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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BRD4
bromodomain containing 4
Chromosome 19 Β· 19p13.12
NCBI Gene: 23476Ensembl: ENSG00000141867.19HGNC: HGNC:13575UniProt: O60885
516PubMed Papers
21Diseases
6Drugs
31Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of transcription by RNA polymerase IIpositive regulation of G2/M transition of mitotic cell cyclepositive regulation of transcription elongation by RNA polymerase IItranscription cis-regulatory region bindingCornelia de Lange syndrome 6Cornelia de Lange syndrome3q26 microduplication syndromeneoplasm
✦AI Summary

BRD4 (bromodomain containing 4) is a multifunctional epigenetic regulator that acts as a chr19 reader and transcriptional coactivator. As a member of the BET protein family, BRD4 interprets histone acetylation marks (H3K27ac, H3K9ac, H4K5/8/12/16ac) and recruits transcriptional machinery to super-enhancers, controlling expression of oncogenes and other target genes 12. Beyond transcriptional regulation, BRD4 functions in genome stability maintenance, DNA damage checkpoint control, and telomere preservation 1. BRD4 exhibits dynamic functional switching: chr19-bound BRD4 employs histone acetyltransferase activity for chr19 remodeling, while promoter-associated BRD4 uses kinase activity to phosphorylate RNA polymerase II and transcriptional factors 3. This switching is regulated by JNK-mediated phosphorylation at Thr1186/Thr1212 3. Pathologically, BRD4 dysregulation associates with cancer, inflammatory diseases (acute gouty arthritis, osteoarthritis), and endocrine disorders (PCOS, where BRD4 activates androgen receptor transcription) 456. BRD4 also facilitates HPV genome replication through recruiting DNA damage response factors 7. BET inhibitors targeting BRD4 show therapeutic promise, though protein degradation via PROTACs or phospho-IDR-targeting compounds may offer improved efficacy 87.

Sources cited
1
BRD4 regulates super-enhancers and oncogene expression; also controls DNA damage checkpoint activation, repair, and telomere maintenance
PMID: 30466442
2
BET proteins including BRD4 interpret histone Kac modifications, control gene expression, remodel chromatin, and prevent replicative stress-induced DNA damage
PMID: 36739915
3
BRD4 regulates pyroptosis in acute gouty arthritis via NF-ΞΊB/NLRP3/GSDMD signaling pathway
PMID: 33162822
4
BRD4 is a therapeutic target in cancer; PROTAC-mediated degradation is more effective than small-molecule inhibitors
PMID: 26051217
5
BRD4 activates androgen receptor transcription and promotes ovarian fibrosis in PCOS
PMID: 37669164
6
BRD4 is highly expressed in M1 macrophages; targeting BRD4 suppresses macrophage polarization and synovial inflammation in osteoarthritis
PMID: 38330742
7
JNK-mediated phosphorylation of BRD4 at Thr1186/Thr1212 switches its function from chromatin-based HAT activity to promoter-based kinase activity
PMID: 39454579
8
Phospho-BRD4 recruits DNA damage response factors (53BP1, BARD1) to facilitate HPV genome replication; phospho-IDR-targeting compounds disrupt this interaction
PMID: 38103559
Disease Associationsβ“˜21
Cornelia de Lange syndrome 6Open Targets
0.68Moderate
Cornelia de Lange syndromeOpen Targets
0.50Moderate
3q26 microduplication syndromeOpen Targets
0.50Moderate
neoplasmOpen Targets
0.46Moderate
syndromic intellectual disabilityOpen Targets
0.45Moderate
genetic disorderOpen Targets
0.42Moderate
esophageal squamous cell carcinomaOpen Targets
0.39Weak
NUT midline carcinomaOpen Targets
0.38Weak
squamous cell lung carcinomaOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
colon adenocarcinomaOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
kidney neoplasmOpen Targets
0.37Weak
bile duct carcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
Hepatobiliary NeoplasmOpen Targets
0.37Weak
lung carcinoid tumorOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
Cornelia de Lange syndrome 6UniProt
Pathogenic Variants31
NM_001379291.1(BRD4):c.1289A>G (p.Tyr430Cys)Likely pathogenic
See cases|Cornelia de Lange syndrome 6
β˜…β˜…β˜†β˜†2024β†’ Residue 430
NM_001379291.1(BRD4):c.2211+2T>CLikely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2026
NM_001379291.1(BRD4):c.3710_3719del (p.Arg1237fs)Likely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2026β†’ Residue 1237
NM_001379291.1(BRD4):c.1552-1G>APathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2025
NM_001379291.1(BRD4):c.3540_3541del (p.Lys1181fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1181
NM_001379291.1(BRD4):c.555_558del (p.Thr186fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 186
NM_001379291.1(BRD4):c.3510del (p.Pro1171fs)Likely pathogenic
Syndromic intellectual disability
β˜…β˜†β˜†β˜†2025β†’ Residue 1171
NM_001379291.1(BRD4):c.1315dup (p.Val439fs)Likely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2025β†’ Residue 439
NM_001379291.1(BRD4):c.1698_1701dup (p.Pro568fs)Likely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2024β†’ Residue 568
NM_001379291.1(BRD4):c.2872dup (p.Leu958fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 958
NM_001379291.1(BRD4):c.766dup (p.Gln256fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 256
NM_001379291.1(BRD4):c.1393_1420delinsCAA (p.Val465fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 465
NM_001379291.1(BRD4):c.703C>T (p.Gln235Ter)Likely pathogenic
Mental disorder
β˜…β˜†β˜†β˜†2024β†’ Residue 235
NM_001379291.1(BRD4):c.3312_3319del (p.Gln1105fs)Likely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2024β†’ Residue 1105
NM_001379291.1(BRD4):c.394_395del (p.Met132fs)Likely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2023β†’ Residue 132
NM_001379291.1(BRD4):c.137dup (p.Pro47fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 47
NM_001379291.1(BRD4):c.338G>T (p.Arg113Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 113
NM_001379291.1(BRD4):c.1807G>T (p.Glu603Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 603
NM_001379291.1(BRD4):c.2728dup (p.Gln910fs)Likely pathogenic
Cornelia de Lange syndrome 6
β˜…β˜†β˜†β˜†2023β†’ Residue 910
NM_001379291.1(BRD4):c.3693_3709dup (p.Arg1237fs)Pathogenic
Intellectual disability
β˜…β˜†β˜†β˜†2022β†’ Residue 1237
View on ClinVar β†—
Drug Targets6
APABETALONEPhase III
Bromodomain and extra-terminal motif (BET) inhibitor
BIRABRESIBPhase II
Bromodomain and extra-terminal motif (BET) inhibitor
glioblastoma multiforme
EZOBRESIBPhase I/II
Bromodomain and extra-terminal motif (BET) inhibitor
MOLIBRESIBPhase II
Bromodomain and extra-terminal motif (BET) inhibitor
neoplasm
PELABRESIBApproved
Bromodomain and extra-terminal motif (BET) inhibitor
neoplasm
RO-6870810Phase I
Bromodomain and extra-terminal motif (BET) inhibitor
Related Genes
BRDTProtein interaction100%CDK8Protein interaction100%CHD4Protein interaction100%DEFB1Protein interaction100%EP300Protein interaction100%AFF1Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Ovary
91%
Liver
87%
Brain
71%
Heart
49%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
BRD4BRDTCDK8CHD4DEFB1EP300AFF1
PROTEIN STRUCTURE
Preparing viewer…
PDB4QB3 Β· 0.94 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.19Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.12 [0.08–0.19]
RankingsWhere BRD4 stands among ~20K protein-coding genes
  • #508of 20,598
    Most Researched516 Β· top 5%
  • #740of 1,025
    FDA-Approved Drug Targets1
  • #1,773of 5,498
    Most Pathogenic Variants31
  • #397of 17,882
    Most Constrained (LOEUF)0.19 Β· top 5%
Genes detectedBRD4
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
BRD4 and Cancer: going beyond transcriptional regulation.
PMID: 30466442
Mol Cancer Β· 2018
1.00
2
BET proteins: Biological functions and therapeutic interventions.
PMID: 36739915
Pharmacol Ther Β· 2023
0.90
3
Targeting BRD4 prevents acute gouty arthritis by regulating pyroptosis.
PMID: 33162822
Int J Biol Sci Β· 2020
0.80
4
Hijacking the E3Β Ubiquitin Ligase Cereblon to Efficiently Target BRD4.
PMID: 26051217
Chem Biol Β· 2015
0.70
5
Enzyme-Activated Sugar-Coated Bifunctional Degraders.
PMID: 40937862
J Am Chem Soc Β· 2025
0.68