TP53BP1

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

Basic information

Region (hg38): 15:43403060-43510728

Links

ENSG00000067369 ∙ NCBI:7158 ∙ OMIM:605230 ∙ HGNC:11999 ∙ Uniprot:Q12888 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TP53BP1 gene.

• not provided (3 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	5	7
missense			71	7	3	81
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding	3	1	31	32	2	69
Total	3	1	102	41	10

Highest pathogenic variant AF is 0.00000657

Variants in TP53BP1

This is a list of pathogenic ClinVar variants found in the TP53BP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-43403665-A-C			Likely benign (Feb 15, 2022)
15-43403665-A-G			Likely benign (Sep 19, 2023)
15-43403665-ACT-A			Uncertain significance (Mar 09, 2022)
15-43403666-C-G			Uncertain significance (Nov 03, 2022)
15-43403669-T-C			Uncertain significance (Jul 19, 2022)
15-43403672-T-C			Likely benign (Aug 16, 2022)
15-43403677-G-A			Uncertain significance (Mar 19, 2022)
15-43403678-G-A			Likely benign (Aug 22, 2022)
15-43403684-T-C			Uncertain significance (Nov 19, 2021)
15-43403691-C-T			Likely benign (Oct 05, 2022)
15-43403697-G-T		Microcephaly and chorioretinopathy 3 • Autosomal recessive chorioretinopathy-microcephaly syndrome • TUBGCP4-related disorder	Conflicting classifications of pathogenicity (Apr 30, 2024)
15-43403711-A-C			Uncertain significance (Aug 27, 2021)
15-43403729-G-A			Uncertain significance (Jan 13, 2022)
15-43403732-C-T		Microcephaly and chorioretinopathy 3 • Inborn genetic diseases	Likely benign (Jan 08, 2024)
15-43403733-G-A			Likely benign (Jan 06, 2024)
15-43403734-C-CT			Pathogenic (Mar 10, 2022)
15-43403750-T-C		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
15-43403761-G-A			Uncertain significance (Mar 31, 2022)
15-43403767-C-T			Uncertain significance (Apr 24, 2022)
15-43403768-G-A			Uncertain significance (Sep 14, 2021)
15-43403775-C-T			Likely benign (Jul 09, 2023)
15-43403776-G-A			Uncertain significance (Mar 26, 2022)
15-43403776-G-T			Uncertain significance (Sep 01, 2021)
15-43403793-C-T			Likely benign (Nov 08, 2022)
15-43403794-G-C			Uncertain significance (Nov 01, 2022)

GnomAD

Source: gnomAD

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: 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}.
• 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