BRPF1

Summary

BRPF1 (bromodomain and PHD finger containing 1, HGNC:14255) is a protein-coding gene on chromosome 3p25.3, encoding Peregrin (P55201). Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity. It is a selective cancer dependency (DepMap: 14.7% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a bromodomain, PHD finger and chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain containing protein. The encoded protein is a component of the MOZ/MORF histone acetyltransferase complexes which function as a transcriptional regulators. This protein binds to the catalytic MYST domains of the MOZ and MORF proteins and may play a role in stimulating acetyltransferase and transcriptional activity of the complex. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7862 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 503 total — 61 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 14.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001003694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14255
Approved symbol	BRPF1
Name	bromodomain and PHD finger containing 1
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	BR140
Ensembl gene	ENSG00000156983
Ensembl biotype	protein_coding
OMIM	602410
Entrez	7862

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 26 protein_coding, 6 nonsense_mediated_decay, 2 retained_intron

ENST00000383829, ENST00000420291, ENST00000424362, ENST00000426583, ENST00000433861, ENST00000457855, ENST00000497565, ENST00000672126, ENST00000672515, ENST00000673551, ENST00000682208, ENST00000682980, ENST00000683423, ENST00000683639, ENST00000683743, ENST00000683986, ENST00000684199, ENST00000684206, ENST00000684223, ENST00000684250, ENST00000684333, ENST00000684573, ENST00000684608, ENST00000879788, ENST00000879789, ENST00000919137, ENST00000919138, ENST00000919139, ENST00000919140, ENST00000919141, ENST00000919142, ENST00000919143, ENST00000919144, ENST00000971788

RefSeq mRNA: 5 — MANE Select: NM_001003694 NM_001003694, NM_001319049, NM_001319050, NM_001410704, NM_004634

CCDS: CCDS2575, CCDS33692, CCDS82729, CCDS82730, CCDS93197

Canonical transcript exons

ENST00000383829 — 14 exons

Exon	Start	End
ENSE00001165176	9745812	9745930
ENSE00001165184	9745573	9745709
ENSE00001165191	9745008	9745155
ENSE00001165200	9744224	9744508
ENSE00001165208	9743578	9743901
ENSE00001165218	9742944	9743253
ENSE00001165232	9741308	9741439
ENSE00001165236	9740779	9740941
ENSE00001165242	9738999	9739958
ENSE00001309022	9747166	9748015
ENSE00001330625	9734131	9734739
ENSE00001498815	9742025	9742171
ENSE00001778810	9731735	9732138
ENSE00003536831	9746300	9746454

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 94.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0762 / max 128.7733, expressed in 1796 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35222	13.0290	1796
35223	0.0472	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.92	gold quality
secondary oocyte	CL:0000655	93.75	gold quality
granulocyte	CL:0000094	88.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.15	gold quality
endometrium epithelium	UBERON:0004811	83.55	silver quality
leukocyte	CL:0000738	83.40	gold quality
monocyte	CL:0000576	83.33	gold quality
mononuclear cell	CL:0000842	83.23	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	83.15	gold quality
gingival epithelium	UBERON:0001949	82.89	silver quality
lower lobe of lung	UBERON:0008949	82.85	gold quality
bone marrow cell	CL:0002092	82.80	gold quality
left testis	UBERON:0004533	82.66	gold quality
tongue squamous epithelium	UBERON:0006919	82.63	gold quality
right testis	UBERON:0004534	82.60	gold quality
cortical plate	UBERON:0005343	82.51	gold quality
parotid gland	UBERON:0001831	82.46	silver quality
ventricular zone	UBERON:0003053	82.46	gold quality
apex of heart	UBERON:0002098	82.42	gold quality
ganglionic eminence	UBERON:0004023	82.39	gold quality
testis	UBERON:0000473	82.17	gold quality
inferior olivary complex	UBERON:0002127	82.14	gold quality
left uterine tube	UBERON:0001303	81.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.55	gold quality
blood	UBERON:0000178	81.50	gold quality
cerebellar hemisphere	UBERON:0002245	81.30	gold quality
cerebellum	UBERON:0002037	81.25	gold quality
cerebellar cortex	UBERON:0002129	81.25	gold quality
amniotic fluid	UBERON:0000173	81.21	gold quality
embryo	UBERON:0000922	81.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ING5	Unknown
MEAF6	Unknown

Upstream regulators (CollecTRI, top): KAT6A, NCOA2

miRNA regulators (miRDB)

60 targeting BRPF1, 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-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-7515	99.31	68.22	1795

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 14.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• Identified is the PWWP domain of bromo and plant homeodomain (PHD) finger-containing protein 1 (BRPF1) as a histone H3 (H3K36me3) binding module; determined is the structure of this domain in complex with an H3K36me3-derived peptide. (PMID:20400950)
• MOZ-TIF2/BRPF1 complex upregulates HOX genes mediated by MOZ-dependent histone acetylation, leading to the development of leukemia. (PMID:24258712)
• novel interactions of the BRPF1 bromodomain with multiple acetyllysine residues on the N-terminus of histones show that it preferentially selects for H2AK5ac, H4K12ac, and H3K14ac (PMID:24333487)
• critical insights into the molecular mechanism of ligand binding by the BRPF1 bromodomain (PMID:25281266)
• comparison of the clinical symptoms of individuals carrying mutations or small deletions of BRPF1 alone or SETD5 alone with those of individuals with deletions encompassing both BRPF1 and SETD5; leads to conclusion that both genes contribute to the phenotypic severity of 3p25 deletion syndrome but that some specific features, such as ptosis and blepharophimosis, are mostly driven by BRPF1 haploinsufficiency (PMID:27939639)
• data indicate that aberrations in the chromatin regulator gene BRPF1 cause histone H3 acetylation deficiency and a previously unrecognized intellectual disability syndrome (PMID:27939640)
• Molecular Basis for the PZP Domain of BRPF1 Association with Chromatin. (PMID:31711755)
• Truncated BRPF1 Cooperates with Smoothened to Promote Adult Shh Medulloblastoma. (PMID:31851932)
• Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer. (PMID:34285329)
• Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Canakkale with intellectual disability and dysmorphic facies: Case report and review of the literature. (PMID:37190896)
• Pygo2 activates BRPF1 via Pygo2-H3K4me2/3 interaction to maintain malignant progression in colon cancer. (PMID:37423512)
• Beyond ‘speech delay’: Expanding the phenotype of BRPF1-related disorder. (PMID:38346666)
• Broadening the ocular phenotypic spectrum of ultra-rare BRPF1 variants: report of two cases. (PMID:38590032)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	brpf1	ENSDARG00000103665
mus_musculus	Brpf1	ENSMUSG00000001632
rattus_norvegicus	Brpf1	ENSRNOG00000008142
drosophila_melanogaster	Br140	FBGN0033155
caenorhabditis_elegans		WBGENE00003034
caenorhabditis_elegans		WBGENE00021810

Paralogs (8): JADE2 (ENSG00000043143), JADE1 (ENSG00000077684), MLLT10 (ENSG00000078403), BRPF3 (ENSG00000096070), BRD1 (ENSG00000100425), JADE3 (ENSG00000102221), PHF14 (ENSG00000106443), MLLT6 (ENSG00000275023)

Protein

Protein identifiers

Peregrin — P55201 (reviewed: P55201)

Alternative names: Bromodomain and PHD finger-containing protein 1, Protein Br140

All UniProt accessions (16): P55201, A0A5F9ZH11, A0A5F9ZHW9, A0A5F9ZHX4, A0A804HHW3, A0A804HI52, A0A804HIN1, A0A804HJV3, A0A804HKK9, A0A804HKU6, A0A804HKY8, A0A804HL48, A0A804HL99, A0A8C8KWW5, A0A8C8L8G4, C9JHC0

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 key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 ‘Lys-14’ acetylation (H3K14ac). Some HAT complexes preferentially mediate histone H3 ‘Lys-23’ (H3K23ac) acetylation. Positively regulates the transcription of RUNX1 and RUNX2.

Subunit / interactions. Component of some HBO1 complex composed of KAT7/HBO1, MEAF6, ING5, and BRPF1. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts (via PHD-type zinc finger domains) with unmethylated histone H3 at ‘Lys-4’ (H3K4me0). Interacts with trimethylated ‘Lys-36’ of histone H3 (H3K36me3). Interacts with ING5; interaction directs BRPF1 to H4K4me3-enriched chromatin at the 5’ of active genes. Interacts with KAT7.

Subcellular location. Nucleus. Chromosome. Cytoplasm.

Tissue specificity. High levels in testis.

Post-translational modifications. Acetylated by KAT6A.

Disease relevance. Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) [MIM:617333] An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and facial dysmorphisms, most notably ptosis. Additional features may include poor growth, hypotonia, and seizures. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
P55201-1	1	yes
P55201-2	2
P55201-3	3
P55201-4	4

RefSeq proteins (5): NP_001003694, NP_001305978, NP_001305979, NP_001397633, NP_004625 (=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
IPR013087	Znf_C2H2_type	Domain
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
IPR042008	BRPF1_PHD	Domain
IPR042061	Peregrin_ePHD	Domain
IPR049583	BRPF1_PWWP	Domain
IPR050701	Histone_Mod_Regulator	Family

Pfam: PF00439, PF00855, PF10513, PF13831, PF13832

UniProt features (97 total): strand 23, helix 17, modified residue 13, sequence variant 9, compositionally biased region 8, region of interest 7, sequence conflict 6, zinc finger region 4, turn 4, splice variant 3, domain 2, chain 1

Structure

Experimental structures (PDB)

66 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5MWZ	X-RAY DIFFRACTION	1.25
3L42	X-RAY DIFFRACTION	1.3
5C6S	X-RAY DIFFRACTION	1.3
5FFV	X-RAY DIFFRACTION	1.3
5O5F	X-RAY DIFFRACTION	1.3
5ETB	X-RAY DIFFRACTION	1.33
5D7X	X-RAY DIFFRACTION	1.35
7C4I	X-RAY DIFFRACTION	1.37
5EM3	X-RAY DIFFRACTION	1.4
5ETD	X-RAY DIFFRACTION	1.4
8QAZ	X-RAY DIFFRACTION	1.4
8QB2	X-RAY DIFFRACTION	1.42
5EV9	X-RAY DIFFRACTION	1.45
5EVA	X-RAY DIFFRACTION	1.45
5O55	X-RAY DIFFRACTION	1.45
8QB0	X-RAY DIFFRACTION	1.45
5EPS	X-RAY DIFFRACTION	1.47
2X4W	X-RAY DIFFRACTION	1.5
5FFW	X-RAY DIFFRACTION	1.5
5FG5	X-RAY DIFFRACTION	1.5
5MWG	X-RAY DIFFRACTION	1.5
5O4T	X-RAY DIFFRACTION	1.5
5T4U	X-RAY DIFFRACTION	1.5
5C87	X-RAY DIFFRACTION	1.55
5EQ1	X-RAY DIFFRACTION	1.55
5FFY	X-RAY DIFFRACTION	1.55
5EWD	X-RAY DIFFRACTION	1.58
5G4S	X-RAY DIFFRACTION	1.6
5O5A	X-RAY DIFFRACTION	1.6
5EWH	X-RAY DIFFRACTION	1.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55201-F1	68.74	0.29

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 (13): 120, 147, 238, 460, 462, 580, 858, 860, 917, 922, 926, 1076, 1187

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
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)

MSigDB gene sets: 376 (showing top): LFA1_Q6, CMYB_01, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, COUP_01, GOBP_REGULATION_OF_HEMOPOIESIS, E2F1DP1_01, E2F1DP2_01, BLALOCK_ALZHEIMERS_DISEASE_UP, INGRAM_SHH_TARGETS_DN, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, CTGYNNCTYTAA_UNKNOWN, GOBP_CHROMATIN_REMODELING, GOBP_REGULATION_OF_CELL_DEVELOPMENT, ACACTCC_MIR122A, GOCC_TRANSFERASE_COMPLEX

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-templated transcription (GO:0045893), regulation of developmental process (GO:0050793), regulation of hemopoiesis (GO:1903706), chromatin organization (GO:0006325)

GO Molecular Function (8): DNA binding (GO:0003677), zinc ion binding (GO:0008270), acetyltransferase activator activity (GO:0010698), protein binding (GO:0005515), 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 (8): histone acetyltransferase complex (GO:0000123), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), MOZ/MORF histone acetyltransferase complex (GO:0070776), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone H4 acetyltransferase activity	3
cellular anatomical structure	3
DNA-templated transcription	2
regulation of DNA-templated transcription	2
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of RNA biosynthetic 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
nucleic acid binding	1
transition metal ion binding	1
enzyme activator activity	1
acetyltransferase activity	1
binding	1
cation binding	1
chromatin	1
protein acetyltransferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
H3 histone acetyltransferase complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRPF1	ING5	Q8WYH8	993
BRPF1	KAT6B	Q8WYB5	991
BRPF1	ASXL2	Q76L83	990
BRPF1	MEAF6	Q9HAF1	984
BRPF1	KAT7	O95251	931
BRPF1	ING4	Q9UNL4	848
BRPF1	H3-3A	P06351	650
BRPF1	H3C1	P02295	637
BRPF1	H3C14	Q71DI3	635
BRPF1	H3-5	Q6NXT2	635
BRPF1	H3-4	Q16695	635
BRPF1	H3-7	Q5TEC6	635
BRPF1	JMJD1C	Q15652	633
BRPF1	KMT2A	Q03164	624
BRPF1	PZP	P20742	571

IntAct

47 interactions, top by confidence:

A	B	Type	Score
BRPF1	H4C16	psi-mi:“MI:0407”(direct interaction)	0.560
BRPF1	H2AC11	psi-mi:“MI:0407”(direct interaction)	0.560
H4C16	BRPF1	psi-mi:“MI:0407”(direct interaction)	0.560
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
ING5	KAT7	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
ARRB1	SAG	psi-mi:“MI:0914”(association)	0.530
MEAF6	ANKRD17	psi-mi:“MI:0914”(association)	0.530
NFE2L2	BRPF1	psi-mi:“MI:0915”(physical association)	0.370
BRPF1	PBXIP1	psi-mi:“MI:0915”(physical association)	0.370
GTF2H1	BRPF1	psi-mi:“MI:0915”(physical association)	0.370
Pik3r2	EDIL3	psi-mi:“MI:0914”(association)	0.350
CSNK2B	OSBPL8	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGN5	SMCHD1	psi-mi:“MI:0914”(association)	0.350
NUCKS1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), BRPF1 (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: 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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA replication	6	55.0×	4e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	61
Likely pathogenic	31
Uncertain significance	294
Likely benign	84
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098370	NM_001003694.2(BRPF1):c.2255del (p.Gly752fs)	Pathogenic
1164021	NM_001003694.2(BRPF1):c.556C>T (p.Gln186Ter)	Pathogenic
1325379	NM_001003694.2(BRPF1):c.2798del (p.Pro933fs)	Pathogenic
1413493	NM_001003694.2(BRPF1):c.751C>T (p.Arg251Ter)	Pathogenic
1675901	NM_001003694.2(BRPF1):c.2953C>T (p.Gln985Ter)	Pathogenic
1685592	NM_001003694.2(BRPF1):c.964C>T (p.Gln322Ter)	Pathogenic
1685593	NM_001003694.2(BRPF1):c.2027A>G (p.Lys676Arg)	Pathogenic
1685594	NM_001003694.2(BRPF1):c.3152G>A (p.Gly1051Asp)	Pathogenic
1695061	NM_001003694.2(BRPF1):c.1755_1758del (p.Lys585fs)	Pathogenic
1700216	NM_001003694.2(BRPF1):c.1775dup (p.Arg593fs)	Pathogenic
1703728	NM_001003694.2(BRPF1):c.2420_2433del (p.Gln807fs)	Pathogenic
1706236	NM_001003694.2(BRPF1):c.883_884del (p.Met295fs)	Pathogenic
1805707	NM_001003694.2(BRPF1):c.1217dup (p.Tyr406Ter)	Pathogenic
2435595	NM_001003694.2(BRPF1):c.598del (p.Arg200fs)	Pathogenic
2442378	NM_001003694.2(BRPF1):c.945G>A (p.Trp315Ter)	Pathogenic
2479150	NM_001003694.2(BRPF1):c.1745G>A (p.Trp582Ter)	Pathogenic
2505774	NM_001003694.2(BRPF1):c.3346C>T (p.Arg1116Ter)	Pathogenic
2536853	NM_001003694.2(BRPF1):c.2430_2451delinsTCTGGCATC (p.Arg811fs)	Pathogenic
2633009	NM_001003694.2(BRPF1):c.789del (p.Gly264fs)	Pathogenic
2672220	NM_001003694.2(BRPF1):c.2545_2566dup (p.Ala856delinsGlyTer)	Pathogenic
268185	NM_001003694.2(BRPF1):c.1052_1053del (p.Val351fs)	Pathogenic
2691274	NM_001003694.2(BRPF1):c.940C>T (p.Gln314Ter)	Pathogenic
3024347	NM_001003694.2(BRPF1):c.2844dup (p.Lys949fs)	Pathogenic
3135110	NM_001003694.2(BRPF1):c.2072dup (p.Tyr691Ter)	Pathogenic
3236572	NM_001003694.2(BRPF1):c.491dup (p.His164fs)	Pathogenic
3254719	NM_001003694.2(BRPF1):c.396del (p.Asn132fs)	Pathogenic
3343955	NM_001003694.2(BRPF1):c.85C>T (p.Arg29Ter)	Pathogenic
3384083	NM_001003694.2(BRPF1):c.2345_2346del (p.Asn782fs)	Pathogenic
3482528	NM_001003694.2(BRPF1):c.2770C>T (p.Gln924Ter)	Pathogenic
3730971	NM_001003694.2(BRPF1):c.199C>T (p.Gln67Ter)	Pathogenic

SpliceAI

1675 predictions. Top by Δscore:

Variant	Effect	Δscore
3:9740774:CCCA:C	acceptor_loss	1.0000
3:9740776:CA:C	acceptor_loss	1.0000
3:9740777:A:AG	acceptor_gain	1.0000
3:9740778:G:GG	acceptor_gain	1.0000
3:9740923:G:GT	donor_gain	1.0000
3:9740924:A:T	donor_gain	1.0000
3:9740937:T:G	donor_gain	1.0000
3:9741297:T:TA	acceptor_gain	1.0000
3:9741303:TACAG:T	acceptor_gain	1.0000
3:9741304:A:AG	acceptor_gain	1.0000
3:9741304:ACAG:A	acceptor_loss	1.0000
3:9741304:ACAGA:A	acceptor_gain	1.0000
3:9741305:C:G	acceptor_gain	1.0000
3:9741305:CA:C	acceptor_loss	1.0000
3:9741305:CAG:C	acceptor_gain	1.0000
3:9741305:CAGAG:C	acceptor_gain	1.0000
3:9741306:A:AC	acceptor_loss	1.0000
3:9741306:A:AG	acceptor_gain	1.0000
3:9741306:AGA:A	acceptor_gain	1.0000
3:9741306:AGAGA:A	acceptor_gain	1.0000
3:9741307:G:GT	acceptor_gain	1.0000
3:9741307:GA:G	acceptor_gain	1.0000
3:9741307:GAG:G	acceptor_gain	1.0000
3:9741307:GAGA:G	acceptor_gain	1.0000
3:9741307:GAGAG:G	acceptor_gain	1.0000
3:9741433:G:GT	donor_gain	1.0000
3:9741435:AGACG:A	donor_gain	1.0000
3:9741436:GACG:G	donor_gain	1.0000
3:9741436:GACGG:G	donor_gain	1.0000
3:9741437:ACG:A	donor_gain	1.0000

AlphaMissense

8063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:9734201:T:G	Y21D	1.000
3:9734207:T:A	C23S	1.000
3:9734207:T:C	C23R	1.000
3:9734208:G:A	C23Y	1.000
3:9734208:G:C	C23S	1.000
3:9734209:C:G	C23W	1.000
3:9734222:T:C	C28R	1.000
3:9734223:G:A	C28Y	1.000
3:9734224:C:G	C28W	1.000
3:9734234:T:G	Y32D	1.000
3:9734250:G:A	G37D	1.000
3:9734261:C:A	H41N	1.000
3:9734261:C:G	H41D	1.000
3:9734263:C:A	H41Q	1.000
3:9734263:C:G	H41Q	1.000
3:9734265:T:C	L42P	1.000
3:9739042:T:C	Y215H	1.000
3:9739042:T:G	Y215D	1.000
3:9739043:A:C	Y215S	1.000
3:9739043:A:G	Y215C	1.000
3:9739051:G:C	D218H	1.000
3:9739052:A:T	D218V	1.000
3:9739060:G:A	D221N	1.000
3:9739060:G:C	D221H	1.000
3:9739060:G:T	D221Y	1.000
3:9739061:A:C	D221A	1.000
3:9739061:A:G	D221G	1.000
3:9739061:A:T	D221V	1.000
3:9739062:C:A	D221E	1.000
3:9739062:C:G	D221E	1.000

dbSNP variants (sampled 300 via entrez): RS1000085562 (3:9746896 A>G), RS1000135415 (3:9737787 G>T), RS1000317009 (3:9740196 C>T), RS1000394474 (3:9733259 A>G), RS1000604556 (3:9745327 CAG>C), RS1000908030 (3:9738356 T>G), RS1001404818 (3:9733302 T>C), RS1001418019 (3:9740506 T>C), RS1001672778 (3:9732191 C>T), RS1001690390 (3:9733458 A>G,T), RS1001725433 (3:9731915 G>C), RS1001792774 (3:9738519 G>A,C), RS1002016613 (3:9731322 G>C,T), RS1002067074 (3:9731083 T>C), RS1002267134 (3:9747433 T>C)

Disease associations

OMIM: gene MIM:602410 | disease phenotypes: MIM:617333, MIM:162200

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with dysmorphic facies and ptosis	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (5): intellectual developmental disorder with dysmorphic facies and ptosis (MONDO:0015022), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), neurofibromatosis type 1 (MONDO:0018975), sudden unexplained death in childhood (MONDO:1010117)

Orphanet (3): Ophthalmological abnormalities-facial dysmorphism-intellectual disability syndrome (Orphanet:698090), Neurofibromatosis type 1 (Orphanet:636), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000175	Cleft palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000356	Abnormality of the outer ear
HP:0000407	Sensorineural hearing impairment
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000960	Sacral dimple
HP:0001182	Tapered finger
HP:0001233	2-3 finger cutaneous syndactyly
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001344	Absent speech
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001677	Coronary artery atherosclerosis

GWAS associations

0 associations (top):

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
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3132741 (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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
PFI-4	Binding	7.89	pKd
NI-57	Binding	7.51	pKd
OF-1	Binding	7.0	pKd
compound 34 [PMID: 25974391]	Binding	6.86	pKd
compound 2 [PMID: 25408830]	Binding	5.6	pIC50
compound 1 [PMID: 25408830]	Binding	5.0	pIC50
compound 3 [PMID: 25408830]	Binding	4.3	pIC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 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
4-Bromo-N-(2,3-dihydro-6-methoxy-1,3-dimethyl-2-oxo-1H-benzimidazol-5-yl)-2-methyl-benzenesulfonamide	IC50	1200 nM
N-[2,3-Dihydro-1,3-dimethyl-2-oxo-6-(1-pyrrolidinyl)-1H-benzimidazol-5-yl]-2-methoxybenzamide	IC50	3520 nM

ChEMBL bioactivities

256 potent at pChembl≥5 of 297 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.50	Kd	0.3162	nM	CHEMBL3828191
9.49	Kd	0.32	nM	CHEMBL3356143
8.68	Kd	2.1	nM	CHEMBL3774575
8.60	IC50	2.512	nM	CHEMBL3828191
8.51	IC50	3.1	nM	CHEMBL3752151
8.30	IC50	5.012	nM	CHEMBL3828311
8.10	IC50	7.943	nM	CHEMBL3828191
8.10	IC50	7.9	nM	CHEMBL4102050
8.10	IC50	7.9	nM	CHEMBL3356143
8.05	IC50	9	nM	CHEMBL4069814
7.92	IC50	12	nM	CHEMBL4105505
7.92	IC50	12	nM	CHEMBL4103077
7.89	Kd	13	nM	CHEMBL3356143
7.85	Kd	14	nM	CHEMBL3774575
7.85	Kd	14	nM	CHEMBL5715923
7.82	IC50	15	nM	CHEMBL4059962
7.82	IC50	15	nM	CHEMBL4097011
7.80	IC50	15.85	nM	CHEMBL3828008
7.77	IC50	17	nM	CHEMBL4087315
7.70	IC50	19.95	nM	CHEMBL3828191
7.70	IC50	20	nM	CHEMBL3356143
7.62	IC50	24	nM	CHEMBL4061727
7.54	IC50	29	nM	CHEMBL4084805
7.51	Kd	31	nM	CHEMBL3752151
7.50	IC50	31.62	nM	CHEMBL3828684
7.50	IC50	31.62	nM	CHEMBL3827767
7.41	IC50	39	nM	CHEMBL4079434
7.40	IC50	40	nM	CHEMBL3356143
7.40	Kd	40	nM	CHEMBL4102050
7.37	IC50	43	nM	CHEMBL4076056
7.36	IC50	44	nM	CHEMBL4099455
7.33	IC50	47.2	nM	CHEMBL3752151
7.30	IC50	50.12	nM	CHEMBL3356143
7.30	IC50	50.12	nM	CHEMBL3828194
7.28	IC50	52	nM	CHEMBL4068981
7.28	IC50	53	nM	CHEMBL4102751
7.26	IC50	55	nM	CHEMBL4103693
7.25	IC50	56	nM	CHEMBL4103432
7.22	IC50	60	nM	CHEMBL4096095
7.21	IC50	62	nM	CHEMBL4081438
7.20	IC50	63.1	nM	CHEMBL3827114
7.19	IC50	65	nM	CHEMBL4067436
7.17	Kd	67	nM	CHEMBL4786813
7.16	IC50	70	nM	CHEMBL3752151
7.10	IC50	79.43	nM	CHEMBL1522313
7.10	IC50	79.43	nM	CHEMBL3827560
7.10	IC50	79.43	nM	CHEMBL3828354
7.10	IC50	80	nM	CHEMBL3770173
7.03	IC50	93	nM	CHEMBL4073708
7.00	IC50	100	nM	CHEMBL3356140

PubChem BioAssay actives

228 with measured affinity, of 556 total; 50 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-[1,3-dimethyl-6-[(2R)-2-methylpiperazin-1-yl]-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313302: Inhibition of human BRPF1 by BROMOscan assay	kd	0.0003	uM
N-[6-[3-[4-(dimethylamino)butoxy]-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282163: Binding affinity to recombinant human BRPF1 expressed in bacterial system by bromoscan assay	kd	0.0021	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0031	uM
N-[1,3-dimethyl-6-[(2R)-2-methylpyrrolidin-1-yl]-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0050	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0079	uM
N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0090	uM
4-cyano-2-methoxy-N-(7-methoxy-1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0120	uM
4-cyano-N-(8-fluoro-1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0120	uM
N-(1,3-dimethyl-2-oxo-6-pyrrolidin-1-ylbenzimidazol-5-yl)-2-methoxybenzamide	1289206: Binding affinity to BRPF1B (unknown origin) by isothermal titration calorimetric analysis	kd	0.0130	uM
4-cyano-N-(1-ethyl-3-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1483626: Inhibition of human BRPF1 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0150	uM
4-cyano-N-(7-methoxy-1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0150	uM
N-[1,3-dimethyl-6-[(2S)-2-methylpyrrolidin-1-yl]-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0158	uM
N-(7-methoxy-1,3-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0170	uM
4-cyano-N-(1,4-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0240	uM
N-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0290	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)-2-methoxypyridine-3-carboxamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0316	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0316	uM
4-cyano-N-(1-methyl-2-oxo-7-propan-2-yloxyquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0390	uM
4-cyano-N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0430	uM
3,4-dichloro-N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1483626: Inhibition of human BRPF1 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0440	uM
N-[6-(dimethylamino)-1,3-dimethyl-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0501	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxy-N-methylbenzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0520	uM
4-cyano-N-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0530	uM
4-cyano-N-(7-ethoxy-1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0550	uM
3-cyano-N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0560	uM
4-cyano-N-(7-methoxy-1,4-dimethyl-2-oxoquinolin-6-yl)benzenesulfonamide	1483626: Inhibition of human BRPF1 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0600	uM
3-chloro-4-cyano-N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1483626: Inhibition of human BRPF1 expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0620	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)pyridine-2-carboxamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0631	uM
N-(1-methyl-2-oxoquinolin-6-yl)benzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0650	uM
3-[(1,3-dimethyl-2-oxoquinolin-6-yl)sulfamoyl]-N-hydroxy-4-methoxybenzamide	1739563: Binding affinity to BRPF1 (unknown origin) by Isothermal titration calorimetry	kd	0.0670	uM
N-[1,3-dimethyl-6-[(3S)-3-methylpiperazin-1-yl]-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0794	uM
N-(1,3-dimethyl-2-oxo-6-piperazin-1-ylbenzimidazol-5-yl)-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.0794	uM
N-(1,3-dimethyl-2-oxo-6-piperidin-1-ylbenzimidazol-5-yl)-2-methoxybenzamide	1171278: Binding affinity to 6H-Flag-tagged Tev-BRPF1 (622-738 aa) (unknown origin) by TR-FRET competitive assay	ic50	0.0794	uM
4-cyano-N-(3-ethyl-1-methyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.0930	uM
4-[4-[(dimethylamino)methyl]-3,5-dimethoxyphenyl]-2-methyl-2,7-naphthyridin-1-one	2191059: Binding affinity to BRPF1B (unknown origin) assessed as dissociation constant by bromoKdselect analysis	kd	0.1000	uM
N-(4-cyanophenyl)-1-methyl-2-oxoquinoline-6-sulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.1000	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)-3-methoxypyridine-2-carboxamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1000	uM
2-[2-(dimethylamino)-2-oxoethoxy]-N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)benzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1000	uM
2-(2-amino-2-oxoethoxy)-N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)benzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1000	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)-2-(2-methoxyethoxy)benzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1000	uM
N-(1,3-dimethyl-2-oxo-6-piperidin-1-ylbenzimidazol-5-yl)benzamide	1171278: Binding affinity to 6H-Flag-tagged Tev-BRPF1 (622-738 aa) (unknown origin) by TR-FRET competitive assay	ic50	0.1000	uM
N-(1,3-dimethyl-2-oxo-6-piperidin-1-ylbenzimidazol-5-yl)-3-methoxybenzamide	1171278: Binding affinity to 6H-Flag-tagged Tev-BRPF1 (622-738 aa) (unknown origin) by TR-FRET competitive assay	ic50	0.1000	uM
4-bromo-N-(6-methoxy-1,3-dimethyl-2-oxobenzimidazol-5-yl)-2-methylbenzenesulfonamide	1289206: Binding affinity to BRPF1B (unknown origin) by isothermal titration calorimetric analysis	kd	0.1000	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-N-ethyl-2-methoxybenzenesulfonamide	1475722: Inhibition of human BRPF1 (627 to 740 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	0.1100	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)pyrimidine-4-carboxamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1259	uM
N-[1,3-dimethyl-6-[(2S)-2-methylpiperazin-1-yl]-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1259	uM
N-[1,3-dimethyl-6-[(3R)-3-methylpiperazin-1-yl]-2-oxobenzimidazol-5-yl]-2-methoxybenzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1259	uM
N-(1,3-dimethyl-2-oxo-6-propan-2-yloxybenzimidazol-5-yl)-2-(2-hydroxyethoxy)benzamide	1313295: Inhibition of synthetic fluorescent ligand binding to recombinant truncated 6H-Flag-TEV-BRPF1 (622 to 738 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells after 30 mins by TR-FRET assay	ic50	0.1259	uM
N-(1,3-dimethyl-6-morpholin-4-yl-2-oxobenzimidazol-5-yl)-2-methoxybenzamide	1171278: Binding affinity to 6H-Flag-tagged Tev-BRPF1 (622-738 aa) (unknown origin) by TR-FRET competitive assay	ic50	0.1259	uM
2-methoxy-N-(6-methoxy-1,3-dimethyl-2-oxobenzimidazol-5-yl)benzamide	1171278: Binding affinity to 6H-Flag-tagged Tev-BRPF1 (622-738 aa) (unknown origin) by TR-FRET competitive assay	ic50	0.1259	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases reaction, affects cotreatment, decreases expression, increases abundance, increases expression (+1 more)	4
perfluorooctanoic acid	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	increases reaction, affects binding	1
Smoke	decreases expression	1
Tamoxifen	increases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

175 unique, capped per target: 172 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3134636	Binding	Binding affinity to BRPF1 (unknown origin) at 4 uM by thermal shift assay	Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography — Medchemcomm
CHEMBL5210071	Functional	Affinity Phenotypic Cellular interaction (Inhibition of murine osteoclast differentiation in BMC cells) EUB0000323b BRPF1	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2T2	Abcam HEK293T BRPF1 KO	Transformed cell line	Female
CVCL_SF75	HAP1 BRPF1 (-) 1	Cancer cell line	Male
CVCL_SF76	HAP1 BRPF1 (-) 2	Cancer cell line	Male
CVCL_SF77	HAP1 BRPF1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice