TCP1

Chr 6

t-complex 1

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

NCBI Gene: 6950 ENSG00000120438 UniProt: P17987

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— TCP1

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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.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 79 VUS of 110 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.60Z-score

OE missense 0.74 (0.67–0.83)

228 obs / 307.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.26)

0≤0.351.4

Missense OE?0.74 (0.67–0.83)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 2 / 24.7Missense obs/exp: 228 / 307.2Syn Z: -0.94

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic1

VUS79

Likely Benign7

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	4	1	0	5
Likely Pathogenic	1	0	0	1
VUS	4	75	0	79
Likely Benign	0	6	1	7
Benign	0	0	1	1
Total	9	82	2	93

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap TCP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →