TP53BP1

Chr 15

tumor protein p53 binding protein 1

Also known as: 53BP1, TDRD30, p202, p53BP1

NCBI Gene: 7158 ENSG00000067369 UniProt: Q12888

This gene encodes a protein that functions in the DNA double-strand break repair pathway choice, promoting non-homologous end joining (NHEJ) pathways, and limiting homologous recombination. This protein plays multiple roles in the DNA damage response, including promoting checkpoint signaling following DNA damage, acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin, and promoting NHEJ pathways by limiting end resection following a double-strand break. These roles are also important during V(D)J recombination, class switch recombination and at unprotected telomeres. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

Research

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

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 1.000

Z-score 7.40

OE 0.16 (0.11–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.88Z-score

OE missense 0.84 (0.79–0.88)

872 obs / 1042.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.11–0.25)

0≤0.351.4

Missense OE?0.84 (0.79–0.88)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 15 / 91.3Missense obs/exp: 872 / 1042.8Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in TP53BP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 33

2,338 rare PASS variants

Rare truncating (LoF)

1 in 1,100

143 rare PASS variants

Rare synonymous (reference)

1 in 70

918 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TP53BP1. 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 50	1 in 1,100
South Asian	~43k	1 in 31	1 in 2,100
Remaining (unassigned)	~30k	1 in 31	1 in 1,700
European (Finnish)	~27k	1 in 110	1 in 1,800
Admixed American	~22k	1 in 32	1 in 980
African / African American	~21k	1 in 24	1 in 1,200
East Asian	~20k	1 in 37	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 82	1 in 2,200
Middle Eastern	~2,884	1 in 35	none seen

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): 24 of 28 coding exons well covered in gnomAD exomes; exons 10, 13, 15, 25 marginal. Genomes: 27 of 28 (exon 13 below).? see exons ↓