GeneBe

CCT5

protein-coding

chaperonin containing TCP1 subunit 5, 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. Mutations in this gene cause hereditary sensory and autonomic neuropathy with spastic paraplegia (HSNSP). Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 13. [provided by RefSeq, Apr 2015]

MANE transcript

NM_012073.5

Inheritance

AD, AR

ClinVar variants

P:1U:154B:68

Top phenotype

Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr5:10,249,929-10,266,389

External References & Databases

Ensembl (ENSG00000150753)NCBI Gene (22948)OMIM (610150)HGNC:1618GenCCUniProt (P48643)AlphaFoldClinVar (CCT5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~16.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

hereditary sensory and autonomic neuropathy with spastic paraplegiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009748

Submitter: Orphanet

hereditary sensory and autonomic neuropathy with spastic paraplegiaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0009748

Submitter: Labcorp Genetics (formerly Invitae)

hereditary sensory and autonomic neuropathy with spastic paraplegiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009748

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessiveAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Among other neurologic features, individuals can demonstrate insensitivity to pain, which can result in injuries and infections

Refs: 16399879Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCT5 variants in ClinVar

5 Conditions Cataloged
Hereditary sensory and autonomic neuropathy with spastic paraplegiaTotal: 237
not specifiedTotal: 58
not providedTotal: 23
CCT5-related disorderTotal: 9
Hereditary spastic paraplegiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012073.5. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
61
clinvar
1
clinvar
 65
missense
1
clinvar
143
clinvar
5
clinvar
1
clinvar
 150
nonsense
0
start loss
3
clinvar
 3
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total01154662223

Highest pathogenic variant AF is 0.000008673521

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012073.5RefSeqNP_036205.111MANE Select
ENST00000280326.9EnsemblENSP00000280326.411MANE Select
NM_001306153.1RefSeqNP_001293082.111Standard
NM_001306154.2RefSeqNP_001293083.110Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
cct5Danio rerio

Structure: skeletal muscle cell

Quality: decreased amount

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
  • response to virus
  • positive regulation of telomere maintenance via telomerase
  • protein stabilization

Molecular Function

  • mRNA 3'-UTR binding
  • protein binding
  • ATP binding
  • G-protein beta-subunit binding
  • mRNA 5'-UTR binding

Cellular Component

  • nucleolus
  • centrosome
  • cytosol
  • chaperonin-containing T-complex
  • microtubule

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000280326
Coding exons
11
Length
16492
Individuals with no LoFs
125742
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
125748
p
0.0000239
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.472393120.7650.00001763590
Missense (PolyPhen)60113.40.529121389
Synonymous-0.4921221151.060.000007301043
Loss of Function4.48125.30.03950.00000144293

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000200.00020rare
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000270.000026rare
South Asian00.0absent
Other00.0absent

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}.;
Disease
DISEASE: Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessive (HSNSP) [MIM:256840]: A disease characterized by spastic paraplegia and progressive distal sensory neuropathy leading to mutilating ulcerations of the upper and lower limbs. {ECO:0000269|PubMed:16399879}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.350

Intolerance Scores

LoFtool
0.0744
RVIS EVS
-0.42
RVIS percentile EVS
25.56

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.990

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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