TP53BP1
tumor protein p53 binding protein 1, the group of Tudor domain containing
Basic information
Region (hg38): 15:43403061-43510728
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (123 variants)
- not_provided (14 variants)
- TP53BP1-related_disorder (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TP53BP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001141980.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | |||||
| missense | 115 | 12 | 129 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 0 | 0 | 117 | 15 | 6 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TP53BP1 | protein_coding | protein_coding | ENST00000382044 | 28 | 103520 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000146 | 125714 | 0 | 34 | 125748 | 0.000135 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.88 | 872 | 1.04e+3 | 0.836 | 0.0000532 | 12941 |
| Missense in Polyphen | 251 | 397.02 | 0.63221 | 4837 | ||
| Synonymous | -0.0585 | 380 | 379 | 1.00 | 0.0000192 | 3902 |
| Loss of Function | 7.40 | 15 | 91.3 | 0.164 | 0.00000511 | 1093 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000120 | 0.000120 |
| Ashkenazi Jewish | 0.000200 | 0.000198 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000185 | 0.000185 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- 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}.;
- Pathway
- 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;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;SUMOylation of transcription factors;Homology Directed Repair;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;SUMOylation;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Processing of DNA double-strand break ends;ATM pathway
(Consensus)
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- loftool
- 0.561
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 32.94
Haploinsufficiency Scores
- pHI
- 0.964
- hipred
- Y
- hipred_score
- 0.678
- ghis
- 0.550
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.684
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Trp53bp1
- Phenotype
- immune system phenotype; hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype;
Gene ontology
- 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;positive regulation of transcription by RNA polymerase II;positive regulation of DNA-binding transcription factor activity;protein homooligomerization;cellular response to X-ray;negative regulation of double-strand break repair via homologous recombination
- Cellular component
- condensed chromosome kinetochore;chromosome, telomeric region;nuclear chromosome, telomeric region;nucleus;nucleoplasm;replication fork;cytoplasm;nuclear body;site of double-strand break;DNA repair complex
- Molecular function
- RNA polymerase II activating transcription factor binding;p53 binding;damaged DNA binding;transcription coregulator activity;protein binding;methylated histone binding;telomeric DNA binding;histone binding;ubiquitin modification-dependent histone binding