BRWD3

bromodomain and WD repeat domain containing 3, the group of WD repeat domain containing|Bromodomain containing

Basic information

Region (hg38): X:80669503-80809877

Links

ENSG00000165288 ∙ NCBI:254065 ∙ OMIM:300553 ∙ HGNC:17342 ∙ Uniprot:Q6RI45 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 93 (Moderate), mode of inheritance: AD
• intellectual disability, X-linked 93 (Strong), mode of inheritance: XL
• self-limited epilepsy with centrotemporal spikes (Limited), mode of inheritance: AD
• infantile spasms (Limited), mode of inheritance: AD
• intellectual disability, X-linked 93 (Definitive), mode of inheritance: XL
• X-linked syndromic intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 93	XL	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; Genitourinary; Musculoskeletal; Neurologic	7943039; 17668385; 19377476

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRWD3 gene.

• not_provided (539 variants)
• Inborn_genetic_diseases (119 variants)
• Intellectual_disability,_X-linked_93 (97 variants)
• not_specified (26 variants)
• BRWD3-related_disorder (24 variants)
• Intellectual_disability (5 variants)
• Neurodevelopmental_disorder (1 variants)
• History_of_neurodevelopmental_disorder (1 variants)
• Conotruncal_heart_malformations (1 variants)
• X-linked_syndromic_intellectual_disability (1 variants)
• BRWD3-related_X-linked_syndromic_intellectual_disability (1 variants)
• Autism_spectrum_disorder (1 variants)
• Developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRWD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153252.5. 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			12	106	17	135
missense	3	4	328	37	8	380
nonsense	12	11	3			26
start loss		1				1
frameshift	12	8	2			22
splice donor/acceptor (+/-2bp)	3	4				7
Total	30	28	345	143	25

Highest pathogenic variant AF is 0.0000036463

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRWD3	protein_coding	protein_coding	ENST00000373275	41	138835

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.77e-11	125725	0	4	125729	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.27	369	683	0.540	0.0000516	11844
Missense in Polyphen		70	193.72	0.36134		3392
Synonymous	-0.904	242	225	1.08	0.0000161	3374
Loss of Function	7.83	2	75.4	0.0265	0.00000587	1253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000365	0.0000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000879	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000275	0.0000176
Middle Eastern	0.0000879	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000269|PubMed:21834987}.
• Disease: DISEASE: Note=A chromosomal aberration involving BRWD3 can be found in patients with B-cell chronic lymphocytic leukemia (B- CLL). Translocation t(X;11)(q21;q23) with ARHGAP20 does not result in fusion transcripts but disrupts both genes.; DISEASE: Mental retardation, X-linked 93 (MRX93) [MIM:300659]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX93 is associated with macrocephaly. {ECO:0000269|PubMed:17668385}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0991

Intolerance Scores

• loftool: 0.0934
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.65

Haploinsufficiency Scores

• pHI: 0.721
• hipred: Y
• hipred_score: 0.728
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brwd3
• Phenotype: growth/size/body region phenotype; embryo phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;cytoskeleton organization;regulation of cell shape
• Cellular component: nucleus