TOPBP1

DNA topoisomerase II binding protein 1, the group of BRCA1 B complex

Basic information

Region (hg38): 3:133598175-133662380

Links

ENSG00000163781 ∙ NCBI:11073 ∙ OMIM:607760 ∙ HGNC:17008 ∙ Uniprot:Q92547 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pulmonary arterial hypertension (No Known Disease Relationship), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TOPBP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOPBP1 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						0
missense			117	8	1	126
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	117	8	1

Variants in TOPBP1

This is a list of pathogenic ClinVar variants found in the TOPBP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-133601269-T-C		not specified	Uncertain significance (Jan 10, 2022)
3-133601277-A-T		not specified	Uncertain significance (Dec 03, 2021)
3-133601285-C-G		not specified	Uncertain significance (Dec 03, 2021)
3-133601320-C-T		not specified	Uncertain significance (Sep 01, 2021)
3-133601342-T-A		not specified	Uncertain significance (Jun 24, 2022)
3-133601359-G-A		not specified	Uncertain significance (Sep 26, 2023)
3-133601366-A-G		not specified	Uncertain significance (Feb 16, 2023)
3-133608560-T-A		not specified	Uncertain significance (May 17, 2023)
3-133608563-G-T		not specified	Uncertain significance (Jul 26, 2021)
3-133608575-T-C		not specified	Uncertain significance (Jul 25, 2023)
3-133608588-C-A		TOPBP1-related disorder	Benign (Mar 20, 2019)
3-133608613-T-C		TOPBP1-related disorder	Benign (Oct 21, 2019)
3-133608620-T-C		not specified	Uncertain significance (Sep 20, 2024)
3-133608899-G-A		not specified	Uncertain significance (Nov 20, 2024)
3-133608925-T-G		not specified	Uncertain significance (Mar 15, 2024)
3-133611025-T-G		not specified	Uncertain significance (Nov 09, 2023)
3-133611067-T-G		TOPBP1-related disorder	Likely benign (Sep 03, 2020)
3-133611076-T-C		TOPBP1-related disorder	Likely benign (Mar 01, 2019)
3-133611079-C-A		not specified	Uncertain significance (Nov 11, 2024)
3-133611120-T-A		not specified	Uncertain significance (Jan 23, 2023)
3-133612386-C-T		TOPBP1-related disorder	Benign (Oct 21, 2019)
3-133612394-C-T		not specified	Uncertain significance (Dec 10, 2024)
3-133612417-G-C			Uncertain significance (Jul 07, 2021)
3-133612432-C-T		not specified	Uncertain significance (Jan 04, 2024)
3-133616846-C-T		not specified	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOPBP1	protein_coding	protein_coding	ENST00000260810	27	63719

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.95e-11	124643	0	9	124652	0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.97	610	763	0.799	0.0000389	9976
Missense in Polyphen		122	197.54	0.61758		2508
Synonymous	-0.455	276	267	1.04	0.0000140	2843
Loss of Function	7.70	2	72.9	0.0274	0.00000384	953

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000973	0.0000973
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000557	0.0000556
Finnish	0.000143	0.000139
European (Non-Finnish)	0.0000278	0.0000265
Middle Eastern	0.0000557	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double- stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1- responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR (PubMed:16530042). {ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042}.
• Pathway: Homologous recombination - Homo sapiens (human);ATR Signaling;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;BARD1 signaling events;Processing of DNA double-strand break ends;ATR signaling pathway;E2F transcription factor network;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.182

Intolerance Scores

• rvis_EVS: -0.37
• rvis_percentile_EVS: 28.29

Haploinsufficiency Scores

• pHI: 0.517
• hipred: Y
• hipred_score: 0.826
• ghis: 0.668

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.673

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Topbp1
• 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); normal phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: topbp1
• Affected structure: hematopoietic stem cell homeostasis
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: DNA metabolic process;DNA repair;cellular response to DNA damage stimulus;response to ionizing radiation;mitotic DNA replication checkpoint
• Cellular component: condensed nuclear chromosome;spindle pole;male germ cell nucleus;nucleus;nucleoplasm;chromosome;cytoplasm;microtubule organizing center;actin cytoskeleton;nuclear body;PML body
• Molecular function: DNA binding;protein binding;protein C-terminus binding;identical protein binding