BRWD3 (bromodomain and WD repeat domain containing 3)

2006-09-01   Claudia Kalla 

DKFZ, 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

Atlas Image
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.

Pseudogene

None.

Proteins

Atlas Image
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

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.

Bibliography

Pubmed IDLast YearTitleAuthors
155436022005Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes.Kalla C et al
160943722005Identification 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 IDTranscript IDUniprot
ENSG00000165288ENST00000373275Q6RI45

Expression (GTEx)

0
5
10
15

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
220245412012Comparative profiling of plasma proteome from breast cancer patients reveals thrombospondin-1 and BRWD3 as serological biomarkers.15
291664132017Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases.15
176683852007Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly.0
193774762009A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation.0
244628862014Clinical assessment of five patients with BRWD3 mutation at Xq21.1 gives further evidence for mild to moderate intellectual disability and macrocephaly.0

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