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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCT5
chaperonin containing TCP1 subunit 5
Chromosome 5 · 5p15.2
NCBI Gene: 22948Ensembl: ENSG00000150753.12HGNC: HGNC:1618UniProt: B4DDU6
360PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of telomere maintenance via telomerasemRNA 3'-UTR bindingprotein bindingresponse to virushereditary sensory and autonomic neuropathy with spastic paraplegianeurodegenerative diseasealcohol drinkingeye injury
✦AI Summary

CCT5 (chaperonin containing TCP1 subunit 5) is a core component of the TRiC/CCT chaperonin complex, an eight-subunit molecular machine that facilitates ATP-dependent protein folding 1. Within TRiC, CCT5 assists in folding actin, tubulin, and other cytoplasmic proteins, and contributes to folding WRAP53/TCAB1 to regulate telomere maintenance 2. CCT5 forms part of the negatively charged hemisphere of the TRiC chamber and participates in hierarchical assembly of the complex 2. Loss-of-function mutations in CCT5 cause autosomal recessive hereditary sensory neuropathy with spastic paraplegia, a neurological disorder characterized by lower limb weakness and axonal degeneration 3. A His147Arg mutation in CCT5 impairs hexadecamer assembly and reduces ATPase activity, compromising the chaperone's protein homeostasis functions 4. Beyond neurological disease, CCT5 is upregulated in gastric cancer, where it promotes epithelial-mesenchymal transition and lymph node metastasis by binding E-cadherin and releasing β-catenin to activate Wnt signaling 5. Pan-cancer analysis reveals CCT5 overexpression correlates with poor prognosis across multiple tumor types, suggesting its potential as a biomarker and therapeutic target 6.

Sources cited
1
CCT5 is a subunit of the TRiC chaperonin complex that forms biologically active homo-oligomers and participates in ATP-dependent protein folding
PMID: 23612981
2
CCT5 comprises the negatively charged hemisphere of the TRiC chamber and participates in hierarchical assembly pathway of the complex
PMID: 37625406
3
CCT5 mutations cause hereditary spastic paraplegia with sensory neuropathy characterized by axonal degeneration
PMID: 23897027
4
His147Arg mutation in CCT5 impairs oligomeric assembly, ATPase activity, and protein homeostasis functions
PMID: 25345891
5
CCT5 is upregulated in gastric cancer lymph node metastases and promotes EMT by binding E-cadherin and activating Wnt/β-catenin signaling
PMID: 35194191
6
Pan-cancer analysis reveals CCT5 overexpression correlates with poor prognosis and serves as potential biomarker across multiple tumor types
PMID: 40274875
Disease Associationsⓘ21
hereditary sensory and autonomic neuropathy with spastic paraplegiaOpen Targets
0.54Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
alcohol drinkingOpen Targets
0.19Weak
eye injuryOpen Targets
0.19Weak
ovarian dysfunctionOpen Targets
0.18Weak
esophageal ulcerOpen Targets
0.17Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.17Weak
cornea transplantationOpen Targets
0.15Weak
glomerulonephritisOpen Targets
0.12Weak
hereditary spastic paraplegiaOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.07Suggestive
gastrointestinal diseaseOpen Targets
0.07Suggestive
Genu valgumOpen Targets
0.06Suggestive
Genu varumOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.04Suggestive
Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessiveUniProt
Pathogenic Variants1
NM_012073.5(CCT5):c.670C>G (p.Leu224Val)Likely pathogenic
Hereditary sensory and autonomic neuropathy with spastic paraplegia|not provided
★☆☆☆2022→ Residue 224
View on ClinVar ↗
Related Genes
CDC20Protein interaction100%PDCLProtein interaction100%PFDN1Protein interaction100%PFDN2Protein interaction100%PFDN4Protein interaction100%PFDN5Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
47%
Lung
43%
Bone Marrow
43%
Liver
30%
Ovary
30%
Gene Interaction Network
Click a node to explore
CCT5CDC20PDCLPFDN1PFDN2PFDN4PFDN5
PROTEIN STRUCTURE
Preparing viewer…
PDB7NVL · 2.50 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.23Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.12 [0.06–0.23]
RankingsWhere CCT5 stands among ~20K protein-coding genes
  • #856of 20,598
    Most Researched360 · top 5%
  • #4,649of 5,498
    Most Pathogenic Variants1
  • #663of 17,882
    Most Constrained (LOEUF)0.23 · top 5%
Genes detectedCCT5
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis · 2022
1.00
2
CCT5 induces epithelial-mesenchymal transition to promote gastric cancer lymph node metastasis by activating the Wnt/β-catenin signalling pathway.
PMID: 35194191
Br J Cancer · 2022
0.90
3
Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
PMID: 23897027
Acta Neuropathol · 2013
0.80
4
Human CCT4 and CCT5 chaperonin subunits expressed in Escherichia coli form biologically active homo-oligomers.
PMID: 23612981
J Biol Chem · 2013
0.70
5
Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy.
PMID: 37237456
Biology (Basel) · 2023
0.64