SMARCE1

Summary

SMARCE1 (SWI/SNF related BAF chromatin remodeling complex subunit E1, HGNC:11109) is a protein-coding gene on chromosome 17q21.2, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (Q969G3). Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). It is a selective cancer dependency (DepMap: 72.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart.

Source: NCBI Gene 6605 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial meningioma (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 1,189 total — 47 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 155
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 72.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11109
Approved symbol	SMARCE1
Name	SWI/SNF related BAF chromatin remodeling complex subunit E1
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	BAF57
Ensembl gene	ENSG00000073584
Ensembl biotype	protein_coding
OMIM	603111
Entrez	6605

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 26 protein_coding, 19 retained_intron, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264640, ENST00000348513, ENST00000377808, ENST00000400122, ENST00000431889, ENST00000447024, ENST00000469334, ENST00000474246, ENST00000478349, ENST00000481231, ENST00000493660, ENST00000577721, ENST00000578044, ENST00000578112, ENST00000578995, ENST00000580419, ENST00000580654, ENST00000582955, ENST00000583294, ENST00000642459, ENST00000642576, ENST00000643030, ENST00000643318, ENST00000643378, ENST00000643580, ENST00000643683, ENST00000643806, ENST00000643893, ENST00000644257, ENST00000644443, ENST00000644523, ENST00000644527, ENST00000644701, ENST00000644909, ENST00000645104, ENST00000645152, ENST00000645155, ENST00000645227, ENST00000645478, ENST00000645663, ENST00000646242, ENST00000646283, ENST00000646401, ENST00000646448, ENST00000646482, ENST00000646856, ENST00000647221, ENST00000647294, ENST00000647347, ENST00000647508, ENST00000647515, ENST00000924673, ENST00000951586

RefSeq mRNA: 1 — MANE Select: NM_003079 NM_003079

CCDS: CCDS11370

Canonical transcript exons

ENST00000348513 — 11 exons

Exon	Start	End
ENSE00001344771	40624962	40628993
ENSE00003464578	40645576	40645619
ENSE00003490655	40645796	40645847
ENSE00003500388	40632195	40632367
ENSE00003501840	40637492	40637572
ENSE00003511870	40631592	40631693
ENSE00003539215	40630714	40630924
ENSE00003596491	40642455	40642559
ENSE00003612347	40635931	40636102
ENSE00003664658	40636395	40636526
ENSE00003819338	40647773	40647818

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8621 / max 509.6753, expressed in 1795 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165780	25.3889	1795
165781	0.4732	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.61	gold quality
embryo	UBERON:0000922	98.26	gold quality
ganglionic eminence	UBERON:0004023	98.26	gold quality
smooth muscle tissue	UBERON:0001135	97.70	gold quality
ventricular zone	UBERON:0003053	97.69	gold quality
islet of Langerhans	UBERON:0000006	97.43	gold quality
cortical plate	UBERON:0005343	97.13	gold quality
body of uterus	UBERON:0009853	97.05	gold quality
gall bladder	UBERON:0002110	96.92	gold quality
endocervix	UBERON:0000458	96.62	gold quality
rectum	UBERON:0001052	96.60	gold quality
stromal cell of endometrium	CL:0002255	96.51	gold quality
popliteal artery	UBERON:0002250	96.45	gold quality
tibial artery	UBERON:0007610	96.45	gold quality
left ovary	UBERON:0002119	96.34	gold quality
right ovary	UBERON:0002118	96.25	gold quality
vermiform appendix	UBERON:0001154	96.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.10	gold quality
lower esophagus	UBERON:0013473	96.09	gold quality
descending thoracic aorta	UBERON:0002345	96.01	gold quality
ectocervix	UBERON:0012249	95.98	gold quality
colonic epithelium	UBERON:0000397	95.95	gold quality
left uterine tube	UBERON:0001303	95.94	gold quality
right coronary artery	UBERON:0001625	95.94	gold quality
mucosa of stomach	UBERON:0001199	95.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.91	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.89	gold quality
artery	UBERON:0001637	95.83	gold quality
nerve	UBERON:0001021	95.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.22
E-CURD-114	yes	7.85
E-CURD-53	no	537.76
E-GEOD-93593	no	11.01

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
MYOD1
MYOG
SMARCA4
SMARCB1
TERT

miRNA regulators (miRDB)

132 targeting SMARCE1, 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-9-5P	100.00	72.28	2361
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548A-5P	99.94	71.27	3482

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 72.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• BAF57-mediated cell death is associated with up-regulation of proapoptotic genes including the tumor suppressor familial cylindromatosis (CYLD), which is found to be a direct target of BAF57. (PMID:16135788)
• protein levels of BAF155/170 dictate the maximum cellular amount of BAF57 (PMID:16199878)
• BAF57 is a critical regulator of estrogen receptor function in breast cancer cells (PMID:16769725)
• Ability of SMARCE 1 in modulating the replication efficiency of HBV. (PMID:17669635)
• Knockdown of BAF57 resulted in an accumulation of cells in the G(2)-M phase, inhibition of colony formation, and impaired growth in soft agar. Knockdown of BAF57 also caused transcriptional misregulation of various cell cycle-related gene. (PMID:20460533)
• Data show that the mechanism of BAF155-mediated stabilization of BAF57 involves blocking its ubiquitination by preventing interaction with TRIP12. (PMID:20829358)
• mutations in BAF57 could impinge on several oncogenic signaling pathways contributing to the origin and/or development of breast cancer. (PMID:21465167)
• BAF57 expression was significantly associated with the surgical stage, grade of the tumor, myometrial invasion, lympho-vascular space invasion and lymph node metastasis in 111 endometrial carcinomas. (PMID:22419023)
• Our findings identify multiple-spinal-meningioma disease as a new discrete entity and establish a key role for the SWI/SNF complex in the pathogenesis of both meningiomas and tumors with clear-cell histology. (PMID:23377182)
• Data indicate that BAF57 deregulation predisposes to metastasis. (PMID:23493350)
• Since both TTF1 and SMARCE1 are involved in chromatin remodeling, our results imply an epigenetic regulatory mechanism for T-cell recruitment that invites deciphering. (PMID:24880093)
• BAF complex gene SMARCE1 is mutated in Coffin-Siris syndrome patients. (PMID:25081545)
• these results demonstrate that loss of SMARCE1 is relevant to cranial as well as spinal meningiomas (PMID:25143307)
• Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SmarCE1 gene. (PMID:25168959)
• The results suggested that BAF57 is involved in ovarian cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a target for ovarian cancer therapy. (PMID:25611552)
• Addition of the EGFR inhibitor gefitinib restores the sensitivity of SMARCE1-knockdown cells to MET and ALK inhibitors in NSCLCs. Our findings link SMARCE1 to EGFR oncogenic signaling and suggest targeted treatment options for SMARCE1-deficient tumors. (PMID:25656847)
• a family with a pediatric CCM patient and an adult CCM patient and several asymptomatic relatives carrying a germline SMARCE1 mutation. (PMID:26803492)
• An exhaustive analysis of the BAF57 molecular and biochemical properties, cellular functions, loss-of-function phenotypes in living organisms and pathological manifestations in cases of human mutations. [review] (PMID:27149204)
• We report here three additional individuals with clinical features consistent with CSS and alterations in SMARCE1, one of which is novel. The probands all exhibited dysmorphic facial features, moderate developmental and cognitive delay, poor growth, and hypoplastic digital nails/phalanges, including digits not typically affected in the other genes associated with CSS. (PMID:27264197)
• SMARCE1 plays an essential role in breast cancer metastasis by protecting cells against anoikis through the HIF1A/PTK2 pathway. (PMID:27495308)
• SMARCE1 mutational hits, including novel SMARCE1 mutations, were found in six of eight tested patients with clear cell meningioma (PMID:27891692)
• High SMARCE1 expression is associated with eventual relapse and metastasis in breast cancer. (PMID:28377514)
• Study showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for clear cell meningioma, useful as a routine diagnostic biomarker. (PMID:28474749)
• the malignancy risk in schwannomatosis is not well defined but may include an increased risk of malignant peripheral nerve sheath tumor in SMARCB1 Imaging protocols are also proposed for SMARCB1 and LZTR1 schwannomatosis and SMARCE1-related meningioma predisposition. (PMID:28620005)
• BAF57, BAF60a and SNF5 might act as novel pro-senescence factors in both normal and tumor human skin cells (PMID:28716547)
• miR-29a promotes hepatitis B virus (HBV) replication and expression through regulating SMARCE1 in HBV-infected HepG2.2.15 cells. (PMID:28740345)
• A de novo splicing mutation in SMARCE1 was identified in a patient with Angelman-like syndrome. (PMID:30548424)
• MicroRNA-802 induces hepatitis B virus replication and replication through regulating SMARCE1 expression in hepatocellular carcinoma. (PMID:31611549)
• Long noncoding RNA HOTTIP promotes the metastatic potential of ovarian cancer through the regulation of the miR-615-3p/SMARCE1 pathway. (PMID:32783402)
• Crystal structure of the HMG domain of human BAF57 and its interaction with four-way junction DNA. (PMID:33010889)
• The importance of genetic counseling and screening for people with pathogenic SMARCE1 variants: A family study. (PMID:33185983)
• Clear cell meningiomas are defined by a highly distinct DNA methylation profile and mutations in SMARCE1. (PMID:33319313)
• BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1. (PMID:33670012)
• BAF57 Is a Potential Determinant of Colorectal Cancer Malignancy. (PMID:34732413)
• Assembly and interaction of core subunits of BAF complexes and crystal study of the SMARCC1/SMARCE1 binary complex. (PMID:35158202)
• SMARCE1 promotes neuroblastoma tumorigenesis through assisting MYCN-mediated transcriptional activation. (PMID:35978151)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	smarce1	ENSDARG00000016871
mus_musculus	Smarce1	ENSMUSG00000037935
rattus_norvegicus	Smarce1	ENSRNOG00000010676
drosophila_melanogaster	Bap111	FBGN0030093
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 — Q969G3 (reviewed: Q969G3)

Alternative names: BRG1-associated factor 57

All UniProt accessions (20): Q969G3, A0A2R8Y4T4, A0A2R8Y765, A0A2R8Y7I9, A0A2R8Y7U4, A0A2R8Y855, A0A2R8YD78, A0A2R8YDD9, A0A2R8YDQ4, A0A2R8YEB8, A0A2R8YES3, A0A2R8YFC8, A0A2U3TZQ7, B4DGM3, J3KT85, J3QKS7, J3QKX6, J3QL66, J3QR61, J3QS32

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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. Required for the coactivation of estrogen responsive promoters by SWI/SNF complexes and the SRC/p160 family of histone acetyltransferases (HATs). Also specifically interacts with the CoREST corepressor resulting in repression of neuronal specific gene promoters in non-neuronal cells.

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 combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM/BAF190B, 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. May be a 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 (ACTB). Interacts with BRDT. Also binds to the SRC/p160 family of histone acetyltransferases (HATs) composed of NCOA1, NCOA2, and NCOA3. Interacts with RCOR1/CoREST, NR3C1 and ZMIM2/ZIMP7.

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated by TRIP12, leading to its degradation by the proteasome. Ubiquitination is prevented upon interaction between TRIP12 and SMARCC1.

Disease relevance. Meningioma (MNGMA) [MIM:607174] A common neoplasm of the central nervous system derived from arachnoidal cells. The majority of meningiomas are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Most cases are sporadic. Familial occurrence of meningioma is rare. Disease susceptibility is associated with variants affecting the gene represented in this entry. Coffin-Siris syndrome 5 (CSS5) [MIM:616938] 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.

Domain organisation. The HMG domain is essential for CD4 silencing and CD8 activation; mutation of this domain blocks thymus development.

Isoforms (6)

UniProt ID	Names	Canonical?
Q969G3-1	1, BAF57	yes
Q969G3-2	2, BAF57v
Q969G3-3	3
Q969G3-4	4
Q969G3-5	5
Q969G3-6	6

RefSeq proteins (1): NP_003070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily

Pfam: PF00505

UniProt features (36 total): cross-link 7, compositionally biased region 5, splice variant 5, helix 5, region of interest 4, modified residue 3, sequence variant 3, chain 1, DNA-binding region 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7CYU	X-RAY DIFFRACTION	2.55
6LTH	ELECTRON MICROSCOPY	3
7VDV	ELECTRON MICROSCOPY	3.4
9RL4	ELECTRON MICROSCOPY	3.5
6LTJ	ELECTRON MICROSCOPY	3.7
9RMC	ELECTRON MICROSCOPY	4.2
7Y8R	ELECTRON MICROSCOPY	4.4
9RN1	ELECTRON MICROSCOPY	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969G3-F1	70.72	0.39

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 (10): 4, 40, 265, 3, 92, 92, 131, 146, 166, 277

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
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-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-1266738	Developmental Biology
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
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-9730414	MITF-M-regulated melanocyte development
R-HSA-9842860	Regulation of endogenous retroelements
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 637 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, PAL_PRMT5_TARGETS_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_DNA_REPAIR, PID_ERB_GENOMIC_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (17): nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), neurogenesis (GO:0022008), regulation of mitotic metaphase/anaphase transition (GO:0030071), positive regulation of T cell differentiation (GO:0045582), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), negative regulation of DNA-templated transcription (GO:0045892), regulation of G0 to G1 transition (GO:0070316), positive regulation of stem cell population maintenance (GO:1902459), 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), nervous system development (GO:0007399), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (8): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), N-acetyltransferase activity (GO:0008080), nuclear receptor binding (GO:0016922), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (13): nuclear chromosome (GO:0000228), kinetochore (GO:0000776), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), RSC-type complex (GO:0016586), protein-containing complex (GO:0032991), brahma complex (GO:0035060), npBAF complex (GO:0071564), nBAF complex (GO:0071565), bBAF complex (GO:0140092)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	4
Gene expression (Transcription)	2
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Developmental Biology	1
Epigenetic regulation of gene expression	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SWI/SNF superfamily-type complex	6
regulation of DNA-templated transcription	3
nuclear lumen	3
cellular anatomical structure	3
cell differentiation	2
regulation of mitotic cell cycle phase transition	2
positive regulation of developmental process	2
DNA-templated transcription	2
nucleic acid binding	2
binding	2
chromosome	2
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
transcription by RNA polymerase II	1
nervous system development	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of metaphase/anaphase transition of cell cycle	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
negative regulation of RNA biosynthetic process	1
regulation of cell cycle process	1
G0 to G1 transition	1
stem cell population maintenance	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
G1/S transition of mitotic cell cycle	1
regulation of cell cycle G1/S phase transition	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
regulation of DNA repair	1
nucleotide-excision repair	1

Protein interactions and networks

STRING

1968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCE1	SMARCC1	Q92922	999
SMARCE1	SMARCC2	Q8TAQ2	999
SMARCE1	SMARCA4	P51532	998
SMARCE1	SMARCB1	Q12824	998
SMARCE1	ARID1A	O14497	996
SMARCE1	ACTL6A	O96019	996
SMARCE1	SMARCD1	Q96GM5	996
SMARCE1	SMARCA2	P51531	993
SMARCE1	ARID2	Q68CP9	992
SMARCE1	ARID1B	Q8NFD5	968
SMARCE1	PHF10	Q8WUB8	965
SMARCE1	SMARCD2	Q92925	952
SMARCE1	BANF1	O75531	919
SMARCE1	DPF2	Q92785	911
SMARCE1	ACTL6B	O94805	908

IntAct

399 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	SMARCA4	psi-mi:“MI:0914”(association)	0.840
SMARCC1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCE1	TFIP11	psi-mi:“MI:0915”(physical association)	0.780
TERT	SMARCA4	psi-mi:“MI:0914”(association)	0.740
SMARCE1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	RALBP1	psi-mi:“MI:0915”(physical association)	0.720
KRT31	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720
KRT40	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720
CEP70	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	SMARCE1	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	KRT40	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (610): SMARCE1 (Two-hybrid), SMARCE1 (Two-hybrid), SMARCE1 (Two-hybrid), SMARCE1 (Two-hybrid), SMARCE1 (Two-hybrid), SMARCE1 (Two-hybrid), SMARCE1 (Two-hybrid), STX11 (Two-hybrid), TRIP10 (Two-hybrid), JAKMIP2 (Two-hybrid), SPAG5 (Two-hybrid), RALBP1 (Two-hybrid), EXOC7 (Two-hybrid), MTUS2 (Two-hybrid), NUP62 (Two-hybrid)

ESM2 similar proteins: A4IGK3, B7ZAP0, O08609, O54941, O55047, O60519, P18847, P26801, P28574, P29596, P37285, P52161, P52162, P52164, P60762, P61244, P61245, P97875, Q07016, Q07866, Q08CW1, Q08DJ0, Q0VCP9, Q0VD32, Q13330, Q28772, Q2KII1, Q32KT0, Q32M00, Q3T0B9, Q56A18, Q5BJU6, Q5R581, Q5ZIL4, Q60765, Q62599, Q642H2, Q6PH81, Q78E65, Q7TMY4

Diamond homologs: B7SBD2, O15405, O54941, O94900, P11633, Q32L68, Q56A18, Q65WY8, Q66JW3, Q6BRB4, Q6CC79, Q6CVH3, Q75B82, Q80W03, Q969G3, Q9DC33, Q9LEF5, Q9LGR0, Q9NP66, Q9P0W2, Q9UVL1, Q9Z104, A4QNG3, B0ZTE2, B3DLD3, O04235, O15347, O42342, O49596, O54879, O94842, O95416, P0CB47, P0CO24, P0CO25, P11632, P17480, P25976, P25977, P25979

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
SMARCE1	“form complex”	“SWI/SNF complex”	binding
SMARCC1	“up-regulates quantity by stabilization”	SMARCE1
SMARCE1	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
SMARCE1	“form complex”	“SWI/SNF ACTL6B varian”	binding
SMARCE1	“form complex”	“Neural progenitor-specific SWI/SNF”	binding
SMARCE1	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
SMARCE1	“form complex”	“Muscle cell-specific SWI/SNF ARID1B variant”	binding
SMARCE1	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
SMARCE1	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
SMARCE1	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding
SMARCE1	“form complex”	“Embryonic stem cell-specific SWI/SNF”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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 embryonic stem cell BAF (esBAF) complex	6	54.6×	2e-07
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	7	48.5×	3e-08
Formation of the canonical BAF (cBAF) complex	5	48.1×	2e-06
Formation of the polybromo-BAF (pBAF) complex	5	48.1×	2e-06
Regulation of endogenous retroelements	6	33.5×	1e-06
Regulation of MITF-M-dependent genes involved in pigmentation	7	28.2×	4e-07
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	6	27.3×	3e-06
MITF-M-dependent gene expression	8	22.0×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome disassembly	6	62.5×	4e-08
regulation of G0 to G1 transition	7	61.3×	8e-09
regulation of nucleotide-excision repair	7	54.7×	8e-09
regulation of mitotic metaphase/anaphase transition	7	45.1×	2e-08
positive regulation of myoblast differentiation	8	38.1×	8e-09
morphogenesis of an epithelium	8	35.7×	9e-09
positive regulation of T cell differentiation	6	35.5×	1e-06
positive regulation of double-strand break repair	7	31.3×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

1189 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	27
Uncertain significance	526
Likely benign	431
Benign	18

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069790	NM_003079.5(SMARCE1):c.472C>T (p.Arg158Ter)	Pathogenic
1076751	NC_000017.10:g.(?38785037)(38804103_?)del	Pathogenic
1172668	NM_003079.5(SMARCE1):c.310T>C (p.Trp104Arg)	Pathogenic
1425601	NM_003079.5(SMARCE1):c.493G>T (p.Glu165Ter)	Pathogenic
1428058	NM_003079.5(SMARCE1):c.808del (p.Arg272fs)	Pathogenic
1435484	NM_003079.5(SMARCE1):c.688C>T (p.Gln230Ter)	Pathogenic
1460319	NM_003079.5(SMARCE1):c.328G>T (p.Glu110Ter)	Pathogenic
1737991	NM_003079.5(SMARCE1):c.411del (p.Ala138fs)	Pathogenic
1740283	NM_003079.5(SMARCE1):c.439del (p.Ser147fs)	Pathogenic
1755184	NM_003079.5(SMARCE1):c.673C>T (p.Gln225Ter)	Pathogenic
1762229	NM_003079.5(SMARCE1):c.816+1G>T	Pathogenic
212264	NM_003079.5(SMARCE1):c.624_627del (p.Ser208fs)	Pathogenic
225845	NM_003079.5(SMARCE1):c.218A>C (p.Tyr73Ser)	Pathogenic
239495	NM_003079.5(SMARCE1):c.525del (p.Ala176fs)	Pathogenic
2626166	NM_003079.5(SMARCE1):c.248_249del (p.Gln83fs)	Pathogenic
2664741	NM_003079.5(SMARCE1):c.587del (p.Phe196fs)	Pathogenic
2709971	NM_003079.5(SMARCE1):c.506del (p.Pro169fs)	Pathogenic
2792205	NM_003079.5(SMARCE1):c.694C>T (p.Gln232Ter)	Pathogenic
2855068	NM_003079.5(SMARCE1):c.376T>G (p.Tyr126Asp)	Pathogenic
2972862	NM_003079.5(SMARCE1):c.814del (p.Arg272fs)	Pathogenic
3223094	NM_003079.5(SMARCE1):c.275dup (p.Leu93fs)	Pathogenic
3320856	NM_003079.5(SMARCE1):c.439dup (p.Ser147fs)	Pathogenic
3320859	NM_003079.5(SMARCE1):c.632_633dup (p.Val212fs)	Pathogenic
3320868	NM_003079.5(SMARCE1):c.370del (p.Lys123_Ile124insTer)	Pathogenic
3446146	NM_003079.5(SMARCE1):c.748del (p.Glu250fs)	Pathogenic
3446152	NM_003079.5(SMARCE1):c.781G>T (p.Glu261Ter)	Pathogenic
3446153	NM_003079.5(SMARCE1):c.601del (p.Arg201fs)	Pathogenic
3648631	NM_003079.5(SMARCE1):c.372dup (p.Glu125fs)	Pathogenic
3651960	NM_003079.5(SMARCE1):c.967G>T (p.Glu323Ter)	Pathogenic
3780998	NM_003079.5(SMARCE1):c.436A>G (p.Lys146Glu)	Pathogenic

SpliceAI

1856 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40628787:A:AC	donor_gain	1.0000
17:40628787:ATT:A	donor_gain	1.0000
17:40628801:T:C	donor_gain	1.0000
17:40628989:CTCCT:C	acceptor_gain	1.0000
17:40628992:CT:C	acceptor_gain	1.0000
17:40628994:C:CC	acceptor_gain	1.0000
17:40630708:GGTTA:G	donor_loss	1.0000
17:40630711:TA:T	donor_loss	1.0000
17:40630712:A:AT	donor_loss	1.0000
17:40630713:CCTGT:C	donor_gain	1.0000
17:40630920:CACAA:C	acceptor_gain	1.0000
17:40630921:ACAA:A	acceptor_gain	1.0000
17:40630922:CAA:C	acceptor_gain	1.0000
17:40630922:CAAC:C	acceptor_gain	1.0000
17:40630923:AA:A	acceptor_gain	1.0000
17:40630925:C:CC	acceptor_gain	1.0000
17:40630925:C:T	acceptor_loss	1.0000
17:40630930:C:CT	acceptor_gain	1.0000
17:40630931:A:T	acceptor_gain	1.0000
17:40631588:ATAC:A	donor_gain	1.0000
17:40631590:AC:A	donor_gain	1.0000
17:40631591:CC:C	donor_gain	1.0000
17:40631626:T:A	donor_gain	1.0000
17:40631690:TTCG:T	acceptor_gain	1.0000
17:40631692:CG:C	acceptor_gain	1.0000
17:40631694:C:CC	acceptor_gain	1.0000
17:40632404:A:T	acceptor_gain	1.0000
17:40632410:C:CT	acceptor_gain	1.0000
17:40635930:CCAT:C	donor_gain	1.0000
17:40636099:CTAT:C	acceptor_gain	1.0000

AlphaMissense

2747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40631599:A:G	L270P	1.000
17:40631653:T:G	H252P	1.000
17:40631654:G:C	H252D	1.000
17:40631674:A:G	L245P	1.000
17:40631674:A:T	L245H	1.000
17:40631677:T:A	E244V	1.000
17:40631678:C:T	E244K	1.000
17:40631681:C:G	A243P	1.000
17:40631686:A:C	L241R	1.000
17:40631686:A:G	L241P	1.000
17:40631686:A:T	L241Q	1.000
17:40631688:T:A	K240N	1.000
17:40631688:T:G	K240N	1.000
17:40631689:T:A	K240I	1.000
17:40631690:T:C	K240E	1.000
17:40631692:C:G	R239P	1.000
17:40632196:T:G	Q238P	1.000
17:40632198:A:C	H237Q	1.000
17:40632198:A:T	H237Q	1.000
17:40632199:T:A	H237L	1.000
17:40632199:T:C	H237R	1.000
17:40632199:T:G	H237P	1.000
17:40632200:G:C	H237D	1.000
17:40632200:G:T	H237N	1.000
17:40632207:T:A	L234F	1.000
17:40632207:T:G	L234F	1.000
17:40632208:A:G	L234S	1.000
17:40632211:G:A	S233F	1.000
17:40632212:A:G	S233P	1.000
17:40632214:T:G	Q232P	1.000

dbSNP variants (sampled 300 via entrez): RS1000245587 (17:40649568 G>A), RS1000349687 (17:40644149 A>T), RS1000417793 (17:40636791 A>G), RS1000696584 (17:40629712 C>G,T), RS1000750973 (17:40638622 T>C), RS1000850765 (17:40643193 C>G), RS1000944631 (17:40638561 C>A,G), RS1000985696 (17:40631087 T>C), RS1001199328 (17:40644943 T>C), RS1001232262 (17:40639723 C>T), RS1001306034 (17:40625639 A>G), RS1001377614 (17:40625966 C>T), RS1001383654 (17:40626773 T>C), RS1001440834 (17:40633126 C>T), RS1001579487 (17:40632864 T>C)

Disease associations

OMIM: gene MIM:603111 | disease phenotypes: MIM:607174, MIM:616938, MIM:609322, MIM:162091

GenCC curated gene-disease

Disease	Classification	Inheritance
familial meningioma	Definitive	Autosomal dominant
Coffin-Siris syndrome 5	Strong	Autosomal dominant
Coffin-Siris syndrome	Supportive	Autosomal dominant
familial multiple meningioma	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
familial meningioma	Definitive	AD
Coffin-Siris syndrome	Definitive	AD

Mondo (10): familial meningioma (MONDO:0011789), hereditary neoplastic syndrome (MONDO:0015356), Coffin-Siris syndrome 5 (MONDO:0014838), facial cleft (MONDO:0015411), rhabdoid tumor predisposition syndrome 1 (MONDO:0012252), SMARCB1-related schwannomatosis (MONDO:0024517), meningioma (MONDO:0016642), intellectual disability (MONDO:0001071), Coffin-Siris syndrome (MONDO:0015452), familial multiple meningioma (MONDO:0016995)

Orphanet (9): Familial multiple meningioma (Orphanet:263662), Inherited cancer-predisposing syndrome (Orphanet:140162), Coffin-Siris syndrome (Orphanet:1465), Facial cleft (Orphanet:141229), Rhabdoid tumor predisposition syndrome (Orphanet:231108), Rhabdoid tumor (Orphanet:69077), Full schwannomatosis (Orphanet:93921), Meningioma (Orphanet:2495), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

155 total (30 of 155 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000141	Amenorrhea
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000322	Short philtrum
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000527	Long eyelashes
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000602	Ophthalmoplegia

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST005038_121	Allergic disease (asthma, hay fever or eczema)	1.000000e-21
GCST005038_97	Allergic disease (asthma, hay fever or eczema)	2.000000e-26
GCST007563_12	Allergic disease (asthma, hay fever or eczema)	2.000000e-16
GCST007564_26	Asthma or allergic disease (pleiotropy)	1.000000e-15
GCST007798_101	Asthma	4.000000e-10
GCST007798_119	Asthma	2.000000e-20
GCST007800_53	Asthma (childhood onset)	2.000000e-18
GCST007800_62	Asthma (childhood onset)	3.000000e-17
GCST008916_33	Asthma	3.000000e-10
GCST009718_15	Eczema	4.000000e-16
GCST009719_2	Allergic rhinitis	3.000000e-17
GCST009798_41	Asthma	3.000000e-08
GCST009798_47	Asthma	3.000000e-10
GCST010984_41	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	8.000000e-15
GCST010985_35	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	7.000000e-14
GCST011742_69	Triglyceride levels in HIV infection	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004530	triglyceride measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008579	Meningioma	C04.557.580.520; C04.557.645.520; C04.588.614.250.580.500; C10.551.240.500.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C536436	Coffin-Siris syndrome (supp.)
C537443	Meningioma, familial (supp.)
C563738	Rhabdoid Tumor Predisposition Syndrome 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725103 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.95	Kd	112	nM	CHEMBL5653589
6.95	ED50	112	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149443: Binding affinity to human SMARCE1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1120	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
methylmercuric chloride	decreases expression, increases expression	2
sodium arsenite	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression	2
Ozone	increases abundance, affects expression, affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
deoxynivalenol	increases expression	1
methylselenic acid	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
phenethyl isothiocyanate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bromovanin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652485	Binding	Binding affinity to human SMARCE1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7ZF	Abcam Raji SMARCE1 KO	Cancer cell line	Male
CVCL_C0A8	Abcam THP-1 SMARCE1 KO	Cancer cell line	Male
CVCL_C7BW	Abcam PC-3 SMARCE1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT04386642	PHASE4	UNKNOWN	Tranexamic Acid Reduce Blood Loss in Meningioma Resection
NCT06377371	PHASE4	RECRUITING	Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01655927	PHASE3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03015701	PHASE3	COMPLETED	S9005 Mifepristone in Meningioma
NCT03558516	PHASE3	COMPLETED	Magnesium and Intraoperative Blood Loss in Meningioma Surgery
NCT04305470	PHASE3	COMPLETED	Gleolan for Visualization of Newly Diagnosed or Recurrent Meningioma
NCT00003483	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Meningioma
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00706810	PHASE2	COMPLETED	Combination of Hydroxyurea and Verapamil for Refractory Meningiomas
NCT00859040	PHASE2	COMPLETED	Monthly SOM230C for Recurrent or Progressive Meningioma
NCT01967823	PHASE2	COMPLETED	T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02523014	PHASE2	RECRUITING	Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02648997	PHASE2	ACTIVE_NOT_RECRUITING	An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
NCT02831257	PHASE2	COMPLETED	AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas
NCT02847559	PHASE2	RECRUITING	Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma
NCT03013387	PHASE2	WITHDRAWN	Dosimetry Guided PRRT With 90Y-DOTATOC
NCT03071874	PHASE2	UNKNOWN	Vistusertib (AZD2014) For Recurrent Grade II-III Meningiomas
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03273712	PHASE2	COMPLETED	Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)
NCT03971461	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
NCT04082520	PHASE2	RECRUITING	Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
NCT04298541	PHASE2	NOT_YET_RECRUITING	Direct Comparison of Ga-68-DOTATATE and Ga-68-DOTATOC
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04659811	PHASE2	ACTIVE_NOT_RECRUITING	Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma
NCT05425004	PHASE2	RECRUITING	Cabozantinib for Patients With Recurrent or Progressive Meningioma
NCT05940493	PHASE2	RECRUITING	Abemaciclib in Newly Diagnosed Meningioma Patients
NCT06012929	PHASE2	WITHDRAWN	A Study of ONC201 for Refractory Meningioma
NCT06126588	PHASE2	RECRUITING	Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT06132685	PHASE2	RECRUITING	Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT06326190	PHASE2	RECRUITING	177Lu-DOTATATE for Recurrent Meningioma
NCT06439420	PHASE2	COMPLETED	CBT-I in Primary Brain Tumor Patients: Phase IIc Randomized Feasibility Pilot Trial
NCT06684795	PHASE2	RECRUITING	FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06710249	PHASE2	RECRUITING	Impact of Salovum® and SPC® Flakes on Brain Tumor Induced Edema
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07428616	PHASE2	RECRUITING	A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07533942	PHASE2	NOT_YET_RECRUITING	A Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma
NCT03267836	PHASE1	TERMINATED	Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma