BRWD3 (bromodomain and WD repeat domain containing 3)
2006-09-01 Claudia Kalla AffiliationDKFZ, Div. Molecular Genetics (B060), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Identity
HGNC
LOCATION
Xq21.1
LOCUSID
ALIAS
BRODL,FLJ38568
FUSION GENES
DNA/RNA
Genomic organization (A) and transcript variants (B) of BRWD3. (A) Gene structure (drawn to scale): black boxes represent exons. (B) Transcripts (drawn to scale): boxes, exons; UTR, untranslated region; light shaded box, coding region; shaded and dark shaded boxes, nucleotide sequences coding for protein domains (WD40: WD40 tandem repeats; BROMO: bromodomain). For transcript variants BRWD3-C to BRWD3-P only the largest possible coding regions are indicated, though translation of different short proteins by using the start sites of BRWD3-A and BRWD3-B might also be possible.
Description
44 exons spanning 132.7 kb genomic DNA
Transcription
5.6-6.2 kb mRNA, coding sequence: 4.2-5.4 kb
Alternative splicing results in the expression of at least 15 transcript variants (BRWD3-A to BRWD3-P): The two most abundant transcript variants A and B are the result of alternative splicing of the first four exons (BRWD3-A contains exons 1 to 4, whereas BRWD3-B starts with an extended version of exon 4). BRWD3-C to BRWD3-P represent alternatively spliced variants of A and B, which contain additional exons 6a, 6b, and/or 12a and lack exons 3, 5, 6, 7, 8, and/or 9.
Alternative splicing results in the expression of at least 15 transcript variants (BRWD3-A to BRWD3-P): The two most abundant transcript variants A and B are the result of alternative splicing of the first four exons (BRWD3-A contains exons 1 to 4, whereas BRWD3-B starts with an extended version of exon 4). BRWD3-C to BRWD3-P represent alternatively spliced variants of A and B, which contain additional exons 6a, 6b, and/or 12a and lack exons 3, 5, 6, 7, 8, and/or 9.
Pseudogene
None.
Proteins
Schematic representation of protein variants BRWD3-A and BRWD3-B as deduced from the transcripts. WD40: WD40 tandem repeats; BROMO: bromodomain. Translation initiation in exons 11 and 13 of transcripts BRWD3-C to BRWD3-P produces proteins, which retain four and three of the eight WD40 repeats, respectively.
Description
The amino-terminal region consists of eight tandem WD40 repeats, which had been identified as the structural determinant of the beta -subunit of the G-proteins that mediateting transmembrane signal transduction. The carboxy terminus is predicted to contain two bromodomains with the potential to mediate protein-protein interactions in DNA-binding proteins. BRWD3-C to BRWD3-P are amino-terminally truncated versions of BRWD3-A and BRWD3-B, which retain three or four of the eight WD40 repeats and both bromodomains.
Expression
Expressed in a variety of adult tissues (lymphocytes, brain, heart, kidney, placenta) and in fetal liver.
Function
By performing a systematic genomewide survey for genes required for JAK/STAT pathway activity (involved in cell proliferation and haematopoiesis), the Drosophila homologon of BRWD3 was isolated as a member of the JAK/STAT signalling cascade acting downstream of JAK. In vivo analysis demonstrated that disrupted Drosophila BRWD3 functions as a suppressor of leukemia-like blood cell tumors.
Homology
Drosophila melanogaster: BRWD3
Mouse: Brwd3
Pan troglodytes: BRWD3
Mouse: Brwd3
Pan troglodytes: BRWD3
Implicated in
Entity name
Note
In the tumour cells of one case of B-cell chronic lymphocytic leukemia (B-CLL), BRWD3 was affected by a translocation that rearranged the gene with ARHGAP20 (11q23). No fusion transcripts were generated. BRWD3 transcript expression is downregulated in B-CLL lymphocytes vs. CD19+ control B cells.
Disease
B-cell chronic lymphocytic leukemia
Cytogenetics
t(X;11)(q21;q23)
Hybrid gene
ARHGAP20 - BRWD3
Fusion protein
None detected.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15543602 | 2005 | Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes. | Kalla C et al |
| 16094372 | 2005 | Identification of JAK/STAT signalling components by genome-wide RNA interference. | Müller P et al |
Other Information
Locus ID:
NCBI: 254065
MIM: 300553
HGNC: 17342
Ensembl: ENSG00000165288
Variants:
dbSNP: 254065
ClinVar: 254065
TCGA: ENSG00000165288
COSMIC: BRWD3
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000165288 | ENST00000373275 | Q6RI45 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36414205 | 2023 | Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway. | 2 |
| 36514184 | 2023 | Variants in BRWD3 associated with X-linked partial epilepsy without intellectual disability. | 3 |
| 36414205 | 2023 | Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway. | 2 |
| 36514184 | 2023 | Variants in BRWD3 associated with X-linked partial epilepsy without intellectual disability. | 3 |
| 29166413 | 2017 | Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases. | 42 |
| 29166413 | 2017 | Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases. | 42 |
| 24462886 | 2014 | Clinical assessment of five patients with BRWD3 mutation at Xq21.1 gives further evidence for mild to moderate intellectual disability and macrocephaly. | 11 |
| 24462886 | 2014 | Clinical assessment of five patients with BRWD3 mutation at Xq21.1 gives further evidence for mild to moderate intellectual disability and macrocephaly. | 11 |
| 22024541 | 2012 | Comparative profiling of plasma proteome from breast cancer patients reveals thrombospondin-1 and BRWD3 as serological biomarkers. | 26 |
| 22024541 | 2012 | Comparative profiling of plasma proteome from breast cancer patients reveals thrombospondin-1 and BRWD3 as serological biomarkers. | 26 |
| 19377476 | 2009 | A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. | 274 |
| 19377476 | 2009 | A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. | 274 |
| 17668385 | 2007 | Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly. | 34 |
| 17668385 | 2007 | Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly. | 34 |
Citation
Claudia Kalla
BRWD3 (bromodomain and WD repeat domain containing 3)
Atlas Genet Cytogenet Oncol Haematol. 2006-09-01
Online version: http://atlasgeneticsoncology.org/gene/42978/brwd3
