BUB1B

Chr 15ADAR

BUB1 mitotic checkpoint serine/threonine kinase B

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

NCBI Gene: 701 ENSG00000156970 UniProt: O60566 OMIM: 602860

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a kinase involved in spindle checkpoint function. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Premature chromatid separation trait]MIM #176430

Colorectal cancer, somaticMIM #114500

Mosaic variegated aneuploidy syndrome 1MIM #257300

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mosaic variegated aneuploidy syndrome 1 · AR · ClinGen 2019

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — BUB1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.000

Z-score 4.31

OE 0.42 (0.31–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.89Z-score

OE missense 0.89 (0.83–0.96)

482 obs / 540.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.31–0.58)

0≤0.351.4

Missense OE?0.89 (0.83–0.96)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 27 / 64.2Missense obs/exp: 482 / 540.4Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in BUB1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 61

1,228 rare PASS variants

Rare truncating (LoF)

1 in 1,000

197 rare PASS variants

Rare synonymous (reference)

1 in 160

441 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BUB1B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 73	1 in 990
South Asian	~43k	1 in 60	1 in 1,100
Remaining (unassigned)	~30k	1 in 48	1 in 560
European (Finnish)	~27k	1 in 150	≈ 1 in 6,700
Admixed American	~22k	1 in 65	1 in 1,000
African / African American	~21k	1 in 42	1 in 890
East Asian	~20k	1 in 78	1 in 1,100
Ashkenazi Jewish	~13k	1 in 360	1 in 2,600
Middle Eastern	~2,884	1 in 51	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 23 coding exons well covered in gnomAD exomes and genomes.? see exons ↓