TPT1

Chr 13

tumor protein, translationally-controlled 1

Also known as: HRF, TCTP, p02, p23

NCBI Gene: 7178 ENSG00000133112 UniProt: P13693

The protein encoded by this gene regulates cellular growth and proliferation, binds calcium, stabilizes microtubules, and acts as a negative regulator of apoptosis. Mutations cause autosomal dominant neurodegeneration with brain atrophy, characterized by progressive developmental regression, intellectual disability, and seizures with onset in infancy or early childhood. The gene is highly constrained against loss-of-function mutations, suggesting that haploinsufficiency may be poorly tolerated.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.805

Z-score 2.60

OE 0.10 (0.04–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.53Z-score

OE missense 0.56 (0.45–0.70)

53 obs / 94.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.48)

0≤0.351.4

Missense OE?0.56 (0.45–0.70)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 1 / 9.8Missense obs/exp: 53 / 94.8Syn Z: -1.33

Background carrier burden — how many people carry a rare variant somewhere in TPT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

223 rare PASS variants

Rare truncating (LoF)

1 in 960

48 rare PASS variants

Rare synonymous (reference)

1 in 840

122 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TPT1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 320	1 in 1,000
South Asian	~43k	1 in 290	1 in 600
Remaining (unassigned)	~30k	1 in 610	1 in 1,000
European (Finnish)	~27k	1 in 660	1 in 1,500
Admixed American	~22k	1 in 390	1 in 650
African / African American	~21k	1 in 460	1 in 680
East Asian	~20k	1 in 330	1 in 510
Ashkenazi Jewish	~13k	1 in 650	1 in 870
Middle Eastern	~2,884	≈ 1 in 700	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓