CCT3

Chr 1AD

chaperonin containing TCP1 subunit 3

Also known as: CCT-gamma, CCTG, NEDSVH, PIG48, TCP-1-gamma, TRIC5

NCBI Gene: 7203 ENSG00000163468 UniProt: P49368 OMIM: 600114

CCT3 encodes a component of the chaperonin-containing T-complex (TRiC), a molecular chaperone that assists ATP-dependent folding of actin, tubulin, and other proteins essential for cellular function. Mutations cause autosomal dominant neurodevelopmental disorder with speech or visual impairment and brain hypomyelination. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.097), indicating intolerance to protein disruption.

OMIM 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 have been characterized for this gene. In addition, a pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.101 OMIM phenotype

Clinical Summary— CCT3

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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

2 unique Pathogenic / Likely Pathogenic· 66 VUS of 106 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 5.13

OE 0.00 (0.00–0.10)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.16Z-score

OE missense 0.82 (0.74–0.91)

276 obs / 335.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.82 (0.74–0.91)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 0 / 30.7Missense obs/exp: 276 / 335.8Syn Z: 0.46

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateCCT3-related neurodevelopmental disorder with hypomyelination of white matterLOFAD

This gene — mechanism propensity

0.3991th %ile

GOF

0.3690th %ile

LOF

0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.10

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS66

Likely Benign3

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	5	61	0	0	66
Likely Benign	0	2	0	1	3
Benign	0	0	1	0	1
Total	7	63	1	1	72

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap CCT3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →