GeneBe

TP53BP1

protein-coding

tumor protein p53 binding protein 1, the group of Tudor domain containing

Gene summary

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]

MANE transcript

NM_001141980.3

Inheritance

—

ClinVar variants

U:153B:24

Top phenotype

TP53BP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr15:43,403,061-43,510,728

External References & Databases

Ensembl (ENSG00000067369)NCBI Gene (7158)OMIM (605230)HGNC:11999GenCCUniProt (Q12888)AlphaFoldClinVar (TP53BP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~107.7 kb
Loading mutation effect viewer...

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 TP53BP1 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 138
not providedTotal: 21
TP53BP1-related disorderTotal: 4
Developmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001141980.3. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
3
clinvar
4
clinvar
 9
missense
136
clinvar
14
clinvar
2
clinvar
 152
nonsense
3
clinvar
1
clinvar
 4
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
10
clinvar
 10
Total00153186177
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001141980.3RefSeqNP_001135452.128MANE Select
ENST00000382044.9EnsemblENSP00000371475.528MANE Select
NM_001141979.3RefSeqNP_001135451.128Standard
NM_001355001.2RefSeqNP_001341930.115Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • NOD-like receptor signaling pathway - Homo sapiens (human)
  • ATM Signaling Pathway
  • ATM Signaling Network in Development and Disease
  • HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
  • DNA Repair

Biological Process

  • DNA damage checkpoint
  • double-strand break repair via nonhomologous end joining
  • cellular response to DNA damage stimulus
  • positive regulation of isotype switching
  • positive regulation of transcription, DNA-templated

Molecular Function

  • RNA polymerase II activating transcription factor binding
  • p53 binding
  • damaged DNA binding
  • transcription coregulator activity
  • protein binding

Cellular Component

  • condensed chromosome kinetochore
  • chromosome, telomeric region
  • nuclear chromosome, telomeric region
  • nucleus
  • nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000382044
Coding exons
28
Length
103520
Individuals with no LoFs
125714
Homozygous LoFs
0
Heterozygous LoFs
34
Defined
125748
p
0.000135
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.888721.04e+30.8360.000053212941
Missense (PolyPhen)251397.020.632214837
Synonymous-0.05853803791.000.00001923902
Loss of Function7.401591.30.1640.000005111093

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.000200.00020rare
East Asian0.0000540.000054rare
Finnish0.000180.00018rare
European (Non-Finnish)0.000190.00018rare
South Asian0.0000650.000065rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:22553214, PubMed:23333306, PubMed:17190600, PubMed:21144835, PubMed:28241136). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23727112, PubMed:23333306). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:23760478, PubMed:28241136, PubMed:17190600). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates to the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:28241136}.;
Disease
DISEASE: Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein. {ECO:0000269|PubMed:15492236}.;

Recessive Scores

pRec
0.106

Intolerance Scores

LoFtool
0.561
RVIS EVS
-0.29
RVIS percentile EVS
32.94

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.684

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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