-168249	Innate Immune System
R-HSA-168256	Immune System
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: 250 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_SINGLE_FERTILIZATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOCC_SECRETORY_GRANULE, MODULE_151, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOCC_MICROTUBULE_ORGANIZING_CENTER

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): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein folding chaperone (GO:0044183), cadherin binding (GO:0045296), 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 (15): zona pellucida receptor complex (GO:0002199), extracellular region (GO:0005576), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), chaperonin-containing T-complex (GO:0005832), microtubule (GO:0005874), secretory granule lumen (GO:0034774), azurophil granule lumen (GO:0035578), cell body (GO:0044297), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-9 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
Innate Immune System	1
Immune System	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	5
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
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
molecular_function	1
protein folding	1
cell adhesion molecule binding	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
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
cytosol	1
protein folding chaperone complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
secretory granule	1
cytoplasmic vesicle lumen	1
vacuolar lumen	1

Protein interactions and networks

STRING

3273 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCT8	CCT4	P50991	989
CCT8	CCT2	P78371	984
CCT8	CCT5	P48643	980
CCT8	CCT3	P49368	978
CCT8	TCP1	P17987	954
CCT8	CCT7	Q99832	927
CCT8	CCT6A	P40227	839
CCT8	TSR1	Q2NL82	643
CCT8	HSPA8	P11142	629
CCT8	DNAJB1	P25685	587
CCT8	HSP90AA1	P07900	586
CCT8	HSP90AB1	P08238	582
CCT8	CCT6B	Q92526	574
CCT8	HSPA5	P11021	537
CCT8	HSPD1	P10809	536

IntAct

477 interactions, top by confidence:

A	B	Type	Score
IGBP1	PPP6C	psi-mi:“MI:0914”(association)	0.940
STK24	STK25	psi-mi:“MI:0914”(association)	0.890
STRN3	STK25	psi-mi:“MI:0914”(association)	0.880
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
PPP2CA	STRN	psi-mi:“MI:0914”(association)	0.840
WRAP53	DKC1	psi-mi:“MI:0914”(association)	0.830
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
CCT6A	CCT8	psi-mi:“MI:0915”(physical association)	0.750
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
STRN4	STRN	psi-mi:“MI:0914”(association)	0.730
MOB4	STK25	psi-mi:“MI:0914”(association)	0.730
TCP1	CCT8	psi-mi:“MI:0915”(physical association)	0.670
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
PPP2R2C	TCP1	psi-mi:“MI:0914”(association)	0.640
CTTNBP2	STK25	psi-mi:“MI:0914”(association)	0.640
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
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
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
KLHDC8A	PEX7	psi-mi:“MI:0914”(association)	0.530

BioGRID (828): CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CCT8 (Affinity Capture-MS)

ESM2 similar proteins: A2VE01, E7F3I6, O35142, O46560, O55029, O95782, O97555, P11029, P11497, P17426, P21856, P31150, P35605, P35606, P50398, P50990, P60028, P80314, Q13085, Q24208, Q28559, Q28I42, Q3ZBH0, Q3ZCI9, Q4R4I8, Q4R4U1, Q4R5J0, Q4R5Y2, Q4R7R3, Q4V7Z0, Q5E982, Q5PQL4, Q5R5F8, Q5R664, Q5R8Q7, Q5RAP1, Q5SWU9, Q5XIM9, Q5ZJL4, Q5ZMA6

Diamond homologs: A0QKR2, A5FPR4, A6NM43, A8EY36, A8YTH8, A9NHL6, B2V8F1, B7H4Q7, B7IUT0, O68324, P42932, P50990, P60545, Q048Y3, Q1G937, Q29068, Q3AUZ9, Q3Z6L3, Q3ZCI9, Q4MPR6, Q4R5J0, Q5RAP1, Q6EE31, Q814B0, Q8R5T7, Q93G07, Q96SF2, Q9KJ23, A8X6I9, O24730, O24731, O24732, O24734, O24735, O26320, O26885, O28045, O28821, O30560, O30561

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CCT8	“form complex”	TRiC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 241 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
Prefoldin mediated transfer of substrate to CCT/TriC	8	21.1×	2e-06
Formation of tubulin folding intermediates by CCT/TriC	7	19.9×	1e-05
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	7	19.2×	1e-05
Chaperonin-mediated protein folding	8	16.1×	1e-05
Protein folding	8	13.9×	1e-05
Association of TriC/CCT with target proteins during biosynthesis	6	11.8×	4e-04
Cargo trafficking to the periciliary membrane	7	11.7×	1e-04
Aggrephagy	7	11.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	6	23.1×	9e-05
protein refolding	5	16.4×	2e-03
positive regulation of type I interferon production	6	13.3×	9e-04
peptidyl-serine phosphorylation	5	13.0×	4e-03
response to heat	5	11.1×	6e-03
mRNA stabilization	5	9.6×	9e-03
mitotic spindle organization	6	8.6×	6e-03
protein dephosphorylation	7	8.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2233 predictions. Top by Δscore:

Variant	Effect	Δscore
21:29060536:CTCA:C	donor_loss	1.0000
21:29060537:TCA:T	donor_loss	1.0000
21:29060538:CAC:C	donor_loss	1.0000
21:29060539:ACCT:A	donor_loss	1.0000
21:29060540:C:A	donor_loss	1.0000
21:29061248:AATAC:A	donor_loss	1.0000
21:29061249:ATAC:A	donor_loss	1.0000
21:29061250:TACC:T	donor_loss	1.0000
21:29061251:A:AT	donor_loss	1.0000
21:29061277:ATTT:A	donor_gain	1.0000
21:29061280:T:A	donor_gain	1.0000
21:29061284:T:TA	donor_gain	1.0000
21:29061314:A:AC	donor_gain	1.0000
21:29061315:C:CC	donor_gain	1.0000
21:29061317:T:TA	donor_gain	1.0000
21:29061319:ATTGG:A	donor_gain	1.0000
21:29061328:AACT:A	donor_gain	1.0000
21:29061329:A:C	donor_gain	1.0000
21:29061413:CATGT:C	acceptor_gain	1.0000
21:29061414:ATGT:A	acceptor_gain	1.0000
21:29061415:TGT:T	acceptor_gain	1.0000
21:29061416:GT:G	acceptor_gain	1.0000
21:29061417:TC:T	acceptor_loss	1.0000
21:29061418:C:CC	acceptor_gain	1.0000
21:29061490:CTGTA:C	donor_loss	1.0000
21:29061491:TGTAC:T	donor_loss	1.0000
21:29061492:GTAC:G	donor_loss	1.0000
21:29061493:TACCT:T	donor_loss	1.0000
21:29061494:AC:A	donor_loss	1.0000
21:29061495:C:T	donor_loss	1.0000

AlphaMissense

3598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:29067692:G:T	A82D	1.000
21:29056548:A:T	I525N	0.999
21:29056551:A:C	I524S	0.999
21:29060542:T:G	Q523P	0.999
21:29060554:A:T	L519H	0.999
21:29062169:C:G	A391P	0.999
21:29062207:C:G	R378P	0.999
21:29066940:T:A	K171N	0.999
21:29066940:T:G	K171N	0.999
21:29067062:C:G	G131R	0.999
21:29067689:G:T	A83E	0.999
21:29067697:A:C	H80Q	0.999
21:29067697:A:T	H80Q	0.999
21:29067698:T:C	H80R	0.999
21:29069451:T:A	D68V	0.999
21:29069457:G:A	T66I	0.999
21:29069487:A:T	V56D	0.999
21:29069492:T:A	K54N	0.999
21:29069492:T:G	K54N	0.999
21:29069494:T:C	K54E	0.999
21:29069502:C:T	G51E	0.999
21:29070255:C:T	G48E	0.999
21:29070290:G:C	C36W	0.999
21:29070302:G:C	N32K	0.999
21:29070302:G:T	N32K	0.999
21:29056551:A:G	I524T	0.998
21:29056551:A:T	I524N	0.998
21:29060545:T:A	D522V	0.998
21:29060554:A:G	L519P	0.998
21:29060557:A:T	V518E	0.998

dbSNP variants (sampled 300 via entrez): RS1000322092 (21:29073321 G>A), RS1000436936 (21:29057732 TGATA>T), RS1000658467 (21:29056701 G>A,C), RS1000772946 (21:29056960 A>AG), RS1000865208 (21:29061029 G>C), RS1000940306 (21:29072995 G>A), RS1001325656 (21:29058333 C>A,G,T), RS1001421679 (21:29068093 C>G), RS1001441370 (21:29058608 T>G), RS1001537663 (21:29063755 G>A), RS1001540054 (21:29066808 T>C,G), RS1001542972 (21:29058042 A>C), RS1001675819 (21:29073956 C>A,T), RS1001857996 (21:29056957 T>A,C,G), RS1002002987 (21:29062078 T>C)

Disease associations

OMIM: gene MIM:617786 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010796_256	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010796_257	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_258	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

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): CHEMBL4295775 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.73	Kd	18.64	nM	CHEMBL3752910
7.73	ED50	18.64	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148026: Binding affinity to human CCT8 incubated for 45 mins by Kinobead based pull down assay	kd	0.0186	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	3
Arsenic Trioxide	decreases reaction, increases expression, affects binding	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, affects expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
arsenite	affects binding, increases reaction	1
ochratoxin A	affects expression	1
cupric oxide	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	decreases expression	1
microcystin RR	increases expression	1
CGP 52608	increases reaction, affects binding	1
chloropicrin	affects expression	1
tanespimycin	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
bromovanin	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
VER 155008	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arbutin	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118778	Binding	Binding affinity to CCT8 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

204 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