TCP1

Chr 6AD

t-complex 1

Also known as: CCT-alpha, CCT1, CCTa, D6S230E, IDDPMGS, TCP-1-alpha

NCBI Gene: 6950ENSG00000120438UniProt: P17987

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. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, three pseudogenes that appear to be derived from this gene have been found. [provided by RefSeq, Jun 2010]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with polymicrogyria and seizuresMIM #621021
AD
136
ClinVar variants
28
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TCP1
⚡
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
28 Pathogenic / Likely Pathogenic· 84 VUS of 136 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.
0.26LOEUF
pLI 0.995
Z-score 4.23
OE 0.08 (0.03–0.26)
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.
1.60Z-score
OE missense 0.74 (0.67–0.83)
228 obs / 307.2 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.0.08 (0.03–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.67–0.83)
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.1.12
0≤1.21.6
LoF obs/exp: 2 / 24.7Missense obs/exp: 228 / 307.2Syn Z: -0.94

ClinVar Variant Classifications

136 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic1
VUS84
Likely Benign6
Benign1
27
Pathogenic
1
Likely Pathogenic
84
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
23
0
27
Likely Pathogenic
0
0
1
0
1
VUS
3
73
8
0
84
Likely Benign
0
5
1
0
6
Benign
0
0
1
0
1
Total679340119

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

View in ClinVar →

Protein Context — Lollipop Plot

TCP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TCP1-related neurodevelopmental disorder with polymicrogyria

moderate
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
frameshift variantstop gainedmissense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
T-COMPLEX 1; TCP1
MIM #186980 · *

Intellectual developmental disorder with polymicrogyria and seizures

MIM #621021

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Chaperonin-containing TCP1 subunit 6A inhibition via TRIM21-mediated K48-linked ubiquitination suppresses triple-negative breast cancer progression through the AKT signalling pathway.
Yang M et al.·Clin Transl Med
2024
ANKRD55 is a key regulator of T cell inflammation in multiple sclerosis.
Wu C et al.·J Clin Invest
2025
CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.
Yu SK et al.·J Transl Med
2024
Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer's disease: findings based on urine proteomics and machine learning.
Wang Y et al.·Alzheimers Res Ther
2023
METTL14-mediated N6-methyladenosine modification of TCP1 mRNA promotes acute myeloid leukemia progression.
Zhang M et al.·Cell Signal
2024
TCP1 regulates PI3K/AKT/mTOR signaling pathway to promote proliferation of ovarian cancer cells.
Weng H et al.·J Ovarian Res
2021
[The Expression and Clinical Significance of TCP1 in Newly Diagnosed Acute Myeloid Leukemia Patients].
Li JJ et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2025Cohort
CCT3 as a Diagnostic and Prognostic Biomarker in Cervical Cancer.
Li M et al.·Crit Rev Eukaryot Gene Expr
2023
Long-term outcome of peripheral T-cell lymphomas: Ten-year follow-up of the International Prospective T-cell Project.
Civallero M et al.·Br J Haematol
2024Natural history
Single-cell RNA-seq reveals breast cancer heterogeneity and identifies TCP1 as a therapeutic target in breast cancer.
Wu H et al.·PeerJ
2025
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