BRWD1

bromodomain and WD repeat domain containing 1, the group of WD repeat domain containing|Bromodomain containing|DDB1 and CUL4 associated factors

Basic information

Region (hg38): 21:39184176-39321559

Previous symbols: [ "C21orf107", "WDR9" ]

Links

ENSG00000185658 ∙ NCBI:54014 ∙ OMIM:617824 ∙ HGNC:12760 ∙ Uniprot:Q9NSI6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ciliary dyskinesia, primary, 51 (Limited), mode of inheritance: AR
• primary ciliary dyskinesia (Disputed Evidence), mode of inheritance: AR
• agammaglobulinemia (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 51	AR	Allergy/Immunology/Infectious; Cardiovascular; Pulmonary	Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, interventions including vaccinations and early and aggressive treatment of respiratory infections may be beneficial; The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	33389130

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRWD1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRWD1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	7	18
missense		1	90	13	9	113
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1		1	2
non coding				3	5	8
Total	0	1	94	27	21

Variants in BRWD1

This is a list of pathogenic ClinVar variants found in the BRWD1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-39187080-A-T		not specified	Uncertain significance (Nov 10, 2022)
21-39187084-A-G		not specified	Uncertain significance (Oct 16, 2023)
21-39187102-T-G		not specified	Uncertain significance (Jul 09, 2021)
21-39187114-T-C		not specified	Uncertain significance (Apr 05, 2023)
21-39187126-T-C		not specified	Uncertain significance (Apr 20, 2024)
21-39187172-A-C		not specified	Uncertain significance (May 30, 2023)
21-39187256-T-C		not specified	Uncertain significance (Dec 27, 2022)
21-39187294-C-T		not specified	Uncertain significance (Oct 28, 2023)
21-39187295-G-A		not specified	Uncertain significance (Jul 25, 2023)
21-39187403-C-T		BRWD1-related disorder	Likely benign (Apr 02, 2019)
21-39196373-A-C			Likely benign (Mar 01, 2022)
21-39196542-G-A		not specified	Uncertain significance (May 05, 2023)
21-39196549-T-C		not specified	Uncertain significance (Jul 13, 2021)
21-39196550-A-G		BRWD1-related disorder	Likely benign (Mar 28, 2019)
21-39196602-T-C		BRWD1-related disorder	Likely benign (Apr 30, 2019)
21-39196630-A-C		not specified	Uncertain significance (May 09, 2024)
21-39196650-A-G		BRWD1-related disorder	Benign (Apr 10, 2019)
21-39196667-T-A		not specified	Uncertain significance (Feb 14, 2023)
21-39196676-C-T		BRWD1-related disorder	Likely benign (Apr 08, 2019)
21-39196732-T-C		not specified	Uncertain significance (Mar 16, 2024)
21-39196921-T-C		BRWD1-related disorder	Benign (Apr 11, 2019)
21-39196950-G-T		not specified	Uncertain significance (Oct 06, 2021)
21-39197049-G-A		not specified	Uncertain significance (Feb 10, 2023)
21-39197176-G-A		BRWD1-related disorder	Likely benign (Apr 01, 2019)
21-39197197-T-G		not specified	Uncertain significance (May 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRWD1	protein_coding	protein_coding	ENST00000333229	42	137384

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.17e-7	125593	0	155	125748	0.000616

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.85	903	1.18e+3	0.767	0.0000597	15279
Missense in Polyphen		359	597.12	0.60122		7763
Synonymous	-0.950	424	400	1.06	0.0000199	4258
Loss of Function	8.46	17	115	0.148	0.00000624	1519

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00207	0.00187
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000979	0.000761
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000483	0.000360
Middle Eastern	0.000979	0.000761
South Asian	0.00167	0.00108
Other	0.00100	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a transcriptional activator. May be involved in chromatin remodeling (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}.
• Pathway: Interleukin-7 signaling;Interleukin-7 signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;Chromatin modifying enzymes;Immune System;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.462
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.646
• hipred: Y
• hipred_score: 0.614
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.702

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brwd1
• Phenotype: reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: chromatin organization;regulation of transcription by RNA polymerase II;cytoskeleton organization;regulation of cell shape;interleukin-7-mediated signaling pathway
• Cellular component: nucleus;nucleoplasm;nucleolus;cytosol
• Molecular function: molecular_function