GeneBe

TCP1

t-complex 1, the group of Chaperonins|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 6:159778498-159789703

Links

ENSG00000120438 ∙ NCBI:6950 ∙ OMIM:186980 ∙ HGNC:11655 ∙ Uniprot:P17987 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • neurodevelopmental disorder (Strong), mode of inheritance: AD
  • intellectual developmental disorder with polymicrogyria and seizures (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder with polymicrogyria and seizuresADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic39480921

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCP1 gene.

  • not_specified (56 variants)
  • not_provided (4 variants)
  • Intellectual_developmental_disorder_with_polymicrogyria_and_seizures (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030752.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
0
missense
54
clinvar
3
clinvar
 57
nonsense
1
clinvar
 1
start loss
0
frameshift
4
clinvar
2
clinvar
 6
splice donor/acceptor (+/-2bp)
0
Total 4 0 57 3 0
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TCP1protein_codingprotein_codingENST00000321394 1211252
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.9950.004731257360111257470.0000437
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.602283070.7420.00001523649
Missense in Polyphen3291.910.348171180
Synonymous-0.9351171051.120.000005061110
Loss of Function4.23224.70.08110.00000123315

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.00009940.0000992
East Asian0.00005540.0000544
Finnish0.00004620.0000462
European (Non-Finnish)0.00006170.0000615
Middle Eastern0.00005540.0000544
South Asian0.000.00
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000305}.;
Pathway
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Metabolism of proteins;Chaperonin-mediated protein folding;Formation of tubulin folding intermediates by CCT/TriC;Association of TriC/CCT with target proteins during biosynthesis;Protein folding;Prefoldin mediated transfer of substrate to CCT/TriC;Folding of actin by CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

pRec
0.656

Intolerance Scores

loftool
0.301
rvis_EVS
-0.36
rvis_percentile_EVS
29.16

Haploinsufficiency Scores

pHI
0.359
hipred
Y
hipred_score
0.831
ghis
0.611

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.925

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tcp1
Phenotype

Zebrafish Information Network

Gene name
tcp1
Affected structure
skeletal muscle cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
protein folding;tubulin complex assembly;binding of sperm to zona pellucida;positive regulation of telomere maintenance via telomerase;interleukin-12-mediated signaling pathway;translocation of peptides or proteins into host cell cytoplasm;protein stabilization;positive regulation of telomerase activity;scaRNA localization to Cajal body;toxin transport;positive regulation of establishment of protein localization to telomere;positive regulation of protein localization to Cajal body;positive regulation of telomerase RNA localization to Cajal body;regulation of macrophage apoptotic process
Cellular component
pericentriolar material;acrosomal vesicle;zona pellucida receptor complex;nuclear heterochromatin;Golgi apparatus;centrosome;cytosol;chaperonin-containing T-complex;microtubule;myelin sheath;cell body;extracellular exosome
Molecular function
RNA binding;protein binding;ATP binding;ubiquitin protein ligase binding;unfolded protein binding