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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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BEX4
brain expressed X-linked 4
Chromosome X · Xq22.1
NCBI Gene: 56271Ensembl: ENSG00000102409.11HGNC: HGNC:25475UniProt: Q9NWD9
20PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindinghistone deacetylase bindingalpha-tubulin bindingnucleoplasmoral squamous cell carcinomaglioblastoma multiformegastric cancerBlackfan-Diamond anemia
✦AI Summary

BEX4 (brain expressed X-linked 4) is a microtubule-associated protein that regulates cellular processes through modulation of tubulin acetylation. The protein localizes to microtubules and spindle poles, where it interacts with α-tubulin and inhibits SIRT2 deacetylase activity, leading to microtubule hyperacetylation 1. This mechanism is crucial for chromosome X and genomic stability, as BEX4 overexpression can induce aneuploidy and resistance to apoptotic cell death 1. BEX4 exhibits context-dependent roles in cancer, functioning as a tumor suppressor in several malignancies including clear cell renal cell carcinoma, oral squamous cell carcinoma, and gastric cancer, where decreased expression correlates with poor prognosis 234. Conversely, BEX4 acts as an oncogene in lung adenocarcinoma and glioblastoma, promoting cell proliferation and radioresistance through YAP/TAZ signaling pathway activation 56. The protein's tumor suppressive effects are mediated through stabilization of SH2D4A by preventing ubiquitination at lysine 69, which requires BEX4-mediated inhibition of SIRT2 activity 2. These findings establish BEX4 as a critical regulator of microtubule dynamics with significant implications for cancer progression and therapeutic targeting.

Sources cited
1
BEX4 localizes to microtubules and spindle poles, interacts with α-tubulin and SIRT2, and causes microtubule hyperacetylation by inhibiting SIRT2 deacetylase activity, leading to aneuploidy
PMID: 27512957
2
BEX4 acts as tumor suppressor in clear cell renal cell carcinoma and stabilizes SH2D4A through SIRT2 inhibition and prevention of ubiquitination at lysine 69
PMID: 39639172
3
BEX4 functions as tumor suppressor in oral squamous cell carcinoma by inhibiting proliferation and growth
PMID: 27297407
4
BEX4 is downregulated in gastric cancer and serves as independent prognostic factor
PMID: 33217815
5
BEX4 acts as oncogene in lung adenocarcinoma, promoting cell proliferation through OCT4 regulation
PMID: 29660335
6
BEX4 promotes glioblastoma progression and radioresistance through YAP/TAZ signaling pathway activation
PMID: 34576008
Disease Associationsⓘ20
oral squamous cell carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
Blackfan-Diamond anemiaOpen Targets
0.06Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.05Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.05Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.05Suggestive
Autosomal dominant methemoglobinemiaOpen Targets
0.05Suggestive
autosomal dominant sideroblastic anemiaOpen Targets
0.04Suggestive
Constitutional sideroblastic anemiaOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TFAP2EShared pathway25%BRICD5Shared pathway25%GKN2Shared pathway25%CENPLShared pathway25%CDCA7Shared pathway25%TFAP2DShared pathway25%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
58%
Heart
41%
Ovary
29%
Lung
8%
Liver
3%
Gene Interaction Network
Click a node to explore
BEX4TFAP2EBRICD5GKN2CENPLCDCA7TFAP2D
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NWD9
View on AlphaFold ↗
RankingsWhere BEX4 stands among ~20K protein-coding genes
  • #14,110of 20,598
    Most Researched20
Genes detectedBEX4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
BEX4 inhibits the progression of clear cell renal cell carcinoma by stabilizing SH2D4A, which is achieved by blocking SIRT2 activity.
PMID: 39639172
Oncogene · 2025
1.00
2
Brain-Expressed X-linked (BEX) proteins in human cancers.
PMID: 26408910
Biochim Biophys Acta · 2015
0.90
3
BEX1 and BEX4 Induce GBM Progression through Regulation of Actin Polymerization and Activation of YAP/TAZ Signaling.
PMID: 34576008
Int J Mol Sci · 2021
0.80
4
mTOR up-regulation of BEX4 promotes lung adenocarcinoma cell proliferation by potentiating OCT4.
PMID: 29660335
Biochem Biophys Res Commun · 2018
0.70
5
Decreased brain-expressed X-linked 4 (BEX4) expression promotes growth of oral squamous cell carcinoma.
PMID: 27297407
J Exp Clin Cancer Res · 2016
0.60