SMARCA4

Summary

SMARCA4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4, HGNC:11100) is a protein-coding gene on chromosome 19p13.2, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (P51532). ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). In precision oncology, SMARCA4 Underexpression confers sensitivity to Cisplatin + Vinorelbine in Lung Non-small Cell Carcinoma (CIViC Level B); 4 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 31.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6597 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Coffin-Siris syndrome (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 37
• Clinical variants (ClinVar): 6,669 total — 204 pathogenic, 119 likely-pathogenic
• Phenotypes (HPO): 91
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 5 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 26 cancer types
• Cancer dependency (DepMap): dependent in 31.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_003072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11100
Approved symbol	SMARCA4
Name	SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	hSNF2b, BRG1, BAF190, SNF2, SWI2, SNF2-BETA, SNF2LB, FLJ39786
Ensembl gene	ENSG00000127616
Ensembl biotype	protein_coding
OMIM	603254
Entrez	6597

Gene structure

Transcript identifiers

Ensembl transcripts: 102 — 83 protein_coding, 9 retained_intron, 8 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000344626, ENST00000429416, ENST00000444061, ENST00000538456, ENST00000541122, ENST00000585799, ENST00000586122, ENST00000586892, ENST00000586921, ENST00000586985, ENST00000587988, ENST00000589677, ENST00000590574, ENST00000591545, ENST00000591595, ENST00000592158, ENST00000592604, ENST00000642350, ENST00000642508, ENST00000642628, ENST00000642726, ENST00000643208, ENST00000643296, ENST00000643534, ENST00000643549, ENST00000643857, ENST00000643929, ENST00000643995, ENST00000644065, ENST00000644267, ENST00000644290, ENST00000644327, ENST00000644737, ENST00000644760, ENST00000644963, ENST00000645061, ENST00000645236, ENST00000645387, ENST00000645460, ENST00000645648, ENST00000646183, ENST00000646236, ENST00000646484, ENST00000646510, ENST00000646513, ENST00000646593, ENST00000646693, ENST00000646746, ENST00000646889, ENST00000647011, ENST00000647230, ENST00000647268, ENST00000704344, ENST00000704345, ENST00000711079, ENST00000896342, ENST00000896343, ENST00000924714, ENST00000924715, ENST00000924716, ENST00000924717, ENST00000924718, ENST00000924719, ENST00000924720, ENST00000924721, ENST00000924722, ENST00000924723, ENST00000924724, ENST00000924725, ENST00000924726, ENST00000924727, ENST00000924728, ENST00000924729, ENST00000924730, ENST00000924731, ENST00000924732, ENST00000924733, ENST00000924734, ENST00000924735, ENST00000924736, ENST00000924737, ENST00000924738, ENST00000924739, ENST00000924740, ENST00000924741, ENST00000924742, ENST00000924743, ENST00000924744, ENST00000924745, ENST00000924746, ENST00000924747, ENST00000924748, ENST00000924749, ENST00000924750, ENST00000924751, ENST00000924752, ENST00000924753, ENST00000924754, ENST00000924755, ENST00000924756, ENST00000970840, ENST00000970841

RefSeq mRNA: 10 — MANE Select: NM_003072 NM_001128844, NM_001128845, NM_001128846, NM_001128847, NM_001128848, NM_001128849, NM_001374457, NM_001387283, NM_001411150, NM_003072

CCDS: CCDS12253, CCDS45972, CCDS45973, CCDS54217, CCDS54218, CCDS92517

Canonical transcript exons

ENST00000344626 — 35 exons

Exon	Start	End
ENSE00000874191	10984121	10984373
ENSE00003459233	11027784	11027950
ENSE00003468652	11058255	11058363
ENSE00003474879	11018957	11019023
ENSE00003477043	11019591	11019701
ENSE00003484961	11023518	11023631
ENSE00003525604	10986189	10986593
ENSE00003527768	10996213	10996380
ENSE00003530860	11010381	11010531
ENSE00003531833	10987666	10987924
ENSE00003539754	11003340	11003397
ENSE00003540089	11021725	11021967
ENSE00003546739	10994828	10995001
ENSE00003547338	11041307	11041560
ENSE00003553172	11024331	11024438
ENSE00003581372	11007902	11008023
ENSE00003582123	11059753	11059885
ENSE00003604518	11026300	11026346
ENSE00003604554	10986905	10987003
ENSE00003607688	10991150	10991323
ENSE00003618181	10985273	10985405
ENSE00003654082	11012949	11013112
ENSE00003655405	11033290	11033517
ENSE00003667107	11003029	11003159
ENSE00003667937	10996494	10996544
ENSE00003670957	10989317	10989443
ENSE00003676000	11030730	11030893
ENSE00003687872	11058788	11058889
ENSE00003692983	11025422	11025508
ENSE00003694052	11060045	11060187
ENSE00003703701	11034123	11034200
ENSE00003708931	11034914	11035132
ENSE00003824516	10961030	10961174
ENSE00004014465	11061784	11062273
ENSE00004014467	11033767	11033865

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.9747 / max 693.1100, expressed in 1823 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173881	37.9050	1815
173878	4.8231	1629
173880	3.1958	1449
173882	1.2455	722
173889	0.7275	396
173879	0.7000	432
173885	0.4838	243
173883	0.3907	222
173886	0.3142	122
208688	0.1892	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.79	gold quality
cortical plate	UBERON:0005343	98.76	gold quality
cervix squamous epithelium	UBERON:0006922	98.61	gold quality
tendon of biceps brachii	UBERON:0008188	98.49	gold quality
ventricular zone	UBERON:0003053	98.48	gold quality
lower esophagus mucosa	UBERON:0035834	98.27	gold quality
amniotic fluid	UBERON:0000173	97.97	gold quality
embryo	UBERON:0000922	97.78	gold quality
endometrium epithelium	UBERON:0004811	97.25	gold quality
epithelium of nasopharynx	UBERON:0001951	97.16	gold quality
sural nerve	UBERON:0015488	96.98	gold quality
squamous epithelium	UBERON:0006914	96.91	gold quality
middle temporal gyrus	UBERON:0002771	96.82	gold quality
esophagus squamous epithelium	UBERON:0006920	96.80	gold quality
primary visual cortex	UBERON:0002436	96.73	gold quality
endothelial cell	CL:0000115	96.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.66	gold quality
mucosa of transverse colon	UBERON:0004991	96.52	gold quality
cerebellar hemisphere	UBERON:0002245	96.46	gold quality
epithelium of esophagus	UBERON:0001976	96.45	gold quality
left testis	UBERON:0004533	96.41	gold quality
gingival epithelium	UBERON:0001949	96.40	gold quality
cerebellar cortex	UBERON:0002129	96.39	gold quality
right frontal lobe	UBERON:0002810	96.29	gold quality
right testis	UBERON:0004534	96.29	gold quality
stromal cell of endometrium	CL:0002255	96.19	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.10	gold quality
cerebellum	UBERON:0002037	96.09	gold quality
esophagus mucosa	UBERON:0002469	96.05	gold quality
pharyngeal mucosa	UBERON:0000355	95.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	40.86
E-ANND-3	yes	11.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
ABCA1	Activation
ABCG2	Activation
CAD	Unknown
CCND1	Repression
CD44	Repression
CDH1	Activation
CDKN1A	Activation
CDKN2A	Activation
FOS	Repression
MECOM	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ARID1B, ARNT, CEBPA, CUX1, DNMT3A, E2F4, ESR1, GTF2I, HIC1, HMGA1, HOXB7, IRF1, KMT2A, MITF, MYC, MYOD1, MYOG, MYRF, NFE2L2, NRG1, PBRM1, RFXAP, RUNX1, SMARCA1, SMARCC1, SMARCE1, STAT1, STAT6, TBX21, TFAP2A, TP53, TP63, VSX2, ZNF436

miRNA regulators (miRDB)

28 targeting SMARCA4, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-3918	96.13	64.65	1300

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 31.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• majority of tumor lines with germ line defects in BRG-1 were sensitive to RB-mediated cell cycle arrest (PMID:11719516)
• generation and interconversion of multiple distinct nucleosomal states as a mechanism for catalyzing chromatin fluidity (PMID:11779498)
• Functional involvement of the Brahma/SWI2-related gene 1 protein in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex (PMID:11805098)
• BRG1 enzymes generate localized changes in DNA topology that drive formation of multiple, remodeled nucleosomal states. (PMID:11937040)
• SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription (PMID:11950834)
• Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent (PMID:11953317)
• Data show that prohibitin recruits Brg-1/Brm to E2F-responsive promoters, and that this recruitment is required for the repression of E2F-mediated transcription by prohibitin. (PMID:12065415)
• CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. (PMID:12077331)
• REST repression of neuronal genes requires components of the hSWI.SNF complex (PMID:12192000)
• BRG1 interacts with signal transducer and activator of transcription 2 (STAT2) - a transcription factor that regulates gene expression mediated by interferon-alpha. (PMID:12244326)
• suggestion of an entirely novel function for BRG1 in modulating HP1alpha-containing heterochromatic structures (PMID:12411497)
• human adrenal carcinoma cells can spontaneously transition between two subtypes by switching expression of BRG1 and Brm at the post-transcriptional level (PMID:12493776)
• This report provides supportive evidence that BRG1 and BRM act as tumor suppressor proteins and implicates a role for their loss in the development of non-small cell lung cancers. (PMID:12566296)
• The Brg1 subunit of SWI/SNF was shown to interact directly with RTA. (PMID:12612078)
• BRG1 and BRM complexes may direct distinct cellular processes by recruitment to specific promoters through protein-protein interactions that are unique to each ATPase. (PMID:12620226)
• Some mutations are found in prostate cancer, such as germline mutation, SNPs, but common mutations are excluded. (PMID:12684665)
• the amino-terminal and carboxyl-terminal regions of Mi-2 beta have distinct transcriptional activities and bind to BRG1 and the RET finger protein, forming a multiprotein supercomplex involved in transcriptional regulation. (PMID:14530259)
• BRG1 has a role in promoting cell proliferation by interacting with EVI1, which blocks its repression on E2F1 activity (PMID:14555651)
• in human cells, SWI/SNF enzyme complex formation and the expression of many BRG1-dependent genes are independent of INI1. (PMID:14990991)
• BRG1 is required for growth suppression by estrogen antagonists. (PMID:15141164)
• BRM and BRG1 participate in two distinct chromosome remodeling complexes that are functionally complementary in non-small cell lung cancer (PMID:15240517)
• Sta3 regulates chromatin remodeling and transcription elongation through its interaction with BRG1 and cdk9 (PMID:15286705)
• Somatic point mutations of the BRG1 gene are present in a small subset of lung tumors (PMID:15287030)
• Somatic point mutations of the SMARCA4 gene are present in a small subset of lung tumors. (PMID:15287030)
• Brg-1 plays a role in regulating the recruitment of Sp1, Sp3, AP-2, and polymerase II to the MMP-2 promoter. (PMID:15317818)
• Brahma and Brahma/SWI2-related gene 1 have roles in hypoxic induction of the erythropoietin gene (PMID:15347669)
• transcriptional activation of ZNF185 and CYP3A4 is mediated by direct association of BRG1 with their promoters and a decreased level of ZNF185 is a common feature of lung tumours (PMID:15731117)
• BRG1 loss in pancreatic tumor cell lines induces an altered cell morphology and disruption in the organization of the actin cytoskeleton. (PMID:15887247)
• Brg1 co-localized with NF1/CTF & RNAP II in HeLa cells. It is isolated together with NF1/CTF & RNAP II in ConA-stimulated, but not resting, T lymphocytes. BAF complexes interact with NF1/CTF & RNAP II, dependent on activation of gene transcription. (PMID:15999204)
• BRG1 has an apical role in cytokine-induced promoter assembly, acting upstream of STAT complexes at multiple IFN target loci. (PMID:16195385)
• Here antibody phage display technology is employed for development of an antibody specifically targeting BRG1. (PMID:16513088)
• TG repeats are assembled in a positioned nucleosome in the silent colony-stimulating factor 1 (CSF1) promoter and that activation by BRG1 disrupts this nucleosome and results in Z-DNA formation. (PMID:16537901)
• The SWI/SNF protein Brg1 is associated with a DNA-binding complex containing TAL1/SCL, E47, GATA-1, LMO2 and Ldb1 complex. Both the E box and GATA DNA-binding sites in these elements are required for Brg1 recruitment. (PMID:16800816)
• These results thus demonstrate that BRG1, through the facilitation of Z-DNA formation and subsequent recruitment of RNA polymerase II, is critical in Nrf2-mediated inducible expression of HO-1. (PMID:16923960)
• BRG1 facilitates REST repression by increasing the interaction between REST and chromatin (PMID:17023429)
• Brg1 and HDAC2 have roles in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease (PMID:17043312)
• Aberrant expression of BRG1 and BRM genes is associated with development and progression of prostate cancers and increased BRG1 expression may promote tumor growth and invasion. (PMID:17075831)
• primary micromolar interaction is through the AT-hook motif (PMID:17081121)
• BRG1 is constitutively present at IL-6-responsive promoters and is required for STAT3 recruitment, downstream histone modifications, and IL-6-induced chromatin remodeling. (PMID:17182572)
• Study reports the solution structure of the Brg1 bromodomain determined by using NMR perturbation studies; it was shown that the Brg1 bromodomain binds acetyllysine in the context of histone tails, with no comparable affinity for unacetylated peptides (PMID:17274598)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	smarca4a	ENSDARG00000077226
danio_rerio	SMARCA4	ENSDARG00000104339
mus_musculus	Smarca4	ENSMUSG00000032187
rattus_norvegicus	Smarca4	ENSRNOG00000009271

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 — P51532 (reviewed: P51532)

Alternative names: BRG1-associated factor 190A, Mitotic growth and transcription activator, Protein BRG-1, Protein brahma homolog 1, SNF2-beta, Transcription activator BRG1

All UniProt accessions (32): P51532, A0A2R8Y440, A0A2R8Y4C5, A0A2R8Y4P4, A0A2R8Y4R6, A0A2R8Y523, A0A2R8Y526, A0A2R8Y583, A0A2R8Y5K3, A0A2R8Y6N0, A0A2R8Y6V2, A0A2R8Y7F3, A0A2R8Y7R0, A0A2R8Y7S2, A0A2R8Y7Y7, A0A2R8Y866, A0A2R8YCY3, A0A2R8YDA1, A0A2R8YF38, A0A2R8YF58, A0A2R8YF80, A0A2R8YFK5, A0A2R8YFV8, A0A2R8YG32, A0A2R8YGG3, A0A2R8YGP5, A0A994J4Z2, A0A994J6Y9, A7E2E1, K7EP28, K7EQF0, Q9HBD4

UniProt curated annotations — full annotation on UniProt →

Function. ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development, a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues. Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1. Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2. Binds to RNA in a promiscuous manner. In brown adipose tissue, involved in the regulation of thermogenic genes expression.

Subunit / interactions. Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible developmental- and tissue-specific combinations. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin. Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A. Component of the BAF53 complex, at least composed of BAF53A, RUVBL1, SMARCA4/BRG1/BAF190A, and TRRAP, which preferentially acetylates histone H4 (and H2A) within nucleosomes. Component of the CREST-BRG1 complex, at least composed of SMARCA4/BRG1/BAF190A, SS18L1/CREST, HDAC1, RB1 and SP1. Interacts with PHF10/BAF45A. Interacts with MYOG. Interacts directly with IKFZ1; the interaction associates IKFZ1 with the BAF complex. Interacts with ZEB1 (via N-terminus). Interacts with NR3C1, PGR, SMARD1, TOPBP1 and ZMIM2/ZIMP7. Interacts with (via the bromodomain) with TERT; the interaction regulates Wnt-mediated signaling. Interacts with TBX21 in a KDM6B-dependent manner. Interacts with KDM6A and KDM6B. Interacts with HNRNPU; this interaction occurs in embryonic stem cells and stimulates global Pol II-mediated transcription. Interacts with ACTL6A. Interacts with DLX1. Interacts with DPF2. Interacts with DPF3a (isoform 2 of DPF3/BAF45C) and with HDGFL2 in a DPF3a-dependent manner. May interact with ADNP2. Interacts with LETMD1 (via C-terminal); the interaction regulates transcriptional expression of thermogenic genes in brown adipose tissue. Interacts (via KIKL motif) with BRD3 (via NET domain).

Subcellular location. Nucleus.

Tissue specificity. Colocalizes with ZEB1 in E-cadherin-negative cells from established lines, and stroma of normal colon as well as in de-differentiated epithelial cells at the invasion front of colorectal carcinomas (at protein level).

Disease relevance. Rhabdoid tumor predisposition syndrome 2 (RTPS2) [MIM:613325] A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood. The disease is caused by variants affecting the gene represented in this entry. Coffin-Siris syndrome 4 (CSS4) [MIM:614609] A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. The disease is caused by variants affecting the gene represented in this entry. Otosclerosis 12 (OTSC12) [MIM:620792] A form of otosclerosis, a pathological condition of the ear characterized by formation of spongy bone in the labyrinth capsule, especially in front of and posterior to the footplate of the stapes, resulting in conductive hearing impairment. Cochlear otosclerosis may also develop, resulting in sensorineural hearing loss. OTSC12 is an autosomal dominant form with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Binding to RNAs including lncRNA Evf2 leads to inhibition of SMARCA4 ATPase and chromatin remodeling activities.

Domain organisation. The KIKL motif recognizes and binds the NET domain of BRD3.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (5)

UniProt ID	Names	Canonical?
P51532-1	1	yes
P51532-2	2
P51532-3	3
P51532-4	4
P51532-5	5

RefSeq proteins (10): NP_001122316, NP_001122317, NP_001122318, NP_001122319, NP_001122320, NP_001122321, NP_001361386, NP_001374212, NP_001398079, NP_003063* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001487	Bromodomain	Domain
IPR001650	Helicase_C-like	Domain
IPR006576	BRK_domain	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR014012	HSA_dom	Domain
IPR014978	Gln-Leu-Gln_QLQ	Domain
IPR018359	Bromodomain_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029295	SnAC	Domain
IPR030100	BRG1_ATP-bd	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR037259	BRK_sf	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain

Pfam: PF00176, PF00271, PF00439, PF07529, PF07533, PF08880, PF14619

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (155 total): helix 46, strand 25, compositionally biased region 17, modified residue 17, turn 12, region of interest 11, sequence variant 9, domain 5, splice variant 3, mutagenesis site 3, short sequence motif 2, chain 1, binding site 1, site 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7TAB	X-RAY DIFFRACTION	1.16
2GRC	X-RAY DIFFRACTION	1.5
6ZS2	X-RAY DIFFRACTION	1.57
7TD9	X-RAY DIFFRACTION	1.61
6HR2	X-RAY DIFFRACTION	1.76
3UVD	X-RAY DIFFRACTION	1.85
5DKD	X-RAY DIFFRACTION	2
5EA1	X-RAY DIFFRACTION	2
9DTX	X-RAY DIFFRACTION	2.11
7VRB	X-RAY DIFFRACTION	2.39
9UXC	ELECTRON MICROSCOPY	2.74
7VDT	ELECTRON MICROSCOPY	2.8
9WBZ	ELECTRON MICROSCOPY	2.9
9UXB	ELECTRON MICROSCOPY	2.92
6LTH	ELECTRON MICROSCOPY	3
9UX9	ELECTRON MICROSCOPY	3.05
8QJR	X-RAY DIFFRACTION	3.17
9UXA	ELECTRON MICROSCOPY	3.28
7VDV	ELECTRON MICROSCOPY	3.4
9WC1	ELECTRON MICROSCOPY	3.4
9RL4	ELECTRON MICROSCOPY	3.5
6LTJ	ELECTRON MICROSCOPY	3.7
8G1Q	X-RAY DIFFRACTION	3.73
9RN2	ELECTRON MICROSCOPY	4.1
9RMC	ELECTRON MICROSCOPY	4.2
7Y8R	ELECTRON MICROSCOPY	4.4
9RN1	ELECTRON MICROSCOPY	5.9
2H60	SOLUTION NMR
6BGH	SOLUTION NMR
6SY2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51532-F1	65.38	0.20

Functional residue map

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

Catalytic / active sites (1): 1539–1540 (required for binding to ’lys-15’-acetylated histone 3)

Ligand- & substrate-binding residues (1): 779–786

Post-translational modifications (18): 11, 188, 353, 609, 610, 613, 626, 695, 699, 1382, 1423, 1452, 1570, 1575, 1586, 1627, 1631, 1365

Mutagenesis-validated functional residues (3):

Position	Phenotype
1484	no effect on binding to ’lys-15’-acetylated histone h3.
1539	abolishes binding to ’lys-15’-acetylated histone h3.
1540	abolishes binding to ’lys-15’-acetylated histone h3.

Function

Pathways and Gene Ontology

Reactome pathways

32 pathways

ID	Pathway
R-HSA-1266695	Interleukin-7 signaling
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9933937	Formation of the canonical BAF (cBAF) complex
R-HSA-9933939	Formation of the polybromo-BAF (pBAF) complex
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-449147	Signaling by Interleukins
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9675108	Nervous system development
R-HSA-9730414	MITF-M-regulated melanocyte development

MSigDB gene sets: 692 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, MORF_SMC1L1, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, TGCGCANK_UNKNOWN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, MATTIOLI_MGUS_VS_PCL, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS

GO Biological Process (34): negative regulation of transcription by RNA polymerase II (GO:0000122), RNA polymerase I preinitiation complex assembly (GO:0001188), neural retina development (GO:0003407), nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), regulation of mitotic metaphase/anaphase transition (GO:0030071), positive regulation of Wnt signaling pathway (GO:0030177), negative regulation of cell growth (GO:0030308), heterochromatin formation (GO:0031507), host-mediated activation of viral transcription (GO:0043923), positive regulation of T cell differentiation (GO:0045582), negative regulation of cell differentiation (GO:0045596), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), transcription initiation-coupled chromatin remodeling (GO:0045815), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of androgen receptor signaling pathway (GO:0060766), regulation of G0 to G1 transition (GO:0070316), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of signal transduction by p53 class mediator (GO:1901798), positive regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901838), positive regulation of stem cell population maintenance (GO:1902459), positive regulation of glucose mediated signaling pathway (GO:1902661), positive regulation of miRNA transcription (GO:1902895), regulation of G1/S transition of mitotic cell cycle (GO:2000045), positive regulation of double-strand break repair (GO:2000781), regulation of nucleotide-excision repair (GO:2000819), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (23): transcription coregulator binding (GO:0001221), p53 binding (GO:0002039), DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), ATP hydrolysis activity (GO:0016887), Tat protein binding (GO:0030957), histone binding (GO:0042393), identical protein binding (GO:0042802), nuclear androgen receptor binding (GO:0050681), DNA polymerase binding (GO:0070182), ATP-dependent chromatin remodeler activity (GO:0140658), nucleosome array spacer activity (GO:0140750), nucleotide binding (GO:0000166), RNA polymerase I core promoter sequence-specific DNA binding (GO:0001164), protein binding (GO:0005515), hydrolase activity (GO:0016787), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (17): kinetochore (GO:0000776), chromatin (GO:0000785), fibrillar center (GO:0001650), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), membrane (GO:0016020), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), RSC-type complex (GO:0016586), protein-containing complex (GO:0032991), npBAF complex (GO:0071564), nBAF complex (GO:0071565), bBAF complex (GO:0140092), GBAF complex (GO:0140288), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	5
Signaling by Interleukins	1
TCF dependent signaling in response to WNT	1
Chromatin modifying enzymes	1
Chromatin organization	1
Transcriptional regulation by RUNX1	1
Nervous system development	1
Regulation of CDH1 Gene Transcription	1
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1
Differentiation of T cells	1
Immune System	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SWI/SNF superfamily-type complex	6
cellular anatomical structure	5
regulation of DNA-templated transcription	3
protein binding	3
ATP-dependent activity	3
intracellular membraneless organelle	3
nuclear lumen	3
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
positive regulation of cellular process	2
negative regulation of cellular process	2
cell differentiation	2
regulation of cell differentiation	2
DNA-templated transcription	2
nucleic acid binding	2
transcription coregulator activity	2
regulation of transcription by RNA polymerase II	1
transcription initiation at RNA polymerase I promoter	1
transcription preinitiation complex assembly	1
anatomical structure development	1
retina development in camera-type eye	1
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of metaphase/anaphase transition of cell cycle	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1

Protein interactions and networks

STRING

5148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCA4	SMARCC1	Q92922	999
SMARCA4	SMARCB1	Q12824	999
SMARCA4	SMARCC2	Q8TAQ2	999
SMARCA4	SMARCE1	Q969G3	998
SMARCA4	BANF1	O75531	998
SMARCA4	SMARCD1	Q96GM5	998
SMARCA4	SMARCD3	Q6STE5	997
SMARCA4	ARID1A	O14497	997
SMARCA4	ARID1B	Q8NFD5	997
SMARCA4	ARID2	Q68CP9	996
SMARCA4	ACTL6A	O96019	996
SMARCA4	PARP1	P09874	995
SMARCA4	PBRM1	Q86U86	992
SMARCA4	CTNNB1	P35222	991
SMARCA4	BRD7	Q9NPI1	986

IntAct

1407 interactions, top by confidence:

A	B	Type	Score
SMARCA4	SMARCB1	psi-mi:“MI:0914”(association)	0.960
SMARCB1	SMARCA4	psi-mi:“MI:0914”(association)	0.960
SMARCB1	SMARCA4	psi-mi:“MI:0915”(physical association)	0.960
WDR77	PRMT5	psi-mi:“MI:0914”(association)	0.960
ARID1A	SMARCA4	psi-mi:“MI:0914”(association)	0.940
SMARCA4	ARID1A	psi-mi:“MI:0914”(association)	0.940
SMARCA4	ARID1A	psi-mi:“MI:0915”(physical association)	0.940
ARID1A	SMARCA4	psi-mi:“MI:0915”(physical association)	0.940
SMARCA4	SMARCC1	psi-mi:“MI:0915”(physical association)	0.930
SMARCA4	SMARCC1	psi-mi:“MI:2364”(proximity)	0.930
SMARCD1	SMARCA4	psi-mi:“MI:0915”(physical association)	0.900
SMARCA4	SMARCD1	psi-mi:“MI:0915”(physical association)	0.900
SMARCD1	SMARCA4	psi-mi:“MI:0914”(association)	0.900
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	SMARCA4	psi-mi:“MI:0914”(association)	0.840
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
PBRM1	SMARCA4	psi-mi:“MI:0915”(physical association)	0.800
SMARCC1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
TERT	SMARCA4	psi-mi:“MI:0914”(association)	0.740

BioGRID (1583): SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Biochemical Activity), HDAC1 (Phenotypic Suppression), SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS), SMARCA4 (Two-hybrid), SMARCA4 (Affinity Capture-MS), ACTL6A (Co-fractionation), BYSL (Co-fractionation)

ESM2 similar proteins: A2VDB3, A7EQA8, A7Z019, O44498, O94842, O95104, O95835, P0CB49, P34333, P34428, P46582, P51531, P51532, P97868, Q08D57, Q09345, Q09556, Q17308, Q1LY77, Q20374, Q3TKT4, Q3TLH4, Q4V7X9, Q5F3P8, Q5HZJ0, Q63623, Q63627, Q66J90, Q66KL9, Q6DIC0, Q6DID3, Q6DRG1, Q6GLQ4, Q7TSH6, Q7Z6E9, Q8BYR2, Q8CGZ0, Q8IWX8, Q8K1P7, Q8NE35

Diamond homologs: A0A0P0WGX7, A2A8L1, A2BGR3, A3KFM7, A6QQR4, A7Z019, A9X4T1, B0R0I6, B0XPE7, B3NAN8, B4GS98, B5BT18, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, F1Q8K0, F4I2H2, F4IV45, F4J9M5, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EF53, O12944, O13682, O14139, O14646, O14981, O43065, O76460, P0CO16, P0CO17, P28370, P31380, P32333

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
SMARCA4	“form complex”	“SWI/SNF complex”	binding
MYOD1	up-regulates	SMARCA4	binding
SMARCA4	up-regulates	ZEB1	binding
SMARCA4	up-regulates	TERT	binding
SMARCA4	“up-regulates quantity by expression”	ABCG2	“transcriptional regulation”
SMARCA4	“form complex”	“SWI/SNF ACTL6B varian”	binding
SMARCA4	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
SMARCA4	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding
CSNK1D	“down-regulates quantity by destabilization”	SMARCA4	phosphorylation
SCF-FBW7	“down-regulates quantity by destabilization”	SMARCA4	polyubiquitination
SMARCB1	“up-regulates activity”	SMARCA4	binding
SMARCA4	up-regulates	SMARCC1	binding
SMARCA4	up-regulates	SMARCC2	binding
SMARCA4	“form complex”	“Embryonic stem cell-specific SWI/SNF”	binding
CHFR	“down-regulates quantity by destabilization”	SMARCA4	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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
Formation of the canonical BAF (cBAF) complex	15	82.0×	1e-25
Formation of the embryonic stem cell BAF (esBAF) complex	15	77.7×	4e-25
Formation of the polybromo-BAF (pBAF) complex	14	76.6×	2e-23
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	19	74.8×	3e-31
Formation of the non-canonical BAF (ncBAF) complex	11	63.7×	6e-17
Regulation of endogenous retroelements	16	50.8×	1e-22
Regulation of MITF-M-dependent genes involved in pigmentation	18	41.2×	2e-23
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	14	36.3×	3e-17

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	19	94.9×	1e-32
regulation of nucleotide-excision repair	19	84.7×	2e-31
regulation of mitotic metaphase/anaphase transition	19	69.8×	2e-29
positive regulation of double-strand break repair	19	48.4×	2e-25
nucleosome disassembly	8	47.5×	2e-10
positive regulation of T cell differentiation	14	47.2×	1e-18
positive regulation of myoblast differentiation	17	46.1×	2e-22
regulation of G1/S transition of mitotic cell cycle	20	45.4×	3e-26

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 26 cancer types — BL, BLADDER, BLCA, CCRCC, CHOL, COAD, COADREAD, EGC, ESCA, ESCC, HCC, HNSC…(+14 more).

Clinical variants and AI predictions

ClinVar

6669 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	204
Likely pathogenic	119
Uncertain significance	2782
Likely benign	2750
Benign	83

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068242	NM_003072.5(SMARCA4):c.3547-1G>A	Pathogenic
1070370	NM_003072.5(SMARCA4):c.2149G>T (p.Glu717Ter)	Pathogenic
1072182	NM_003072.5(SMARCA4):c.2826G>A (p.Trp942Ter)	Pathogenic
1072302	NM_003072.5(SMARCA4):c.574del (p.Arg192fs)	Pathogenic
1072497	NM_003072.5(SMARCA4):c.3129del (p.Lys1044fs)	Pathogenic
1072687	NC_000019.9:g.(?11094822)(11172498_?)del	Pathogenic
1072688	NC_000019.9:g.(?11094828)(11152246_?)del	Pathogenic
1072689	NC_000019.9:g.(?11101816)(11152246_?)del	Pathogenic
1073889	NM_003072.5(SMARCA4):c.4077T>A (p.Cys1359Ter)	Pathogenic
1074336	NM_003072.5(SMARCA4):c.336dup (p.Met113fs)	Pathogenic
1342164	NM_003072.5(SMARCA4):c.2475G>T (p.Trp825Cys)	Pathogenic
1360114	NM_003072.5(SMARCA4):c.2780del (p.Phe927fs)	Pathogenic
1360962	NM_003072.5(SMARCA4):c.917_941del (p.Gln306fs)	Pathogenic
1382120	NM_003072.5(SMARCA4):c.1378C>T (p.Gln460Ter)	Pathogenic
139439	NM_003072.5(SMARCA4):c.3533G>A (p.Trp1178Ter)	Pathogenic
139440	NM_003072.5(SMARCA4):c.4170+1G>A	Pathogenic
139441	NM_003072.5(SMARCA4):c.643C>T (p.Gln215Ter)	Pathogenic
139442	NM_003072.5(SMARCA4):c.2617-3C>G	Pathogenic
139443	NM_003072.5(SMARCA4):c.3239G>A (p.Gly1080Asp)	Pathogenic
1396816	NM_003072.5(SMARCA4):c.2838del (p.Phe947fs)	Pathogenic
1397435	NM_003072.5(SMARCA4):c.3228C>G (p.Tyr1076Ter)	Pathogenic
1402988	NM_003072.5(SMARCA4):c.3013C>T (p.Arg1005Ter)	Pathogenic
1418798	NC_000019.9:g.(?11118568)(11118709_?)del	Pathogenic
1422718	NM_003072.5(SMARCA4):c.343C>T (p.Gln115Ter)	Pathogenic
1426263	NM_003072.5(SMARCA4):c.1472_1473insGCAAA (p.Ser492fs)	Pathogenic
1436624	NM_003072.5(SMARCA4):c.490C>T (p.Gln164Ter)	Pathogenic
1442150	NM_003072.5(SMARCA4):c.2527del (p.Ala843fs)	Pathogenic
1443479	NM_003072.5(SMARCA4):c.561C>G (p.Tyr187Ter)	Pathogenic
1453398	NM_003072.5(SMARCA4):c.3910C>T (p.Gln1304Ter)	Pathogenic
1454001	NM_003072.5(SMARCA4):c.2111_2115del (p.Arg704fs)	Pathogenic

SpliceAI

5408 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10961172:CTGGT:C	donor_loss	1.0000
19:10961173:TGG:T	donor_loss	1.0000
19:10961174:GGTA:G	donor_loss	1.0000
19:10961175:G:GG	donor_gain	1.0000
19:10961175:GTAA:G	donor_loss	1.0000
19:10961176:T:A	donor_loss	1.0000
19:10985271:A:AG	acceptor_gain	1.0000
19:10985272:G:GG	acceptor_gain	1.0000
19:10985272:GCCC:G	acceptor_gain	1.0000
19:10985334:G:GT	donor_gain	1.0000
19:10986592:TGGTA:T	donor_loss	1.0000
19:10986593:GGTAA:G	donor_loss	1.0000
19:10986594:GTAA:G	donor_loss	1.0000
19:10986903:AGG:A	acceptor_loss	1.0000
19:10987923:AG:A	donor_loss	1.0000
19:10987925:G:GG	donor_gain	1.0000
19:10987925:G:T	donor_loss	1.0000
19:10989441:CAG:C	donor_loss	1.0000
19:10989442:AGG:A	donor_loss	1.0000
19:10989444:GT:G	donor_loss	1.0000
19:10989445:T:A	donor_loss	1.0000
19:10991148:A:AG	acceptor_gain	1.0000
19:10991149:G:GG	acceptor_gain	1.0000
19:10991149:GCT:G	acceptor_gain	1.0000
19:10991149:GCTGC:G	acceptor_gain	1.0000
19:10991320:CCAG:C	donor_gain	1.0000
19:10991320:CCAGG:C	donor_loss	1.0000
19:10991321:CAG:C	donor_gain	1.0000
19:10991322:AG:A	donor_gain	1.0000
19:10991322:AGGTA:A	donor_loss	1.0000

AlphaMissense

10850 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10986372:T:A	L180H	1.000
19:10986372:T:C	L180P	1.000
19:10986375:G:T	R181I	1.000
19:10986378:C:A	A182D	1.000
19:10986384:T:A	I184N	1.000
19:10986384:T:C	I184T	1.000
19:10986384:T:G	I184S	1.000
19:10986389:G:C	A186P	1.000
19:10986390:C:A	A186D	1.000
19:10986392:T:G	Y187D	1.000
19:10986395:A:G	K188E	1.000
19:10986397:G:C	K188N	1.000
19:10986397:G:T	K188N	1.000
19:10989319:T:C	L374P	1.000
19:10989340:G:C	R381P	1.000
19:10989352:T:C	L385P	1.000
19:10989409:T:C	L404P	1.000
19:10989418:T:A	L407H	1.000
19:10989418:T:C	L407P	1.000
19:10989424:T:C	L409P	1.000
19:10989427:T:C	L410P	1.000
19:10991151:T:C	L416P	1.000
19:10991233:G:C	K443N	1.000
19:10991233:G:T	K443N	1.000
19:10991246:C:A	R448S	1.000
19:10991252:G:C	A450P	1.000
19:10991255:C:A	R451S	1.000
19:10991256:G:C	R451P	1.000
19:10991267:A:G	K455E	1.000
19:10991271:T:C	L456P	1.000

dbSNP variants (sampled 300 via entrez): RS1000020901 (19:10959474 C>A), RS1000034162 (19:11032155 A>T), RS1000087193 (19:10987144 C>A,T), RS1000095734 (19:11062628 G>C), RS1000125029 (19:11029217 A>G), RS1000137072 (19:11042217 A>G), RS1000143228 (19:10993562 G>A,C), RS1000163959 (19:10960644 C>T), RS1000172852 (19:10962410 T>C), RS1000184332 (19:10981378 C>T), RS1000194447 (19:11001538 G>A,T), RS1000203218 (19:10998862 G>A), RS1000241924 (19:11053241 C>T), RS1000254090 (19:10998494 T>G), RS1000254479 (19:11034649 C>A,T)

Disease associations

OMIM: gene MIM:603254 | disease phenotypes: MIM:613325, MIM:614609, MIM:620792, MIM:135900, MIM:120435, MIM:614429, MIM:155255, MIM:609943, MIM:614562, MIM:108800

GenCC curated gene-disease

Disease	Classification	Inheritance
rhabdoid tumor predisposition syndrome 2	Definitive	Autosomal dominant
intellectual disability, autosomal dominant 16	Definitive	Autosomal dominant
Coffin-Siris syndrome	Definitive	Autosomal dominant
otosclerosis	Strong	Autosomal dominant
uterine corpus sarcoma	Moderate	Autosomal recessive
familial rhabdoid tumor	Supportive	Autosomal dominant
hereditary nonpolyposis colon cancer	Limited	Unknown

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
Coffin-Siris syndrome	Definitive	AD
rhabdoid tumor predisposition syndrome 2	Definitive	AD
hereditary nonpolyposis colon cancer	Limited	AD

Mondo (25): rhabdoid tumor predisposition syndrome 2 (MONDO:0013224), hereditary neoplastic syndrome (MONDO:0015356), intellectual disability, autosomal dominant 16 (MONDO:0013821), otosclerosis 12 (MONDO:0968980), Coffin-Siris syndrome (MONDO:0015452), neurodevelopmental disorder (MONDO:0700092), hereditary nonpolyposis colon cancer (MONDO:0018630), cleft palate (MONDO:0016064), childhood neoplasm (MONDO:0021079), intellectual disability (MONDO:0001071), breast cancer (MONDO:0007254), obesity disorder (MONDO:0011122), ventricular septal defect (MONDO:0002070), strabismus (MONDO:0003432), ovarian neoplasm (MONDO:0021068)

Orphanet (14): Rhabdoid tumor predisposition syndrome (Orphanet:231108), Rhabdoid tumor (Orphanet:69077), Inherited cancer-predisposing syndrome (Orphanet:140162), Coffin-Siris syndrome (Orphanet:1465), Hereditary nonpolyposis colon cancer (Orphanet:443909), Cleft palate (Orphanet:2014), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Medulloblastoma (Orphanet:616), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Neuroblastoma (Orphanet:635), Interatrial communication (Orphanet:1478), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399), NON RARE IN EUROPE: Ventricular septal defect (Orphanet:1480)

HPO phenotypes

91 total (30 of 91 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000362	Otosclerosis
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000446	Narrow nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000684	Delayed eruption of teeth

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST000975_15	LDL cholesterol	1.000000e-08
GCST002287_14	Coronary artery disease or ischemic stroke	3.000000e-12
GCST002289_2	Coronary artery disease	3.000000e-11
GCST002290_4	Coronary artery disease or large artery stroke	2.000000e-11
GCST002740_9	Inflammatory skin disease	3.000000e-06
GCST007480_1	Disorders of lipid metabolism	3.000000e-10
GCST007931_49	Medication use (HMG CoA reductase inhibitors)	1.000000e-09
GCST008077_2	LDL cholesterol levels	1.000000e-96
GCST008077_32	LDL cholesterol levels	3.000000e-07
GCST008077_37	LDL cholesterol levels	3.000000e-11
GCST008077_44	LDL cholesterol levels	8.000000e-12
GCST008077_48	LDL cholesterol levels	1.000000e-119
GCST008078_132	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-193
GCST008078_76	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-09
GCST008078_80	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-11
GCST008078_88	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	7.000000e-19
GCST008078_95	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-226
GCST008079_103	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-213
GCST008079_30	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-273
GCST008079_77	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-12
GCST008079_87	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-13
GCST008079_98	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-19
GCST008084_56	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-06
GCST008086_104	LDL cholesterol levels in current drinkers	4.000000e-193
GCST008086_110	LDL cholesterol levels in current drinkers	2.000000e-172
GCST008086_47	LDL cholesterol levels in current drinkers	8.000000e-07
GCST008086_49	LDL cholesterol levels in current drinkers	7.000000e-10
GCST008086_98	LDL cholesterol levels in current drinkers	5.000000e-16
GCST009597_205	Multiple sclerosis	5.000000e-09
GCST010243_208	Apolipoprotein B levels	0.000000e+00

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004574	total cholesterol measurement

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D006345	Heart Septal Defects, Ventricular	C14.240.400.560.540; C14.280.400.560.540; C16.131.240.400.560.540
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
D065886	Neurodevelopmental Disorders	F03.625
D010040	Otosclerosis	C09.218.768
D013285	Strabismus	C10.292.562.887; C11.590.810
C536436	Coffin-Siris syndrome (supp.)
C567643	Rhabdoid Tumor Predisposition Syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3085620 (SINGLE PROTEIN), CHEMBL4748227 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195536 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,578 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL5095181	CAMIBIRSTAT	2	40

Clinical evidence (CIViC)

Drug × variant × indication: 5 predictive associations from 5 curated evidence items; also 4 diagnostic, 2 oncogenic, 2 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
SMARCA4 Underexpression	Cisplatin + Vinorelbine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID837
SMARCA4 Underexpression	Tazemetostat	Cancer	Sensitivity/Response	CIViC C	EID6373
SMARCA4 INACTIVATING MUTATION	Tozasertib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID5928
SMARCA4 Loss	Palbociclib + Ribociclib + Abemaciclib	Ovarian Small Cell Carcinoma	Sensitivity/Response	CIViC D	EID7154
SMARCA4 Loss	Palbociclib + Abemaciclib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID7155

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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
SMD-3040	Binding	7.89	pKd
GNE-064	Inhibition	7.46	pIC50
A947	Binding	7.19	pKd
PFI-3	Binding	7.05	pKd

Binding affinities (BindingDB)

238 measured of 238 human assays (238 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[6-amino-5-[8-(5-fluoro-3-pyridinyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	IC50	3.4 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-pyridin-2-yl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	3.9 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[8-(5-fluoro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	IC50	4 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-pyridin-3-yl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	4.1 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-phenyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	4.3 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[8-(2-fluoro-4-pyridinyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	IC50	4.5 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-pyrimidin-2-yl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	5 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[1-(1-phenylethyl)pyrazol-4-yl]pyridazin-3-yl]phenol	IC50	5.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[1-(1-phenylethyl)imidazol-4-yl]pyridazin-3-yl]phenol	IC50	6.3 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[8-(1,3-thiazol-2-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	IC50	6.5 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[8-(4-fluorophenyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	IC50	6.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(2-phenylpropoxy)pyridazin-3-yl]phenol	IC50	7.2 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-cyclohexylpyridazin-3-yl)phenol	IC50	8.8 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(1-methylpyrazol-4-yl)pyridazin-3-yl]phenol	IC50	10 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-pyrazin-2-yl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	10.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[(1R,4R)-5-pyridin-2-yl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridazin-3-yl]phenol	IC50	10.6 nM	US-10308614: Therapeutic compounds and uses thereof
(4aR,8aR)-2-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-1,3,4,5,6,7,8,8a-octahydroisoquinolin-4a-ol	IC50	11 nM	US-10308614: Therapeutic compounds and uses thereof
1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-4-phenylpiperidin-4-ol	IC50	11.3 nM	US-10308614: Therapeutic compounds and uses thereof
[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-methylpiperazin-1-yl]-phenylmethanone	IC50	11.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[(1R,2R)-2-phenylcyclopropyl]pyridazin-3-yl]phenol	IC50	12.1 nM	US-10308614: Therapeutic compounds and uses thereof
[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-methylpiperazin-1-yl]-(1,3-thiazol-5-yl)methanone	IC50	12.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[(1S)-1-phenylethoxy]pyridazin-3-yl]phenol	IC50	14.9 nM	US-10308614: Therapeutic compounds and uses thereof
1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-phenylpiperidin-3-ol	IC50	15.8 nM	US-10308614: Therapeutic compounds and uses thereof
(4aS,8aR)-2-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-1,3,4,5,6,7,8,8a-octahydroisoquinolin-4a-ol	IC50	17.2 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(1-phenylpiperidin-3-yl)oxypyridazin-3-yl]phenol	IC50	17.2 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(4-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)pyridazin-3-yl]phenol	IC50	17.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-(benzenesulfonyl)-3-methylpiperazin-1-yl]pyridazin-3-yl]phenol	IC50	17.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-cyclopropylpyridazin-3-yl)phenol	IC50	17.6 nM	US-10308614: Therapeutic compounds and uses thereof
1-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-methylpiperazin-1-yl]-2,2-dimethylpropan-1-one	IC50	18.4 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[(3S)-3-methyl-4-[(1-methylimidazol-2-yl)methyl]piperazin-1-yl]pyridazin-3-yl]phenol	IC50	18.5 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(2-phenylethoxy)pyridazin-3-yl]phenol	IC50	19 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(4-methylcyclohexyl)pyridazin-3-yl]phenol	IC50	19 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-[(1R)-1-phenylethyl]piperazin-1-yl]pyridazin-3-yl]phenol	IC50	19.1 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-pyrimidin-5-yl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	19.3 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(4-cyclopropylsulfonyl-3-methylpiperazin-1-yl)pyridazin-3-yl]phenol	IC50	19.7 nM	US-10308614: Therapeutic compounds and uses thereof
[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-(1,3-thiazol-5-yl)methanone	IC50	20.3 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(1-benzyl-3,6-dihydro-2H-pyridin-4-yl)pyridazin-3-yl]phenol	IC50	20.5 nM	US-10308614: Therapeutic compounds and uses thereof
[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-(hydroxymethyl)piperazin-1-yl]-(1,3-thiazol-5-yl)methanone	IC50	20.6 nM	US-10308614: Therapeutic compounds and uses thereof
1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-4-[(dimethylamino)methyl]piperidin-4-ol	IC50	20.8 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(4-methylcyclohexyl)pyridazin-3-yl]phenol	IC50	20.9 nM	US-10308614: Therapeutic compounds and uses thereof
tert-butyl 4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazine-1-carboxylate	IC50	21.4 nM	US-10308614: Therapeutic compounds and uses thereof
(2R)-2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]pyrazol-1-yl]-N,N-dimethylpropanamide	IC50	21.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(4-ethylsulfonyl-3-methylpiperazin-1-yl)pyridazin-3-yl]phenol	IC50	21.9 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-[(dimethylamino)methyl]piperidin-1-yl]pyridazin-3-yl]phenol	IC50	22.5 nM	US-10308614: Therapeutic compounds and uses thereof
3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-N,N-dimethyl-3,8-diazabicyclo[3.2.1]octane-8-carboxamide	IC50	22.5 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[(3R)-3-methyl-4-[(1-methylimidazol-2-yl)methyl]piperazin-1-yl]pyridazin-3-yl]phenol	IC50	23.8 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-[(1S)-1-(dimethylamino)ethyl]piperidin-1-yl]pyridazin-3-yl]phenol	IC50	24.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]pyrazol-1-yl]-N,N-dimethylpropanamide	IC50	24.7 nM	US-10308614: Therapeutic compounds and uses thereof
(2S)-2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]pyrazol-1-yl]-N,N-dimethylpropanamide	IC50	24.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-cyclopentylpyridazin-3-yl)phenol	IC50	25 nM	US-10308614: Therapeutic compounds and uses thereof

ChEMBL bioactivities

246 potent at pChembl≥5 of 279 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CAMIBIRSTAT
8.70	Kd	2	nM	CHEMBL5412292
8.55	IC50	2.8	nM	CHEMBL5571722
8.52	IC50	3	nM	CHEMBL6133855
8.48	IC50	3.3	nM	CHEMBL5564941
8.40	IC50	4	nM	CHEMBL6168539
8.40	IC50	4	nM	CHEMBL6166760
8.40	IC50	4	nM	CHEMBL6164767
8.40	IC50	4	nM	CHEMBL6145659
8.30	IC50	5	nM	CHEMBL6152639
8.26	IC50	5.5	nM	CHEMBL6162599
8.22	IC50	6	nM	CHEMBL4278436
8.22	Kd	6	nM	CHEMBL5415064
8.22	IC50	6	nM	CAMIBIRSTAT
8.15	IC50	7	nM	CHEMBL6167580
8.05	IC50	9	nM	CHEMBL6141585
8.00	IC50	10	nM	CHEMBL4294655
8.00	Kd	10	nM	CHEMBL5207330
8.00	IC50	10	nM	CHEMBL6162246
7.96	EC50	11	nM	CHEMBL5278697
7.96	Kd	11	nM	CHEMBL5424811
7.96	Kd	11	nM	CHEMBL5398829
7.92	IC50	12	nM	CHEMBL6162908
7.89	Kd	12.8	nM	CHEMBL5420238
7.82	IC50	15	nM	CHEMBL6144331
7.82	IC50	15	nM	CHEMBL6143779
7.82	IC50	15	nM	CHEMBL6133150
7.80	EC50	16	nM	CHEMBL4748407
7.80	EC50	16	nM	CHEMBL4782828
7.80	Kd	16	nM	CHEMBL5401472
7.80	IC50	16	nM	CHEMBL5574201
7.75	IC50	18	nM	CHEMBL6102929
7.75	IC50	18	nM	CHEMBL6148030
7.72	IC50	19	nM	CHEMBL6141925
7.70	Kd	20	nM	CHEMBL5409404
7.68	Kd	21	nM	CHEMBL3752911
7.68	Kd	21	nM	CHEMBL5406315
7.68	Kd	21	nM	MOLIBRESIB
7.68	IC50	21	nM	CHEMBL6149590
7.66	IC50	22	nM	CHEMBL6141585
7.64	IC50	23	nM	CHEMBL6171674
7.62	IC50	24	nM	CHEMBL6159990
7.60	EC50	25	nM	CHEMBL4792708
7.60	IC50	25	nM	CHEMBL6133150
7.58	EC50	26	nM	CHEMBL4739926
7.58	IC50	26.1	nM	CHEMBL5308262
7.58	IC50	26	nM	CHEMBL6152213
7.58	IC50	26	nM	CHEMBL6162601
7.57	IC50	27	nM	CHEMBL6168026
7.57	IC50	27	nM	CHEMBL6144331

PubChem BioAssay actives

79 with measured affinity, of 425 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
tert-butyl (3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methylpiperazine-1-carboxylate	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0020	uM
2-[6-amino-5-[8-[2-(2-methoxyethoxy)-4-pyridinyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	2098145: Binding affinity to his-tagged BRG1 bromodomain (unknown origin) by alpha-LISA assay	ic50	0.0028	uM
2-[6-amino-5-[8-(2-methoxy-4-pyridinyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	2098145: Binding affinity to his-tagged BRG1 bromodomain (unknown origin) by alpha-LISA assay	ic50	0.0033	uM
1-[3-(difluoromethyl)-1,2-thiazol-5-yl]-3-[2-fluoro-5-(hydroxymethyl)-4-pyridinyl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0050	uM
1-(5-amino-2-fluoro-4-pyridinyl)-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0050	uM
1-[2-chloro-5-(hydroxymethyl)-4-pyridinyl]-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0050	uM
1-(5-amino-2-chloro-4-pyridinyl)-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0050	uM
2-(6-amino-5-pyrrolidin-1-ylpyridazin-3-yl)phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0060	uM
1-(2-chloro-4-pyridinyl)-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0060	uM
1-[(2R)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-methylpiperazin-1-yl]ethanone	1886340: Binding affinity to human SMARCA4 (A1448 to S1575 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0100	uM
1-(2-chloro-4-pyridinyl)-3-[3-(trifluoromethyl)-1,2-thiazol-5-yl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0100	uM
2-(6-amino-5-piperidin-1-ylpyridazin-3-yl)phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0110	uM
(2R,4S)-N-[[2-[2-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenoxy]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2R)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1928109: PROTAC activity at SMARCA4/VHL in human MV4-11 cells assessed as degradation protein measured after 18 hrs	ec50	0.0110	uM
1-[(3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methylpiperazin-1-yl]ethanone	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0110	uM
(2S,4R)-N-[[2-[2-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenoxy]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1724885: Protac activity at VHL/SMARCA4 in human A549 cells assessed as induction of SMARCA4 bromodomain degradation using anti-SMARCA4 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0160	uM
(2S,4R)-N-[[2-[3-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenoxy]propoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1724885: Protac activity at VHL/SMARCA4 in human A549 cells assessed as induction of SMARCA4 bromodomain degradation using anti-SMARCA4 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0160	uM
2-[6-amino-5-[(2S)-2-methylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0160	uM
2-[6-amino-5-[4-(2-methoxy-4-pyridinyl)piperazin-1-yl]pyridazin-3-yl]phenol	2098145: Binding affinity to his-tagged BRG1 bromodomain (unknown origin) by alpha-LISA assay	ic50	0.0160	uM
2-[6-amino-5-[(2R)-2-propan-2-ylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0200	uM
2-[6-amino-5-[(2S)-2-ethylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0210	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179217: Binding affinity against SMARCA4 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0210	uM
(E)-1-(2-hydroxyphenyl)-3-[(1R,4R)-5-pyridin-2-yl-2,5-diazabicyclo[2.2.1]heptan-2-yl]prop-2-en-1-one	1886340: Binding affinity to human SMARCA4 (A1448 to S1575 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0210	uM
(2S,4R)-N-[[2-[3-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenyl]propoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1724885: Protac activity at VHL/SMARCA4 in human A549 cells assessed as induction of SMARCA4 bromodomain degradation using anti-SMARCA4 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0250	uM
(2S,4R)-N-[[2-[2-[4-[2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]ethoxy]phenyl]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1724885: Protac activity at VHL/SMARCA4 in human A549 cells assessed as induction of SMARCA4 bromodomain degradation using anti-SMARCA4 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0260	uM
2-(6-amino-5-phenylpyridazin-3-yl)phenol	1886335: Inhibition of His-tagged SMARCA4 (unknown origin) (1448 to 1575 residues) using biotinylated ARTKQTARKSTGG-K(Ac)-APR-K(Ac)-QLAT-K(Ac)-AAR-K(Ac)-SAPGG-K as substrate incubated for 10 mins by TR-FRET assay	ic50	0.0300	uM
1-(2-chloro-4-pyridinyl)-3-[2-(trifluoromethyl)-4-pyridinyl]urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0300	uM
1-(2-chloro-4-pyridinyl)-3-(3-methyl-1,2-thiazol-5-yl)urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.0300	uM
(2S,4R)-N-[[2-[2-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]-3-fluorophenyl]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1724885: Protac activity at VHL/SMARCA4 in human A549 cells assessed as induction of SMARCA4 bromodomain degradation using anti-SMARCA4 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0330	uM
2-[6-amino-5-[(2R)-2-methylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0330	uM
tert-butyl 4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazine-1-carboxylate	1683128: Binding affinity to SMARCA4 (unknown origin) by ITC analysis	kd	0.0360	uM
2-[6-amino-5-[(2S)-2-methylpiperidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0400	uM
(E)-3-[4-(cyclopropylamino)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-7-yl]-1-(2-hydroxyphenyl)prop-2-en-1-one	1308371: Binding affinity to human SMARCA4 expressed in BL21 (DE3)-R3-BirA cells by isothermal titration calorimetry	kd	0.0490	uM
2-[6-amino-5-[(2R)-2-cyclopropylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0550	uM
2-[6-amino-5-[(2R)-2-methylpiperidin-1-yl]pyridazin-3-yl]phenol	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0600	uM
1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperidin-4-ol	1683128: Binding affinity to SMARCA4 (unknown origin) by ITC analysis	kd	0.0610	uM
(2S,4R)-1-[(2R)-2-[3-[4-[[4-[3-[[4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-pyridinyl]oxy]cyclobutyl]oxypiperidin-1-yl]methyl]piperidin-1-yl]-1,2-oxazol-5-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2098175: Binding affinity to his-tagged BRG1 bromodomain (unknown origin) assessed as dissociation constant	kd	0.0650	uM
2-(6-amino-5-piperazin-1-ylpyridazin-3-yl)phenol	1683128: Binding affinity to SMARCA4 (unknown origin) by ITC analysis	kd	0.0730	uM
(3R)-1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperidin-3-ol	1683128: Binding affinity to SMARCA4 (unknown origin) by ITC analysis	kd	0.1000	uM
(2S,4R)-1-[(2R)-2-[3-[2-[4-[3-[[4-[3-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-pyridinyl]oxy]cyclobutyl]oxypiperidin-1-yl]ethoxy]-1,2-oxazol-5-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2098175: Binding affinity to his-tagged BRG1 bromodomain (unknown origin) assessed as dissociation constant	kd	0.1080	uM
(2S,4R)-N-[[2-[2-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenyl]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1724885: Protac activity at VHL/SMARCA4 in human A549 cells assessed as induction of SMARCA4 bromodomain degradation using anti-SMARCA4 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.1170	uM
1-(2-chloro-4-pyridinyl)-3-(2-methyl-4-pyridinyl)urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.1500	uM
1-(2-chloro-4-pyridinyl)-3-pyridin-4-ylurea	1409139: Binding affinity to His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells by ITC method	kd	0.2800	uM
(3E)-6-chloro-3-[(4-methylpiperazin-1-yl)methylidene]-1,2-dihydropyrrolo[1,2-a]quinazolin-5-one	1310278: Binding affinity to His6-tagged human recombinant SMARCA4 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by VP-ITC microcalorimetry	kd	0.4170	uM
4-phenyl-5H-pyridazino[4,3-b]indol-3-amine	1886340: Binding affinity to human SMARCA4 (A1448 to S1575 residues) expressed in bacterial expression system by bromoscan assay	kd	0.5100	uM
1-(2-chloro-4-pyridinyl)-3-(4-methyl-1,3-thiazol-2-yl)urea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	0.5700	uM
1-(2-chloro-4-pyridinyl)-3-pyridin-2-ylurea	1409133: Inhibition of recombinant His6-tagged BRG1 ATPase-SnAC (658 to 1361 residues) (unknown origin) expressed in insect sf9 cells preincubated for 5 mins followed by pCMV-dR8.91 plasmid and ATP addition measured after 60 mins by ADP-Glo assay	ic50	1.7000	uM
(3E)-6-chloro-3-(2-ethylbutylidene)-1,2-dihydropyrrolo[1,2-a]quinazolin-5-one	1310278: Binding affinity to His6-tagged human recombinant SMARCA4 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by VP-ITC microcalorimetry	kd	2.0300	uM
6-(furan-2-yl)-4-[(2S)-2-methylpiperidin-1-yl]pyridazin-3-amine	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	4.0000	uM
6-(furan-2-yl)-4-piperidin-1-ylpyridazin-3-amine	2014571: Binding affinity to SMARCA4 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	4.9000	uM
(2S,4R)-1-[(2R)-2-[3-[4-[[4-[3-[[4-[3-(3-amino-6-phenylpyridazin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-pyridinyl]oxy]cyclobutyl]oxypiperidin-1-yl]methyl]piperidin-1-yl]-1,2-oxazol-5-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	2098175: Binding affinity to his-tagged BRG1 bromodomain (unknown origin) assessed as dissociation constant	kd	5.2200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance, affects reaction	4
methylmercuric chloride	increases expression, affects cotreatment	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
graphene oxide	increases expression	2
cobaltous chloride	affects binding, increases reaction, decreases expression	2
Air Pollutants	increases abundance, increases oxidation, increases expression, affects cotreatment	2
Arsenic	increases abundance, affects methylation, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
1,12-benzoperylene	increases expression	1
deoxynivalenol	increases expression	1
lead acetate	increases expression	1
methylselenic acid	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
beta-lapachone	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
bicalutamide	affects cotreatment, affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

230 unique, capped per target: 207 binding, 12 admet, 11 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3089615	Binding	Displacement of fluorescein-labeled MS239 from recombinant human SMARCA4 bromodomain after 1 hr by fluorescence anisotropy assay	Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains. — J Med Chem
CHEMBL5304678	Functional	Measurement of the ATPase catalytic activity using the ADP-Glo detection (SMARCA4)	Data for DCP probe FHT-2344
CHEMBL5328366	ADMET	In vivo PROTAC activity at VHL/SMARCA4 in SCID mouse xenografted with human MV4-11 cells assessed as reduction of SMARCA4 level in tumor at 50 mg/kg, iv administered as single dose measured after 2 hrs by Western blotting analysis	Discovery of SMD-3040 as a Potent and Selective SMARCA2 PROTAC Degrader with Strong in vivo Antitumor Activity. — J Med Chem

Cellosaurus cell lines

55 cell lines: 42 cancer cell line, 5 telomerase immortalized cell line, 3 embryonic stem cell, 3 transformed cell line, 1 induced pluripotent stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0463	NCI-H157	Cancer cell line	Male
CVCL_0542	SW13	Cancer cell line	Female
CVCL_1174	DMS 114	Cancer cell line	Male
CVCL_1488	NCI-H1693	Cancer cell line	Female
CVCL_1515	NCI-H2023	Cancer cell line	Male
CVCL_1523	NCI-H2085	Cancer cell line	Male
CVCL_1532	NCI-H2126	Cancer cell line	Male
CVCL_1545	NCI-H2286	Cancer cell line	Female
CVCL_1595	NCI-H841	Cancer cell line	Male
CVCL_1679	SBC-5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00525551	PHASE4	COMPLETED	Efficacy of Acetylcysteine in Patients Undergoing Surgery for Otosclerosis
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,
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00002706	PHASE3	COMPLETED	Laparoscopic Surgery or Standard Surgery in Treating Patients With Endometrial Cancer or Cancer of the Uterus
NCT00162721	PHASE3	UNKNOWN	The Addition of Polychemotherapy to Adjuvant Radiotherapy in the Treatment of Non-Metastatic Uterine Sarcomas
NCT00954174	PHASE3	UNKNOWN	Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer
NCT01012297	PHASE3	TERMINATED	Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma
NCT01533207	PHASE3	TERMINATED	Gemcitabine Hydrochloride and Docetaxel Followed by Doxorubicin Hydrochloride or Observation in Treating Patients With High-Risk Uterine Leiomyosarcoma Previously Removed by Surgery
NCT03422198	PHASE3	RECRUITING	Short Course Vaginal Cuff Brachytherapy in Treating Participants With Stage I-II Endometrial Cancer
NCT01617057	PHASE3	TERMINATED	Therapeutic Efficacy of Tiludronic Acid on Inner Ear Involvement in Advanced Otosclerosis
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
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00025220	PHASE2	COMPLETED	Thalidomide in Treating Patients With Recurrent or Persistent Cancer of the Uterus
NCT00025506	PHASE2	COMPLETED	Thalidomide in Treating Patients With Recurrent or Persistent Carcinosarcoma of the Uterus
NCT00031629	PHASE2	COMPLETED	Combination Chemotherapy and Filgrastim or Pegfilgrastim in Treating Patients With Recurrent or Persistent Cancer of the Uterus
NCT00075400	PHASE2	COMPLETED	Imatinib Mesylate in Treating Patients With Recurrent or Persistent Uterine Cancer
NCT00114218	PHASE2	COMPLETED	Gemcitabine and Docetaxel in Treating Patients With Recurrent or Persistent Uterine Cancer
NCT00238121	PHASE2	COMPLETED	Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer
NCT00245102	PHASE2	COMPLETED	Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma
NCT00378911	PHASE2	COMPLETED	Sunitinib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus
NCT00390234	PHASE2	COMPLETED	Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma
NCT00659360	PHASE2	COMPLETED	AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma
NCT01061606	PHASE2	TERMINATED	Temsirolimus in Treating Patients With Recurrent or Persistent Cancer of the Uterus
NCT01079832	PHASE2	COMPLETED	Stereotactic Radiosurgery Using CyberKnife in Treating Women With Advanced or Recurrent Gynecological Malignancies
NCT01168232	PHASE2	COMPLETED	Ixabepilone in Treating Patients With Recurrent or Persistent Uterine Cancer
NCT01220609	PHASE2	COMPLETED	Ixabepilone in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus Previously Treated With Chemotherapy
NCT01247571	PHASE2	COMPLETED	Pazopanib Hydrochloride in Treating Patients With Recurrent or Persistent Uterine Cancer
NCT01303094	PHASE2	COMPLETED	Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma
NCT01553539	PHASE2	COMPLETED	Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery