BUB1B

Chr 15ADAR

BUB1 mitotic checkpoint serine/threonine kinase B

Also known as: BUB1beta, BUBR1, Bub1A, MAD3L, MVA1, SSK1, hBUBR1

The protein is an essential mitotic checkpoint kinase that inhibits the anaphase-promoting complex to ensure proper chromosome segregation during cell division. Mutations cause mosaic variegated aneuploidy syndrome 1, characterized by growth retardation, intellectual disability, microcephaly, and increased cancer risk, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants, reflecting its essential role in cell cycle regulation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.583 OMIM phenotypes
Clinical SummaryBUB1B
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Gene-Disease Validity (ClinGen)
mosaic variegated aneuploidy syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 4.31
OE 0.42 (0.310.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.89Z-score
OE missense 0.89 (0.830.96)
482 obs / 540.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.310.58)
00.351.4
Missense OE0.89 (0.830.96)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 27 / 64.2Missense obs/exp: 482 / 540.4Syn Z: -0.06
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBUB1B-related mosaic variegated aneuploidy syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6744th %ile
GOF
0.4381th %ile
LOF
0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFWhether carriers of pathogenic BUB1B mutations, such as the parents of MVA syndrome patients, have an increased risk for cancer remains of interest, as studies in mice have suggested that haploinsufficiency of BUB1B may cause an increase in carcinogen-induced tumors.PMID:27239782

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BUB1B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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