CCT5

Chr 5AR

chaperonin containing TCP1 subunit 5

Also known as: CCT-epsilon, CCTE, HEL-S-69, HSNSP, PNAS-102, TCP-1-epsilon

NCBI Gene: 22948ENSG00000150753UniProt: P48643

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]

Primary Disease Associations & Inheritance

?Neuropathy, hereditary sensory, with spastic paraplegiaMIM #256840
AR
480
ClinVar variants
99
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CCT5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 200 VUS of 480 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 0.999
Z-score 4.48
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.47Z-score
OE missense 0.77 (0.69–0.85)
239 obs / 312.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 1 / 25.3Missense obs/exp: 239 / 312.4Syn Z: -0.49

ClinVar Variant Classifications

480 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic98
Likely Pathogenic1
VUS200
Likely Benign107
Benign66
Conflicting8
98
Pathogenic
1
Likely Pathogenic
200
VUS
107
Likely Benign
66
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
98
0
98
Likely Pathogenic
0
1
0
0
1
VUS
3
140
55
2
200
Likely Benign
0
3
47
57
107
Benign
0
2
59
5
66
Conflicting
—8
Total314625964480

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCT5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CCT5-related neurodevelopmental disorder with brain abnormalities

limited
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Neuropathy, hereditary sensory, with spastic paraplegia

MIM #256840

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Increased CCT5 expression is a potential unfavourable factor promoting the growth of nasopharyngeal carcinoma.
Wu S et al.·J Int Med Res
2024
Bridging human chaperonopathies and microbial chaperonins.
Conway de Macario E et al.·Commun Biol
2019Review
ANKRD55 is a key regulator of T cell inflammation in multiple sclerosis.
Wu C et al.·J Clin Invest
2025
Biochemical characterization of mutants in chaperonin proteins CCT4 and CCT5 associated with hereditary sensory neuropathy.
Sergeeva OA et al.·J Biol Chem
2014
A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy.
Antona V et al.·Int J Mol Sci
2020Case report
Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome.
Wang Y et al.·Sci Rep
2025
Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.
Peters MJ et al.·Ann Rheum Dis
2013Meta-analysis
Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies.
Macario AJ et al.·J Pathol
2020Review
Whole Exome Sequencing in 26 Saudi Patients Expands the Mutational and Clinical Spectrum of Diabetic Nephropathy.
Elfaki I et al.·Medicina (Kaunas)
2025Cohort
TMEM106C, BSG, COPE, CDCA8, KPNA2, LIG1, UQCRH, and CCT5: Predictive of Survival and Immunotherapy Resistance in Hepatocellular Carcinoma.
Yu K et al.·Hum Mutat
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools