BUB3

protein-coding

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

Gene summary

This gene encodes a protein involved in spindle checkpoint function. The encoded protein contains four WD repeat domains and has sequence similarity with the yeast BUB3 protein. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004725.4

Inheritance

ClinVar variants

U:276B:178

Top phenotype

mosaic variegated aneuploidy syndrome

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr10:123,154,402-123,170,467

External References & Databases

Ensembl (ENSG00000154473)

Transcript & Mutation Effects

hg38 • Region Span ~16.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mosaic variegated aneuploidy syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000141

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BUB3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 449

not providedTotal: 5

BUB3-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004725.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				178 clinvar		178
missense			272 clinvar			272
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	276	178	0	454

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004725.4	RefSeq	NP_004716.1	7	MANE Select
ENST00000368865.9	Ensembl	ENSP00000357858.4	7	MANE Select
NM_001007793.3	RefSeq	NP_001007794.1	7	Standard
ENST00000368858.10	Ensembl	ENSP00000357851.5	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

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

Molecular Function

protein binding
ubiquitin binding

Cellular Component

kinetochore
condensed chromosome kinetochore
nucleoplasm
cytosol
mitotic checkpoint complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368865
Coding exons: 7
Length: 11094
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125746
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.98	115	192	0.597	0.0000103	2157
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00015	0.00014	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.203

Intolerance Scores

LoFtool: 0.270
RVIS EVS: -0.21
RVIS percentile EVS: 38.28

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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