TEP1

protein-coding

telomerase associated protein 1, the group of WD repeat domain containing

Gene summary

This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

MANE transcript

NM_007110.5

Inheritance

ClinVar variants

U:430B:50

Top phenotype

TEP1-related condition

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr14:20,365,667-20,413,501

External References & Databases

Ensembl (ENSG00000129566)

Transcript & Mutation Effects

hg38 • Region Span ~47.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral palsyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0006497

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TEP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 429

not providedTotal: 26

TEP1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007110.5. 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			7 clinvar	6 clinvar	4 clinvar	17
missense			407 clinvar	33 clinvar	7 clinvar	447
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	430	39	11	480

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007110.5	RefSeq	NP_009041.2	54	MANE Select
ENST00000262715.10	Ensembl	ENSP00000262715.5	54	MANE Select
NM_001319035.2	RefSeq	NP_001305964.1	52	Standard
ENST00000471684.2	Ensembl	ENSP00000451919.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

telomeres telomerase cellular aging and immortality

Biological Process

telomere maintenance via recombination
RNA-dependent DNA biosynthetic process

Molecular Function

p53 binding
telomerase activity
RNA binding
ATP binding
enzyme binding

Cellular Component

chromosome, telomeric region
telomerase holoenzyme complex
cytoplasm
nuclear matrix
ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262715
Coding exons: 54
Length: 47763
Individuals with no LoFs: 125265
Homozygous LoFs: 4
Heterozygous LoFs: 479
Defined: 125748
p: 0.00192

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0789	1470	1.48e+3	0.994	0.0000875	16837
Missense (PolyPhen)		434	460.08	0.94331		5489
Synonymous	1.05	563	596	0.945	0.0000333	5546
Loss of Function	3.18	98	138	0.709	0.00000724	1485

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0030	notable
Latino/Admixed American	0.0024	0.0023	notable
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.0040	0.0035	notable
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.0040	0.0039	notable
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the telomerase ribonucleoprotein complex that is essential for the replication of chromosome termini (PubMed:19179534). Also component of the ribonucleoprotein vaults particle, a multi-subunit structure involved in nucleo-cytoplasmic transport (By similarity). Responsible for the localizing and stabilizing vault RNA (vRNA) association in the vault ribonucleoprotein particle. Binds to TERC (By similarity). {ECO:0000250|UniProtKB:P97499, ECO:0000269|PubMed:19179534}.;

Recessive Scores

pRec: 0.0972

Intolerance Scores

LoFtool: 0.920
RVIS EVS: 4.19
RVIS percentile EVS: 99.71

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.343

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High