BRWD3 (bromodomain and WD repeat domain containing 3)

2006-09-01 Claudia Kalla Affiliation

DKFZ, Div. Molecular Genetics (B060), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany

Identity

HGNC

BRWD3

LOCATION

Xq21.1

LOCUSID

254065

ALIAS

BRODL,FLJ38568

FUSION GENES

Show Gene Fusions

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.

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

Implicated in

Entity name

t(X;11)(q21;q23)

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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-(bromodomain-and-wd-repeat-domain-containing-3)