CCT6A

Summary

CCT6A (chaperonin containing TCP1 subunit 6A, HGNC:1620) is a protein-coding gene on chromosome 7p11.2, encoding T-complex protein 1 subunit zeta (P40227). 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 98.8% 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. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, several pseudogenes of this gene have been located.

Source: NCBI Gene 908 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 93 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001762

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1620
Approved symbol	CCT6A
Name	chaperonin containing TCP1 subunit 6A
Location	7p11.2
Locus type	gene with protein product
Status	Approved
Aliases	TTCP20, TCPZ, Cctz, HTR3, TCP20
Ensembl gene	ENSG00000146731
Ensembl biotype	protein_coding
OMIM	104613
Entrez	908

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000275603, ENST00000335503, ENST00000462133, ENST00000466479, ENST00000466572, ENST00000482776, ENST00000492618, ENST00000493855, ENST00000494736, ENST00000905208, ENST00000905209, ENST00000905210, ENST00000905211, ENST00000905212, ENST00000905213, ENST00000923889, ENST00000923890, ENST00000923891, ENST00000923892, ENST00000923893, ENST00000923894, ENST00000923895, ENST00000960811, ENST00000960812

RefSeq mRNA: 2 — MANE Select: NM_001762 NM_001009186, NM_001762

CCDS: CCDS34640, CCDS5523

Canonical transcript exons

ENST00000275603 — 14 exons

Exon	Start	End
ENSE00001018724	56056311	56056414
ENSE00001335414	56063013	56063989
ENSE00001602680	56055624	56055797
ENSE00001603806	56058620	56058702
ENSE00001717319	56052422	56052485
ENSE00001768061	56054369	56054503
ENSE00001818557	56051765	56051985
ENSE00003485737	56058362	56058521
ENSE00003496791	56060269	56060416
ENSE00003555290	56062683	56062755
ENSE00003605749	56057993	56058103
ENSE00003624409	56059544	56059640
ENSE00003667805	56061747	56061849
ENSE00003688571	56060807	56060940

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 207.3144 / max 1267.3190, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78770	118.7233	1828
78771	84.6033	1828
78769	3.2328	1450
78773	0.7550	377

Top tissues by expression

296 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	99.35	gold quality
cortical plate	UBERON:0005343	98.94	gold quality
ganglionic eminence	UBERON:0004023	98.68	gold quality
ventricular zone	UBERON:0003053	98.64	gold quality
body of pancreas	UBERON:0001150	98.55	gold quality
skin of abdomen	UBERON:0001416	98.42	gold quality
superior surface of tongue	UBERON:0007371	98.36	gold quality
adrenal tissue	UBERON:0018303	98.33	gold quality
skin of leg	UBERON:0001511	98.29	gold quality
mucosa of transverse colon	UBERON:0004991	98.29	gold quality
islet of Langerhans	UBERON:0000006	98.25	gold quality
metanephros cortex	UBERON:0010533	98.22	gold quality
stromal cell of endometrium	CL:0002255	98.18	gold quality
embryo	UBERON:0000922	98.10	gold quality
adenohypophysis	UBERON:0002196	98.09	gold quality
esophagus mucosa	UBERON:0002469	98.04	gold quality
lower esophagus mucosa	UBERON:0035834	98.00	gold quality
right adrenal gland	UBERON:0001233	97.96	gold quality
left uterine tube	UBERON:0001303	97.96	gold quality
lower esophagus	UBERON:0013473	97.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.96	gold quality
esophagus	UBERON:0001043	97.95	gold quality
pancreas	UBERON:0001264	97.93	gold quality
right adrenal gland cortex	UBERON:0035827	97.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.90	gold quality
zone of skin	UBERON:0000014	97.89	gold quality
rectum	UBERON:0001052	97.89	gold quality
mucosa of stomach	UBERON:0001199	97.89	gold quality
body of stomach	UBERON:0001161	97.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	142.11
E-GEOD-84465	yes	24.49
E-CURD-122	yes	20.91
E-MTAB-10042	yes	13.42
E-CURD-112	yes	8.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, PGR

miRNA regulators (miRDB)

43 targeting CCT6A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-1261	98.62	68.10	896

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• identified genes, which include Tcp20, may play important role in conferring radioresistance to oral squamous cell carcinoma and could be useful in identifying cases with more radioresistance (PMID:16211299)
• These data suggest that CCT6A is a novel autoantigen recognized by Vdelta2 gammadelta T cells, which deepens our understanding of mechanisms in autoimmune diseases. (PMID:27489109)
• High expression of CCT6A is associated with Non-Small Cell Lung Cancer. (PMID:28104536)
• selective inhibition of SMAD3 or CCT6A efficiently suppresses TGF-beta-mediated metastasis. Findings provide a mechanism that directs TGF-beta signaling toward its prometastatic arm and may contribute to the development of therapeutic strategies targeting TGF-beta for non-small-cell lung carcinoma. (PMID:28375158)
• Chaperonin containing t-complex polypeptide 1 subunit 6A correlates with lymph node metastasis, abnormal carcinoembryonic antigen and poor survival profiles in non-small cell lung carcinoma. (PMID:32631353)
• CCT6A, a novel prognostic biomarker for Ewing sarcoma. (PMID:33530265)
• CCT6A may act as a potential biomarker reflecting tumor size, lymphatic metastasis, FIGO stage, and prognosis in cervical cancer patients. (PMID:34196992)
• Chaperonin-containing tailless complex polypeptide 1 subunit 6A correlates with increased World Health Organization grade, less isocitrate dehydrogenase mutation, and deteriorative survival of astrocytoma patients. (PMID:34312925)
• Dynamic Network Biomarker of Pre-Exhausted CD8(+) T Cells Contributed to T Cell Exhaustion in Colorectal Cancer. (PMID:34434188)
• CCT6A expression in hepatocellular carcinoma and its correlation with clinical characteristics, liver function indexes, tumor markers and prognosis. (PMID:34500119)
• Chaperonin-containing tailless complex polypeptide 1 subunit 6A links with aggravating tumor features and disease-free survival in surgical gastric cancer patients: A long-term follow-up study. (PMID:35346891)
• CCT6A knockdown suppresses osteosarcoma cell growth and Akt pathway activation in vitro. (PMID:36584147)
• CCT6A promotes esophageal squamous cell carcinoma cell proliferation, invasion and epithelial-mesenchymal transition by activating TGF-beta/Smad/c-Myc pathway. (PMID:37017854)
• Chaperonin containing TCP1 subunit 6A may activate Notch and Wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma. (PMID:38084868)
• CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis. (PMID:38750462)
• CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status. (PMID:38997438)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cct6a	ENSMUSG00000029447
rattus_norvegicus	Cct6a	ENSRNOG00000000923

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

T-complex protein 1 subunit zeta — P40227 (reviewed: P40227)

Alternative names: Acute morphine dependence-related protein 2, CCT-zeta-1, Chaperonin containing T-complex polypeptide 1 subunit 6A, HTR3, Tcp20

All UniProt accessions (1): P40227

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.

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.

Subcellular location. Cytoplasm.

Disease relevance. De novo genetic variants in nearly every subunit of the TRiC complex, including CCT6A, 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 (2)

UniProt ID	Names	Canonical?
P40227-1	1	yes
P40227-2	2

RefSeq proteins (2): NP_001009186, NP_001753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002194	Chaperonin_TCP-1_CS	Conserved_site
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR012722	Chap_CCT_zeta	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 (84 total): helix 24, strand 24, binding site 18, modified residue 8, turn 4, initiator methionine 1, chain 1, cross-link 1, splice variant 1, sequence variant 1, sequence conflict 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-P40227-F1	89.97	0.66

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 (18): 93; 94; 158; 159; 411; 411; 412; 496; 496; 501; 39; 39 …

Post-translational modifications (9): 2, 5, 199, 205, 287, 365, 377, 388, 251

Function

Pathways and Gene Ontology

Reactome pathways

15 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-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-162582	Signal Transduction
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-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 300 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, MODULE_16, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (6): protein folding (GO:0006457), positive regulation of telomere maintenance via telomerase (GO:0032212), protein stabilization (GO:0050821), positive regulation of establishment of protein localization to telomere (GO:1904851), positive regulation of protein localization to Cajal body (GO:1904871), positive regulation of telomerase RNA localization to Cajal body (GO:1904874)

GO Molecular Function (10): RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), WD40-repeat domain binding (GO:0071987), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), chaperonin-containing T-complex (GO:0005832), microtubule (GO:0005874), extracellular exosome (GO:0070062)

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
RHOBTB GTPase Cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Protein folding	1
Metabolism of proteins	1
Signaling by Rho GTPases	1
RHO GTPase cycle	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	2
cellular anatomical structure	2
cellular process	1
protein maturation	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
establishment of protein localization to telomere	1
regulation of establishment of protein localization to telomere	1
positive regulation of establishment of protein localization	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 domain specific binding	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
cytosol	1
protein folding chaperone complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
extracellular vesicle	1

Protein interactions and networks

STRING

4530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCT6A	CCT3	P49368	982
CCT6A	CCT4	P50991	978
CCT6A	CCT5	P48643	974
CCT6A	CCT2	P78371	949
CCT6A	CCT7	Q99832	936
CCT6A	TCP1	P17987	912
CCT6A	CCT8	P50990	839
CCT6A	MRPS17	Q9Y2R5	634
CCT6A	SUMF2	Q8NBJ7	600
CCT6A	HSP90AA1	P07900	592
CCT6A	STRN	O43815	473
CCT6A	ANXA2	P07355	468
CCT6A	HSPA9	P30036	458
CCT6A	PPP2R1B	P30154	456
CCT6A	ZNF713	Q8N859	455

IntAct

609 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
WRAP53	DKC1	psi-mi:“MI:0914”(association)	0.830
CCT6A	CCT8	psi-mi:“MI:0915”(physical association)	0.750
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
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
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
PPP2R2D	TCP1	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
METTL6	TYW5	psi-mi:“MI:0914”(association)	0.530
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
DYNC2I2	TCP1	psi-mi:“MI:0914”(association)	0.530
WDR37	CLUH	psi-mi:“MI:0914”(association)	0.530
KLHDC8A	PEX7	psi-mi:“MI:0914”(association)	0.530
FBXW4	TXNDC9	psi-mi:“MI:0914”(association)	0.530
TUBG2	TXNDC9	psi-mi:“MI:0914”(association)	0.530
HCFC2	SETD1A	psi-mi:“MI:0914”(association)	0.530
GNB2	PFDN6	psi-mi:“MI:0914”(association)	0.530

BioGRID (895): CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT6A (Affinity Capture-MS)

ESM2 similar proteins: A0B601, A0RUB4, A2BK92, A3MTA9, A4YIL9, A5UJN3, A6UT51, A6UV44, A8A912, A9A2Z3, B1Y9V4, B8D6E8, C3MJN1, C3MYY9, C3N038, C3N8Q2, C3NMR6, C4KJ77, O26355, O77622, O94515, P40227, P46550, P54066, P55858, P62426, P80317, Q0W8W9, Q2NGM2, Q2T9X2, Q3MHL7, Q3T084, Q466D1, Q4J8P1, Q54CL2, Q54PX9, Q5RCD2, Q5ZJ54, Q60YI3, Q6C100

Diamond homologs: A1TKQ5, A1W3W8, A9BXL3, B9MDC5, C0Z361, O04450, O15891, O24730, O24731, O24732, O24734, O24735, O26320, O26885, O28045, O28821, O30560, O30561, O57762, O74341, O77622, O93624, O94515, P21240, P28488, P39079, P40227, P40412, P40413, P46219, P46550, P47209, P48424, P48425, P48643, P50016, P50157, P50991, P53451, P54411

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CCT6A	“form complex”	TRiC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 254 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	29.6×	1e-11
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	11	28.6×	1e-11
Prefoldin mediated transfer of substrate to CCT/TriC	11	27.6×	1e-11
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	7	24.2×	4e-07
Transport of connexons to the plasma membrane	7	24.2×	4e-07
Chaperonin-mediated protein folding	12	23.0×	1e-11
Gap junction trafficking and regulation	7	21.2×	9e-07
Gap junction trafficking	7	21.2×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	7	25.1×	3e-06
mitotic cell cycle	17	11.2×	3e-10
mitotic spindle organization	7	9.3×	2e-03
microtubule cytoskeleton organization	14	8.3×	1e-06
protein stabilization	15	4.9×	1e-04
cilium assembly	12	4.3×	3e-03
cell division	16	3.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	63
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
395009	GRCh37/hg19 7p11.2(chr7:54972516-56172165)x1	Pathogenic
545348	Single allele	Likely pathogenic

SpliceAI

1426 predictions. Top by Δscore:

Variant	Effect	Δscore
7:56051942:G:GT	donor_gain	1.0000
7:56051948:C:G	donor_gain	1.0000
7:56051953:G:GT	donor_gain	1.0000
7:56051981:AAGAT:A	donor_gain	1.0000
7:56051982:AGAT:A	donor_gain	1.0000
7:56051982:AGATG:A	donor_loss	1.0000
7:56051983:GAT:G	donor_gain	1.0000
7:56051983:GATG:G	donor_gain	1.0000
7:56051983:GATGT:G	donor_loss	1.0000
7:56051984:ATGT:A	donor_loss	1.0000
7:56051985:TG:T	donor_loss	1.0000
7:56051986:G:GG	donor_gain	1.0000
7:56051986:GTAA:G	donor_loss	1.0000
7:56051987:T:A	donor_loss	1.0000
7:56054367:A:AG	acceptor_gain	1.0000
7:56054368:G:GA	acceptor_gain	1.0000
7:56054368:GC:G	acceptor_gain	1.0000
7:56054368:GCA:G	acceptor_gain	1.0000
7:56054368:GCAA:G	acceptor_gain	1.0000
7:56054368:GCAAA:G	acceptor_gain	1.0000
7:56054500:TGAA:T	donor_gain	1.0000
7:56054501:G:GT	donor_gain	1.0000
7:56054501:GAA:G	donor_gain	1.0000
7:56054502:AA:A	donor_gain	1.0000
7:56054503:AG:A	donor_loss	1.0000
7:56054504:G:GG	donor_gain	1.0000
7:56055621:TA:T	acceptor_loss	1.0000
7:56055622:A:AC	acceptor_loss	1.0000
7:56055622:A:AG	acceptor_gain	1.0000
7:56055622:AG:A	acceptor_gain	1.0000

AlphaMissense

3490 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:56054388:C:A	A74D	1.000
7:56054483:G:C	A106P	1.000
7:56058620:G:A	G296R	1.000
7:56058620:G:C	G296R	1.000
7:56058678:G:C	R315T	1.000
7:56058684:A:T	K317I	1.000
7:56051928:C:A	A27E	0.999
7:56051963:G:A	G39R	0.999
7:56051963:G:C	G39R	0.999
7:56051964:G:A	G39E	0.999
7:56051972:G:C	G42R	0.999
7:56051973:G:A	G42D	0.999
7:56051981:A:G	K45E	0.999
7:56051983:G:C	K45N	0.999
7:56051983:G:T	K45N	0.999
7:56052424:T:A	L47H	0.999
7:56052424:T:C	L47P	0.999
7:56052427:T:A	V48D	0.999
7:56052460:A:T	D59V	0.999
7:56052462:G:C	G60R	0.999
7:56052463:G:A	G60D	0.999
7:56052463:G:T	G60V	0.999
7:56052475:T:A	L64H	0.999
7:56052475:T:C	L64P	0.999
7:56054373:T:C	I69T	0.999
7:56054397:T:A	I77K	0.999
7:56054397:T:G	I77R	0.999
7:56054408:G:C	A81P	0.999
7:56054409:C:A	A81E	0.999
7:56054414:G:C	A83P	0.999

dbSNP variants (sampled 300 via entrez): RS1000246801 (7:56057178 T>C), RS1000925152 (7:56063059 G>A), RS1000975607 (7:56063258 T>A), RS1001134575 (7:56056969 G>A,T), RS1001406975 (7:56051585 G>A,C), RS1002419113 (7:56062239 A>G), RS1002468107 (7:56062523 CG>C,CGG), RS1003695123 (7:56050108 C>G), RS1004040483 (7:56055131 A>C,T), RS1004870974 (7:56063600 T>TA), RS1004983335 (7:56057442 T>C), RS1005128371 (7:56052015 C>T), RS1005223967 (7:56063361 CAT>C), RS1005330155 (7:56063814 C>A,T), RS1005532616 (7:56060410 G>T)

Disease associations

OMIM: gene MIM:104613 | disease phenotypes: MIM:614023, MIM:209850

GenCC curated gene-disease

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

Mondo (5): PSPH deficiency (MONDO:0013531), male infertility (MONDO:0005372), autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): 3-phosphoserine phosphatase deficiency, infantile/juvenile form (Orphanet:79350)

HPO phenotypes

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

HPO	Term
HP:0000717	Autism

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST006624_92	Systolic blood pressure	8.000000e-09
GCST007382_31	Plasma free amino acid levels (adjusted for twenty other PFAAs)	1.000000e-24
GCST007385_14	Plasma free amino acid levels	2.000000e-21
GCST007876_103	Estimated glomerular filtration rate	1.000000e-08
GCST010866_124	Coronary artery disease	4.000000e-09
GCST012227_120	Hip circumference adjusted for BMI	6.000000e-09
GCST012251_16	Macular telangiectasia type 2	3.000000e-07
GCST012252_7	Macular telangiectasia type 2	6.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005134	amino acid measurement
EFO:0009774	serine measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:1002009	macular telangiectasia type 2

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066279 (SINGLE PROTEIN)

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

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
6.17	Kd	676.5	nM	CHEMBL5653589
6.17	ED50	676.5	nM	CHEMBL5653589
5.26	Kd	5444	nM	CHEMBL3752910
5.26	ED50	5444	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148024: Binding affinity to human CCT6A incubated for 45 mins by Kinobead based pull down assay	kd	0.6765	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148024: Binding affinity to human CCT6A incubated for 45 mins by Kinobead based pull down assay	kd	5.4439	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
sodium arsenite	decreases expression	2
Lead	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CD 437	decreases expression	1
deguelin	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
bromovanin	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Irinotecan	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651066	Binding	Binding affinity to human CCT6A 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)

504 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,
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
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