BRWD3

Summary

BRWD3 (bromodomain and WD repeat domain containing 3, HGNC:17342) is a protein-coding gene on chromosome Xq21.1, encoding Bromodomain and WD repeat-containing protein 3 (Q6RI45). Plays a role in the regulation of cell morphology and cytoskeletal organization. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene contains a bromodomain and several WD repeats. It is thought to have a chromatin-modifying function, and may thus play a role in transcription. Mutations in this gene are associated with a spectrum of cognitive disabilities and X-linked macrocephaly. This gene is also associated with translocations in patients with B-cell chronic lymphocytic leukemia.

Source: NCBI Gene 254065 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked syndromic intellectual disability (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,187 total — 35 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_153252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17342
Approved symbol	BRWD3
Name	bromodomain and WD repeat domain containing 3
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	BRODL, MRX93, FLJ38568
Ensembl gene	ENSG00000165288
Ensembl biotype	protein_coding
OMIM	300553
Entrez	254065

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000373275, ENST00000473691, ENST00000478415, ENST00000487313, ENST00000497335

RefSeq mRNA: 1 — MANE Select: NM_153252 NM_153252

CCDS: CCDS14447

Canonical transcript exons

ENST00000373275 — 41 exons

Exon	Start	End
ENSE00001091952	80684010	80684162
ENSE00001369808	80724933	80725067
ENSE00001372257	80722562	80722787
ENSE00001386011	80728752	80728905
ENSE00001663157	80669503	80677363
ENSE00001677495	80744032	80744253
ENSE00001678338	80734118	80734218
ENSE00001681938	80735127	80735197
ENSE00001727377	80735988	80736088
ENSE00001728371	80733456	80733496
ENSE00001750623	80723748	80723876
ENSE00001791950	80729916	80730020
ENSE00001819035	80809441	80809877
ENSE00003459642	80691053	80691173
ENSE00003465014	80681997	80682094
ENSE00003466009	80809246	80809304
ENSE00003485557	80692940	80693051
ENSE00003485605	80716157	80716250
ENSE00003488326	80719489	80719656
ENSE00003503536	80689768	80689846
ENSE00003503733	80808539	80808598
ENSE00003511415	80686863	80687003
ENSE00003516887	80707427	80707503
ENSE00003518912	80703480	80703593
ENSE00003539840	80689967	80690092
ENSE00003544179	80682465	80682628
ENSE00003567192	80809013	80809042
ENSE00003576696	80791854	80791952
ENSE00003576914	80692089	80692150
ENSE00003587015	80709428	80709577
ENSE00003588936	80793622	80793772
ENSE00003595475	80681341	80681499
ENSE00003603925	80745569	80745729
ENSE00003613937	80717573	80717759
ENSE00003614601	80691823	80691978
ENSE00003618190	80696739	80696863
ENSE00003622873	80688069	80688125
ENSE00003648829	80704678	80704846
ENSE00003656837	80699957	80700064
ENSE00003660051	80685462	80685536
ENSE00003683494	80695908	80695990

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 90.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5226 / max 114.6246, expressed in 1503 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199840	2.3032	1079
199842	2.1511	850
199841	1.0312	566
199839	0.0372	6

Top tissues by expression

242 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	90.36	silver quality
epithelial cell of pancreas	CL:0000083	88.59	silver quality
calcaneal tendon	UBERON:0003701	88.56	gold quality
tendon	UBERON:0000043	88.07	gold quality
colonic epithelium	UBERON:0000397	87.36	gold quality
sural nerve	UBERON:0015488	87.07	gold quality
bone marrow cell	CL:0002092	86.32	gold quality
medial globus pallidus	UBERON:0002477	84.09	silver quality
adrenal tissue	UBERON:0018303	83.72	gold quality
esophagus squamous epithelium	UBERON:0006920	83.43	gold quality
kidney epithelium	UBERON:0004819	83.31	gold quality
pancreatic ductal cell	CL:0002079	82.81	gold quality
buccal mucosa cell	CL:0002336	82.57	gold quality
sperm	CL:0000019	82.55	silver quality
gingival epithelium	UBERON:0001949	82.54	silver quality
secondary oocyte	CL:0000655	82.06	gold quality
monocyte	CL:0000576	81.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.36	gold quality
leukocyte	CL:0000738	81.24	gold quality
ganglionic eminence	UBERON:0004023	80.58	gold quality
oocyte	CL:0000023	80.54	gold quality
globus pallidus	UBERON:0001875	80.50	silver quality
tonsil	UBERON:0002372	80.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.08	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.95	gold quality
corpus callosum	UBERON:0002336	79.71	gold quality
blood	UBERON:0000178	79.48	gold quality
bone marrow	UBERON:0002371	79.30	gold quality
superficial temporal artery	UBERON:0001614	79.26	gold quality
gingiva	UBERON:0001828	79.02	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

478 targeting BRWD3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6856-5P	100.00	65.47	1298

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• BRWD3 is therefore a new gene implicated in the etiology of XLMR associated with macrocephaly and may cause disease by altering intracellular signaling pathways affecting cellular proliferation. (PMID:17668385)
• Includes the identification of truncating mutations in this gene that segregated with mental retardation in the families tested. (PMID:19377476)
• potential serological biomarker of breast cancer (PMID:22024541)
• A nonsense mutation in BRWD3 in a family with X-linked intellectual disability associated with macrocephaly. (PMID:24462886)
• BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations. (PMID:29166413)
• 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)
• Variants in BRWD3 associated with X-linked partial epilepsy without intellectual disability. (PMID:36514184)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	brwd3	ENSDARG00000035540
mus_musculus	Brwd3	ENSMUSG00000063663
rattus_norvegicus	Brwd3	ENSRNOG00000002291
drosophila_melanogaster	BRWD3	FBGN0011785

Paralogs (2): PHIP (ENSG00000146247), BRWD1 (ENSG00000185658)

Protein

Protein identifiers

Bromodomain and WD repeat-containing protein 3 — Q6RI45 (reviewed: Q6RI45)

All UniProt accessions (1): Q6RI45

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.

Tissue specificity. Found in most adult tissues. Down-regulated in a majority of the B-CLL cases examined.

Disease relevance. 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. Intellectual developmental disorder, X-linked 93 (XLID93) [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 forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID93 is associated with macrocephaly. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6RI45-1	1, BRWD3-A	yes
Q6RI45-2	2, BRWD3-B
Q6RI45-3	3, BRWD3-C, BRWD3-D, BRWD3-E, BRWD3-F, BRWD3-G, BRWD3-L, BRWD3-M, BRWD3-N, BRWD3-O
Q6RI45-4	4, BRWD3-H, BRWD3-I, BRWD3-K, BRWD3-P
Q6RI45-5	5

RefSeq proteins (1): NP_694984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR052060	Bromo_WD_repeat	Family
IPR057451	BRWD/PHIP_AD	Domain
IPR057452	BRWD/PHIP_N	Domain

Pfam: PF00400, PF00439, PF25313, PF25437

UniProt features (46 total): compositionally biased region 16, repeat 8, modified residue 7, region of interest 5, splice variant 5, domain 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6RI45-F1	65.11	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 693, 703, 885, 886, 1577, 1579, 1763

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 308 (showing top): GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, CCAWYNNGAAR_UNKNOWN, ACTGCAG_MIR173P, GGGTGGRR_PAX4_03, GATA6_01, ZIC1_01, HIF1_Q3, AACTTT_UNKNOWN, LXR_Q3, EGR1_01, GOBP_REGULATION_OF_CELL_SHAPE, RFX1_01, SCGGAAGY_ELK1_02

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
organelle organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRWD3	ARHGAP20	Q9P2F6	957
BRWD3	CUL4B	Q13620	520
BRWD3	ZNF711	Q9Y462	508
BRWD3	UPF3B	Q9BZI7	437
BRWD3	CECR2	Q9BXF3	431
BRWD3	SP140L	Q9H930	421
BRWD3	ZDHHC9	Q9Y397	420
BRWD3	ATAD2B	Q9ULI0	405
BRWD3	SATL1	Q86VE3	398
BRWD3	ZNF891	A8MT65	396
BRWD3	CYLC1	P35663	391
BRWD3	TIMELESS	Q9UNS1	376
BRWD3	DDB1	Q16531	375
BRWD3	POF1B	Q8WVV4	375
BRWD3	NEXMIF	Q5QGS0	370

IntAct

12 interactions, top by confidence:

A	B	Type	Score
Rbm8a	GOSR1	psi-mi:“MI:0914”(association)	0.350
CUL4B	GPS1	psi-mi:“MI:0914”(association)	0.350
Cul4a	GPS1	psi-mi:“MI:0914”(association)	0.350
TERF1	XPO1	psi-mi:“MI:0914”(association)	0.350
Tpx2		psi-mi:“MI:0914”(association)	0.350
UBXN7	PJA2	psi-mi:“MI:0914”(association)	0.350
POLR2K	BDP1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
LLGL2	NKTR	psi-mi:“MI:0914”(association)	0.350
BRWD3	acnA	psi-mi:“MI:0915”(physical association)	0.000
ITSN1	BRWD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): BRWD3 (Co-fractionation), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-MS), BRWD3 (Affinity Capture-RNA), BRWD3 (Affinity Capture-RNA), DDB1 (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CUL4B (Affinity Capture-MS), USP7 (Affinity Capture-MS), HIST1H4A (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GLK3, A0A974CYQ5, A2AHJ4, A5WW08, D2HNY3, D2HWM5, E7F6T8, F1ND48, O15040, O70260, O95071, P59328, Q3TLR7, Q4V837, Q58DC2, Q58WW2, Q5E9J6, Q5F479, Q5FWP4, Q5NVC7, Q5R9B8, Q5RF77, Q5RGA4, Q5RHI5, Q5ZLG9, Q62671, Q66JG1, Q6DDH2, Q6P1W0, Q6P256, Q6PCD5, Q6PJI9, Q6RI45, Q80TP3, Q80U93, Q810L3, Q8C0M0, Q8CBW4, Q8CIK8, Q8CIN9

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1187 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	31
Uncertain significance	479
Likely benign	173
Benign	140

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
10802	NM_153252.5(BRWD3):c.3325+1G>T	Pathogenic
10803	NM_153252.5(BRWD3):c.946dup (p.Arg316fs)	Pathogenic
10804	NM_153252.5(BRWD3):c.4786A>G (p.Lys1596Glu)	Pathogenic
1203572	NM_153252.5(BRWD3):c.3729-1G>C	Pathogenic
1526410	NM_153252.5(BRWD3):c.3976C>T (p.Arg1326Ter)	Pathogenic
1526411	NM_153252.5(BRWD3):c.3413G>T (p.Trp1138Leu)	Pathogenic
1741595	NM_153252.5(BRWD3):c.4576G>T (p.Gly1526Ter)	Pathogenic
2230326	NM_153252.5(BRWD3):c.746G>A (p.Trp249Ter)	Pathogenic
2430139	NM_153252.5(BRWD3):c.828_829dup (p.Lys277fs)	Pathogenic
2498284	NM_153252.5(BRWD3):c.2864C>G (p.Ala955Gly)	Pathogenic
2501335	NM_153252.5(BRWD3):c.3784C>T (p.Arg1262Ter)	Pathogenic
2719614	NM_153252.5(BRWD3):c.2103_2104del (p.His701fs)	Pathogenic
2755363	NM_153252.5(BRWD3):c.4288dup (p.Ile1430fs)	Pathogenic
2866301	NM_153252.5(BRWD3):c.3448del (p.Val1150fs)	Pathogenic
3372637	NM_153252.4(BRWD3):c.593del	Pathogenic
3377339	NM_153252.5(BRWD3):c.2473G>T (p.Glu825Ter)	Pathogenic
3641921	NM_153252.5(BRWD3):c.2248C>T (p.Arg750Ter)	Pathogenic
373083	NM_153252.5(BRWD3):c.2598_2601dup (p.Leu868fs)	Pathogenic
374258	NM_153252.5(BRWD3):c.568C>T (p.Arg190Ter)	Pathogenic
3764597	NM_153252.5(BRWD3):c.263del (p.Pro88fs)	Pathogenic
3778600	NM_153252.5(BRWD3):c.3255_3256del (p.Tyr1085_Ser1086delinsTer)	Pathogenic
3905818	NM_153252.5(BRWD3):c.3264-1G>T	Pathogenic
4531357	NM_153252.5(BRWD3):c.3119del (p.Tyr1040fs)	Pathogenic
4531358	NM_153252.5(BRWD3):c.2620C>T (p.Gln874Ter)	Pathogenic
4599472	NM_153252.5(BRWD3):c.3254_3255insAGGA (p.Tyr1085Ter)	Pathogenic
4686406	NM_153252.5(BRWD3):c.4225A>T (p.Lys1409Ter)	Pathogenic
4713093	NM_153252.5(BRWD3):c.987del (p.Gly330fs)	Pathogenic
620222	NM_153252.5(BRWD3):c.4054A>T (p.Arg1352Ter)	Pathogenic
620311	NM_153252.5(BRWD3):c.5089C>T (p.Arg1697Ter)	Pathogenic
620459	NM_153252.5(BRWD3):c.4015G>T (p.Glu1339Ter)	Pathogenic

SpliceAI

6113 predictions. Top by Δscore:

Variant	Effect	Δscore
X:80681335:TCCTA:T	donor_loss	1.0000
X:80681336:CCTA:C	donor_loss	1.0000
X:80681337:CTAC:C	donor_loss	1.0000
X:80681338:TAC:T	donor_loss	1.0000
X:80681339:ACCTT:A	donor_loss	1.0000
X:80681340:CCT:C	donor_loss	1.0000
X:80681501:T:C	acceptor_gain	1.0000
X:80682468:G:C	donor_gain	1.0000
X:80684006:ATAC:A	donor_gain	1.0000
X:80684008:AC:A	donor_gain	1.0000
X:80684009:CC:C	donor_gain	1.0000
X:80684062:ACAT:A	donor_gain	1.0000
X:80684063:CATC:C	donor_gain	1.0000
X:80684065:T:TA	donor_gain	1.0000
X:80684093:AGTTT:A	donor_gain	1.0000
X:80684158:TAATC:T	acceptor_gain	1.0000
X:80684161:TC:T	acceptor_gain	1.0000
X:80684162:CC:C	acceptor_gain	1.0000
X:80684162:CCTA:C	acceptor_loss	1.0000
X:80684163:C:CC	acceptor_gain	1.0000
X:80684164:T:G	acceptor_loss	1.0000
X:80684415:AG:A	donor_gain	1.0000
X:80686861:A:AC	donor_gain	1.0000
X:80686862:C:CT	donor_gain	1.0000
X:80686862:CTG:C	donor_gain	1.0000
X:80686862:CTGG:C	donor_gain	1.0000
X:80688125:CCT:C	acceptor_gain	1.0000
X:80688127:T:C	acceptor_gain	1.0000
X:80688131:T:C	acceptor_gain	1.0000
X:80688131:T:TC	acceptor_gain	1.0000

AlphaMissense

11873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:80690073:A:G	W1208R	1.000
X:80690073:A:T	W1208R	1.000
X:80691892:A:G	W1138R	1.000
X:80691892:A:T	W1138R	1.000
X:80692116:A:G	W1100R	1.000
X:80692116:A:T	W1100R	1.000
X:80692120:G:C	S1098R	1.000
X:80692120:G:T	S1098R	1.000
X:80692122:T:G	S1098R	1.000
X:80692147:C:A	W1089C	1.000
X:80692147:C:G	W1089C	1.000
X:80692148:C:G	W1089S	1.000
X:80692149:A:G	W1089R	1.000
X:80692149:A:T	W1089R	1.000
X:80692943:A:T	V1087D	1.000
X:80693009:C:T	G1065E	1.000
X:80693010:C:A	G1065W	1.000
X:80693010:C:G	G1065R	1.000
X:80693010:C:T	G1065R	1.000
X:80693014:C:A	W1063C	1.000
X:80693014:C:G	W1063C	1.000
X:80693016:A:G	W1063R	1.000
X:80693016:A:T	W1063R	1.000
X:80693019:A:G	W1062R	1.000
X:80693019:A:T	W1062R	1.000
X:80693030:A:T	I1058K	1.000
X:80693035:A:C	S1056R	1.000
X:80693035:A:T	S1056R	1.000
X:80693037:T:G	S1056R	1.000
X:80693039:C:G	R1055P	1.000

dbSNP variants (sampled 300 via entrez): RS1000003134 (X:80718244 G>A), RS1000009584 (X:80690345 T>C), RS1000023398 (X:80750330 A>G), RS1000046026 (X:80687672 A>T), RS1000102599 (X:80737021 T>C), RS1000124590 (X:80708916 T>A), RS1000157988 (X:80677245 C>G), RS1000176443 (X:80755707 C>A), RS1000247727 (X:80714123 G>A), RS1000251807 (X:80740872 T>A), RS1000303472 (X:80773951 A>T), RS1000357339 (X:80731818 C>A), RS1000374009 (X:80791657 G>A), RS1000409576 (X:80683133 C>A,T), RS1000457865 (X:80706642 C>A)

Disease associations

OMIM: gene MIM:300553 | disease phenotypes: MIM:300659, MIM:217095, MIM:309510

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 93	Definitive	X-linked
self-limited epilepsy with centrotemporal spikes	Limited	Autosomal dominant
infantile spasms	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked syndromic intellectual disability	Definitive	XL

Mondo (8): intellectual disability, X-linked 93 (MONDO:0010393), intellectual disability (MONDO:0001071), conotruncal heart malformations (MONDO:0016581), autism spectrum disorder (MONDO:0005258), X-linked syndromic intellectual disability (MONDO:0020119), neurodevelopmental disorder (MONDO:0700092), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), infantile spasms (MONDO:0018097)

Orphanet (6): Conotruncal heart malformations (Orphanet:2445), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), OBSOLETE: X-linked syndromic intellectual disability (Orphanet:98464)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000378	Cupped ear
HP:0000400	Macrotia
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001419	X-linked recessive inheritance
HP:0001763	Pes planus
HP:0002007	Frontal bossing
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0011220	Prominent forehead

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003992_18	Photic sneeze reflex	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C567066	Mental Retardation, X-Linked 93 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3769296 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	3
sodium arsenite	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
arsenite	decreases reaction, affects binding	1
monomethylarsonic acid	increases expression	1
manganese chloride	increases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3773121	Binding	Binding affinity to biotinylated BRWD3 bromodomain-2 (unknown origin) expressed in Escherichia coli at 0.2 to 1 uM by Biolayer Interferometric analysis	Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SF86	HAP1 BRWD3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

236 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03490487	PHASE4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	PHASE4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00441896	PHASE2	COMPLETED	A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
NCT00442104	PHASE2	TERMINATED	Open-label Extension to Protocol 1042-0500
NCT02829827	PHASE2	TERMINATED	A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
NCT03976076	PHASE2	TERMINATED	A Study of Orally Administered JBPOS0101 in Refractory Infantile Spasms Patients
NCT06819670	PHASE2	RECRUITING	A Study to Prevent Infantile Spasms Relapse
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01046760	Not specified	UNKNOWN	Scholar Performance and Praxis Assessment in Children With Rolandic Epilepsy
NCT01335425	Not specified	COMPLETED	The Rolandic Epilepsy/ESES/Landau-Kleffner Syndrome and Correlation With Language Impairment Study
NCT01515436	Not specified	COMPLETED	The Effect of Music Periodicity on Interictal Epileptiform Discharges
NCT03465566	Not specified	UNKNOWN	Emotion Recognition in Benign Epilepsy of Childhood With Centro-Temporal Spikes (BECTS)
NCT03547050	Not specified	COMPLETED	Rolandic Epilepsy Genomewide Association International Study
NCT03865771	Not specified	RECRUITING	Sleep Related Memory Consolidation in Children With Age Related Focal Epilepsy.
NCT04325282	Not specified	COMPLETED	Transcranial Magnetic Stimulation for BECTS
NCT04357236	Not specified	COMPLETED	18F-FDG PET Imaging Analysis of Antiepileptic Drug Response in BECTS
NCT04569708	Not specified	COMPLETED	Sleep Spindles and Memory in Rolandic Epilepsy
NCT06545708	Not specified	RECRUITING	Music Perception in SeLECTs
NCT01006811	PHASE2/PHASE3	COMPLETED	Use of the Modified Atkins Diet in Infantile Spasms
NCT01549288	PHASE2/PHASE3	WITHDRAWN	Trial of the Modified Atkins Diet in Infantile Spasms Refractory to Hormonal Therapy