TCP1

Summary

TCP1 (t-complex 1, HGNC:11655) is a protein-coding gene on chromosome 6q25.3, encoding T-complex protein 1 subunit alpha (P17987). Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis. It is a common-essential gene (DepMap: required in 99.9% 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, three pseudogenes that appear to be derived from this gene have been found.

Source: NCBI Gene 6950 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 90 total — 5 pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_030752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11655
Approved symbol	TCP1
Name	t-complex 1
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	D6S230E, CCT1, Ccta
Ensembl gene	ENSG00000120438
Ensembl biotype	protein_coding
OMIM	186980
Entrez	6950

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000321394, ENST00000392168, ENST00000420894, ENST00000467544, ENST00000536394, ENST00000536607, ENST00000536807, ENST00000537390, ENST00000538128, ENST00000538530, ENST00000539756, ENST00000539948, ENST00000543517, ENST00000543532, ENST00000544255, ENST00000545764, ENST00000546023, ENST00000546204, ENST00000869774, ENST00000869775, ENST00000934596, ENST00000934597, ENST00000934598

RefSeq mRNA: 2 — MANE Select: NM_030752 NM_001008897, NM_030752

CCDS: CCDS43522, CCDS5269

Canonical transcript exons

ENST00000321394 — 12 exons

Exon	Start	End
ENSE00000765649	159779627	159779790
ENSE00000765650	159779895	159780087
ENSE00000765651	159780443	159780566
ENSE00000765653	159780935	159781110
ENSE00001840956	159778498	159779261
ENSE00002292808	159789405	159789602
ENSE00003488228	159785900	159785997
ENSE00003510682	159787743	159787871
ENSE00003543145	159785386	159785496
ENSE00003582699	159788058	159788143
ENSE00003592754	159783941	159784067
ENSE00003615444	159784666	159784847

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.4512 / max 864.2320, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76537	70.9739	1824
76538	16.4336	1795
76539	2.7316	1404
76536	0.3121	149

Top tissues by expression

288 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	99.59	gold quality
cortical plate	UBERON:0005343	99.36	gold quality
ganglionic eminence	UBERON:0004023	99.26	gold quality
left testis	UBERON:0004533	98.91	gold quality
right testis	UBERON:0004534	98.90	gold quality
adrenal tissue	UBERON:0018303	98.78	gold quality
ventricular zone	UBERON:0003053	98.72	gold quality
left ovary	UBERON:0002119	98.59	gold quality
mucosa of stomach	UBERON:0001199	98.43	gold quality
body of pancreas	UBERON:0001150	98.42	gold quality
right ovary	UBERON:0002118	98.42	gold quality
skin of abdomen	UBERON:0001416	98.38	gold quality
body of uterus	UBERON:0009853	98.35	gold quality
rectum	UBERON:0001052	98.33	gold quality
left uterine tube	UBERON:0001303	98.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.28	gold quality
transverse colon	UBERON:0001157	98.25	gold quality
skin of leg	UBERON:0001511	98.24	gold quality
minor salivary gland	UBERON:0001830	98.19	gold quality
omental fat pad	UBERON:0010414	98.19	gold quality
peritoneum	UBERON:0002358	98.15	gold quality
tibial artery	UBERON:0007610	98.15	gold quality
stromal cell of endometrium	CL:0002255	98.14	gold quality
popliteal artery	UBERON:0002250	98.14	gold quality
mucosa of transverse colon	UBERON:0004991	98.12	gold quality
calcaneal tendon	UBERON:0003701	98.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.09	gold quality
endocervix	UBERON:0000458	98.08	gold quality
metanephros cortex	UBERON:0010533	98.06	gold quality
lower esophagus	UBERON:0013473	98.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	19.80
E-MTAB-10137	no	934.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF143, ZNF76

miRNA regulators (miRDB)

40 targeting TCP1, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
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-10522-5P	99.26	68.50	2087
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-3916	98.99	68.04	2155

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 39)

• a paper describing a pathway in which this gene product functions (PMID:10353914)
• a paper describing a pathway in which this gene product functions (PMID:10524223)
• Expression patterns of chaperone proteins in cerebral cortex of the fetus with Down syndrome: dysregulation of T-complex protein 1. (PMID:11771755)
• TRiC chaperonin binds to HIF prolyl hydroxylase PHD3 (PMID:15251459)
• the strong inhibitory action of PhLP(S) on Gbetagamma signaling is the result of a previously unrecognized mechanism of Gbetagamma-regulation, inhibition of Gbetagamma-folding by interference with TCP-1alpha (PMID:15745879)
• Data show that Plk1 associates with chaperonin-containing TCP1 complex (CCT) both in vitro and in vivo. (PMID:15923617)
• a paper describing a pathway in which this gene product functions (PMID:1630491)
• The specific and directed rearrangement of the beta-actin structure, seen in the natural beta-actin-TRiC system, is vital for guiding beta-actin to the native state. (PMID:17939680)
• a paper describing a pathway in which this gene product functions (PMID:1901944)
• the membrane binding domain of CTP:phosphocholine cytidylyltransferase has a role in alveolar type II cells (PMID:19684306)
• Data suggest that specific molecular mediators involved in glucocerebrosidase maturation and degradation, and abnormal interaction with TCP1 and c-Cbl, could be responsible for phenotypic variation among patients with the same genotypes. (PMID:21098288)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• identified 6 of the 8 components of the chaperonin-containing TCP-1 (CCT) complex bound to LOX-1 cytoplasmic domain (PMID:24846140)
• CCT8 might be an oncogene and participate in HCC cell proliferation. (PMID:24862099)
• Changes for CRMP2, TCP1epsilon, TPM2 and 14-3-3gamma were confirmed in experimental tumors and in a series of 28 human SI-NETs. (PMID:25224486)
• A role for the TRiC subunits TCP1 and CCT2, and potentially the entire TRiC complex, in breast cancer. (PMID:25704758)
• Result suggest the positive correlation between purinergic receptor P2X 7 (P2X7R) and T-complex protein 1 (TCP-1) in lymphoma patients. (PMID:26556873)
• Data suggest that biosynthesis and folding of leukemogenic fusion oncoprotein AML1-ETO/RUNX1-RUNX1T1 is facilitated by interaction with the chaperonin TRiC/CCT1/TCP1 and HSP70 (heat shock protein 70). (PMID:26706127)
• chaperonin-containing TCP-1 complex required for lysosomal functioning and autophagosome degradation (PMID:27929117)
• Chaperonin CCT interferes with fibre assembly by interaction of its CCTzeta and CCTgamma subunits with the A53T central hydrophobic region. This interaction is specific to NAC conformation, as it is produced once soluble alpha-synuclein A53T oligomers form and blocks the reaction before fibres begin to grow. (PMID:28102321)
• TCP1alpha, essential for actin and tubulin folding, was directly bound by the DeltaN-HtrA3L/S but not cleaved. (PMID:29477555)
• Combined use of GM2AP and TCP1-eta urinary levels predicts recovery from intrinsic acute kidney injury. (PMID:32665654)
• TCP1 regulates Wnt7b/beta-catenin pathway through P53 to influence the proliferation and migration of hepatocellular carcinoma cells. (PMID:32843620)
• Native mass spectrometry analyses of chaperonin complex TRiC/CCT reveal subunit N-terminal processing and re-association patterns. (PMID:34158536)
• TCP1 regulates PI3K/AKT/mTOR signaling pathway to promote proliferation of ovarian cancer cells. (PMID:34162426)
• Low expression of TCP1 (T-Complex 1) and PSMC1 (Proteasome 26S subunit, ATPase 1) in heterotopic ossification during ankylosing spondylitis. (PMID:34612770)
• a paper describing a pathway in which this gene product functions (PMID:3653076)
• [The Effect of TCP1 Expression on the Proliferation and the Accumulation of Intracellular Drug of HL60/A and HL60 Cell and Its Mechanism]. (PMID:38387902)
• METTL14-mediated N6-methyladenosine modification of TCP1 mRNA promotes acute myeloid leukemia progression. (PMID:39033992)
• a paper describing a pathway in which this gene product functions (PMID:7615668)
• a paper describing a pathway in which this gene product functions (PMID:7904580)
• a paper describing a pathway in which this gene product functions (PMID:7908441)
• a paper describing a pathway in which this gene product functions (PMID:7916460)
• a paper describing a pathway in which this gene product functions (PMID:8098536)
• a paper describing a pathway in which this gene product functions (PMID:8633246)
• a paper describing a pathway in which this gene product functions (PMID:8718679)
• a paper describing a pathway in which this gene product functions (PMID:8733136)
• a paper describing a pathway in which this gene product functions (PMID:9189717)
• a paper describing a pathway in which this gene product functions (PMID:9337846)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcp1	ENSDARG00000017891
mus_musculus	Tcp1	ENSMUSG00000068039
rattus_norvegicus	Tcp1	ENSRNOG00000014160
drosophila_melanogaster	CCT1	FBGN0003676
caenorhabditis_elegans		WBGENE00000377

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), CCT7 (ENSG00000135624), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

T-complex protein 1 subunit alpha — P17987 (reviewed: P17987)

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

All UniProt accessions (11): P17987, E7EQR6, E7ERF2, F5GYL4, F5GZ03, F5GZI8, F5H136, F5H282, F5H676, F5H726, F5H7Y1

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 GBA1. Interacts with DLEC1.

Subcellular location. Cytoplasm. Cytosol. Cytoskeleton. Microtubule organizing center. Centrosome.

Disease relevance. Intellectual developmental disorder with polymicrogyria and seizures (IDDPMGS) [MIM:621021] An autosomal dominant neurologic disorder characterized by a broad phenotypic spectrum. Main clinical features are developmental delay of varying severity, intellectual disability, seizures, and polymicrogyria. Additional variable features are non-specific pyramidal or cerebellar signs, and visual impairment. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TCP-1 chaperonin family.

RefSeq proteins (2): NP_001008897, NP_110379* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002194	Chaperonin_TCP-1_CS	Conserved_site
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR012715	Chap_CCT_alpha	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 (88 total): strand 28, helix 26, binding site 14, modified residue 9, sequence variant 5, turn 3, sequence conflict 2, chain 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-P17987-F1	88.97	0.63

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 (14): 37; 92; 158; 159; 412; 505; 37; 88; 89; 89; 90; 90 …

Post-translational modifications (9): 1, 6, 181, 199, 400, 491, 494, 544, 551

Function

Pathways and Gene Ontology

Reactome pathways

19 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-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-1280215	Cytokine Signaling in 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-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 302 (showing top): GNF2_CKS1B, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_SINGLE_FERTILIZATION, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_SECRETORY_GRANULE, GCM_NPM1, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (9): protein folding (GO:0006457), tubulin complex assembly (GO:0007021), binding of sperm to zona pellucida (GO:0007339), positive regulation of telomere maintenance via telomerase (GO:0032212), protein stabilization (GO:0050821), scaRNA localization to Cajal body (GO:0090666), 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), ubiquitin protein ligase binding (GO:0031625), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (15): pericentriolar material (GO:0000242), heterochromatin (GO:0000792), acrosomal vesicle (GO:0001669), zona pellucida receptor complex (GO:0002199), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), chaperonin-containing T-complex (GO:0005832), microtubule (GO:0005874), cell body (GO:0044297), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), intracellular protein-containing complex (GO:0140535)

Reactome top-level categories

Rollup of top-12 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
Interleukin-12 signaling	1
Immune System	1
Protein folding	1
Metabolism of proteins	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
ATP-dependent activity	2
protein-containing complex	2
cytoplasm	2
microtubule cytoskeleton	2
cellular process	1
protein maturation	1
protein-containing complex assembly	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
RNA localization to Cajal body	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
ubiquitin-like protein ligase binding	1
molecular_function	1
protein folding	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
centrosome	1
chromatin	1
secretory granule	1
chaperonin-containing T-complex	1

Protein interactions and networks

STRING

5140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCP1	CCT4	P50991	980
TCP1	CCT3	P49368	965
TCP1	CCT8	P50990	954
TCP1	CCT5	P48643	929
TCP1	CCT2	P78371	917
TCP1	CCT6A	P40227	912
TCP1	Q12799	Q12799	851
TCP1	HSPD1	P10809	834
TCP1	CCT7	Q99832	824
TCP1	PDCL3	Q9H2J4	756
TCP1	HSP90AA1	P07900	745
TCP1	DYNLT2	Q8IZS6	744
TCP1	PFDN1	O60925	716
TCP1	ACAT2	Q9BWD1	698
TCP1	CFAP52	Q8N1V2	692

IntAct

626 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
TCP1	CCT2	psi-mi:“MI:0915”(physical association)	0.860
HDAC1	CDK2AP1	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
TCP1	CCT5	psi-mi:“MI:0915”(physical association)	0.740
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
WRAP53	TCP1	psi-mi:“MI:0914”(association)	0.690
TCP1	CCT4	psi-mi:“MI:0915”(physical association)	0.670
TCP1	CCT8	psi-mi:“MI:0915”(physical association)	0.670
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
TUBA1B	TXNDC9	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
TCP1	CBFA2T2	psi-mi:“MI:0915”(physical association)	0.560
CBFA2T2	TCP1	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

BioGRID (925): TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CBFA2T2 (Two-hybrid), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), TCP1 (Affinity Capture-MS)

ESM2 similar proteins: A0RXU1, A2C412, A2C794, A8WQQ5, A8X9U4, A9A5C9, B1ZS98, B4U8T3, C4YJQ8, G5EG59, O14460, O23755, O42872, O42894, O74918, O77264, P11983, P15112, P17987, P18279, P28480, P42943, P46948, P53256, P87153, Q05636, Q10205, Q17533, Q1MPL7, Q23716, Q2NKZ1, Q32L40, Q46JM7, Q4R5G2, Q54ER7, Q5A0M4, Q5ZJK8, Q6BJ25, Q6MJR9, Q6P0I8

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

3 interactions.

A	Effect	B	Mechanism
ZNF143	“up-regulates quantity by expression”	TCP1	“transcriptional regulation”
ZNF76	“up-regulates quantity by expression”	TCP1	“transcriptional regulation”
TCP1	“form complex”	TRiC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 237 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	31.0×	4e-12
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	11	29.9×	5e-12
Prefoldin mediated transfer of substrate to CCT/TriC	11	28.9×	5e-12
BBSome-mediated cargo-targeting to cilium	8	26.5×	3e-08
Chaperonin-mediated protein folding	12	24.0×	5e-12
Cargo trafficking to the periciliary membrane	13	21.5×	4e-12
Association of TriC/CCT with target proteins during biosynthesis	11	21.5×	2e-10
Protein folding	12	20.8×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	9	34.0×	1e-09
chaperone-mediated protein complex assembly	6	21.7×	4e-05
binding of sperm to zona pellucida	6	13.0×	8e-04
mitotic spindle organization	7	9.8×	9e-04
mitotic cell cycle	13	9.0×	8e-07
JNK cascade	6	8.4×	7e-03
microtubule cytoskeleton organization	13	8.1×	2e-06
protein folding	12	6.4×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3544396	NM_030752.3(TCP1):c.583_584del (p.Ser194_Val195insTer)	Pathogenic
3544397	NM_030752.3(TCP1):c.252_255del (p.Glu85fs)	Pathogenic
3544398	NM_030752.3(TCP1):c.1502dup (p.Gly502fs)	Pathogenic
3544399	NM_030752.3(TCP1):c.793_796del (p.Gln265fs)	Pathogenic
4282422	NM_030752.3(TCP1):c.476A>G (p.Lys159Arg)	Pathogenic

SpliceAI

1464 predictions. Top by Δscore:

Variant	Effect	Δscore
6:159779257:CAATC:C	acceptor_gain	1.0000
6:159779621:GCTTA:G	donor_loss	1.0000
6:159779622:CTTAC:C	donor_loss	1.0000
6:159779623:TTAC:T	donor_loss	1.0000
6:159779624:TA:T	donor_loss	1.0000
6:159779625:A:AC	donor_gain	1.0000
6:159779625:ACC:A	donor_loss	1.0000
6:159779626:C:CA	donor_loss	1.0000
6:159779626:C:CC	donor_gain	1.0000
6:159779626:CCA:C	donor_gain	1.0000
6:159779786:GACCC:G	acceptor_gain	1.0000
6:159779787:ACCC:A	acceptor_gain	1.0000
6:159779788:CCC:C	acceptor_gain	1.0000
6:159779788:CCCC:C	acceptor_gain	1.0000
6:159779789:CC:C	acceptor_gain	1.0000
6:159779789:CCC:C	acceptor_gain	1.0000
6:159779790:CC:C	acceptor_gain	1.0000
6:159779791:C:CC	acceptor_gain	1.0000
6:159779792:T:C	acceptor_loss	1.0000
6:159780088:C:CC	acceptor_gain	1.0000
6:159780436:CTCTT:C	donor_loss	1.0000
6:159780437:TCTTA:T	donor_loss	1.0000
6:159780438:CTTAC:C	donor_loss	1.0000
6:159780439:TTACT:T	donor_loss	1.0000
6:159780440:TACT:T	donor_loss	1.0000
6:159780441:A:AC	donor_gain	1.0000
6:159780442:C:CC	donor_gain	1.0000
6:159780442:CTT:C	donor_gain	1.0000
6:159780547:C:CT	acceptor_gain	1.0000
6:159780563:GTTG:G	acceptor_gain	1.0000

AlphaMissense

3654 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:159779139:C:G	R526P	1.000
6:159779155:C:G	A521P	1.000
6:159779158:C:G	A520P	1.000
6:159779166:G:T	A517E	1.000
6:159779715:C:G	A456P	1.000
6:159785398:T:A	K159I	1.000
6:159785492:C:G	A128P	1.000
6:159785906:G:T	A124D	1.000
6:159785918:C:T	G120D	1.000
6:159785940:G:C	H113D	1.000
6:159785975:A:G	L101P	1.000
6:159785978:A:G	L100P	1.000
6:159787756:C:A	G89V	1.000
6:159787756:C:T	G89E	1.000
6:159787757:C:G	G89R	1.000
6:159787757:C:T	G89R	1.000
6:159787758:A:C	D88E	1.000
6:159787758:A:T	D88E	1.000
6:159787759:T:A	D88V	1.000
6:159787760:C:G	D88H	1.000
6:159787762:C:T	G87E	1.000
6:159787786:G:T	A79D	1.000
6:159787837:A:G	L62P	1.000
6:159787849:C:T	G58D	1.000
6:159787850:C:G	G58R	1.000
6:159787851:A:C	D57E	1.000
6:159787851:A:T	D57E	1.000
6:159787852:T:A	D57V	1.000
6:159787852:T:C	D57G	1.000
6:159787852:T:G	D57A	1.000

dbSNP variants (sampled 300 via entrez): RS1000196918 (6:159786139 G>A), RS1000332075 (6:159786281 C>G,T), RS1000518769 (6:159789892 G>GT), RS1000545945 (6:159785159 TACTG>T), RS1000704230 (6:159786515 G>A), RS1000860197 (6:159790878 G>C), RS1001708806 (6:159787766 C>T), RS1001947512 (6:159781910 T>C), RS1001977996 (6:159789687 A>C), RS1002100347 (6:159784894 G>A), RS1002556045 (6:159784558 C>G), RS1002693876 (6:159789081 G>A), RS1002745988 (6:159788970 G>A,C,T), RS1002941285 (6:159778400 C>A,T), RS1003177683 (6:159783132 T>C)

Disease associations

OMIM: gene MIM:186980 | disease phenotypes: MIM:621021

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
intellectual developmental disorder with polymicrogyria and seizures	Strong	Autosomal dominant

Mondo (2): intellectual developmental disorder with polymicrogyria and seizures (MONDO:0976124), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000319	Smooth philtrum
HP:0000347	Micrognathia
HP:0000505	Visual impairment
HP:0000582	Upslanted palpebral fissure
HP:0000629	Periorbital fullness
HP:0000637	Long palpebral fissure
HP:0000678	Dental crowding
HP:0000750	Delayed speech and language development
HP:0000952	Jaundice
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001508	Failure to thrive
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002282	Gray matter heterotopia
HP:0002384	Focal impaired awareness seizure
HP:0002553	Highly arched eyebrow
HP:0007021	Pain insensitivity
HP:0007165	Periventricular heterotopia
HP:0007359	Focal-onset seizure
HP:0010546	Muscle fibrillation
HP:0010841	Multifocal epileptiform discharges

GWAS associations

0 associations (top):

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): CHEMBL6066167 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.63	Kd	23.41	nM	CHEMBL3752910
7.63	ED50	23.41	nM	CHEMBL3752910
7.09	Kd	81.99	nM	CHEMBL5653589
7.09	ED50	81.99	nM	CHEMBL5653589
5.72	IC50	1900	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149566: Binding affinity to human TCP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0234	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149566: Binding affinity to human TCP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0820	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178984: Inhibition of TCP1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, affects expression, increases expression, affects cotreatment	3
Tobacco Smoke Pollution	affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
Arsenic Trioxide	increases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Caffeine	affects phosphorylation, increases expression	2
Ivermectin	decreases expression, affects cotreatment, increases expression	2
Lead	affects splicing, increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Silicon Dioxide	affects expression, affects secretion	2
Cyclosporine	decreases expression	2
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
Okadaic Acid	increases expression	2
Particulate Matter	increases reaction, increases expression, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
lasiocarpine	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
bufalin	decreases expression	1
bleomycetin	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
dinophysistoxin 1	increases expression	1
chromium hexavalent ion	increases 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
CHEMBL5652608	Binding	Binding affinity to human TCP1 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