BUB1

Chr 2AR

BUB1 mitotic checkpoint serine/threonine kinase

Also known as: BUB1A, BUB1L, MCPH30, hBUB1

NCBI Gene: 699ENSG00000169679UniProt: O43683

This gene encodes a serine/threonine-protein kinase that play a central role in mitosis. The encoded protein functions in part by phosphorylating members of the mitotic checkpoint complex and activating the spindle checkpoint. This protein also plays a role in inhibiting the activation of the anaphase promoting complex/cyclosome. This protein may also function in the DNA damage response. Mutations in this gene have been associated with aneuploidy and several forms of cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Colorectal cancer with chromosomal instability, somaticMIM #114500
Microcephaly 30, primary, autosomal recessiveMIM #620183
AR
1
Active trials
2
Pathogenic / LP
381
ClinVar variants
89
Pubs (1 yr)
0.8
Missense Z
0.60
LOEUF
Clinical Summary— BUB1
🧬
Gene-Disease Validity (ClinGen)
colorectal cancer · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 Pathogenic / Likely Pathogenic· 270 VUS of 381 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 3.98
OE 0.43 (0.31–0.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.85Z-score
OE missense 0.90 (0.83–0.97)
500 obs / 556.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.31–0.60)
0≤0.351.4
Missense OE0.90 (0.83–0.97)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 24 / 56.2Missense obs/exp: 500 / 556.3Syn Z: 0.44
DN
DN
0.7132th %ile
GOF
0.4282th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

381 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS270
Likely Benign106
Benign2
Conflicting1
1
Pathogenic
1
Likely Pathogenic
270
VUS
106
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
1
0
0
0
1
VUS
7
240
19
4
270
Likely Benign
0
10
33
63
106
Benign
0
0
2
0
2
Conflicting
—1
Total82505567381

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

BUB1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

BUB1-related microcephaly and developmental disorder

moderate
ARUndeterminedAbsent Gene Product, Decreased Gene Product Level
Dev. Disorders
G2P ↗
splice region variantframeshift variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients