BUB3

BUB3 mitotic checkpoint protein, the group of WD repeat domain containing

Basic information

Region (hg38): 10:123154402-123170467

Links

ENSG00000154473 ∙ NCBI:9184 ∙ OMIM:603719 ∙ HGNC:1151 ∙ Uniprot:O43684 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mosaic variegated aneuploidy syndrome (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BUB3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BUB3 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				173		173
missense			261			261
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				5	1	6
non coding						0
Total	0	0	261	173	0

Variants in BUB3

This is a list of pathogenic ClinVar variants found in the BUB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-123154923-C-G		not specified	Likely benign (Jul 27, 2023)
10-123154923-C-T		not specified	Likely benign (Mar 08, 2022)
10-123154924-G-A		not specified	Uncertain significance (Apr 20, 2022)
10-123154928-C-G		not specified	Uncertain significance (Sep 12, 2022)
10-123154932-C-T		not specified	Likely benign (Mar 07, 2022)
10-123154942-C-A		not specified	Uncertain significance (Feb 02, 2024)
10-123154942-C-T		not specified	Likely benign (Aug 03, 2019)
10-123154946-A-G		not specified	Uncertain significance (Oct 05, 2024)
10-123154947-C-T		not specified	Likely benign (Jul 11, 2022)
10-123154950-G-A		not specified	Likely benign (Feb 02, 2020)
10-123154951-C-A		not specified	Uncertain significance (Jul 15, 2024)
10-123154951-C-T		not specified	Uncertain significance (Jun 21, 2024)
10-123154952-C-A		not specified	Uncertain significance (Mar 14, 2024)
10-123154953-A-C		not specified	Likely benign (Feb 03, 2023)
10-123154953-A-G		not specified	Likely benign (Dec 06, 2021)
10-123154954-C-A		not specified	Uncertain significance (Jun 07, 2022)
10-123154954-C-T		not specified	Uncertain significance (Jan 11, 2023)
10-123154955-C-A		not specified	Uncertain significance (Mar 25, 2023)
10-123154955-C-T		not specified	Uncertain significance (Jun 22, 2024)
10-123154956-C-G		not specified	Likely benign (Nov 10, 2022)
10-123154956-C-T		not specified	Likely benign (Jul 16, 2022)
10-123154957-G-A		not specified	Uncertain significance (Aug 12, 2024)
10-123154958-A-G		not specified	Uncertain significance (Feb 12, 2024)
10-123154959-G-A		not specified	Likely benign (May 29, 2024)
10-123154963-G-A		not specified	Uncertain significance (Apr 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BUB3	protein_coding	protein_coding	ENST00000368865	7	11094

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.809	0.191	125738	0	8	125746	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	115	192	0.597	0.0000103	2157
Missense in Polyphen		25	43.324	0.57704		493
Synonymous	-0.764	82	73.7	1.11	0.00000384	630
Loss of Function	3.36	3	18.6	0.161	0.00000107	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000148	0.000139
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000658	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. Regulates chromosome segregation during oocyte meiosis. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (APC/C) when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:18199686}.
• Pathway: Cell cycle - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Cell Cycle;Regulation of sister chromatid separation at the metaphase-anaphase transition;Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Inactivation of APC/C via direct inhibition of the APC/C complex;Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;p73 transcription factor network;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Regulation of APC/C activators between G1/S and early anaphase;Cdc20:Phospho-APC/C mediated degradation of Cyclin A;APC-Cdc20 mediated degradation of Nek2A;APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint;APC/C:Cdc20 mediated degradation of mitotic proteins;Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.270
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.956
• hipred: Y
• hipred_score: 0.825
• ghis: 0.730

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bub3
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; neoplasm; 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); embryo phenotype; skeleton phenotype; vision/eye phenotype

Gene ontology

• Biological process: mitotic sister chromatid segregation;mitotic spindle assembly checkpoint;attachment of spindle microtubules to kinetochore;anaphase-promoting complex-dependent catabolic process;protein localization to kinetochore;cell division;meiotic cell cycle;regulation of mitotic cell cycle phase transition
• Cellular component: kinetochore;condensed chromosome kinetochore;nucleoplasm;cytosol;mitotic checkpoint complex;bub1-bub3 complex
• Molecular function: protein binding;ubiquitin binding