CCT2

protein-coding

chaperonin containing TCP1 subunit 2, the group of Chaperonins

Gene summary

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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

MANE transcript

NM_006431.3

Inheritance

ClinVar variants

P:2U:230B:86

Top phenotype

Leber congenital amaurosis

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr12:69,585,426-69,601,570

External References & Databases

Ensembl (ENSG00000166226)

Transcript & Mutation Effects

hg38 • Region Span ~16.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Leber congenital amaurosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0018998

Submitter: Franklin by Genoox

Compound heterozygous mutation of CCT2 was found to be associated with Leber Congenital Amaurosis in a Chinese family https://doi.org/10.1038/srep33742

Leber congenital amaurosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018998

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCT2 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 377

not specifiedTotal: 69

Retinal dystrophyTotal: 3

Leber congenital amaurosisTotal: 2

CCT2-related conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006431.3. 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				84 clinvar	1 clinvar	85
missense		2 clinvar	215 clinvar	1 clinvar		218
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	2	230	85	1	318

Highest pathogenic variant AF is 0.0000027379933

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006431.3	RefSeq	NP_006422.1	16	MANE Select
ENST00000299300.11	Ensembl	ENSP00000299300.6	16	MANE Select
NM_001198842.2	RefSeq	NP_001185771.1	14	Standard
ENST00000543146.2	Ensembl	ENSP00000445471.2	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cct2	Danio rerio	Structure: skeletal muscle cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

cct2

Danio rerio

Structure: skeletal muscle cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
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

Biological Process

protein folding
binding of sperm to zona pellucida
positive regulation of telomere maintenance via telomerase
neutrophil degranulation
protein stabilization

Molecular Function

protein binding
ATP binding
ubiquitin protein ligase binding
protein folding chaperone
unfolded protein binding

Cellular Component

zona pellucida receptor complex
extracellular region
cytosol
chaperonin-containing T-complex
microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299300
Coding exons: 16
Length: 16237
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125744
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	226	298	0.759	0.0000151	3503
Missense (PolyPhen)		36	95.194	0.37818		1218
Synonymous	0.0724	97	97.9	0.991	0.00000500	1054
Loss of Function	4.54	2	27.8	0.0719	0.00000146	349

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
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). 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 (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000305}.;

Recessive Scores

pRec: 0.506

Intolerance Scores

LoFtool: 0.361
RVIS EVS: -0.63
RVIS percentile EVS: 17.03

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.876

Gene Damage Prediction

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