BRPF3

Summary

BRPF3 (bromodomain and PHD finger containing 3, HGNC:14256) is a protein-coding gene on chromosome 6p21.31, encoding Bromodomain and PHD finger-containing protein 3 (Q9ULD4). Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity.

Contributes to histone acetyltransferase activity. Involved in positive regulation of DNA replication. Located in nucleus. Part of MOZ/MORF histone acetyltransferase complex.

Source: NCBI Gene 27154 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 177 total — 1 pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_015695

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14256
Approved symbol	BRPF3
Name	bromodomain and PHD finger containing 3
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1286
Ensembl gene	ENSG00000096070
Ensembl biotype	protein_coding
OMIM	616856
Entrez	27154

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000339717, ENST00000357641, ENST00000441123, ENST00000441730, ENST00000446974, ENST00000449261, ENST00000454960, ENST00000527657, ENST00000532330, ENST00000532538, ENST00000534400, ENST00000534694, ENST00000926623, ENST00000926624, ENST00000926625, ENST00000926626, ENST00000926627, ENST00000926628, ENST00000926629, ENST00000968964, ENST00000968965

RefSeq mRNA: 1 — MANE Select: NM_015695 NM_015695

CCDS: CCDS34437

Canonical transcript exons

ENST00000357641 — 13 exons

Exon	Start	End
ENSE00001192931	36207313	36207444
ENSE00001264032	36204658	36204814
ENSE00001518899	36200297	36201770
ENSE00002187140	36196744	36196970
ENSE00002245383	36210216	36210528
ENSE00002461152	36222168	36222265
ENSE00002510864	36209787	36209915
ENSE00003460600	36211258	36211560
ENSE00003487136	36225267	36225364
ENSE00003544323	36213880	36214386
ENSE00003559027	36217917	36218010
ENSE00003609848	36230426	36232790
ENSE00003616997	36228902	36229056

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 91.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6202 / max 297.4962, expressed in 1811 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67495	19.2156	1806
67496	0.8945	504
67500	0.8788	509
67493	0.3933	188
67494	0.1136	43
67499	0.1129	22
67498	0.0116	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	91.73	gold quality
ventricular zone	UBERON:0003053	91.11	gold quality
sural nerve	UBERON:0015488	90.91	gold quality
right adrenal gland cortex	UBERON:0035827	90.38	gold quality
ileal mucosa	UBERON:0000331	90.17	gold quality
cortical plate	UBERON:0005343	90.14	gold quality
transverse colon	UBERON:0001157	89.87	gold quality
right adrenal gland	UBERON:0001233	89.75	gold quality
left adrenal gland	UBERON:0001234	89.64	gold quality
mucosa of transverse colon	UBERON:0004991	89.42	gold quality
left adrenal gland cortex	UBERON:0035825	89.15	gold quality
right testis	UBERON:0004534	89.13	gold quality
bone marrow cell	CL:0002092	88.61	gold quality
rectum	UBERON:0001052	88.42	gold quality
left testis	UBERON:0004533	88.38	gold quality
adrenal tissue	UBERON:0018303	88.33	gold quality
gastrocnemius	UBERON:0001388	88.26	gold quality
adrenal gland	UBERON:0002369	88.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.01	gold quality
cerebellar hemisphere	UBERON:0002245	87.90	gold quality
cerebellar cortex	UBERON:0002129	87.80	gold quality
islet of Langerhans	UBERON:0000006	87.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.63	gold quality
prefrontal cortex	UBERON:0000451	87.60	gold quality
testis	UBERON:0000473	87.57	gold quality
muscle of leg	UBERON:0001383	87.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.25	gold quality
minor salivary gland	UBERON:0001830	86.67	gold quality
right frontal lobe	UBERON:0002810	86.65	gold quality
adrenal cortex	UBERON:0001235	86.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

210 targeting BRPF3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	brpf3a	ENSDARG00000070513
danio_rerio	brpf3b	ENSDARG00000074238
mus_musculus	Brpf3	ENSMUSG00000063952
rattus_norvegicus	Brpf3	ENSRNOG00000028641
drosophila_melanogaster	Br140	FBGN0033155
caenorhabditis_elegans		WBGENE00003034
caenorhabditis_elegans		WBGENE00021810

Paralogs (8): JADE2 (ENSG00000043143), JADE1 (ENSG00000077684), MLLT10 (ENSG00000078403), BRD1 (ENSG00000100425), JADE3 (ENSG00000102221), PHF14 (ENSG00000106443), BRPF1 (ENSG00000156983), MLLT6 (ENSG00000275023)

Protein

Protein identifiers

Bromodomain and PHD finger-containing protein 3 — Q9ULD4 (reviewed: Q9ULD4)

All UniProt accessions (9): Q9ULD4, A8WI61, A8WI62, E9PI60, E9PJ12, E9PSF3, F6XDC4, H0Y7B4, H0Y7I6

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity. Plays a role in DNA replication initiation by directing KAT7/HBO1 specificity towards histone H3 ‘Lys-14’ acetylation (H3K14ac), thereby facilitating the activation of replication origins. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.

Subunit / interactions. Component of some HBO1 complex composed of KAT7/HBO1, MEAF6, ING4 or ING5, and BRPF3. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with KAT7/HBO1; the interaction is direct.

Subcellular location. Nucleus.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9ULD4-1	1	yes
Q9ULD4-2	2
Q9ULD4-3	3

RefSeq proteins (1): NP_056510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000313	PWWP_dom	Domain
IPR001487	Bromodomain	Domain
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018359	Bromodomain_CS	Conserved_site
IPR019542	Enhancer_polycomb-like_N	Domain
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR034732	EPHD	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR042005	BRPF3_ePHD	Domain
IPR050701	Histone_Mod_Regulator	Family

Pfam: PF00439, PF00855, PF10513, PF13831, PF13832

UniProt features (48 total): modified residue 11, compositionally biased region 8, strand 7, region of interest 6, helix 4, zinc finger region 3, domain 2, splice variant 2, sequence variant 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3PFS	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULD4-F1	68.07	0.36

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 (11): 17, 400, 403, 447, 449, 671, 713, 740, 900, 962, 965

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-3214847	HATs acetylate histones
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-109582	Hemostasis
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 179 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GCM_GSPT1, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GCM_ZNF198, GCM_BCL2L1, GOBP_REGULATION_OF_HEMOPOIESIS, AAAGGGA_MIR204_MIR211, GCM_SUFU, ACTTTAT_MIR1425P, CCCAGAG_MIR326, GOBP_CHROMATIN_REMODELING, GTGACTT_MIR224, GOBP_DNA_REPLICATION, GOBP_REGULATION_OF_CELL_DEVELOPMENT, GCM_RBM8A

GO Biological Process (7): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA replication (GO:0045740), regulation of developmental process (GO:0050793), regulation of hemopoiesis (GO:1903706), chromatin organization (GO:0006325)

GO Molecular Function (7): zinc ion binding (GO:0008270), protein binding (GO:0005515), histone H3K14 acetyltransferase activity (GO:0036408), histone H4K5 acetyltransferase activity (GO:0043995), histone H4K8 acetyltransferase activity (GO:0043996), histone H4K12 acetyltransferase activity (GO:0043997), metal ion binding (GO:0046872)

GO Cellular Component (5): histone acetyltransferase complex (GO:0000123), extracellular region (GO:0005576), nucleus (GO:0005634), cytosol (GO:0005829), MOZ/MORF histone acetyltransferase complex (GO:0070776)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Chromatin modifying enzymes	1
Regulation of TP53 Activity	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone H4 acetyltransferase activity	3
cellular anatomical structure	2
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
developmental process	1
regulation of biological process	1
regulation of immune system process	1
hemopoiesis	1
regulation of cell development	1
regulation of multicellular organismal development	1
cellular component organization	1
transition metal ion binding	1
binding	1
histone H3 acetyltransferase activity	1
cation binding	1
chromatin	1
protein acetyltransferase complex	1
intracellular membrane-bounded organelle	1
cytoplasm	1
H3 histone acetyltransferase complex	1

Protein interactions and networks

STRING

1232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRPF3	KAT7	O95251	916
BRPF3	MEAF6	Q9HAF1	767
BRPF3	ASXL2	Q76L83	744
BRPF3	ING4	Q9UNL4	646
BRPF3	KAT6B	Q8WYB5	568
BRPF3	JADE3	Q92613	486
BRPF3	ING5	Q8WYH8	485
BRPF3	BRD9	Q9H8M2	474
BRPF3	ASH1L	Q9NR48	447
BRPF3	JADE2	Q9NQC1	428
BRPF3	TAF12	Q16514	424
BRPF3	TAF2	Q6P1X5	421
BRPF3	TAF6L	Q9Y6J9	390
BRPF3	YEATS4	O95619	380
BRPF3	BRD1	O95696	379

IntAct

42 interactions, top by confidence:

A	B	Type	Score
KAT7	JADE1	psi-mi:“MI:0914”(association)	0.720
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
ING5	KAT7	psi-mi:“MI:0914”(association)	0.530
KAT7	BRD1	psi-mi:“MI:0914”(association)	0.530
MEAF6	ANKRD17	psi-mi:“MI:0914”(association)	0.530
NFE2L2	BRPF3	psi-mi:“MI:0915”(physical association)	0.510
BRPF3	ABL1	psi-mi:“MI:0915”(physical association)	0.400
FYN	BRPF3	psi-mi:“MI:0915”(physical association)	0.400
GRB2	BRPF3	psi-mi:“MI:0915”(physical association)	0.400
BRPF3	NCK1	psi-mi:“MI:0915”(physical association)	0.400
BRPF3	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
BRPF3	H3-4	psi-mi:“MI:0915”(physical association)	0.400
BRPF3	PES1	psi-mi:“MI:0915”(physical association)	0.400
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
WEE1	CEP350	psi-mi:“MI:0914”(association)	0.350
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
MEAF6	DAPK3	psi-mi:“MI:0914”(association)	0.350
KAT7	BRD1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ING5	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MEAF6	KPNA5	psi-mi:“MI:0914”(association)	0.350
BRD1	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (188): BRPF3 (Affinity Capture-MS), BRPF3 (Affinity Capture-MS), BRPF3 (Affinity Capture-MS), BRPF3 (Affinity Capture-MS), BRPF3 (Co-localization), BRPF3 (Affinity Capture-MS), BRPF3 (Affinity Capture-RNA), BRPF3 (Two-hybrid), BRPF3 (Proximity Label-MS), BRPF3 (Proximity Label-MS), BRPF3 (Affinity Capture-MS), BRPF3 (Affinity Capture-MS), KAT7 (Affinity Capture-MS), TP53 (Affinity Capture-MS), MCC (Affinity Capture-MS)

ESM2 similar proteins: A0A286Y9D1, A0JMK9, A2BIL7, A8DZJ1, B2KF05, B2RRD7, B4KLY7, F4IDY7, O15042, O94880, O97159, P55201, P97496, Q05913, Q20448, Q2T9V9, Q3T095, Q4V7A6, Q5EA28, Q5R7X2, Q61103, Q63ZP1, Q6DD45, Q6FSB1, Q6GQJ2, Q6IE81, Q6IE82, Q6NV83, Q6NWE1, Q6P2L6, Q6ZPI0, Q7KRW8, Q7ZVP1, Q803A0, Q8BRB7, Q8WML3, Q8WUB8, Q92613, Q92785, Q92922

Diamond homologs: A0A286Y9D1, A1YVX4, A7E320, B2KF05, B2RRD7, B6CHA3, F4KBP5, F6UA42, G5E8P1, G5EBZ4, O54826, O75164, O94880, O94953, P0CB22, P29375, P34447, P41229, P41230, P47156, P55197, P55198, P55201, Q0P4S5, Q12311, Q20318, Q22516, Q29EQ3, Q30DN6, Q38JA7, Q3UXZ9, Q5E9T7, Q5RD88, Q5TKR9, Q62240, Q6GQJ2, Q6IE81, Q6IE82, Q6IQX0, Q6K431

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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
HATs acetylate histones	7	17.9×	4e-05
Chromatin organization	5	13.2×	2e-03
Chromatin modifying enzymes	5	11.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA replication	5	53.9×	6e-06
regulation of cell growth	5	32.6×	4e-05
regulation of cell cycle	7	15.3×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	161
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3246250	NC_000006.11:g.(?35773448)(36953949_?)del	Pathogenic

SpliceAI

2112 predictions. Top by Δscore:

Variant	Effect	Δscore
6:36207308:T:A	acceptor_gain	1.0000
6:36207310:TAGCG:T	acceptor_gain	1.0000
6:36207311:A:AG	acceptor_gain	1.0000
6:36207311:A:AT	acceptor_loss	1.0000
6:36207311:AGC:A	acceptor_gain	1.0000
6:36207311:AGCGA:A	acceptor_gain	1.0000
6:36207312:G:GA	acceptor_gain	1.0000
6:36207312:GC:G	acceptor_gain	1.0000
6:36207312:GCG:G	acceptor_gain	1.0000
6:36207312:GCGA:G	acceptor_gain	1.0000
6:36207312:GCGAG:G	acceptor_gain	1.0000
6:36207440:AGCAG:A	donor_gain	1.0000
6:36207441:GCAG:G	donor_gain	1.0000
6:36207441:GCAGG:G	donor_gain	1.0000
6:36207442:CAG:C	donor_gain	1.0000
6:36207443:AG:A	donor_gain	1.0000
6:36207443:AGG:A	donor_loss	1.0000
6:36207444:GG:G	donor_gain	1.0000
6:36207445:G:GG	donor_gain	1.0000
6:36207445:GTAA:G	donor_loss	1.0000
6:36209782:CACA:C	acceptor_loss	1.0000
6:36209784:CA:C	acceptor_loss	1.0000
6:36209785:A:AG	acceptor_gain	1.0000
6:36209785:A:C	acceptor_loss	1.0000
6:36209785:AG:A	acceptor_gain	1.0000
6:36209786:G:GT	acceptor_gain	1.0000
6:36209786:GG:G	acceptor_gain	1.0000
6:36209786:GGT:G	acceptor_gain	1.0000
6:36209786:GGTC:G	acceptor_gain	1.0000
6:36209786:GGTCA:G	acceptor_gain	1.0000

AlphaMissense

7901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:36200431:G:C	A37P	1.000
6:36200444:T:A	V41D	1.000
6:36200809:T:A	W163R	1.000
6:36200809:T:C	W163R	1.000
6:36200894:T:C	L191P	1.000
6:36200965:T:C	C215R	1.000
6:36200966:G:A	C215Y	1.000
6:36200967:C:G	C215W	1.000
6:36200974:T:A	C218S	1.000
6:36200974:T:C	C218R	1.000
6:36200975:G:A	C218Y	1.000
6:36200975:G:C	C218S	1.000
6:36200976:C:G	C218W	1.000
6:36201008:T:A	I229N	1.000
6:36201011:T:C	L230P	1.000
6:36201013:T:C	F231L	1.000
6:36201015:C:A	F231L	1.000
6:36201015:C:G	F231L	1.000
6:36201016:T:A	C232S	1.000
6:36201016:T:C	C232R	1.000
6:36201017:G:A	C232Y	1.000
6:36201017:G:C	C232S	1.000
6:36201017:G:T	C232F	1.000
6:36201018:T:G	C232W	1.000
6:36201025:T:A	C235S	1.000
6:36201025:T:C	C235R	1.000
6:36201026:G:A	C235Y	1.000
6:36201026:G:C	C235S	1.000
6:36201026:G:T	C235F	1.000
6:36201027:C:G	C235W	1.000

dbSNP variants (sampled 300 via entrez): RS1000004050 (6:36219853 C>G), RS1000151670 (6:36220575 T>A,G), RS1000156091 (6:36213505 G>C), RS1000209649 (6:36213820 T>C), RS1000326677 (6:36231255 GTC>G), RS1000370622 (6:36207086 A>C,G), RS1000504138 (6:36220174 A>G), RS1000608771 (6:36215287 T>G), RS1000673404 (6:36208733 A>C,G), RS1000759224 (6:36196731 T>C,G), RS1000790265 (6:36196546 GC>G), RS1000835112 (6:36201856 A>G), RS1000853912 (6:36201489 A>T), RS1001025779 (6:36195323 C>A,G), RS1001039330 (6:36232878 A>C)

Disease associations

OMIM: gene MIM:616856 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (2): autism (MONDO:0005260), colitis (MONDO:0005292)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000717	Autism
HP:0002583	Colitis

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D003092	Colitis	C06.405.205.265; C06.405.469.158.188

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3108644 (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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
NI-57	Binding	6.39	pKd
OF-1	Binding	5.62	pKd

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	IC50	1010 nM

ChEMBL bioactivities

52 potent at pChembl≥5 of 60 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.57	Kd	27	nM	CHEMBL3774575
7.57	Kd	27	nM	CHEMBL5715923
7.00	Ki	100	nM	CHEMBL4069412
6.90	Kd	125.9	nM	CHEMBL4449894
6.85	IC50	140	nM	CHEMBL3752151
6.72	IC50	190	nM	CHEMBL4103077
6.58	IC50	260	nM	CHEMBL4102050
6.55	IC50	280	nM	CHEMBL4059962
6.39	Kd	408	nM	CHEMBL3752151
6.39	Kd	410	nM	CHEMBL3752151
6.39	Kd	409	nM	CHEMBL3752151
6.23	IC50	590	nM	CHEMBL4087315
6.10	Ki	794.3	nM	CHEMBL3590408
6.03	Kd	940	nM	CHEMBL4102050
6.00	IC50	1010	nM	CHEMBL3752151
6.00	IC50	1000	nM	CHEMBL4076056
6.00	IC50	1011	nM	CHEMBL3752151
6.00	Kd	1000	nM	CHEMBL3356143
5.70	IC50	2000	nM	CHEMBL4102050
5.66	IC50	2200	nM	CHEMBL4102751
5.66	IC50	2200	nM	CHEMBL4084805
5.66	IC50	2200	nM	CHEMBL4064071
5.64	IC50	2300	nM	CHEMBL4081438
5.62	Kd	2400	nM	CHEMBL3770173
5.62	Kd	2406	nM	CHEMBL3770173
5.61	IC50	2450	nM	CHEMBL4086276
5.34	IC50	4600	nM	CHEMBL4067917
5.34	IC50	4600	nM	CHEMBL4065116
5.29	IC50	5110	nM	CHEMBL3356143
5.27	Kd	5400	nM	CHEMBL4208820
5.26	IC50	5550	nM	CHEMBL4086276
5.16	IC50	7000	nM	CHEMBL3769965
5.12	IC50	7600	nM	CHEMBL4067436
5.06	Kd	8621	nM	CHEMBL3133807
5.03	IC50	9300	nM	CHEMBL4096095
5.00	IC50	1e+04	nM	CHEMBL4105505
5.00	IC50	1e+04	nM	CHEMBL4583297
5.00	Kd	1e+04	nM	CHEMBL5394573

PubChem BioAssay actives

41 with measured affinity, of 136 total; 26 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
N-[6-[3-[4-(dimethylamino)butoxy]-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282165: Binding affinity to recombinant human BRPF3 expressed in bacterial system by bromoscan assay	kd	0.0270	uM
4-bromo-2-methyl-5-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one	1436237: Binding affinity to human partial length BRPF3 expressed in bacterial expression system by BROMOscan method	ki	0.1000	uM
N-[4-bromo-3-[(3S)-3-methylpyrrolidin-1-yl]sulfonylphenyl]-2-[(4S)-4-cyclopropyl-4-methyl-2,5-dioxoimidazolidin-1-yl]acetamide	1561909: Binding affinity to human partial length BRPF3 (E588 to G701 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.1259	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.1400	uM
4-cyano-2-methoxy-N-(7-methoxy-1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.1900	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.2600	uM
4-cyano-N-(7-methoxy-1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.2800	uM
N-(7-methoxy-1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.5900	uM
8-[[(3R,4R)-3-[(1,1-dioxothian-4-yl)methoxy]-1-methylpiperidin-4-yl]amino]-3-methyl-5-(5-methyl-3-pyridinyl)-1H-1,7-naphthyridin-2-one	1234387: Binding affinity to BRPF3 (unknown origin) by BROMOscan panel based assay	ki	0.7943	uM
4-cyano-N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	1.0000	uM
4-cyano-N-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	2.2000	uM
N-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	2.2000	uM
N-(4-cyanophenyl)-1-methyl-2-oxoquinoline-6-sulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	2.2000	uM
3-chloro-4-cyano-N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1483635: Inhibition of human BRPF3 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	2.3000	uM
4-bromo-N-(6-methoxy-1,3-dimethyl-2-oxobenzimidazol-5-yl)-2-methylbenzenesulfonamide	1289208: Binding affinity to BRPF3 (unknown origin) by isothermal titration calorimetric analysis	kd	2.4000	uM
6-(3-hydroxypropyl)-2-(1,3,6-trimethyl-2-oxobenzimidazol-5-yl)benzo[de]isoquinoline-1,3-dione	1482490: Inhibition of BRPF3 (592 to 711 residues) (unknown origin) using biotin-acetylated histone H4 peptide as substrate after 30 mins by AlphaScreen assay	ic50	2.4500	uM
4-cyano-N-(1,3-diethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	4.6000	uM
4-cyano-2-methoxy-N-(1-methyl-2-oxo-3-propan-2-ylquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	4.6000	uM
N-(1,3-dimethyl-2-oxo-6-pyrrolidin-1-ylbenzimidazol-5-yl)-2-methoxybenzamide	1482418: Inhibition of BRPF3 (592 to 711 residues) (unknown origin) preincubated for 15 mins followed by addition of C-terminal biotinylated synthetic K5,12 diacetylated histone H4 (1 to 20 residues) peptide as substrate measured after 1 hr by TR-FRET assay	ic50	5.1100	uM
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	1372260: Binding affinity to human partial length BRPF3 (E588 to G701 residues) expressed in bacterial expression system by BROMOscan assay	kd	5.4000	uM
3,4-dimethoxy-N-[6-(4-methoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]benzenesulfonamide	1279919: Inhibition of BRPF3 (unknown origin) by Alpha Screen assay	ic50	7.0000	uM
N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	7.6000	uM
4-cyano-N-(7-methoxy-1,4-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1483635: Inhibition of human BRPF3 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	9.3000	uM
4-cyano-N-(8-fluoro-1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475726: Inhibition of human BRPF3 (588 to 701 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	10.0000	uM
N-(4-bromo-3-piperidin-1-ylsulfonylphenyl)-2-(4-cyclopropyl-4-methyl-2,5-dioxoimidazolidin-1-yl)acetamide	1516824: Inhibition of BRPF3 (unknown origin) by TR-FRET assay	ic50	10.0000	uM
4-acetyl-N-[(2,8-dihydroxynaphthalen-1-yl)methyl]-3-ethyl-5-methylpyrrolidine-2-carboxamide	2027185: Binding affinity to BRPF3 (unknown origin) assessed as dissociation constant	kd	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	8
Ozone	affects cotreatment, increases expression, affects expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
glycidyl methacrylate	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases expression	1

ChEMBL screening assays

89 unique, capped per target: 88 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3111500	Binding	Binding affinity to BRPF3 bromodomain (unknown origin) assessed as change in melting temperature at 10 uM by differential scanning fluorimetric analysis	[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains. — J Med Chem
CHEMBL5210072	Functional	Affinity Phenotypic Cellular interaction (Inhibition of murine osteoclast differentiation in BMC cells) EUB0000323b BRPF3	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SF78	HAP1 BRPF3 (-) 1	Cancer cell line	Male
CVCL_SF79	HAP1 BRPF3 (-) 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