BUB1

BUB1 mitotic checkpoint serine/threonine kinase

Basic information

Region (hg38): 2:110637528-110678063

Previous symbols: [ "BUB1L" ]

Links

ENSG00000169679 ∙ NCBI:699 ∙ OMIM:602452 ∙ HGNC:1148 ∙ Uniprot:O43683 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mosaic variegated aneuploidy syndrome (Supportive), mode of inheritance: AD
• microcephaly 30, primary, autosomal recessive (Limited), mode of inheritance: AR
• colorectal cancer (Limited), mode of inheritance: AD
• microcephaly 30, primary, autosomal recessive (Limited), mode of inheritance: Unknown
• colorectal cancer (Limited), mode of inheritance: AD
• microcephaly 30, primary, autosomal recessive (Moderate), mode of inheritance: AR
• familial colorectal cancer (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 30, primary, autosomal recessive	AR	Cardiovascular; Endocrine	The condition has been described as involving congenital cardiac anomalies, and awareness may allow early diagnosis and management; Growth hormone deficiency has been described, and awareness may allow medical management	Cardiovascular; Craniofacial; Endocrine; Neurologic	35044816

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BUB1 gene.

• not_specified (1369 variants)
• not_provided (188 variants)
• BUB1-related_disorder (9 variants)
• Microcephaly_30,_primary,_autosomal_recessive (5 variants)
• Colorectal_cancer_with_chromosomal_instability,_somatic (2 variants)
• Carcinoma_of_colon (1 variants)
• Inborn_genetic_diseases (1 variants)
• Colorectal_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BUB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004336.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	434	1	436
missense	1		914	55		970
nonsense			1			1
start loss			1			1
frameshift	2	1	4			7
splice donor/acceptor (+/-2bp)	2		2			4
Total	5	1	923	489	1

Highest pathogenic variant AF is 0.000014407482

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BUB1	protein_coding	protein_coding	ENST00000302759	25	40417

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.88e-9	1.00	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.848	500	556	0.899	0.0000267	7181
Missense in Polyphen		148	190.89	0.77531		2587
Synonymous	0.444	184	192	0.959	0.00000943	1958
Loss of Function	3.98	24	56.2	0.427	0.00000248	744

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000571	0.000570
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000321	0.000316
Middle Eastern	0.000218	0.000217
South Asian	0.000362	0.000359
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of 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. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936}.
• Pathway: Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Cell Cycle;ATM Signaling Network in Development and Disease;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;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;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;Aurora B signaling;PLK1 signaling events (Consensus)

Recessive Scores

• pRec: 0.258

Intolerance Scores

• loftool: 0.829
• rvis_EVS: -1.22
• rvis_percentile_EVS: 5.64

Haploinsufficiency Scores

• pHI: 0.996
• hipred: Y
• hipred_score: 0.644
• ghis: 0.707

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.832

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bub1
• Phenotype: normal 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); reproductive system phenotype; hematopoietic system phenotype; neoplasm; liver/biliary system phenotype; immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: protein phosphorylation;apoptotic process;regulation of sister chromatid cohesion;mitotic cell cycle checkpoint;mitotic spindle assembly checkpoint;cell population proliferation;viral process;cell division;meiotic sister chromatid cohesion, centromeric;regulation of chromosome segregation
• Cellular component: kinetochore;condensed chromosome kinetochore;condensed nuclear chromosome kinetochore;condensed nuclear chromosome outer kinetochore;nucleoplasm;cytosol;membrane
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding