CCT7

Summary

CCT7 (chaperonin containing TCP1 subunit 7, HGNC:1622) is a protein-coding gene on chromosome 2p13.2, encoding T-complex protein 1 subunit eta (Q99832). 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 92.5% of cancer cell lines).

This gene encodes 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. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 6.

Source: NCBI Gene 10574 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 79 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 92.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_006429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1622
Approved symbol	CCT7
Name	chaperonin containing TCP1 subunit 7
Location	2p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Ccth, Nip7-1
Ensembl gene	ENSG00000135624
Ensembl biotype	protein_coding
OMIM	605140
Entrez	10574

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 28 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000258091, ENST00000398422, ENST00000399032, ENST00000409924, ENST00000461290, ENST00000464397, ENST00000469844, ENST00000471927, ENST00000473197, ENST00000473786, ENST00000480489, ENST00000482064, ENST00000488856, ENST00000492253, ENST00000539919, ENST00000540468, ENST00000882897, ENST00000882898, ENST00000882899, ENST00000882900, ENST00000882901, ENST00000915137, ENST00000915138, ENST00000915139, ENST00000915140, ENST00000915141, ENST00000915142, ENST00000915143, ENST00000915144, ENST00000915145, ENST00000915146, ENST00000915147, ENST00000915148, ENST00000915149, ENST00000915150, ENST00000962765, ENST00000962766, ENST00000962767, ENST00000962768

RefSeq mRNA: 4 — MANE Select: NM_006429 NM_001009570, NM_001166284, NM_001166285, NM_006429

CCDS: CCDS42696, CCDS46336, CCDS54366, CCDS54367

Canonical transcript exons

ENST00000258091 — 12 exons

Exon	Start	End
ENSE00000920803	73249819	73249916
ENSE00000920804	73250306	73250438
ENSE00000920805	73251226	73251432
ENSE00003488195	73240437	73240543
ENSE00003516549	73244544	73244715
ENSE00003576094	73239643	73239796
ENSE00003584711	73243997	73244049
ENSE00003599902	73234308	73234384
ENSE00003636468	73248991	73249179
ENSE00003638328	73247762	73247926
ENSE00003675475	73243004	73243129
ENSE00003847914	73252640	73253005

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 122.9894 / max 1041.5104, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20947	117.6032	1827
20946	5.2523	1685
20945	0.0990	38
20944	0.0209	5
20943	0.0140	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.17	gold quality
ventricular zone	UBERON:0003053	99.06	gold quality
islet of Langerhans	UBERON:0000006	98.95	gold quality
left testis	UBERON:0004533	98.93	gold quality
right testis	UBERON:0004534	98.93	gold quality
cortical plate	UBERON:0005343	98.91	gold quality
right adrenal gland	UBERON:0001233	98.68	gold quality
right adrenal gland cortex	UBERON:0035827	98.64	gold quality
embryo	UBERON:0000922	98.55	gold quality
left adrenal gland	UBERON:0001234	98.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.44	gold quality
gastrocnemius	UBERON:0001388	98.41	gold quality
smooth muscle tissue	UBERON:0001135	98.38	gold quality
left adrenal gland cortex	UBERON:0035825	98.37	gold quality
muscle of leg	UBERON:0001383	98.34	gold quality
right ovary	UBERON:0002118	98.32	gold quality
adrenal gland	UBERON:0002369	98.32	gold quality
left ovary	UBERON:0002119	98.26	gold quality
rectum	UBERON:0001052	98.24	gold quality
left uterine tube	UBERON:0001303	98.23	gold quality
cerebellar hemisphere	UBERON:0002245	98.23	gold quality
body of uterus	UBERON:0009853	98.23	gold quality
cerebellar cortex	UBERON:0002129	98.22	gold quality
right uterine tube	UBERON:0001302	98.21	gold quality
apex of heart	UBERON:0002098	98.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.17	gold quality
stromal cell of endometrium	CL:0002255	98.16	gold quality
lower esophagus	UBERON:0013473	98.16	gold quality
adrenal tissue	UBERON:0018303	98.15	gold quality
adrenal cortex	UBERON:0001235	98.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	21.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting CCT7, 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-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-200C-5P	97.71	67.73	596
HSA-MIR-101-5P	96.84	65.66	649
HSA-MIR-3194-5P	96.80	64.90	1027

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Functional characterization of the CCT complex and its subunits in mouse. (PMID:11532003)
• A protein in mouse, that is highly similar to the one described in this record, was found to interact with a protein involved in the Nitric oxide (NO) signal transduction pathway, soluble guanylyl cyclase (sGC). (PMID:15347653)
• the increased expression of CCT-eta appears to be a marker for latent and active Dupuytren’s contracture and to be essential for the increased contractility exhibited by these fibroblasts (PMID:23292503)
• Overexpression of chaperonin containing TCP1 subunit 7 has diagnostic and prognostic value for hepatocellular carcinoma. (PMID:35073517)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cct7	ENSDARG00000007385
mus_musculus	Cct7	ENSMUSG00000030007
rattus_norvegicus	Cct7	ENSRNOG00000015630
drosophila_melanogaster	CCT7	FBGN0037632
caenorhabditis_elegans		WBGENE00020391

Paralogs (13): PIKFYVE (ENSG00000115020), CCT4 (ENSG00000115484), TCP1 (ENSG00000120438), MKKS (ENSG00000125863), CCT6B (ENSG00000132141), HSPD1 (ENSG00000144381), CCT6A (ENSG00000146731), CCT5 (ENSG00000150753), CCT8 (ENSG00000156261), CCT3 (ENSG00000163468), CCT2 (ENSG00000166226), BBS12 (ENSG00000181004), CCT8L2 (ENSG00000198445)

Protein

Protein identifiers

T-complex protein 1 subunit eta — Q99832 (reviewed: Q99832)

Alternative names: CCT-eta, Chaperonin containing T-complex polypeptide 1 subunit 7, HIV-1 Nef-interacting protein

All UniProt accessions (3): Q99832, F8WAM2, F8WBP8

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. Interacts with DLEC1.

Subcellular location. Cytoplasm.

Disease relevance. De novo genetic variants in nearly every subunit of the TRiC complex, including CCT7, 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 (4)

UniProt ID	Names	Canonical?
Q99832-1	1	yes
Q99832-2	2
Q99832-3	3
Q99832-4	4

RefSeq proteins (4): NP_001009570, NP_001159756, NP_001159757, NP_006420* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002194	Chaperonin_TCP-1_CS	Conserved_site
IPR002423	Cpn60/GroEL/TCP-1	Family
IPR012720	Chap_CCT_eta	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 (94 total): strand 26, helix 19, binding site 17, turn 9, sequence conflict 7, modified residue 6, splice variant 3, chain 2, sequence variant 2, initiator methionine 1, cross-link 1, region of interest 1

Structure

Experimental structures (PDB)

64 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-Q99832-F1	89.03	0.67

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

Functional residue map

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

Ligand- & substrate-binding residues (17): 95; 96; 96; 164; 165; 398; 409; 409; 494; 499; 499; 41 …

Post-translational modifications (7): 1, 67, 250, 320, 535, 430, 1

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-6814122	Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-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: 266 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_SINGLE_FERTILIZATION, GOBP_CHROMOSOME_ORGANIZATION, HORIUCHI_WTAP_TARGETS_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, CCAWYNNGAAR_UNKNOWN, MORF_UBE2I, MORF_HDAC1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (7): 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), protein refolding (GO:0042026)

GO Molecular Function (9): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), identical protein binding (GO:0042802), 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 (6): cytoplasm (GO:0005737), cytosol (GO:0005829), chaperonin-containing T-complex (GO:0005832), microtubule (GO:0005874), cell body (GO:0044297), 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	2
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
cellular anatomical structure	3
protein folding	2
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
protein binding	1
molecular_function	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

4854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCT7	CCT5	P48643	988
CCT7	CCT4	P50991	988
CCT7	CCT2	P78371	986
CCT7	CCT3	P49368	985
CCT7	CCT6A	P40227	936
CCT7	CCT8	P50990	927
CCT7	TCP1	P17987	824
CCT7	HSP90AA1	P07900	616
CCT7	CCNE1	P24864	608
CCT7	HSP90AB1	P08238	600
CCT7	HSPA8	P11142	595
CCT7	CCT6B	Q92526	555
CCT7	PFDN5	Q99471	536
CCT7	RPS2	P15880	535
CCT7	HSPA5	P11021	523

IntAct

588 interactions, top by confidence:

A	B	Type	Score
IGBP1	PPP6C	psi-mi:“MI:0914”(association)	0.940
PPP6C	ANKRD28	psi-mi:“MI:0914”(association)	0.870
CDK5	FIBP	psi-mi:“MI:0914”(association)	0.840
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
CCT7	ZNRD2	psi-mi:“MI:0915”(physical association)	0.830
WRAP53	DKC1	psi-mi:“MI:0914”(association)	0.830
CCT2	CCT7	psi-mi:“MI:0915”(physical association)	0.800
TUBG1	TUBG1	psi-mi:“MI:2364”(proximity)	0.760
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
DDB2	CCT2	psi-mi:“MI:0914”(association)	0.730
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
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
WDR25	CCT7	psi-mi:“MI:0915”(physical association)	0.560
NHLH1	CCT7	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
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
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
DCAF8	DCAF8L1	psi-mi:“MI:0914”(association)	0.530

BioGRID (940): CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Two-hybrid), CCT7 (Affinity Capture-RNA), CCT7 (Affinity Capture-RNA), CCT7 (Affinity Capture-RNA), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT7 (Affinity Capture-MS)

ESM2 similar proteins: A3M836, A8X6I9, B2HXB6, B7GY36, O00782, O15891, O74261, O94501, P11983, P12613, P17987, P18279, P19882, P26004, P28480, P28769, P29185, P29197, P39077, P41988, P42943, P47079, P50140, P54408, P54409, P78921, P80313, P87153, Q2NKZ1, Q32L40, Q37683, Q39727, Q43298, Q4R5G2, Q54ER7, Q54TH8, Q552J0, Q5R5C8, Q5ZJK8, Q84WV1

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CCT7	“form complex”	TRiC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 250 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	10	25.3×	1e-09
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	10	24.4×	1e-09
Prefoldin mediated transfer of substrate to CCT/TriC	10	23.6×	1e-09
Chaperonin-mediated protein folding	11	19.8×	1e-09
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	19.5×	1e-05
Transport of connexons to the plasma membrane	6	19.5×	1e-05
Protein folding	11	17.1×	4e-09
Gap junction trafficking and regulation	6	17.1×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	7	24.8×	5e-06
mitotic cell cycle	17	11.0×	3e-10
mitotic spindle organization	7	9.2×	1e-03
microtubule cytoskeleton organization	13	7.6×	8e-06
protein folding	10	5.0×	4e-03
protein stabilization	14	4.5×	5e-04
cilium assembly	12	4.3×	3e-03
cell division	19	4.2×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	55
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
65429	NM_006429.4(CCT7):c.1574C>T (p.Ser525Leu)	Pathogenic

SpliceAI

1700 predictions. Top by Δscore:

Variant	Effect	Δscore
2:73239641:A:AG	acceptor_gain	1.0000
2:73239642:G:A	acceptor_loss	1.0000
2:73239642:G:GT	acceptor_gain	1.0000
2:73239642:GC:G	acceptor_gain	1.0000
2:73239642:GCC:G	acceptor_gain	1.0000
2:73239642:GCCC:G	acceptor_gain	1.0000
2:73239794:GAG:G	donor_gain	1.0000
2:73239795:AGGTA:A	donor_loss	1.0000
2:73239796:GGTA:G	donor_loss	1.0000
2:73239797:GTAAG:G	donor_loss	1.0000
2:73239798:T:A	donor_loss	1.0000
2:73240435:A:G	acceptor_gain	1.0000
2:73242998:TTCCA:T	acceptor_loss	1.0000
2:73242999:TCCA:T	acceptor_loss	1.0000
2:73243000:CCA:C	acceptor_loss	1.0000
2:73243001:CA:C	acceptor_loss	1.0000
2:73243003:G:A	acceptor_loss	1.0000
2:73243126:GCTG:G	donor_gain	1.0000
2:73243130:G:GG	donor_gain	1.0000
2:73243130:GTAT:G	donor_loss	1.0000
2:73243131:T:A	donor_loss	1.0000
2:73243138:G:GG	donor_gain	1.0000
2:73243187:G:GT	donor_gain	1.0000
2:73244536:T:TA	acceptor_gain	1.0000
2:73244540:CCAG:C	acceptor_loss	1.0000
2:73244542:A:AG	acceptor_gain	1.0000
2:73244542:AG:A	acceptor_gain	1.0000
2:73244542:AGGG:A	acceptor_loss	1.0000
2:73244543:G:A	acceptor_loss	1.0000
2:73244543:G:GA	acceptor_gain	1.0000

AlphaMissense

3563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:73239757:G:C	G41R	1.000
2:73239758:G:A	G41D	1.000
2:73240458:A:C	D61A	1.000
2:73240458:A:T	D61V	1.000
2:73240459:T:A	D61E	1.000
2:73240459:T:G	D61E	1.000
2:73240460:G:T	G62W	1.000
2:73243010:G:C	D92H	1.000
2:73243011:A:C	D92A	1.000
2:73243011:A:T	D92V	1.000
2:73243012:T:A	D92E	1.000
2:73243012:T:G	D92E	1.000
2:73244595:G:C	K166N	1.000
2:73244595:G:T	K166N	1.000
2:73249012:G:C	A269P	1.000
2:73250407:A:C	D391A	1.000
2:73250407:A:T	D391V	1.000
2:73250408:T:A	D391E	1.000
2:73250408:T:G	D391E	1.000
2:73239711:C:A	N25K	0.999
2:73239711:C:G	N25K	0.999
2:73239721:T:C	C29R	0.999
2:73239723:C:G	C29W	0.999
2:73239757:G:T	G41C	0.999
2:73239758:G:T	G41V	0.999
2:73239766:G:C	G44R	0.999
2:73239767:G:A	G44D	0.999
2:73239772:G:C	D46H	0.999
2:73239779:T:C	L48P	0.999
2:73240452:C:T	S59F	0.999

dbSNP variants (sampled 300 via entrez): RS1000062074 (2:73238093 G>A), RS1000238228 (2:73237548 A>T), RS1000265149 (2:73243433 T>G), RS1000666126 (2:73236521 A>G,T), RS1000701721 (2:73236193 G>A,C,T), RS1000795536 (2:73249814 C>G,T), RS1001166269 (2:73241573 C>A,G,T), RS1001169692 (2:73250652 T>C), RS1001267651 (2:73241858 A>C), RS1001318097 (2:73234918 T>A,C), RS1001415975 (2:73248191 C>T), RS1001845787 (2:73248551 C>T), RS1001853713 (2:73253067 T>G), RS1002048491 (2:73244409 C>G), RS1002073161 (2:73235122 C>T)

Disease associations

OMIM: gene MIM:605140 | 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

1 associations (top):

Study	Trait	p-value
GCST006269_710	General cognitive ability	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

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): CHEMBL5725076 (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
6.93	Kd	117.4	nM	CHEMBL5653589
6.93	ED50	117.4	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 10 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148025: Binding affinity to human CCT7 incubated for 45 mins by Kinobead based pull down assay	kd	0.1174	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases abundance, increases expression	5
Smoke	decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
beta-N-methylamino-L-alanine	increases expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
dinophysistoxin 1	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Aminoglutethimide	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	affects expression, increases reaction	1
Benztropine	decreases expression	1
Cadmium	increases abundance, 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
CHEMBL5651067	Binding	Binding affinity to human CCT7 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)

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