TPT1

protein-coding

tumor protein, translationally-controlled 1, the group of Small nucleolar RNA protein coding host genes

Gene summary

This gene encodes a protein that is a regulator of cellular growth and proliferation. Its mRNA is highly structured and contains an oligopyrimidine tract (5'-TOP) in its 5' untranslated region that functions to repress its translation under quiescent conditions. The encoded protein is involved in a variety of cellular pathways, including apoptosis, protein synthesis and cell division. It binds to and stabilizes microtubules, and removal of this protein through phosphorylation is required for progression through mitotic and meiotic cell divisions. This gene is known to play a role in carcinogenesis, and is upregulated in some cancer cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

MANE transcript

NM_003295.4

Inheritance

—

ClinVar variants

U:8B:2

Top phenotype

Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr13:45,333,471-45,341,284

External References & Databases

Ensembl (ENSG00000133112)

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TPT1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 8

Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10Total: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003295.4. 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					1 clinvar	1
missense			7 clinvar		1 clinvar	8
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	8	0	2	10

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 88 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003295.4	RefSeq	NP_003286.1	6	MANE Select
ENST00000530705.6	Ensembl	ENSP00000431872.2	6	MANE Select
NM_001286272.2	RefSeq	NP_001273201.1	6	Standard
NM_001286273.2	RefSeq	NP_001273202.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PLK1 signaling events

Biological Process

calcium ion transport
cellular calcium ion homeostasis
response to virus
regulation of apoptotic process
negative regulation of apoptotic process

Molecular Function

RNA binding
calcium ion binding
protein binding

Cellular Component

spindle pole
extracellular space
nucleus
cytoplasm
multivesicular body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000530705
Coding exons: 5
Length: 4498
Individuals with no LoFs: 125578
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125580
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.53	53	94.8	0.559	0.00000433	1163
Missense (PolyPhen)		2	10.073	0.19855		169
Synonymous	-1.33	41	31.5	1.30	0.00000143	289
Loss of Function	2.60	1	9.77	0.102	4.93e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in calcium binding and microtubule stabilization.;

Recessive Scores

pRec: 0.350

Intolerance Scores

LoFtool: 0.749
RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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