BRD4

bromodomain containing 4, the group of Bromodomain and extra-terminal domain family|Bromodomain containing

Basic information

Region (hg38): 19:15235519-15332545

Links

ENSG00000141867 ∙ NCBI:23476 ∙ OMIM:608749 ∙ HGNC:13575 ∙ Uniprot:O60885 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
• multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD
• Cornelia de Lange syndrome 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cornelia de Lange syndrome 6	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	29379197; 35470444

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRD4 gene.

• not_provided (713 variants)
• Inborn_genetic_diseases (73 variants)
• BRD4-related_disorder (41 variants)
• Cornelia_de_Lange_syndrome_6 (11 variants)
• not_specified (10 variants)
• De_Lange_syndrome (7 variants)
• Syndromic_intellectual_disability (2 variants)
• Mental_disorder (2 variants)
• Short_stature (2 variants)
• Cornelia_de_Lange-like_syndrome (2 variants)
• Neurodevelopmental_disorder (1 variants)
• Learning_Disabilities,_Adolescent (1 variants)
• Cornelia_de_Lange_syndrome_1 (1 variants)
• Intellectual_disability (1 variants)
• See_cases (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRD4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379291.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		4	236	20	261
missense	1	3	307	22	6	339
nonsense	2	1				3
start loss						0
frameshift	8	9	2			19
splice donor/acceptor (+/-2bp)	1	1	1			3
Total	13	14	314	258	26

Highest pathogenic variant AF is 0.00008557736

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRD4	protein_coding	protein_coding	ENST00000263377	19	95710

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.83e-10	125742	0	2	125744	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.59	519	805	0.644	0.0000505	8836
Missense in Polyphen		8	14.834	0.53929		142
Synonymous	-3.62	426	341	1.25	0.0000244	2678
Loss of Function	7.27	0	61.5	0.00	0.00000319	689

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P- TEFb complex and recruiting it to promoters: BRD4 is required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P- TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II. Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II. According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B. Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters. {ECO:0000269|PubMed:22509028}.
• Disease: DISEASE: Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein. {ECO:0000269|PubMed:11733348, ECO:0000269|PubMed:12543779}.
• Pathway: Chemical Compounds to monitor Proteins (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.363
• rvis_EVS: -1.48
• rvis_percentile_EVS: 3.69

Haploinsufficiency Scores

• pHI: 0.428
• hipred: Y
• hipred_score: 0.831
• ghis: 0.614

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.963

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Brd4
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; liver/biliary system phenotype; skeleton phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Zebrafish Information Network

• Gene name: brd4
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription involved in G1/S transition of mitotic cell cycle;chromatin organization;protein phosphorylation;cellular response to DNA damage stimulus;positive regulation of G2/M transition of mitotic cell cycle;viral process;positive regulation of transcription elongation from RNA polymerase II promoter;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of inflammatory response;regulation of phosphorylation of RNA polymerase II C-terminal domain;positive regulation of histone H3-K36 trimethylation
• Cellular component: condensed nuclear chromosome;nucleus;nucleoplasm;cytosol
• Molecular function: p53 binding;chromatin binding;protein binding;RNA polymerase II CTD heptapeptide repeat kinase activity;enzyme binding;lysine-acetylated histone binding;RNA polymerase II C-terminal domain binding