CCT5

chaperonin containing TCP1 subunit 5, the group of Chaperonins

Basic information

Region (hg38): 5:10249928-10266389

Links

ENSG00000150753 ∙ NCBI:22948 ∙ OMIM:610150 ∙ HGNC:1618 ∙ Uniprot:P48643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary sensory and autonomic neuropathy with spastic paraplegia (Supportive), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy with spastic paraplegia (Limited), mode of inheritance: Unknown
• hereditary sensory and autonomic neuropathy with spastic paraplegia (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory, with spastic paraplegia	AR	General	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	Neurologic	16399879
Among other neurologic features, individuals can demonstrate insensitivity to pain, which can result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCT5 gene.

• Hereditary sensory and autonomic neuropathy with spastic paraplegia (232 variants)
• not provided (58 variants)
• Inborn genetic diseases (12 variants)
• Sensory Neuropathy with Spastic Paraplegia (7 variants)
• not specified (7 variants)
• Hereditary spastic paraplegia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCT5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	35	5	44
missense		1	84	2	2	89
nonsense						0
start loss			2			2
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	10		13
non coding			46	21	55	122
Total	0	1	136	58	62

Highest pathogenic variant AF is 0.00000657

Variants in CCT5

This is a list of pathogenic ClinVar variants found in the CCT5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-10250216-A-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jan 12, 2018)
5-10250229-G-A		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jan 12, 2018)
5-10250282-A-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jan 12, 2018)
5-10250285-C-T		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jan 12, 2018)
5-10250293-C-T		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jan 13, 2018)
5-10250318-G-A		Hereditary sensory and autonomic neuropathy with spastic paraplegia • not specified	Benign (Jul 14, 2021)
5-10250331-T-C		Hereditary sensory and autonomic neuropathy with spastic paraplegia • not specified	Benign (Jul 14, 2021)
5-10250341-A-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jan 08, 2024)
5-10250341-A-T		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (May 31, 2021)
5-10250342-T-G			Uncertain significance (Oct 13, 2017)
5-10250346-G-A		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Likely benign (Dec 22, 2023)
5-10250350-A-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Nov 30, 2021)
5-10250353-G-A		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Apr 10, 2023)
5-10250358-C-T		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Likely benign (Aug 21, 2023)
5-10250373-A-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Feb 01, 2022)
5-10250376-T-C		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Likely benign (Feb 21, 2021)
5-10250380-C-T		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jun 21, 2023)
5-10250388-C-T		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Likely benign (Nov 21, 2023)
5-10250397-C-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Aug 30, 2022)
5-10250425-A-C		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jul 04, 2021)
5-10250426-T-C		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Jul 19, 2023)
5-10250427-G-A		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Uncertain significance (Mar 08, 2023)
5-10250432-T-C		not specified	Uncertain significance (Sep 12, 2023)
5-10250439-C-G		Hereditary sensory and autonomic neuropathy with spastic paraplegia	Likely benign (Mar 15, 2022)
5-10250616-C-G			Benign (Jun 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCT5	protein_coding	protein_coding	ENST00000280326	11	16492

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000722	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.47	239	312	0.765	0.0000176	3590
Missense in Polyphen		60	113.4	0.52912		1389
Synonymous	-0.492	122	115	1.06	0.00000730	1043
Loss of Function	4.48	1	25.3	0.0395	0.00000144	293

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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;Protein folding;Prefoldin mediated transfer of substrate to CCT/TriC;Folding of actin by CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.350

Intolerance Scores

• loftool: 0.0744
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.813
• hipred: Y
• hipred_score: 0.748
• ghis: 0.659

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cct5

Zebrafish Information Network

• Gene name: cct5
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: protein folding;binding of sperm to zona pellucida;response to virus;positive regulation of telomere maintenance via telomerase;protein stabilization;toxin transport;positive regulation of establishment of protein localization to telomere;positive regulation of protein localization to Cajal body;positive regulation of telomerase RNA localization to Cajal body
• Cellular component: nucleolus;centrosome;cytosol;chaperonin-containing T-complex;microtubule;myelin sheath;cell body;extracellular exosome
• Molecular function: mRNA 3'-UTR binding;protein binding;ATP binding;G-protein beta-subunit binding;mRNA 5'-UTR binding;beta-tubulin binding;unfolded protein binding