TCP1

Chr 6AD

t-complex 1

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

The TCP1 protein is a molecular chaperone that forms part of the TRiC complex, which folds critical cellular proteins including actin and tubulin in an ATP-dependent manner. Mutations cause autosomal dominant intellectual developmental disorder with polymicrogyria and seizures. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.26), reflecting its essential cellular role.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.261 OMIM phenotype
Clinical SummaryTCP1
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 unique Pathogenic / Likely Pathogenic· 85 VUS of 138 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.995
Z-score 4.23
OE 0.08 (0.030.26)
Highly constrained

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

Missense Constraint
1.60Z-score
OE missense 0.74 (0.670.83)
228 obs / 307.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.26)
00.351.4
Missense OE0.74 (0.670.83)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 2 / 24.7Missense obs/exp: 228 / 307.2Syn Z: -0.94

ClinVar Variant Classifications

138 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic1
VUS85
Likely Benign7
Benign1
27
Pathogenic
1
Likely Pathogenic
85
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
22
0
27
Likely Pathogenic
0
0
1
0
1
VUS
4
75
6
0
85
Likely Benign
0
6
1
0
7
Benign
0
0
1
0
1
Total882310121

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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