SMARCA2

Summary

SMARCA2 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2, HGNC:11098) is a protein-coding gene on chromosome 9p24.3, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (P51531). ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism.

Source: NCBI Gene 6595 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability-sparse hair-brachydactyly syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 19
• Clinical variants (ClinVar): 1,562 total — 49 pathogenic, 64 likely-pathogenic
• Phenotypes (HPO): 154
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11098
Approved symbol	SMARCA2
Name	SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2
Location	9p24.3
Locus type	gene with protein product
Status	Approved
Aliases	BAF190, hSNF2a, hBRM, Sth1p, SNF2LA, BRM, SNF2, SWI2
Ensembl gene	ENSG00000080503
Ensembl biotype	protein_coding
OMIM	600014
Entrez	6595

Gene structure

Transcript identifiers

Ensembl transcripts: 79 — 54 protein_coding, 14 protein_coding_CDS_not_defined, 7 nonsense_mediated_decay, 4 retained_intron

ENST00000302401, ENST00000324954, ENST00000349721, ENST00000357248, ENST00000382183, ENST00000382185, ENST00000382186, ENST00000382194, ENST00000382203, ENST00000416751, ENST00000417599, ENST00000423555, ENST00000439732, ENST00000450198, ENST00000452193, ENST00000457226, ENST00000491574, ENST00000634271, ENST00000634287, ENST00000634338, ENST00000634343, ENST00000634403, ENST00000634435, ENST00000634536, ENST00000634688, ENST00000634706, ENST00000634760, ENST00000634772, ENST00000634781, ENST00000634925, ENST00000634931, ENST00000634989, ENST00000635030, ENST00000635129, ENST00000635133, ENST00000635185, ENST00000635226, ENST00000635273, ENST00000635388, ENST00000635392, ENST00000635397, ENST00000635530, ENST00000635590, ENST00000635659, ENST00000635688, ENST00000635739, ENST00000636157, ENST00000636221, ENST00000636233, ENST00000636367, ENST00000636501, ENST00000636559, ENST00000636758, ENST00000636903, ENST00000636916, ENST00000636969, ENST00000637097, ENST00000637103, ENST00000637134, ENST00000637352, ENST00000637371, ENST00000637383, ENST00000637806, ENST00000637856, ENST00000638139, ENST00000639760, ENST00000704350, ENST00000704351, ENST00000704352, ENST00000704353, ENST00000704354, ENST00000704355, ENST00000866695, ENST00000866696, ENST00000866697, ENST00000866698, ENST00000915468, ENST00000953438, ENST00000953439

RefSeq mRNA: 7 — MANE Select: NM_003070 NM_001289396, NM_001289397, NM_001289398, NM_001289399, NM_001289400, NM_003070, NM_139045

CCDS: CCDS34977, CCDS34978, CCDS75807, CCDS75808, CCDS83338, CCDS83339

Canonical transcript exons

ENST00000349721 — 34 exons

Exon	Start	End
ENSE00000682837	2170419	2170472
ENSE00001319715	2192704	2193620
ENSE00001347320	2191266	2191408
ENSE00001602679	2097385	2097471
ENSE00001614170	2083347	2083413
ENSE00001618959	2056672	2056845
ENSE00001627711	2096657	2096764
ENSE00001640446	2060816	2060986
ENSE00001641509	2039466	2039900
ENSE00001650940	2119458	2119535
ENSE00001655472	2081832	2081995
ENSE00001658189	2015347	2015404
ENSE00001683881	2076229	2076329
ENSE00001690900	2086829	2087071
ENSE00001710512	2058291	2058464
ENSE00001731542	2110254	2110417
ENSE00001735544	2088500	2088613
ENSE00001743929	2123719	2123937
ENSE00001748584	2073212	2073342
ENSE00001750260	2181571	2181676
ENSE00001757188	2115822	2116049
ENSE00001759748	2084086	2084196
ENSE00001768957	2077629	2077776
ENSE00001776737	2101570	2101616
ENSE00001778439	2073566	2073623
ENSE00001784172	2047229	2047484
ENSE00001786095	2104003	2104169
ENSE00001797754	2054597	2054723
ENSE00001798327	2070418	2070471
ENSE00002184505	2028987	2029247
ENSE00003231127	2182141	2182242
ENSE00003522731	2186096	2186228
ENSE00003544355	2032952	2033081
ENSE00003658720	2161686	2161903

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3898 / max 744.3741, expressed in 1805 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95833	17.5868	1698
95843	9.8053	1655
95858	3.0243	1033
95832	2.7225	1013
95837	1.9672	1174
95841	1.6766	829
95835	1.5978	756
95834	1.2242	664
95842	1.1962	630
95831	0.9974	500

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.54	gold quality
colonic epithelium	UBERON:0000397	98.95	gold quality
cortical plate	UBERON:0005343	98.80	gold quality
adrenal tissue	UBERON:0018303	98.76	gold quality
left ovary	UBERON:0002119	98.27	gold quality
tendon	UBERON:0000043	98.26	gold quality
ventricular zone	UBERON:0003053	98.26	gold quality
sural nerve	UBERON:0015488	98.16	gold quality
right ovary	UBERON:0002118	98.06	gold quality
ovary	UBERON:0000992	98.01	gold quality
secondary oocyte	CL:0000655	97.86	gold quality
germinal epithelium of ovary	UBERON:0001304	97.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.81	gold quality
epithelium of nasopharynx	UBERON:0001951	97.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.65	gold quality
nasopharynx	UBERON:0001728	97.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.64	gold quality
cerebellar hemisphere	UBERON:0002245	97.62	gold quality
cerebellar cortex	UBERON:0002129	97.61	gold quality
nucleus accumbens	UBERON:0001882	97.58	gold quality
caudate nucleus	UBERON:0001873	97.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.46	gold quality
tonsil	UBERON:0002372	97.44	gold quality
frontal pole	UBERON:0002795	97.42	gold quality
cingulate cortex	UBERON:0003027	97.41	gold quality
cerebellum	UBERON:0002037	97.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.40	gold quality
anterior cingulate cortex	UBERON:0009835	97.39	gold quality
prefrontal cortex	UBERON:0000451	97.34	gold quality
skin of abdomen	UBERON:0001416	97.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	4.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ABCA1	Activation

Upstream regulators (CollecTRI, top): AR, ARID1A, CEBPA, CEBPB, CUX1, ESR1, GATA2, GATA3, KAT6A, KAT6B, KAT7, KAT8, KMT2A, PBRM1, SMARCA1

miRNA regulators (miRDB)

117 targeting SMARCA2, 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-6867-5P	100.00	82.21	3464
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-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9-3P	99.96	70.88	2068
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-128-3P	99.95	71.17	2484

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Brm could also drive expression of CD44; Brm can compensate for BRG-1 loss as pertains to RB sensitivity (PMID:11719516)
• Brm-containing SWI/SNF complex subfamily (trithorax-G) and a complex including YY1 and HDACs (Polycomb-G) counteract each other to maintain transcription of exogenously introduced genes (PMID:11850427)
• 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)
• 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)
• Cell culture in the presence of HDAC inhibitors facilitates the isolation of clones overexpressing Brm. (PMID:14657023)
• BRM and BRG1 participate in two distinct chromosome remodeling complexes that are functionally complementary in non-small cell lung cancer (PMID:15240517)
• on genes regulated by SWI/SNF, Brm contributes to the crosstalk between transcription and RNA processing by decreasing RNAPII elongation rate and facilitating recruitment of the splicing machinery to variant exons with suboptimal splice sites (PMID:16341228)
• family-based and case-control association study suggest that there is no association between the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia (PMID:16749937)
• Aberrant expression of BRM genes is associated with disease development and progression in prostate cancers. (PMID:17075831)
• Loss of BRM through epigenetic silencing is associated with neoplasms (PMID:17546055)
• p53 activity is differentially regulated by Brm- and Brg1-containing SWI/SNF chromatin remodeling complexes (PMID:17938176)
• Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation (PMID:18006815)
• at the TERT gene locus in human tumour cells containing a functional SWI/SNF complex, Brm, and possibly BRG1, in concert with p54(nrb), would initiate efficient transcription and could be involved in the subsequent splicing of TERT transcripts (PMID:18042045)
• C/EBPbeta and GATAs may developmentally regulate the expression of brm by mutually exclusive binding. (PMID:18082132)
• Hotspot mutation of Brahma in non-melanoma skin cancer. (PMID:18923443)
• BRM and BRG1 SWI/SNF complexes have roles in differentiation (PMID:19144648)
• A missense polymorphism (rs2296212)induced a lower nuclear localization of BRM was associated with low SMARCA2 expression in the postmortem prefrontal cortex of schizophrenia patients. (PMID:19363039)
• Cdx2 regulates intestinal villin expression through recruiting Brm-type SWI/SNF complex to the villin promoter. (PMID:19371634)
• Loss of heterozygosity at the 9p21-24 region and identification of BRM as a candidate tumor suppressor gene in head and neck squamous cell carcinoma. (PMID:19488910)
• Data suggest that heterogeneous SWI/SNF complexes composed of either the BRG1 or BRM subunit promote expression of distinct and overlapping MITF target genes. (PMID:19784067)
• show that SWI/SNF activity favors (from subunits Brg1/Brm) loading of HP1 proteins to chromatin both in vivo and in vitro (PMID:20011120)
• Knockdown of either BRM or BRG1 resulted in an inhibition of cell proliferation in monolayer cultures. (PMID:20333683)
• The SWI/SNF chromatin-remodelin complex asa key component of the genetic architecture of schizophrenia. (PMID:20457675)
• REQ functions as an efficient adaptor protein between the SWI/SNF complex and RelB/p52 and plays important roles in noncanonical NF-kappaB transcriptional activation and its associated oncogenic activity. (PMID:20460684)
• The methylation levels of CpG islands within Brahma increased during spermatogenesis and decreased during oogenesis (PMID:20719309)
• The hBrm/Brg1 switch is an indicator of the responsiveness of a gene to heat-shock or IFNgamma stimulation and may represent an “on-off switch” of gene expression in vivo. (PMID:21079652)
• The expression of BRG1 and BRM correlates with the development of prostatic cancer. (PMID:21092585)
• results reveal that miR-199a and Brm form a double-negative feedback loop through Egr1, leading to the generation of two distinct cell types during carcinogenesis. (PMID:21189327)
• multiple distinct transcriptional patterns of GR and Brm interdependence (PMID:21646426)
• sequenced the exomes of ten individuals with Nicolaides-Baraitser syndrome and identified heterozygous variants in SMARCA2 in eight of them. (PMID:22366787)
• SWI/SNF chromatin remodeling complex catalytic subunits Brg1 and Brm modulate cisplatin cytotoxicity by facilitating efficient repair of the cisplatin DNA lesions. (PMID:22721696)
• Reduced expression of BRM may contribute to the carcinogenesis of hepatocellular carcinoma. (PMID:23088494)
• Loss of BRG1 and BRM was frequent in E-cadherin-low, TTF-1-low, and vimentin-high cases. (PMID:23163725)
• SMARCA2 rs2296212 and rs4741651 variants were associated with oligodendroglioma risk. (PMID:23276717)
• BRM expression was lost in 25% of cell lines and 16% of tumors. (PMID:23322154)
• findings suggest that BRM promoter polymorphism (BRM-1321) could regulate BRM expression and may serve as a potential marker for genetic susceptibility to HCC (PMID:23359823)
• the mitogen-activated protein kinase pathway regulates both BRM acetylation and BRM silencing as MAP kinase pathway inhibitors both induced BRM as well as caused BRM deacetylation. (PMID:23524580)
• High SMARCA2 expression is associated with lung cancer (PMID:23872584)
• Data indicate that transient knockdown of BRG1 or BRM reduces hypoxia induction of several known HIF1 and HIF2 target genes in Hep3B cells. (PMID:23897427)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-226m8.10	ENSDARG00000060578
mus_musculus	Smarca2	ENSMUSG00000024921
rattus_norvegicus	Smarca2	ENSRNOG00000011931
drosophila_melanogaster	brm	FBGN0000212

Paralogs (30): HLTF (ENSG00000071794), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), 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 2 — P51531 (reviewed: P51531)

Alternative names: BRG1-associated factor 190B, Probable global transcription activator SNF2L2, Protein brahma homolog, SNF2-alpha

All UniProt accessions (42): P51531, A0A0A0MSS5, A0A0A0MT03, A0A0U1RQE1, A0A0U1RQP3, A0A0U1RQS1, A0A0U1RQU0, A0A0U1RQW7, A0A0U1RQX3, A0A0U1RQZ9, A0A0U1RR09, A0A0U1RR26, A0A0U1RR45, A0A0U1RR83, A0A0U1RRD6, A0A0U1RRF5, A0A0U1RRF8, A0A0U1RRG6, A0A0U1RRJ4, A0A0U1RRJ8, A0A0U1RRN2, A0A1B0GTC9, A0A1B0GU54, A0A1B0GUV6, A0A1B0GWA8, A0A1W2PS06, A0A994HRU5, A0A994J4C9, A0A994J4K2, A0A994J4Z7, A0A994J501, A0A994J6Z7, A0A994J7D9, B1ALF6, B1ALG1, B1ALG2, B4DNT1, F6RS74, F6T8Q0, F6UH26, F6VDE0, F6XE55

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. Binds DNA non-specifically. 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.

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, mutually exclusive) 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, 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. Interacts with PHF10/BAF45A. Interacts with CEBPB (when not methylated). Interacts with TOPBP1. Interacts with CEBPA (when phosphorylated). Interacts with DPF2. Interacts with ERCC6.

Subcellular location. Nucleus.

Post-translational modifications. During apoptosis, cleaved by cathepsin CTSG to produce a 160 kDa cleavage product which localizes to the cytosol. Ubiquitinated.

Disease relevance. Nicolaides-Baraitser syndrome (NCBRS) [MIM:601358] A rare disorder characterized by severe intellectual disability with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, prominent finger joints and broad distal phalanges. Some of the features are progressive with time. The disease is caused by variants affecting the gene represented in this entry. Blepharophimosis-impaired intellectual development syndrome (BIS) [MIM:619293] An autosomal dominant congenital syndrome characterized by blepharophimosis, facial dysmorphism, global development delay, delayed motor skills, impaired intellectual development with poor or absent speech, and behavioral abnormalities in some patients. Additional variable features include distal skeletal anomalies, feeding difficulties with poor growth, respiratory infections, and hypotonia with peripheral spasticity. The disease is caused by variants affecting the gene represented in this entry. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51531-1	Long	yes
P51531-2	Short

RefSeq proteins (7): NP_001276325, NP_001276326, NP_001276327, NP_001276328, NP_001276329, NP_003061, NP_620614 (=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
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 (141 total): sequence variant 49, helix 20, modified residue 18, compositionally biased region 17, strand 9, region of interest 7, sequence conflict 7, domain 5, binding site 3, turn 2, chain 1, short sequence motif 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6HAZ	X-RAY DIFFRACTION	1.31
7Z76	X-RAY DIFFRACTION	1.32
7Z78	X-RAY DIFFRACTION	1.32
5DKC	X-RAY DIFFRACTION	1.6
9D11	X-RAY DIFFRACTION	1.68
5DKH	X-RAY DIFFRACTION	1.7
9E30	X-RAY DIFFRACTION	1.71
9E31	X-RAY DIFFRACTION	1.96
4QY4	X-RAY DIFFRACTION	1.97
7Z77	X-RAY DIFFRACTION	1.97
9QAC	X-RAY DIFFRACTION	2.07
9QAD	X-RAY DIFFRACTION	2.08
9D12	X-RAY DIFFRACTION	2.1
9HYP	X-RAY DIFFRACTION	2.2
6HAY	X-RAY DIFFRACTION	2.24
7Z6L	X-RAY DIFFRACTION	2.24
7S4E	X-RAY DIFFRACTION	2.25
9E1K	X-RAY DIFFRACTION	2.26
6HAX	X-RAY DIFFRACTION	2.35
9HYN	X-RAY DIFFRACTION	2.37
8QJT	X-RAY DIFFRACTION	2.57
8G1P	X-RAY DIFFRACTION	2.7
6EG3	X-RAY DIFFRACTION	2.84
9HYB	X-RAY DIFFRACTION	2.84
9AYQ	X-RAY DIFFRACTION	2.9
6EG2	X-RAY DIFFRACTION	2.98
9DU0	X-RAY DIFFRACTION	3
9DTY	X-RAY DIFFRACTION	3.19
9MR9	X-RAY DIFFRACTION	3.3
9S3R	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51531-F1	66.06	0.19

Functional residue map

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

Ligand- & substrate-binding residues (3): 749–756; 1459; 1476

Post-translational modifications (19): 172, 175, 190, 316, 329, 588, 591, 604, 666, 670, 997, 999, 1377, 1512, 1516, 1528, 1568, 1572, 1302

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-9933947	Formation of the non-canonical BAF (ncBAF) 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: 772 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, RRAGTTGT_UNKNOWN, AP1_01, WWTAAGGC_UNKNOWN, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, LU_IL4_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, AP4_Q6

GO Biological Process (24): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), spermatid development (GO:0007286), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), regulation of mitotic metaphase/anaphase transition (GO:0030071), negative regulation of cell growth (GO:0030308), heterochromatin formation (GO:0031507), 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), 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), 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)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), nucleosome array spacer activity (GO:0140750), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), SWI/SNF complex (GO:0016514), brahma complex (GO:0035060), intermediate filament cytoskeleton (GO:0045111), npBAF complex (GO:0071564), nBAF complex (GO:0071565), bBAF complex (GO:0140092), GBAF complex (GO:0140288), chromosome (GO:0005694), RSC-type complex (GO:0016586)

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	7
transcription by RNA polymerase II	3
DNA-templated transcription	3
regulation of DNA-templated transcription	3
negative regulation of cellular process	3
ATP-dependent activity	3
regulation of transcription by RNA polymerase II	2
cell population proliferation	2
regulation of cell population proliferation	2
positive regulation of cellular process	2
cell differentiation	2
regulation of cell differentiation	2
positive regulation of developmental process	2
positive regulation of DNA-templated transcription	2
binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
germ cell development	1
spermatid differentiation	1
system development	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
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
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
negative regulation of developmental process	1
myoblast differentiation	1
positive regulation of cell differentiation	1

Protein interactions and networks

STRING

3380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCA2	SMARCC1	Q92922	997
SMARCA2	SMARCB1	Q12824	997
SMARCA2	ARID1A	O14497	996
SMARCA2	SMARCC2	Q8TAQ2	995
SMARCA2	SMARCE1	Q969G3	993
SMARCA2	ACTL6A	O96019	984
SMARCA2	SMARCA4	P51532	982
SMARCA2	ARID1B	Q8NFD5	980
SMARCA2	PBRM1	Q86U86	966
SMARCA2	SMARCD1	Q96GM5	945
SMARCA2	SMARCA1	P28370	928
SMARCA2	ARID2	Q68CP9	925
SMARCA2	PHF10	Q8WUB8	909
SMARCA2	SMARCD3	Q6STE5	898
SMARCA2	BRD9	Q9H8M2	876

IntAct

236 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCA2	SMARCB1	psi-mi:“MI:0914”(association)	0.850
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
SMARCC1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCC2	ARID1A	psi-mi:“MI:0914”(association)	0.790
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760
DPF2	ARID1A	psi-mi:“MI:0914”(association)	0.730
SMARCE1	SMARCA2	psi-mi:“MI:0914”(association)	0.730
SMARCC2	SMARCA2	psi-mi:“MI:0915”(physical association)	0.720
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
SMARCD2	ARID1A	psi-mi:“MI:0914”(association)	0.670
RELB	NFKBIE	psi-mi:“MI:0914”(association)	0.670
DPF2	SMARCA2	psi-mi:“MI:0914”(association)	0.640
SMARCD3	ARID1A	psi-mi:“MI:0914”(association)	0.640

BioGRID (621): SMARCA2 (Two-hybrid), BEND7 (Two-hybrid), SMARCA2 (Reconstituted Complex), SMARCA2 (Reconstituted Complex), SMARCA2 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS), SMARCA2 (Two-hybrid), ACTL6A (Co-fractionation), BCL7A (Co-fractionation), BCL7B (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

10 interactions.

A	Effect	B	Mechanism
SMARCA2	“form complex”	CERF	binding
SMARCA2	“form complex”	GBAF	binding
SMARCA2	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
SMARCA2	“form complex”	“Neural progenitor-specific SWI/SNF”	binding
SMARCA2	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
SMARCA2	“form complex”	“Muscle cell-specific SWI/SNF ARID1B variant”	binding
SMARCA2	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
SMARCB1	“up-regulates activity”	SMARCA2	binding
SMARCA2	up-regulates	SMARCC1	binding
SMARCA2	up-regulates	SMARCC2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 173 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	14	68.3×	2e-22
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	19	66.8×	4e-30
Formation of the embryonic stem cell BAF (esBAF) complex	14	64.7×	6e-22
Formation of the polybromo-BAF (pBAF) complex	11	53.7×	8e-16
Formation of the non-canonical BAF (ncBAF) complex	10	51.7×	4e-14
Regulation of endogenous retroelements	14	39.7×	1e-17
Regulation of MITF-M-dependent genes involved in pigmentation	19	38.8×	7e-24
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	12	27.7×	4e-13

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	17	73.0×	6e-27
regulation of nucleotide-excision repair	17	65.2×	9e-26
regulation of mitotic metaphase/anaphase transition	17	53.7×	8e-24
nucleosome disassembly	8	40.9×	7e-10
positive regulation of T cell differentiation	13	37.7×	8e-16
positive regulation of double-strand break repair	17	37.2×	1e-20
regulation of G1/S transition of mitotic cell cycle	17	33.2×	1e-19
positive regulation of myoblast differentiation	14	32.7×	5e-16

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — SACA.

Clinical variants and AI predictions

ClinVar

1562 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	64
Uncertain significance	533
Likely benign	498
Benign	210

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1177354	NM_003070.5(SMARCA2):c.2554G>C (p.Glu852Gln)	Pathogenic
1177355	NM_003070.5(SMARCA2):c.2564G>A (p.Arg855Gln)	Pathogenic
1320261	NM_003070.5(SMARCA2):c.3479C>G (p.Ala1160Gly)	Pathogenic
1334325	NM_003070.5(SMARCA2):c.3298A>C (p.Thr1100Pro)	Pathogenic
1686216	NM_003070.5(SMARCA2):c.2258T>A (p.Leu753His)	Pathogenic
1701009	NM_003070.5(SMARCA2):c.2647C>G (p.Pro883Ala)	Pathogenic
1804427	NM_003070.5(SMARCA2):c.3484C>A (p.Arg1162Ser)	Pathogenic
1805414	NM_003070.5(SMARCA2):c.3292G>A (p.Gly1098Ser)	Pathogenic
1805420	NM_003070.5(SMARCA2):c.2838A>C (p.Leu946Phe)	Pathogenic
212225	NM_003070.5(SMARCA2):c.2486C>T (p.Thr829Ile)	Pathogenic
2412962	NM_003070.5(SMARCA2):c.3466G>A (p.Ala1156Thr)	Pathogenic
2580925	NM_003070.5(SMARCA2):c.3655G>C (p.Ala1219Pro)	Pathogenic
280726	NM_003070.5(SMARCA2):c.3313C>G (p.Arg1105Gly)	Pathogenic
280814	NM_003070.5(SMARCA2):c.3650T>C (p.Leu1217Pro)	Pathogenic
30009	NM_003070.5(SMARCA2):c.3604G>T (p.Gly1202Cys)	Pathogenic
30011	NM_003070.5(SMARCA2):c.3473A>T (p.Asp1158Val)	Pathogenic
30012	NM_003070.5(SMARCA2):c.3475C>G (p.Arg1159Gly)	Pathogenic
30013	NM_003070.5(SMARCA2):c.2642G>T (p.Gly881Val)	Pathogenic
30015	NM_003070.5(SMARCA2):c.3476G>T (p.Arg1159Leu)	Pathogenic
30016	NM_003070.5(SMARCA2):c.2648C>T (p.Pro883Leu)	Pathogenic
30017	NM_003070.5(SMARCA2):c.3602C>T (p.Ala1201Val)	Pathogenic
30018	NM_003070.5(SMARCA2):c.2815C>T (p.His939Tyr)	Pathogenic
30019	NM_003070.5(SMARCA2):c.2255G>C (p.Gly752Ala)	Pathogenic
30020	NG_032162.2:g.118997_171770del	Pathogenic
31687	NM_003070.5(SMARCA2):c.3395G>A (p.Gly1132Asp)	Pathogenic
3252168	NM_003070.5(SMARCA2):c.2639C>T (p.Thr880Ile)	Pathogenic
3704417	NM_003070.5(SMARCA2):c.3440A>C (p.Asp1147Ala)	Pathogenic
379917	NM_003070.5(SMARCA2):c.3446A>G (p.Asn1149Ser)	Pathogenic
3895529	NM_003070.5(SMARCA2):c.2558G>A (p.Gly853Asp)	Pathogenic
390604	NM_003070.5(SMARCA2):c.3386G>A (p.Gly1129Asp)	Pathogenic

SpliceAI

6261 predictions. Top by Δscore:

Variant	Effect	Δscore
9:2054583:A:AG	acceptor_gain	1.0000
9:2054583:ATT:A	acceptor_gain	1.0000
9:2054584:T:G	acceptor_gain	1.0000
9:2054585:T:A	acceptor_gain	1.0000
9:2054593:TTA:T	acceptor_loss	1.0000
9:2054595:A:AG	acceptor_gain	1.0000
9:2054595:A:C	acceptor_loss	1.0000
9:2054596:G:GG	acceptor_gain	1.0000
9:2054596:GA:G	acceptor_gain	1.0000
9:2054596:GACT:G	acceptor_gain	1.0000
9:2054720:TCAGG:T	donor_loss	1.0000
9:2054721:CAGGT:C	donor_loss	1.0000
9:2054722:AG:A	donor_loss	1.0000
9:2054723:GG:G	donor_loss	1.0000
9:2056670:A:AG	acceptor_gain	1.0000
9:2056670:AGCT:A	acceptor_gain	1.0000
9:2056671:G:GT	acceptor_gain	1.0000
9:2056671:GCT:G	acceptor_gain	1.0000
9:2056671:GCTG:G	acceptor_gain	1.0000
9:2056671:GCTGA:G	acceptor_gain	1.0000
9:2056819:G:GT	donor_gain	1.0000
9:2056820:A:T	donor_gain	1.0000
9:2056824:G:GT	donor_gain	1.0000
9:2056825:A:T	donor_gain	1.0000
9:2056841:ACCAG:A	donor_loss	1.0000
9:2056842:CCAGG:C	donor_loss	1.0000
9:2056843:CAG:C	donor_loss	1.0000
9:2056844:AGGT:A	donor_loss	1.0000
9:2056845:GGTT:G	donor_loss	1.0000
9:2056846:G:GC	donor_loss	1.0000

AlphaMissense

10533 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:2039655:T:A	L182H	1.000
9:2039655:T:C	L182P	1.000
9:2039667:T:A	I186N	1.000
9:2039667:T:C	I186T	1.000
9:2039667:T:G	I186S	1.000
9:2039673:C:A	A188D	1.000
9:2039675:T:G	Y189D	1.000
9:2039727:T:A	V206D	1.000
9:2054620:G:T	R357M	1.000
9:2054632:T:C	L361P	1.000
9:2054689:T:C	L380P	1.000
9:2054694:G:C	A382P	1.000
9:2054698:T:A	L383H	1.000
9:2054698:T:C	L383P	1.000
9:2054707:T:C	L386P	1.000
9:2054716:A:C	Q389P	1.000
9:2054719:G:C	R390P	1.000
9:2056673:T:C	L392P	1.000
9:2056753:A:G	K419E	1.000
9:2056755:G:C	K419N	1.000
9:2056755:G:T	K419N	1.000
9:2056766:T:A	L423Q	1.000
9:2056766:T:C	L423P	1.000
9:2056769:G:C	R424T	1.000
9:2056769:G:T	R424I	1.000
9:2056770:A:C	R424S	1.000
9:2056770:A:T	R424S	1.000
9:2056774:G:C	A426P	1.000
9:2056777:C:A	R427S	1.000
9:2056777:C:G	R427G	1.000

dbSNP variants (sampled 300 via entrez): RS1000008099 (9:2085693 T>A), RS1000023092 (9:2122381 C>T), RS1000025500 (9:2188868 A>G), RS1000042951 (9:2135351 C>A,G), RS1000059058 (9:2082585 A>G), RS1000077619 (9:2168133 T>C), RS1000083977 (9:2117187 T>C), RS1000091565 (9:2122539 T>C), RS1000103918 (9:2017386 CGTGA>C), RS1000104393 (9:2075192 T>C), RS1000109468 (9:2114733 T>C,G), RS1000125250 (9:2192229 G>C,T), RS1000137055 (9:2169684 G>A), RS1000185046 (9:2149192 T>C), RS1000193779 (9:2168007 T>G)

Disease associations

OMIM: gene MIM:600014 | disease phenotypes: MIM:601358, MIM:619293, MIM:156200, MIM:135900, MIM:609943, MIM:614562, MIM:130000

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability-sparse hair-brachydactyly syndrome	Definitive	Autosomal dominant
blepharophimosis-impaired intellectual development syndrome	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual disability-sparse hair-brachydactyly syndrome	Definitive	AD

Mondo (16): intellectual disability-sparse hair-brachydactyly syndrome (MONDO:0011053), blepharophimosis-impaired intellectual development syndrome (MONDO:0859139), neurodevelopmental disorder (MONDO:0700092), vein of Galen aneurysm (MONDO:0015196), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), intellectual disability, autosomal dominant (MONDO:0100172), cleft palate (MONDO:0016064), Coffin-Siris syndrome 1 (MONDO:0007617), Coffin-Siris syndrome (MONDO:0015452), microcephaly (MONDO:0001149), Chiari malformation (MONDO:0000115), Ehlers-Danlos syndrome (MONDO:0020066), pituitary stalk interruption syndrome (MONDO:0019828), blepharophimosis (MONDO:0001008)

Orphanet (10): Nicolaides-Baraitser syndrome (Orphanet:3051), SMARCA2-related blepharophimosis-intellectual disability syndrome (Orphanet:637013), Vein of Galen malformation (Orphanet:1053), Cleft palate (Orphanet:2014), Coffin-Siris syndrome (Orphanet:1465), Ehlers-Danlos syndrome (Orphanet:98249), Pituitary stalk interruption syndrome (Orphanet:95496), Blepharophimosis-intellectual disability syndrome (Orphanet:293642), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

154 total (30 of 154 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000066	Labial hypoplasia
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000200	Short lingual frenulum
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000418	Narrow nasal ridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001877_65	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	7.000000e-06
GCST002178_2	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+doxorubicin+/-5FU)	2.000000e-06
GCST002337_144	Amyotrophic lateral sclerosis (sporadic)	1.000000e-06
GCST002663_4	Superior frontal gyrus grey matter volume	3.000000e-06
GCST002935_18	Lead levels	6.000000e-06
GCST003059_15	Parkinson’s disease	1.000000e-06
GCST003670_6	Systolic blood pressure	9.000000e-09
GCST003832_7	Asthma (childhood onset)	5.000000e-06
GCST003996_2	Monobrow	4.000000e-62
GCST003999_7	Nose size	1.000000e-09
GCST006481_17	Lung function (FEV1)	5.000000e-08
GCST006481_41	Lung function (FEV1)	5.000000e-06
GCST006483_64	Lung function (FVC)	3.000000e-08
GCST006483_65	Lung function (FVC)	1.000000e-07
GCST006483_68	Lung function (FVC)	7.000000e-09
GCST008822_8	Neuritic plaque	2.000000e-06
GCST009997_2	Thyroid volume in Hashimoto’s thyroiditis	3.000000e-08
GCST010654_3	Arterial stiffness (brachial-femoral pulse wave velocity)	1.000000e-07
GCST010703_62	Brain morphology (MOSTest)	2.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006516	superior frontal gyrus grey matter volume measurement
EFO:0006335	systolic blood pressure
EFO:0007906	synophrys measurement
EFO:0004314	forced expiratory volume
EFO:0004312	vital capacity
EFO:0006798	neuritic plaque measurement
EFO:0004517	arterial stiffness measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D001139	Arnold-Chiari Malformation	C10.500.680.291; C16.131.666.680.291
D016569	Blepharophimosis	C11.250.090; C11.338.190; C16.131.384.190
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
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
C536436	Coffin-Siris syndrome (supp.)
C536116	Nicolaides Baraitser syndrome (supp.)
C536535	Vein of Galen aneurysm (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2362979 (SINGLE PROTEIN), CHEMBL5465235 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066045 (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

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	8.0	pKd
GNE-064	Inhibition	7.8	pIC50
A947	Binding	7.03	pKd
GNE-235	Binding	5.22	pKd

Binding affinities (BindingDB)

31 measured of 31 human assays (31 total across all organisms); most potent 31 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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-(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-[(1S)-1-phenylethoxy]pyridazin-3-yl]phenol	IC50	14.9 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-(2-phenylethoxy)pyridazin-3-yl]phenol	IC50	19 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
2-(6-amino-5-cyclopentylpyridazin-3-yl)phenol	IC50	25 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(3-phenoxyazetidin-1-yl)pyridazin-3-yl]phenol	IC50	35.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(3-methyl-4-methylsulfonylpiperazin-1-yl)pyridazin-3-yl]phenol	IC50	35.8 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-(1-phenylethyl)piperazin-1-yl]pyridazin-3-yl]phenol	IC50	36.1 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-phenylpyridazin-3-yl)phenol	IC50	37.3 nM	US-10308614: Therapeutic compounds and uses thereof
1-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-methylpiperazin-1-yl]ethanone	IC50	39 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(1-benzylpiperidin-4-yl)pyridazin-3-yl]phenol	IC50	39.3 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-piperidin-1-ylpyridazin-3-yl)phenol	IC50	45.9 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(3-benzyl-4-methylsulfonylpiperazin-1-yl)pyridazin-3-yl]phenol	IC50	46.8 nM	US-10308614: Therapeutic compounds and uses thereof
2-[5-[(3aR,6aS)-2-benzyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-6-aminopyridazin-3-yl]phenol	IC50	47.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-[(dimethylamino)methyl]phenyl]pyridazin-3-yl]phenol	IC50	49.3 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(1-benzylpyrrolidin-3-yl)oxypyridazin-3-yl]phenol	IC50	59.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[4-(pyridin-3-ylmethyl)piperazin-1-yl]pyridazin-3-yl]phenol	IC50	60.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(2,6-dimethylmorpholin-4-yl)pyridazin-3-yl]phenol	IC50	69.6 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-morpholin-4-ylpyridazin-3-yl)phenol	IC50	71.5 nM	US-10308614: Therapeutic compounds and uses thereof
1-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]ethanone	IC50	71.7 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(8-benzyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenol	IC50	79 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-(1-phenylpropan-2-yloxy)pyridazin-3-yl]phenol	IC50	92.5 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[1-(oxan-4-yl)ethoxy]pyridazin-3-yl]phenol	IC50	197 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[2-(dimethylamino)ethoxy]pyridazin-3-yl]phenol	IC50	276 nM	US-10308614: Therapeutic compounds and uses thereof
2-(6-amino-5-phenylpyridazin-3-yl)-6-fluorophenol	IC50	320 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-amino-5-[1-(benzenesulfonyl)pyrrolidin-3-yl]pyridazin-3-yl]phenol	IC50	466 nM	US-10308614: Therapeutic compounds and uses thereof
2-[6-(methylamino)pyridazin-3-yl]phenol	IC50	1040 nM	US-10308614: Therapeutic compounds and uses thereof

ChEMBL bioactivities

261 potent at pChembl≥5 of 305 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL6152639
8.92	IC50	1.2	nM	CHEMBL5564941
8.79	IC50	1.63	nM	CHEMBL6162306
8.70	Kd	2	nM	CHEMBL5415064
8.64	IC50	2.27	nM	CHEMBL6163796
8.57	IC50	2.7	nM	CHEMBL5571722
8.55	IC50	2.8	nM	CHEMBL6162599
8.52	Kd	3	nM	CHEMBL5412292
8.52	IC50	3	nM	CHEMBL6133855
8.52	IC50	3	nM	CHEMBL6152639
8.48	EC50	3.3	nM	CHEMBL5278697
8.44	IC50	3.6	nM	CHEMBL6160404
8.40	IC50	4	nM	CHEMBL6166760
8.40	IC50	4	nM	CHEMBL6164767
8.40	IC50	4	nM	CHEMBL6145659
8.34	IC50	4.6	nM	CHEMBL6162246
8.30	IC50	5	nM	CHEMBL4278436
8.30	IC50	5	nM	CAMIBIRSTAT
8.30	IC50	5	nM	CHEMBL6141585
8.30	IC50	5	nM	CHEMBL6162637
8.22	EC50	6	nM	CHEMBL5278697
8.22	IC50	6	nM	CHEMBL6162908
8.22	IC50	6	nM	CHEMBL6167580
8.22	IC50	6	nM	CHEMBL6144331
8.20	IC50	6.33	nM	CHEMBL6134086
8.17	IC50	6.7	nM	CHEMBL6165182
8.15	IC50	7	nM	CHEMBL6133150
8.15	IC50	7	nM	CHEMBL6141585
8.10	IC50	8	nM	CHEMBL6144331
8.10	IC50	8	nM	CHEMBL6143779
8.09	IC50	8.14	nM	CHEMBL6168928
8.06	IC50	8.8	nM	CHEMBL6102929
8.05	IC50	9	nM	CHEMBL6150430
8.05	IC50	9	nM	CHEMBL6133150
8.00	IC50	10	nM	CHEMBL4294655
8.00	Kd	10	nM	CHEMBL5420238
7.96	IC50	11	nM	CHEMBL6171674
7.92	EC50	12	nM	CHEMBL4748407
7.92	IC50	12	nM	CHEMBL6160059
7.92	IC50	12	nM	CHEMBL6148030
7.89	Kd	13	nM	CHEMBL4278436
7.89	Kd	13	nM	CHEMBL5409404
7.89	IC50	13	nM	CHEMBL6159990
7.89	IC50	13	nM	CHEMBL6149296
7.89	IC50	13	nM	CHEMBL6162601
7.86	IC50	13.8	nM	CHEMBL5308262
7.85	IC50	14	nM	CHEMBL6141925
7.82	IC50	15	nM	CHEMBL6153009
7.82	IC50	15	nM	CHEMBL6145908
7.82	IC50	15	nM	CHEMBL6145659

PubChem BioAssay actives

80 with measured affinity, of 457 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
2-[6-amino-5-[8-(2-methoxy-4-pyridinyl)-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol	2098144: Binding affinity to his-tagged BRM bromodomain (unknown origin) by alpha-LISA assay	ic50	0.0012	uM
2-(6-amino-5-pyrrolidin-1-ylpyridazin-3-yl)phenol	2014570: Binding affinity to SMARCA2 (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	2098144: Binding affinity to his-tagged BRM bromodomain (unknown origin) by alpha-LISA assay	ic50	0.0027	uM
tert-butyl (3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methylpiperazine-1-carboxylate	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0030	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	1928111: PROTAC activity at SMARCA2/VHL in human NCI-H1568 cells assessed as degradation protein measured after 18 hrs	ec50	0.0033	uM
1-[3-(difluoromethyl)-1,2-thiazol-5-yl]-3-[2-fluoro-5-(hydroxymethyl)-4-pyridinyl]urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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-4-pyridinyl)-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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-(1-methylpyrazol-4-yl)pyridazin-3-yl]phenol	1975769: Binding affinity to SMARCA2 (unknown origin)	kd	0.0100	uM
1-(2-chloro-4-pyridinyl)-3-[3-(trifluoromethyl)-1,2-thiazol-5-yl]urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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
(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	1724883: Protac activity at VHL/SMARCA2 in human A549 cells assessed as induction of SMARCA2 bromodomain degradation using rabbit anti-SMARCA2 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0120	uM
2-[6-amino-5-[(2R)-2-propan-2-ylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0130	uM
1-[(2R)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-2-methylpiperazin-1-yl]ethanone	1886341: Binding affinity to human SMARCA2 (S1337 to Q1486 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0160	uM
2-[6-amino-5-[4-(2-methoxy-4-pyridinyl)piperazin-1-yl]pyridazin-3-yl]phenol	2098144: Binding affinity to his-tagged BRM bromodomain (unknown origin) by alpha-LISA assay	ic50	0.0180	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	1886341: Binding affinity to human SMARCA2 (S1337 to Q1486 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0180	uM
2-[6-amino-5-[(2S)-2-methylpiperidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0200	uM
1-[(3S)-4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-3-methylpiperazin-1-yl]ethanone	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0200	uM
2-[6-amino-5-[(2S)-2-methylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0200	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	2178775: Inhibition of SMARCA2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0200	uM
2-[6-amino-5-[(2R)-2-methylpiperidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0240	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	1724883: Protac activity at VHL/SMARCA2 in human A549 cells assessed as induction of SMARCA2 bromodomain degradation using rabbit anti-SMARCA2 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0260	uM
2-[6-amino-5-[(2S)-2-ethylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0300	uM
2-[6-amino-5-[(2R)-2-methylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0320	uM
1-(2-chloro-4-pyridinyl)-3-(3-methyl-1,2-thiazol-5-yl)urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	0.0330	uM
tert-butyl 4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazine-1-carboxylate	1683129: Binding affinity to SMARCA2 (unknown origin) by ITC analysis	kd	0.0350	uM
2-(6-amino-5-phenylpyridazin-3-yl)phenol	1886336: Inhibition of SMARCA2 (unknown origin) by TR-FRET assay	ic50	0.0370	uM
(E)-3-[(1R,9S)-6-(cyclopropylamino)-3,5,12-triazatricyclo[7.2.1.02,7]dodeca-2(7),3,5-trien-12-yl]-1-(2-hydroxyphenyl)prop-2-en-1-one	1308387: Binding affinity to human SMARCA2 expressed in BL21 (DE3)-R3-BirA cells by isothermal titration calorimetry	kd	0.0373	uM
2-[6-amino-5-[(2R)-2-cyclopropylpyrrolidin-1-yl]pyridazin-3-yl]phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0400	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	1724883: Protac activity at VHL/SMARCA2 in human A549 cells assessed as induction of SMARCA2 bromodomain degradation using rabbit anti-SMARCA2 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0410	uM
4-bromo-7-cyclopentyl-9-piperidin-4-ylbenzimidazolo[1,2-a]quinazolin-5-one	2010441: Inhibition of SMARCA2 (unknown origin) assessed as dissociation constant	kd	0.0460	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	1724883: Protac activity at VHL/SMARCA2 in human A549 cells assessed as induction of SMARCA2 bromodomain degradation using rabbit anti-SMARCA2 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0550	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	1724883: Protac activity at VHL/SMARCA2 in human A549 cells assessed as induction of SMARCA2 bromodomain degradation using rabbit anti-SMARCA2 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0580	uM
1-(2-chloro-4-pyridinyl)-3-[2-(trifluoromethyl)-4-pyridinyl]urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	0.0600	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	1724883: Protac activity at VHL/SMARCA2 in human A549 cells assessed as induction of SMARCA2 bromodomain degradation using rabbit anti-SMARCA2 antibody incubated for 18 hrs by WES capillary electrophoresis	ec50	0.0670	uM
1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperidin-4-ol	1683129: Binding affinity to SMARCA2 (unknown origin) by ITC analysis	kd	0.0690	uM
(3R)-1-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperidin-3-ol	1683129: Binding affinity to SMARCA2 (unknown origin) by ITC analysis	kd	0.0710	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	2098174: Binding affinity to his-tagged BRM bromodomain (unknown origin) assessed as dissociation constant	kd	0.0720	uM
1-(2-chloro-4-pyridinyl)-3-pyridin-4-ylurea	1409137: Binding affinity to N-terminal avi-tagged BRM ATPase-SnAC domain (unknown origin) in absence of ADP by SPR assay	kd	0.0870	uM
2-(6-amino-5-piperidin-1-ylpyridazin-3-yl)phenol	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	0.0900	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	2098174: Binding affinity to his-tagged BRM bromodomain (unknown origin) assessed as dissociation constant	kd	0.0930	uM
1-(2-chloro-4-pyridinyl)-3-[2-(difluoromethyl)-4-pyridinyl]urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	0.1100	uM
2-(6-amino-5-piperazin-1-ylpyridazin-3-yl)phenol	1683129: Binding affinity to SMARCA2 (unknown origin) by ITC analysis	kd	0.1350	uM
1-(2-chloro-4-pyridinyl)-3-(2-methyl-4-pyridinyl)urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	0.2000	uM
(3E)-6-chloro-3-[(4-methylpiperazin-1-yl)methylidene]-1,2-dihydropyrrolo[1,2-a]quinazolin-5-one	1310279: Binding affinity to His6-tagged human recombinant SMARCA2B bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by VP-ITC microcalorimetry	kd	0.2620	uM
4-phenyl-5H-pyridazino[4,3-b]indol-3-amine	1886341: Binding affinity to human SMARCA2 (S1337 to Q1486 residues) expressed in bacterial expression system by bromoscan assay	kd	0.3400	uM
1-(2-chloro-4-pyridinyl)-3-(4-methyl-1,3-thiazol-2-yl)urea	1409132: Inhibition of recombinant His10-tagged ZZ-HCV3C-BRM ATPase-SnAC (636 to 1331 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	0.9700	uM
N-[3-(3-methyl-4-oxo-2,5,6,7-tetrahydroisoindol-1-yl)-4-phenoxyphenyl]methanesulfonamide	1455975: Inhibition of human SMARCA2 (S1377 to Q1486 residues) expressed in bacterial expression system by BROMOscan assay	ic50	1.0000	uM
6-(furan-2-yl)-4-[(2R)-2-methylpiperidin-1-yl]pyridazin-3-amine	2014570: Binding affinity to SMARCA2 (unknown origin) assessed as dissociation constant by BROMOscan LeadHunter assay	kd	1.4500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	8
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Tretinoin	increases expression	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
bisphenol A	decreases expression, affects cotreatment, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Doxorubicin	decreases expression, increases expression, affects reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
geraniol	decreases expression	1
lead acetate	increases expression	1
decabromobiphenyl ether	decreases expression	1
riddelliine	increases expression, increases metabolic processing	1
beta-lapachone	decreases expression, increases expression	1
cobaltous chloride	affects binding, increases reaction	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1

ChEMBL screening assays

311 unique, capped per target: 274 binding, 25 functional, 12 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354206	Functional	PubChem BioAssay. Luminescence-based cell-based high throughput dose response assay to identify activators of the function of SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 (SMARCA2, BRM).	PubChem BioAssay data set
CHEMBL3383429	Binding	Inhibition of human SMARCA2 by BROMOscan assay	The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor. — J Med Chem
CHEMBL5328354	ADMET	In vivo PROTAC activity at VHL/SMARCA2 in SCID mouse xenografted with human MV4-11 cells assessed as reduction of SMARCA2 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

8 cell lines: 7 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_AW43	K562 eGFP-SMARCA2	Cancer cell line	Female
CVCL_B2GL	Abcam HeLa SMARCA2 KO	Cancer cell line	Female
CVCL_B9S4	Abcam A-549 SMARCA2 KO	Cancer cell line	Male
CVCL_C8E0	SDQLCHi056-A	Induced pluripotent stem cell	Female
CVCL_D3YY	CCLF-NEURO-0108-T	Cancer cell line	Male
CVCL_D8AV	Ubigene A-549 SMARCA2 KO	Cancer cell line	Male
CVCL_TP48	HAP1 SMARCA2 (-) 1	Cancer cell line	Male
CVCL_TP49	HAP1 SMARCA2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
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
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder