TCP1

protein-coding

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

Gene summary

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]

MANE transcript

NM_030752.3

Inheritance

ClinVar variants

P:6U:75B:4

Top phenotype

Intellectual developmental disorder with polymicrogyria and seizures

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr6:159,778,498-159,789,703

External References & Databases

Ensembl (ENSG00000120438)

Transcript & Mutation Effects

hg38 • Region Span ~11.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with polymicrogyria and seizuresSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0976124

Submitter: PanelApp Australia

intellectual developmental disorder with polymicrogyria and seizuresMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0976124

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder with polymicrogyria and seizuresAD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 39480921

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TCP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 12

Intellectual developmental disorder with polymicrogyria and seizuresTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030752.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	1 clinvar		68 clinvar	4 clinvar		73
nonsense			2 clinvar			2
start loss						0
frameshift	4 clinvar	1 clinvar	2 clinvar			7
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	5	1	75	4	0	85

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030752.3	RefSeq	NP_110379.2	12	MANE Select
ENST00000321394.12	Ensembl	ENSP00000317334.7	12	MANE Select
NM_001008897.2	RefSeq	NP_001008897.1	8	Standard
ENST00000392168.6	Ensembl	ENSP00000376008.2	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tcp1	Danio rerio	Structure: skeletal muscle cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

tcp1

Danio rerio

Structure: skeletal muscle cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

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

Molecular Function

RNA binding
protein binding
ATP binding
ubiquitin protein ligase binding
unfolded protein binding

Cellular Component

pericentriolar material
acrosomal vesicle
zona pellucida receptor complex
nuclear heterochromatin
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321394
Coding exons: 12
Length: 11252
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125747
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	228	307	0.742	0.0000152	3649
Missense (PolyPhen)		32	91.91	0.34817		1180
Synonymous	-0.935	117	105	1.12	0.00000506	1110
Loss of Function	4.23	2	24.7	0.0811	0.00000123	315

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.656

Intolerance Scores

LoFtool: 0.301
RVIS EVS: -0.36
RVIS percentile EVS: 29.16

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium