BRWD1

Summary

BRWD1 (bromodomain and WD repeat domain containing 1, HGNC:12760) is a protein-coding gene on chromosome 21q22.2, encoding Bromodomain and WD repeat-containing protein 1 (Q9NSI6). May be a transcriptional activator.

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) residues which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 2 bromodomains and multiple WD repeats. This gene is located within the Down syndrome region-2 on chromosome 21. Alternative splicing of this gene generates multiple transcript variants encoding distinct isoforms. In mouse, this gene encodes a nuclear protein that has a polyglutamine-containing region that functions as a transcriptional activation domain which may regulate chromatin remodelling and associates with a component of the SWI/SNF chromatin remodelling complex.

Source: NCBI Gene 54014 — RefSeq curated summary.

At a glance

• Gene–disease (curated): agammaglobulinemia (Limited, ClinGen) — +2 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 338 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 58
• Druggable target: yes
• MANE Select transcript: NM_033656

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12760
Approved symbol	BRWD1
Name	bromodomain and WD repeat domain containing 1
Location	21q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11315, N143, DCAF19
Ensembl gene	ENSG00000185658
Ensembl biotype	protein_coding
OMIM	617824
Entrez	54014

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 8 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000333229, ENST00000341322, ENST00000342449, ENST00000380800, ENST00000412604, ENST00000424441, ENST00000430093, ENST00000445245, ENST00000445668, ENST00000446924, ENST00000455867, ENST00000470108, ENST00000473813, ENST00000484090, ENST00000491564, ENST00000496759, ENST00000938703, ENST00000938704

RefSeq mRNA: 3 — MANE Select: NM_033656 NM_001007246, NM_018963, NM_033656

CCDS: CCDS13662, CCDS13663, CCDS33557

Canonical transcript exons

ENST00000342449 — 41 exons

Exon	Start	End
ENSE00001383767	39185482	39197415
ENSE00001622845	39224408	39224469
ENSE00001651462	39225086	39225197
ENSE00001674297	39228500	39228582
ENSE00001788177	39229312	39229436
ENSE00001883590	39313443	39313632
ENSE00002431924	39298432	39298582
ENSE00002433897	39276173	39276213
ENSE00002437169	39232177	39232284
ENSE00002446443	39236595	39236784
ENSE00002446887	39264891	39265019
ENSE00002458215	39293811	39294032
ENSE00002462623	39295743	39295903
ENSE00002465628	39280148	39280248
ENSE00002470382	39232373	39232498
ENSE00002482303	39278743	39278813
ENSE00002497178	39296265	39296363
ENSE00002497896	39269899	39270033
ENSE00002506458	39274374	39274472
ENSE00002520544	39277251	39277351
ENSE00002521348	39270283	39270433
ENSE00003490914	39264460	39264685
ENSE00003497316	39210786	39210929
ENSE00003515339	39313241	39313299
ENSE00003519259	39247701	39247832
ENSE00003520595	39209995	39210147
ENSE00003525602	39218152	39218272
ENSE00003529207	39213481	39213553
ENSE00003536179	39258487	39258672
ENSE00003562855	39202325	39202545
ENSE00003582172	39218505	39218660
ENSE00003583448	39206108	39206274
ENSE00003584341	39238479	39238573
ENSE00003600281	39255645	39255828
ENSE00003621343	39212666	39212707
ENSE00003641761	39312841	39312900
ENSE00003653232	39313072	39313101
ENSE00003655791	39250796	39250889
ENSE00003674456	39200219	39200386
ENSE00003675873	39198763	39199662
ENSE00003677382	39215237	39215362

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4478 / max 247.5100, expressed in 1811 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190485	21.3956	1811
190483	0.5625	340
190484	0.3701	199
190486	0.0946	47
190487	0.0251	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.52	gold quality
sural nerve	UBERON:0015488	96.56	gold quality
calcaneal tendon	UBERON:0003701	96.52	gold quality
middle temporal gyrus	UBERON:0002771	95.60	gold quality
adrenal tissue	UBERON:0018303	95.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.26	gold quality
secondary oocyte	CL:0000655	94.21	gold quality
nucleus accumbens	UBERON:0001882	94.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.95	gold quality
colonic epithelium	UBERON:0000397	93.77	gold quality
prefrontal cortex	UBERON:0000451	93.57	gold quality
tendon	UBERON:0000043	93.42	gold quality
ganglionic eminence	UBERON:0004023	93.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.82	gold quality
right frontal lobe	UBERON:0002810	92.78	gold quality
oocyte	CL:0000023	92.69	gold quality
amygdala	UBERON:0001876	92.63	gold quality
primary visual cortex	UBERON:0002436	92.63	gold quality
ventricular zone	UBERON:0003053	92.10	gold quality
buccal mucosa cell	CL:0002336	91.97	gold quality
caudate nucleus	UBERON:0001873	91.88	gold quality
cingulate cortex	UBERON:0003027	91.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.57	gold quality
anterior cingulate cortex	UBERON:0009835	91.37	gold quality
temporal lobe	UBERON:0001871	91.19	gold quality
putamen	UBERON:0001874	91.13	gold quality
telencephalon	UBERON:0001893	90.94	gold quality
tendon of biceps brachii	UBERON:0008188	90.90	gold quality
neocortex	UBERON:0001950	90.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

448 targeting BRWD1, 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-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-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4425	100.00	67.59	1049
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-188-3P	100.00	68.76	1240
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772

Literature-anchored findings (GeneRIF, showing 4)

• isolation and characterization of the gene located in the Down Syndrome critical region-2 of chromosome 21 (PMID:12359327)
• RNA-seq evidence of biallelic expression of BRWD1 and 10 neighboring genes in at least one primary human tissue tested indicates that the expression of BRWD1 is uncoupled from the control of the maternally inherited 5mCpG imprints at the WRB differentially methylated region (DMR) in disomic controls or trisomy (Down syndrome) individuals. (PMID:27100087)
• Study data indicate that, in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with transcription factor networks to drive late B-cell development. (PMID:30250168)
• Bi-allelic BRWD1 variants cause male infertility with asthenoteratozoospermia and likely primary ciliary dyskinesia. (PMID:33389130)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	brwd1	ENSDARG00000074747
mus_musculus	Brwd1	ENSMUSG00000022914
rattus_norvegicus	Brwd1	ENSRNOG00000001632
drosophila_melanogaster	BRWD3	FBGN0011785

Paralogs (2): PHIP (ENSG00000146247), BRWD3 (ENSG00000165288)

Protein

Protein identifiers

Bromodomain and WD repeat-containing protein 1 — Q9NSI6 (reviewed: Q9NSI6)

Alternative names: WD repeat-containing protein 9

All UniProt accessions (8): H0Y463, H0Y4A7, H0Y4R9, Q9NSI6, H0Y500, H0Y5I9, H7BZR9, H7C409

UniProt curated annotations — full annotation on UniProt →

Function. May be a transcriptional activator. May be involved in chromatin remodeling. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.

Subunit / interactions. Interacts with SMARCA4.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Cilium membrane. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Ubiquitously expressed. Expressed in respiratory epithelial cells and testis spermatozoa.

Disease relevance. Ciliary dyskinesia, primary, 51 (CILD51) [MIM:620438] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD51 is an autosomal recessive form characterized by male infertility due to multiple morphologic abnormalities of the sperm flagella, resulting in severely reduced progressive motility. Affected individuals have recurrent upper and lower respiratory infections, and some exhibit dextrocardia and/or situs inversus. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NSI6-1	A	yes
Q9NSI6-2	B
Q9NSI6-3	C
Q9NSI6-4	D

RefSeq proteins (3): NP_001007247, NP_061836, NP_387505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR018359	Bromodomain_CS	Conserved_site
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 (96 total): modified residue 33, compositionally biased region 19, region of interest 10, repeat 8, sequence variant 8, helix 6, splice variant 5, sequence conflict 3, domain 2, chain 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3Q2E	X-RAY DIFFRACTION	1.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSI6-F1	56.20	0.11

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 (33): 687, 696, 701, 710, 1289, 1475, 1477, 1479, 1605, 1607, 1678, 1683, 1686, 1755, 1756, 1786, 1788, 1793, 1820, 1867 …

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1266695	Interleukin-7 signaling
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-449147	Signaling by Interleukins
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360), regulation of cell morphogenesis (GO:0022604)

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

GO Cellular Component (13): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), axoneme (GO:0005930), motile cilium (GO:0031514), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by Interleukins	1
Chromatin organization	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
nuclear lumen	2
intracellular membraneless organelle	2
cilium	2
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
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cell projection membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2607 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRWD1	PSMG1	O95456	603
BRWD1	HMGN1	P05114	474
BRWD1	CRYZL1	O95825	468
BRWD1	LCA5L	O95447	464
BRWD1	SP140L	Q9H930	438
BRWD1	ADNP	Q9H2P0	404
BRWD1	SH3BGR	P55822	398
BRWD1	FAM120A2P	Q5T035	398
BRWD1	DCAF16	Q9NXF7	398
BRWD1	SH3BGRL	O75368	388
BRWD1	URB1	O60287	375
BRWD1	TLE3	Q04726	374
BRWD1	CREBBP	Q92793	371
BRWD1	GET1	O00258	369
BRWD1	DET1	Q7L5Y6	353

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
BRWD1	ITGB1	psi-mi:“MI:0915”(physical association)	0.400
BRWD1	PDIA3	psi-mi:“MI:0915”(physical association)	0.400
Lin28a	TAF12	psi-mi:“MI:0914”(association)	0.350
MMGT1	DERL1	psi-mi:“MI:0914”(association)	0.350
UBXN7	PJA2	psi-mi:“MI:0914”(association)	0.350
UBXN7	UBR5	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	KLHL18	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
	BRWD1	psi-mi:“MI:0915”(physical association)	0.000
BRWD1	PPP5C	psi-mi:“MI:0915”(physical association)	0.000
BRWD1	COPS5	psi-mi:“MI:0915”(physical association)	0.000
BRWD1	HIVEP2	psi-mi:“MI:0915”(physical association)	0.000
BRWD1	TAF1	psi-mi:“MI:0915”(physical association)	0.000
BRWD1	SYT4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (65): BRWD1 (Co-fractionation), BRWD1 (Co-fractionation), BRWD1 (Two-hybrid), BRWD1 (Two-hybrid), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Affinity Capture-MS), BRWD1 (Proximity Label-MS), BRWD1 (Proximity Label-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, A2AHJ4, D4A7T3, F1QW93, F1R5H6, O54927, O54929, O60885, P45481, Q08D75, Q0V8J1, Q1LUC3, Q4R8Y1, Q54BA2, Q54ZP5, Q5ZKG2, Q6DFF2, Q6JHU9, Q6RI45, Q7T2F6, Q86U86, Q8BSQ9, Q8K2F0, Q8VDD9, Q8WWQ0, Q90941, Q91Y44, Q921C3, Q92793, Q92830, Q9ESU6, Q9FGW9, Q9JHD2, Q9LXA7, Q9NSI6, Q9NYS7, Q9UIG0, Q9W5Z5, Q9Y6I7, Q9Z277

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	5	11.8×	5e-03
Viral Infection Pathways	5	7.7×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	6	11.2×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	246
Likely benign	34
Benign	20

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
816166	GRCh37/hg19 21q22.13-22.3(chr21:39410438-45171756)x1	Pathogenic
929785	NM_033656.4(BRWD1):c.656G>A (p.Arg219His)	Likely pathogenic
982437	NM_033656.4(BRWD1):c.5573A>T (p.Gln1858Leu)	Likely pathogenic

SpliceAI

6959 predictions. Top by Δscore:

Variant	Effect	Δscore
21:39198758:ATTAC:A	donor_loss	1.0000
21:39198759:TTAC:T	donor_loss	1.0000
21:39198760:TACCT:T	donor_loss	1.0000
21:39198761:ACCT:A	donor_loss	1.0000
21:39198762:C:CT	donor_loss	1.0000
21:39200214:CTTAC:C	donor_loss	1.0000
21:39200216:TA:T	donor_loss	1.0000
21:39200217:A:AC	donor_gain	1.0000
21:39200217:ACCAG:A	donor_loss	1.0000
21:39200218:C:CC	donor_gain	1.0000
21:39200383:CTTT:C	acceptor_gain	1.0000
21:39200384:TTT:T	acceptor_gain	1.0000
21:39200385:TT:T	acceptor_gain	1.0000
21:39200386:TC:T	acceptor_loss	1.0000
21:39200387:C:CA	acceptor_loss	1.0000
21:39200387:C:CC	acceptor_gain	1.0000
21:39200388:T:C	acceptor_loss	1.0000
21:39202556:A:C	acceptor_gain	1.0000
21:39206157:TGA:T	donor_gain	1.0000
21:39206270:TAAAT:T	acceptor_gain	1.0000
21:39206271:AAAT:A	acceptor_gain	1.0000
21:39206272:AAT:A	acceptor_gain	1.0000
21:39206274:TC:T	acceptor_loss	1.0000
21:39206275:C:CC	acceptor_gain	1.0000
21:39206275:CT:C	acceptor_loss	1.0000
21:39209990:ATTAC:A	donor_loss	1.0000
21:39209991:TTA:T	donor_loss	1.0000
21:39209992:TAC:T	donor_loss	1.0000
21:39209993:AC:A	donor_loss	1.0000
21:39209994:CCT:C	donor_loss	1.0000

AlphaMissense

15018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:39206263:C:A	M1403I	1.000
21:39206263:C:G	M1403I	1.000
21:39206263:C:T	M1403I	1.000
21:39210000:A:G	S1398P	1.000
21:39210018:A:C	Y1392D	1.000
21:39210028:A:C	N1388K	1.000
21:39210028:A:T	N1388K	1.000
21:39210030:T:C	N1388D	1.000
21:39210038:A:C	I1385R	1.000
21:39210038:A:T	I1385K	1.000
21:39210041:A:G	L1384P	1.000
21:39210050:T:G	D1381A	1.000
21:39210122:G:T	P1357Q	1.000
21:39210144:A:G	Y1350H	1.000
21:39210805:A:T	V1342D	1.000
21:39210816:A:C	F1338L	1.000
21:39210816:A:T	F1338L	1.000
21:39210817:A:C	F1338C	1.000
21:39210817:A:G	F1338S	1.000
21:39210818:A:G	F1338L	1.000
21:39210826:G:A	S1335F	1.000
21:39210827:A:G	S1335P	1.000
21:39224435:A:G	W1119R	1.000
21:39224435:A:T	W1119R	1.000
21:39224439:G:C	S1117R	1.000
21:39224439:G:T	S1117R	1.000
21:39224441:T:G	S1117R	1.000
21:39224466:C:A	W1108C	1.000
21:39224466:C:G	W1108C	1.000
21:39224468:A:G	W1108R	1.000

dbSNP variants (sampled 300 via entrez): RS1000017157 (21:39242884 T>C), RS1000075201 (21:39201114 C>T), RS1000080824 (21:39227327 C>T), RS1000099712 (21:39279325 T>C,G), RS1000145144 (21:39199669 A>G), RS1000151777 (21:39322115 T>C), RS1000156880 (21:39316469 G>A), RS1000169562 (21:39268896 G>A), RS1000248650 (21:39263966 C>T), RS1000264772 (21:39236866 CAGAG>C,CAG), RS1000270680 (21:39302987 A>G), RS1000281183 (21:39309465 G>T), RS1000291021 (21:39187669 A>T), RS1000325085 (21:39223870 G>A,C), RS1000330008 (21:39233945 G>A,C)

Disease associations

OMIM: gene MIM:617824 | disease phenotypes: MIM:620438, MIM:209850, MIM:211400

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 51	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
primary ciliary dyskinesia	Disputed	AR
agammaglobulinemia	Limited	AD

Mondo (6): ciliary dyskinesia, primary, 51 (MONDO:0957396), autism (MONDO:0005260), primary ovarian failure (MONDO:0005387), bronchiectasis (MONDO:0004822), male infertility (MONDO:0005372), situs inversus (MONDO:0010029)

Orphanet (2): Situs inversus totalis (Orphanet:101063), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000798	Oligozoospermia
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002205	Recurrent respiratory infections
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001419_13	Temperament (bipolar disorder)	4.000000e-06
GCST002541_120	Menarche (age at onset)	6.000000e-11
GCST002774_33	Cognitive function	9.000000e-07
GCST003518_70	Daytime sleep phenotypes	3.000000e-06
GCST006269_1212	General cognitive ability	4.000000e-08
GCST006269_1236	General cognitive ability	5.000000e-08
GCST006612_41	LDL cholesterol	2.000000e-14
GCST006614_108	Total cholesterol levels	5.000000e-19
GCST010243_130	Apolipoprotein B levels	2.000000e-16
GCST010988_333	Adult body size	4.000000e-08
GCST011494_104	Daytime nap	9.000000e-09
GCST011703_97	Smoking initiation	3.000000e-08
GCST90000047_268	Age at first sexual intercourse	3.000000e-08
GCST90002401_340	Platelet distribution width	4.000000e-09
GCST90011898_165	Alanine aminotransferase levels	6.000000e-11
GCST90013405_18	Liver enzyme levels (alanine transaminase)	4.000000e-13

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004703	age at menarche
EFO:0004337	intelligence
EFO:0007828	daytime rest measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0005670	smoking initiation
EFO:0009749	age at first sexual intercourse measurement
EFO:0007984	platelet component distribution width

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D001987	Bronchiectasis	C08.127.384
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D012857	Situs Inversus	C16.131.810

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3351192 (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

ChEMBL bioactivities

2 potent at pChembl≥5 of 10 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.92	Kd	1200	nM	CHEMBL4208820
5.00	IC50	1e+04	nM	CHEMBL4063051

PubChem BioAssay actives

2 with measured affinity, of 41 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-methylpyridine-2-carboxamide	1372276: Binding affinity to human partial length WDR9 bromodomain 2 (A1310 to E1430 residues) expressed in bacterial expression system by BROMOscan assay	kd	1.2000	uM
N-[3-(3-methyl-4-oxo-2,5,6,7-tetrahydroisoindol-1-yl)-4-phenoxyphenyl]methanesulfonamide	1455985: Inhibition of human WDR9 bromodomain 2 (A1310 to E1430 residues) expressed in bacterial expression system by BROMOscan assay	ic50	10.0000	uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation, increases expression	7
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
butylbenzyl phthalate	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, increases expression	1
Clorgyline	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1

ChEMBL screening assays

37 unique, capped per target: 37 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3383436	Binding	Inhibition of human WDR9 bromodomain 2 by BROMOscan assay	The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1LL	Abcam HeLa BRWD1 KO	Cancer cell line	Female
CVCL_SF84	HAP1 BRWD1 (-) 1	Cancer cell line	Male
CVCL_SF85	HAP1 BRWD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms