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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
BRWD3
bromodomain and WD repeat domain containing 3
Chromosome X Β· Xq21.1
NCBI Gene: 254065Ensembl: ENSG00000165288.11HGNC: HGNC:17342UniProt: Q6RI45
35PubMed Papers
21Diseases
0Drugs
67Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of transcription by RNA polymerase IIcytoskeleton organizationregulation of cell shapenucleusintellectual disability, X-linked 93genetic disorderIntellectual disabilityX-linked syndromic intellectual disability
✦AI Summary

BRWD3 (bromodomain and WD repeat domain containing 3) is an X-linked gene that encodes a protein containing bromodomain and WD40 repeat domains, which are involved in chrX remodeling and transcriptional regulation 1. The protein plays a critical role in neurodevelopment, with pathogenic variants causing X-linked intellectual developmental disorder 93 2. Loss-of-function variants typically result in moderate to mild intellectual disability (65% and 35% respectively), postnatal macrocephaly (mean +2.8 SD), obesity (mean BMI +2.0 SD), speech delay, and behavioral issues including aggressive behavior and autism spectrum disorders 3. The clinical phenotype shows genotype-phenotype correlation: null variants and deletions cause intellectual disability with overgrowth features 3, while specific missense variants in the WD40 repeat and bromodomain regions are associated with X-linked partial epilepsy without intellectual disability 1. BRWD3 has also been implicated in cancer biology, where it shows high expression in lung adenocarcinoma and regulates cell proliferation and apoptosis through p53 and p65 pathways 4. The gene's involvement in chrX regulation and transcriptional control underlies its diverse roles in neurodevelopment and cellular growth control.

Sources cited
1
BRWD3 variants cause X-linked intellectual developmental disorder with common features including ID, speech delay, macrocephaly, and obesity
PMID: 36414205
2
Null variants cause moderate-mild intellectual disability with macrocephaly/obesity phenotype and behavioral issues
PMID: 31714006
3
Missense variants in WD40 repeat and bromodomain regions cause X-linked partial epilepsy without intellectual disability
PMID: 36514184
4
BRWD3 is highly expressed in lung adenocarcinoma and regulates proliferation/apoptosis via p53 and p65 pathways
PMID: 39190898
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
intellectual disability, X-linked 93Open Targets
0.76Strong
genetic disorderOpen Targets
0.50Moderate
Intellectual disabilityOpen Targets
0.46Moderate
X-linked syndromic intellectual disabilityOpen Targets
0.40Weak
MacrocephalyOpen Targets
0.37Weak
complex neurodevelopmental disorderOpen Targets
0.37Weak
X-linked non-syndromic intellectual disabilityOpen Targets
0.37Weak
angina pectorisOpen Targets
0.32Weak
autosomal dominant compelling helio-ophthalmic outburst syndromeOpen Targets
0.31Weak
Neurodevelopmental disorderOpen Targets
0.27Weak
non-syndromic X-linked intellectual disabilityOpen Targets
0.17Weak
autism spectrum disorderOpen Targets
0.12Weak
developmental disabilityOpen Targets
0.11Weak
congenital herpes simplex virus infectionOpen Targets
0.05Suggestive
autosomal recessive primary microcephalyOpen Targets
0.05Suggestive
Seckel syndrome 6Open Targets
0.05Suggestive
lymphomaOpen Targets
0.03Suggestive
epilepsyOpen Targets
0.02Suggestive
obesityOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
Intellectual developmental disorder, X-linked 93UniProt
Pathogenic Variants67
NM_153252.5(BRWD3):c.4006-1G>ALikely pathogenic
Intellectual disability, X-linked 93
β˜…β˜…β˜†β˜†2025
NM_153252.5(BRWD3):c.665_666del (p.Ser222fs)Pathogenic
Intellectual disability, X-linked 93|BRWD3- related syndromic intellectual disability
β˜…β˜…β˜†β˜†2025β†’ Residue 222
NM_153252.5(BRWD3):c.2248C>T (p.Arg750Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 750
NM_153252.5(BRWD3):c.3718C>T (p.Arg1240Ter)Pathogenic
not provided|Intellectual disability, X-linked 93
β˜…β˜…β˜†β˜†2024β†’ Residue 1240
NM_153252.5(BRWD3):c.3413G>A (p.Trp1138Ter)Pathogenic
Neurodevelopmental disorder|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 1138
NM_153252.5(BRWD3):c.5080C>T (p.Arg1694Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 1694
NM_153252.5(BRWD3):c.3119del (p.Tyr1040fs)Pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2025β†’ Residue 1040
NM_153252.5(BRWD3):c.3784C>T (p.Arg1262Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1262
NM_153252.5(BRWD3):c.3254_3255insAGGA (p.Tyr1085Ter)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 1085
NM_153252.5(BRWD3):c.160C>T (p.Arg54Ter)Likely pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2025β†’ Residue 54
NM_153252.5(BRWD3):c.3373G>T (p.Glu1125Ter)Likely pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2025β†’ Residue 1125
NM_153252.5(BRWD3):c.4429C>T (p.Gln1477Ter)Likely pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2025β†’ Residue 1477
NM_153252.5(BRWD3):c.4225A>T (p.Lys1409Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1409
NM_153252.5(BRWD3):c.2620C>T (p.Gln874Ter)Pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2025β†’ Residue 874
NM_153252.5(BRWD3):c.3255_3256del (p.Tyr1085_Ser1086delinsTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1085
NM_153252.5(BRWD3):c.3264-1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_153252.5(BRWD3):c.3605G>T (p.Arg1202Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1202
NM_153252.5(BRWD3):c.987del (p.Gly330fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 330
NM_153252.5(BRWD3):c.1150C>T (p.Arg384Ter)Likely pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2025β†’ Residue 384
NM_153252.5(BRWD3):c.4186del (p.Gln1396fs)Likely pathogenic
Intellectual disability, X-linked 93
β˜…β˜†β˜†β˜†2024β†’ Residue 1396
View on ClinVar β†—
Related Genes
BRWD1Shared pathway100%ARHGAP20Protein interaction96%CUL4BProtein interaction81%UBXN7Protein interaction75%SYNE3Shared pathway50%PALM2AKAP2Shared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
68%
Lung
52%
Brain
38%
Liver
32%
Heart
26%
Gene Interaction Network
Click a node to explore
BRWD3BRWD1ARHGAP20CUL4BUBXN7SYNE3PALM2AKAP2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6RI45
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.11Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.07 [0.04–0.11]
RankingsWhere BRWD3 stands among ~20K protein-coding genes
  • #10,922of 20,598
    Most Researched35
  • #1,094of 5,498
    Most Pathogenic Variants67 Β· top quartile
  • #92of 17,882
    Most Constrained (LOEUF)0.11 Β· top 1%
Genes detectedBRWD3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway.
PMID: 36414205
Eur J Med Genet Β· 2023
1.00
2
Genomic characterization of lymphomas in patients with inborn errors of immunity.
PMID: 35687490
Blood Adv Β· 2022
0.90
3
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
PMID: 38114583
Eur J Hum Genet Β· 2024
0.80
4
Whole-genome sequencing identifies new candidate genes for nonobstructive azoospermia.
PMID: 36017582
Andrology Β· 2022
0.70
5
Variants in BRWD3 associated with X-linked partial epilepsy without intellectual disability.
PMID: 36514184
CNS Neurosci Ther Β· 2023
0.60