CCT7

protein-coding

chaperonin containing TCP1 subunit 7, the group of Chaperonins

Gene summary

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. [provided by RefSeq, Oct 2009]

MANE transcript

NM_006429.4

Inheritance

ClinVar variants

P:1U:67

Top phenotype

Myocardial infarction, susceptibility to, 1

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr2:73,233,420-73,253,021

External References & Databases

Ensembl (ENSG00000135624)

Transcript & Mutation Effects

hg38 • Region Span ~19.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: G2P

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCT7 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 1

Myocardial infarction, susceptibility to, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006429.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar			4
missense	1 clinvar		57 clinvar			58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	0	67	0	0	68

Highest pathogenic variant AF is 0.000017347988

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 75 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006429.4	RefSeq	NP_006420.1	12	MANE Select
ENST00000258091.10	Ensembl	ENSP00000258091.5	12	MANE Select
NM_001009570.3	RefSeq	NP_001009570.1	7	Standard
NM_001166284.2	RefSeq	NP_001159756.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cct7	Danio rerio	Structure: head Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

cct7

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
Metabolism of proteins
Chaperonin-mediated protein folding
Formation of tubulin folding intermediates by CCT/TriC
Association of TriC/CCT with target proteins during biosynthesis

Biological Process

protein folding
binding of sperm to zona pellucida
positive regulation of telomere maintenance via telomerase
protein stabilization
toxin transport

Molecular Function

protein binding
ATP binding
identical protein binding
unfolded protein binding

Cellular Component

cytoplasm
cytosol
chaperonin-containing T-complex
microtubule
cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258091
Coding exons: 12
Length: 19602
Individuals with no LoFs: 124795
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 124799
p: 0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.26	204	317	0.643	0.0000177	3555
Missense (PolyPhen)		41	73.83	0.55533		959
Synonymous	-0.326	123	118	1.04	0.00000655	1089
Loss of Function	4.15	3	25.7	0.117	0.00000131	303

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). The TRiC complex plays a role in the folding of actin and tubulin (Probable). {ECO:0000269|PubMed:25467444, ECO:0000305}.;

Recessive Scores

pRec: 0.229

Intolerance Scores

LoFtool: 0.447
RVIS EVS: -0.8
RVIS percentile EVS: 12.33

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.929

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium