BUB1

Chr 2

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 essential for spindle-assembly checkpoint signaling and correct chromosome alignment during mitosis. Mutations cause primary microcephaly 30, an autosomal recessive condition characterized by congenital small head size due to reduced brain growth. The gene is highly constrained against loss-of-function variants in the general population, consistent with its essential role in cell division.

ResearchSummary from RefSeq, OMIM, UniProt
DNmechanismLOEUF 0.60
Clinical Summary— BUB1
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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.
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ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 343 VUS of 500 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateBUB1-related microcephaly and developmental disorderOTHERAR

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

DN
0.7132th %ile
GOF
0.4282th %ile
LOF
0.3356th %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.

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

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS343
Likely Benign131
Benign2
Conflicting2
2
Pathogenic
1
Likely Pathogenic
343
VUS
131
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
1
0
0
0
1
VUS
8
313
18
4
343
Likely Benign
0
14
34
83
131
Benign
0
0
2
0
2
Conflicting
—2
Total93275687481

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

View in ClinVar →

Protein Context — Lollipop Plot

BUB1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
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