SMARCA1

Summary

SMARCA1 (SNF2 related chromatin remodeling ATPase 1, HGNC:11097) is a protein-coding gene on chromosome Xq25-q26.1, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 1 (P28370). ATPase that possesses intrinsic ATP-dependent chromatin-remodeling activity.

This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6594 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 398 total — 5 pathogenic, 12 likely-pathogenic
• Druggable target: yes
• Transcription factor: yes — 62 downstream targets (CollecTRI)
• MANE Select transcript: NM_001282874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11097
Approved symbol	SMARCA1
Name	SNF2 related chromatin remodeling ATPase 1
Location	Xq25-q26.1
Locus type	gene with protein product
Status	Approved
Aliases	SNF2LB, NURF140, ISWI, SWI, hSNF2L
Ensembl gene	ENSG00000102038
Ensembl biotype	protein_coding
OMIM	300012
Entrez	6594

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 25 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000371121, ENST00000371122, ENST00000371123, ENST00000478420, ENST00000617310, ENST00000856438, ENST00000856439, ENST00000856440, ENST00000856441, ENST00000856442, ENST00000931469, ENST00000931470, ENST00000931471, ENST00000931472, ENST00000931473, ENST00000931474, ENST00000931475, ENST00000950301, ENST00000950302, ENST00000950303, ENST00000950304, ENST00000950305, ENST00000950306, ENST00000950307, ENST00000950308, ENST00000950309, ENST00000950310

RefSeq mRNA: 7 — MANE Select: NM_001282874 NM_001282874, NM_001282875, NM_001378261, NM_001378262, NM_001378263, NM_001378264, NM_003069

CCDS: CCDS14612, CCDS76018, CCDS76019

Canonical transcript exons

ENST00000371121 — 25 exons

Exon	Start	End
ENSE00000676483	129471204	129471326
ENSE00000676488	129465520	129465732
ENSE00000828202	129507941	129508096
ENSE00000828203	129506080	129506211
ENSE00000828204	129504734	129504802
ENSE00000828205	129499732	129499841
ENSE00000828206	129497845	129498071
ENSE00000828212	129491941	129492093
ENSE00000828213	129490060	129490192
ENSE00000828214	129488937	129489085
ENSE00000828215	129487018	129487137
ENSE00001027614	129496750	129496871
ENSE00001027631	129516331	129516497
ENSE00001093271	129481075	129481185
ENSE00001320447	129465844	129465962
ENSE00001454390	129446506	129447233
ENSE00001605247	129493040	129493075
ENSE00001735083	129480701	129480814
ENSE00001774786	129468773	129468905
ENSE00003466306	129518361	129518447
ENSE00003519519	129515894	129515994
ENSE00003567532	129515687	129515787
ENSE00003581175	129511804	129511983
ENSE00003744137	129523197	129523490
ENSE00003750248	129448333	129448443

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4698 / max 243.9932, expressed in 1385 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200434	12.4801	1350
200433	9.7054	1276
200432	0.2843	140

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.86	gold quality
choroid plexus epithelium	UBERON:0003911	96.80	gold quality
tibia	UBERON:0000979	96.05	gold quality
endothelial cell	CL:0000115	95.86	gold quality
ventricular zone	UBERON:0003053	95.81	gold quality
right adrenal gland cortex	UBERON:0035827	95.72	gold quality
right adrenal gland	UBERON:0001233	95.31	gold quality
adrenal cortex	UBERON:0001235	95.15	gold quality
left adrenal gland cortex	UBERON:0035825	95.15	gold quality
left adrenal gland	UBERON:0001234	95.08	gold quality
adrenal gland	UBERON:0002369	94.86	gold quality
parietal pleura	UBERON:0002400	94.81	gold quality
stromal cell of endometrium	CL:0002255	94.59	gold quality
seminal vesicle	UBERON:0000998	94.59	gold quality
cartilage tissue	UBERON:0002418	94.13	gold quality
left ovary	UBERON:0002119	93.91	gold quality
pleura	UBERON:0000977	93.79	gold quality
right ovary	UBERON:0002118	93.67	gold quality
islet of Langerhans	UBERON:0000006	93.62	gold quality
cauda epididymis	UBERON:0004360	93.59	gold quality
germinal epithelium of ovary	UBERON:0001304	93.57	gold quality
right testis	UBERON:0004534	93.55	gold quality
ovary	UBERON:0000992	93.46	gold quality
ganglionic eminence	UBERON:0004023	93.24	gold quality
visceral pleura	UBERON:0002401	93.00	gold quality
calcaneal tendon	UBERON:0003701	92.77	gold quality
pituitary gland	UBERON:0000007	92.76	gold quality
testis	UBERON:0000473	92.53	gold quality
adenohypophysis	UBERON:0002196	92.49	gold quality
embryo	UBERON:0000922	92.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.49
E-MTAB-7249	no	2.56

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

62 targets.

Target	Regulation
ACOT8
BGLAP
BIN1
BRCA1
CD44	Repression
CD74
CDH1
CDKN1C
CDKN2A	Activation
CEBPB
CECR2
CHD1
CLC
CREBBP
CRYAB
CSN1S2AP
DNAH8
DNASE1
DYNC1H1
EIF3K
EN1	Unknown
EN2
EPB42
EPO
GADD45A
H2AZ1
HAND2
HBB
HMOX1
HSPA4

Upstream regulators (CollecTRI, top): AP1, AR, ARID1A, CREB1, KLF1, MYC, MYOD1, RBPJ, SMARCA1, SMARCA5, SOX10, SP1, TP53, TP63, TXK, USF1

miRNA regulators (miRDB)

93 targeting SMARCA1, 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-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
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-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 16)

• a neuronal SNF2L variant inactivates chromatin remodeling (PMID:15310751)
• Brahma and Brahma/SWI2-related gene 1 have roles in hypoxic induction of the erythropoietin gene (PMID:15347669)
• This study provides the first insight into the mechanisms that control basal expression of human SNF2L gene. (PMID:18243132)
• SNF2L mutations are not a cause of X-linked mental retardation in our cohort of patients, although we cannot exclude the possibility that regulatory mutations might exist (PMID:18302774)
• Cancers are sensitive to SNF2L knockdown because, unlike their normal counterparts, they lack sufficient compensation from other family members. (PMID:19996304)
• ISWI proteins Snf2H, Snf2L as well as Acf1 accumulate at UV-induced DNA damage sites within tens of seconds and reach a plateau after a few minutes. (PMID:21738833)
• expression profiling analyses revealed that SWI/SNF likely antagonizes Polycomb repressive complex 2, implicating this as one possible mechanism of tumor suppression (PMID:22233809)
• The effect of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling with increased proliferation and locomotion. High levels of SNF2L expression in normal melanocytes contrast with undetectable expression in melanoma. (PMID:22508985)
• The results suggest that the cAMP-response element consensus sequence in the SNF2L proximal promoter most likely confers constitutive activation and regulation by cAMP in neural cells. (PMID:23549828)
• Depletion of a chromatin remodeler, SMARCA1, in cancer cell lines promoted their growth. (PMID:25462860)
• In one family, four siblings with a psychotic illness and their unaffected mother each carry a novel private missense variant in the SMARCA1 gene on the X chromosome. (PMID:27001614)
• Data identified SMARCA1 as an interactive protein of DLEU1 in colorectal cancer to regulate cancer cell proliferation. (PMID:30098595)
• High SNF2L expression is associated with gastric cancer growth and invasion. (PMID:30922402)
• This is the first report of an interstitial deletion encompassing OCRL and SMARCA1 gene in Lowe syndrome. (PMID:31376231)
• A pan-cancer bioinformatic analysis of the carcinogenic role of SMARCA1 in human carcinomas. (PMID:36126083)
• The lncRNA MIR99AHG directs alternative splicing of SMARCA1 by PTBP1 to enable invadopodia formation in colorectal cancer cells. (PMID:37725664)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smarca1	ENSDARG00000012776
mus_musculus	Smarca1	ENSMUSG00000031099
rattus_norvegicus	Smarca1	ENSRNOG00000003762
drosophila_melanogaster	Iswi	FBGN0011604
caenorhabditis_elegans		WBGENE00002169

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), 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 1 — P28370 (reviewed: P28370)

Alternative names: Global transcription activator SNF2L1, Nucleosome-remodeling factor subunit SNF2L, SNF2 related chromatin remodeling ATPase 1

All UniProt accessions (3): P28370, A0A0A0MRP6, B7ZLQ5

UniProt curated annotations — full annotation on UniProt →

Function. ATPase that possesses intrinsic ATP-dependent chromatin-remodeling activity. ATPase activity is substrate-dependent, and is increased when nucleosomes are the substrate, but is also catalytically active when DNA alone is the substrate. Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template. Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes. The BAZ1A-, BAZ1B-, BAZ2A- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template. The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template. Within the NURF-1 and CERF-1 ISWI chromatin remodeling complexes, nucleosomes are the preferred substrate for its ATPase activity. Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development. May promote neurite outgrowth. May be involved in the development of luteal cells. Facilitates nucleosome assembly during DNA replication, ensuring replication fork progression and genomic stability by preventing replication stress and nascent DNA gaps. Catalytically inactive when either DNA or nucleosomes are the substrate and does not possess chromatin-remodeling activity. Acts as a negative regulator of chromatin remodelers by generating inactive complexes.

Subunit / interactions. May form homodimers. Component of the ACF-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ1A, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA. Within the complex interacts with BAZ1A; the interaction is direct. Component of the WICH-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ1B/WSTF. Within the complex interacts with BAZ1B/WSTF. Component of the NoRC-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ2A/TIP5. Within the complex interacts with BAZ2A/TIP5. Component of the BRF-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ2B. Within the complex interacts with BAZ2B. Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1, BPTF, RBBP4 and RBBP7. Within the complex interacts with BPTF. Within the complex interacts with RBBP4 and RBBP7. Component of the CERF-1 ISWI chromatin remodeling complex (also called the CECR2-containing-remodeling factor (CERF) complex) at least composed of CECR2 and SMARCA1. LUZP1 is detected as part of the CERF-1 complex in embryonic stem cells where it is involved in complex stabilization but is not detected in the complex in the testis. Component of the RSF-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and RSF1. Within the complex interacts with RSF1. Interacts with PRLR. Interacts with ERCC6. May form homodimers. Component of the BPFT-SMARCA1 complex at least composed of SMARCA1, BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin. Within the complex interacts with BPTF, RBBP4 and RBBP7. Component of the BAZ1A-1-SMARCA1 complex at least composed of SMARCA1 and BAZ1A; the complex is catalytically inactive and does not remodel chromatin. Component of the BAZ1B-1-SMARCA1 complex at least composed of SMARCA1 and BAZ1B; the complex is catalytically inactive and does not remodel chromatin.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in lung, breast, kidney, ovary, skeletal muscle and brain. Mainly expressed in non-neuronal tissues such as lung, breast, kidney, and ovary.

Miscellaneous. Active as an ATPase due to the absence of exon 13. Inactive as an ATPase due to the presence of exon 13, but retains its ability to correctly fold and incorporate into complexes.

Similarity. Belongs to the SNF2/RAD54 helicase family. ISWI subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P28370-2	1, SMARCA1, SNF2L	yes
P28370-1	2, SMARCA1.13, SNF2L+13

RefSeq proteins (7): NP_001269803, NP_001269804, NP_001365190, NP_001365191, NP_001365192, NP_001365193, NP_003060 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR001005	SANT/Myb	Domain
IPR001650	Helicase_C-like	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR014001	Helicase_ATP-bd	Domain
IPR015194	ISWI_HAND-dom	Domain
IPR015195	SLIDE	Domain
IPR017884	SANT_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036306	ISWI_HAND-dom_sf	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR044755	SMARCA1_N	Domain
IPR049730	SNF2/RAD54-like_C	Domain

Pfam: PF00176, PF00271, PF09110, PF09111

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (25 total): domain 4, compositionally biased region 4, modified residue 3, cross-link 3, region of interest 3, sequence variant 2, mutagenesis site 2, chain 1, binding site 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28370-F1	75.48	0.30

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 (1): 208–215

Post-translational modifications (6): 116, 119, 942, 650, 716, 738

Mutagenesis-validated functional residues (2):

Position	Phenotype
214	loss of atpase activity. no effect on replication fork location.
214	no effect on neurite outgrowth.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): KAAB_FAILED_HEART_ATRIUM_DN, ZHAN_MULTIPLE_MYELOMA_MF_UP, GCANCTGNY_MYOD_Q6, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, MEF2_02, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, ROZANOV_MMP14_TARGETS_UP, NF1_Q6_01, E4F1_Q6, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, MAGRANGEAS_MULTIPLE_MYELOMA_IGLL_VS_IGLK_UP

GO Biological Process (9): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), brain development (GO:0007420), neuron differentiation (GO:0030182), heterochromatin formation (GO:0031507), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), chromatin organization (GO:0006325), regulation of neural precursor cell proliferation (GO:2000177)

GO Molecular Function (14): DNA binding (GO:0003677), chromatin binding (GO:0003682), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleosome binding (GO:0031491), ATP-dependent DNA/DNA annealing activity (GO:0036310), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), ATP-dependent chromatin remodeler activity (GO:0140658), nucleosome array spacer activity (GO:0140750), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), hydrolase activity (GO:0016787)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), NURF complex (GO:0016589), CERF complex (GO:0090537), ATPase complex (GO:1904949), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	3
DNA-templated transcription	2
binding	2
ATP-dependent activity, acting on DNA	2
cellular anatomical structure	2
ISWI-type complex	2
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
cell differentiation	1
generation of neurons	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular component organization	1
regulation of cell population proliferation	1
neural precursor cell proliferation	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
chromatin binding	1
protein-containing complex binding	1
DNA/DNA annealing activity	1
DNA-binding transcription factor binding	1
DNA binding	1
chromatin remodeling	1
histone octamer slider activity	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

4092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCA1	BAZ1A	Q9NRL2	999
SMARCA1	BPTF	Q12830	996
SMARCA1	BAZ1B	Q9UIG0	987
SMARCA1	CECR2	Q9BXF3	972
SMARCA1	SMARCA2	P51531	928
SMARCA1	CHRAC1	Q9NRG0	912
SMARCA1	SMARCA4	P51532	906
SMARCA1	POLE3	Q9NRF9	878
SMARCA1	BAZ2B	Q9UIF8	862
SMARCA1	SMARCB1	Q12824	835
SMARCA1	RBBP4	P31149	827
SMARCA1	H3-3A	P06351	815
SMARCA1	H3C1	P02295	815
SMARCA1	SMARCC1	Q92922	784
SMARCA1	H2AZ1	P0C0S5	772

IntAct

110 interactions, top by confidence:

A	B	Type	Score
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
SMARCA1	RBBP4	psi-mi:“MI:0914”(association)	0.770
SMARCA1	RBBP4	psi-mi:“MI:0915”(physical association)	0.770
SMARCA1	BPTF	psi-mi:“MI:0915”(physical association)	0.750
BPTF	SMARCA1	psi-mi:“MI:0914”(association)	0.750
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
CECR2	SMARCA1	psi-mi:“MI:0915”(physical association)	0.620
DPY30	AKAP8	psi-mi:“MI:0914”(association)	0.610
BAZ2B		psi-mi:“MI:0914”(association)	0.610
BAZ1B	SMARCA1	psi-mi:“MI:0915”(physical association)	0.560
SMARCA1		psi-mi:“MI:0915”(physical association)	0.560
	SMARCA5	psi-mi:“MI:0914”(association)	0.560
MAP4K4	STRN	psi-mi:“MI:0914”(association)	0.530
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
BACC1	SMARCA1	psi-mi:“MI:0914”(association)	0.530
POLE3	SMARCA5	psi-mi:“MI:0914”(association)	0.530
BACC1	SMARCA5	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
SMARCA1	TUFM	psi-mi:“MI:0915”(physical association)	0.400
TXNIP	SMARCA1	psi-mi:“MI:0915”(physical association)	0.400
FOXC1	NFIX	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXG1	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (245): SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), POLE3 (Co-fractionation), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS), SMARCA1 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9L3, A2A4P0, A3KFM7, A3KMI0, B2RR83, D3ZA12, D4A2Z8, E9PZM4, F4IJV4, F4JY24, O14647, O42643, O45244, O60231, O60264, P28370, P34498, P40201, P41877, P93008, Q05B79, Q09530, Q10752, Q14562, Q17R09, Q24368, Q38953, Q4TVV3, Q53RK8, Q54F05, Q569Z5, Q5R6D8, Q5R746, Q62780, Q6PGB8, Q767K6, Q7G8Y3, Q7L014, Q7YR39, Q7ZU90

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

2 interactions.

A	Effect	B	Mechanism
SMARCA1	“form complex”	HNuRF	binding
SMARCA1	“down-regulates quantity by repression”	ST7	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Regulation of PD-L1(CD274) transcription	9	10.8×	9e-05
Signaling by ROBO receptors	6	8.2×	9e-03
Oxidative Stress Induced Senescence	7	7.0×	8e-03
Infectious disease	15	4.1×	1e-03
Viral Infection Pathways	12	4.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of protein localization to nucleus	6	19.4×	1e-04
heterochromatin formation	7	14.8×	9e-05
chromatin remodeling	14	8.4×	4e-07
nucleosome assembly	7	8.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	12
Uncertain significance	138
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
3958395	NM_001282874.2(SMARCA1):c.2251C>T (p.Arg751Ter)	Pathogenic
4170111	NM_001282874.2(SMARCA1):c.3005G>A (p.Trp1002Ter)	Pathogenic
4469690	NM_001282874.2(SMARCA1):c.1342C>T (p.Arg448Ter)	Pathogenic
4822868	NM_001282874.2(SMARCA1):c.2782C>T (p.Arg928Ter)	Pathogenic
4832218	NM_001282874.2(SMARCA1):c.2977C>T (p.Arg993Ter)	Pathogenic
3250359	NM_001282874.2(SMARCA1):c.413T>G (p.Leu138Ter)	Likely pathogenic
3250360	NM_001282874.2(SMARCA1):c.193C>T (p.Gln65Ter)	Likely pathogenic
3901122	NM_001282874.2(SMARCA1):c.271C>T (p.Arg91Ter)	Likely pathogenic
3901123	NM_001282874.2(SMARCA1):c.1070T>G (p.Leu357Ter)	Likely pathogenic
3901124	NM_001282874.2(SMARCA1):c.1071dup (p.Leu358fs)	Likely pathogenic
3901129	NM_001282874.2(SMARCA1):c.1971dup (p.Asn658Ter)	Likely pathogenic
3901139	NM_001282874.2(SMARCA1):c.543dup (p.Pro182fs)	Likely pathogenic
3901140	NM_001282874.2(SMARCA1):c.565C>T (p.Arg189Ter)	Likely pathogenic
3901142	NM_001282874.2(SMARCA1):c.685C>T (p.Arg229Ter)	Likely pathogenic
3901143	NM_001282874.2(SMARCA1):c.757C>T (p.Arg253Ter)	Likely pathogenic
402137	NM_001282874.2(SMARCA1):c.7C>T (p.Gln3Ter)	Likely pathogenic
4532156	NM_001282874.2(SMARCA1):c.2122C>T (p.Gln708Ter)	Likely pathogenic

SpliceAI

3571 predictions. Top by Δscore:

Variant	Effect	Δscore
X:129465656:T:TA	donor_gain	1.0000
X:129465842:A:AC	donor_gain	1.0000
X:129465843:C:CC	donor_gain	1.0000
X:129465851:T:TA	donor_gain	1.0000
X:129465861:T:A	donor_gain	1.0000
X:129465872:AT:A	donor_gain	1.0000
X:129465958:TACAG:T	acceptor_gain	1.0000
X:129465960:CAG:C	acceptor_gain	1.0000
X:129465963:C:CC	acceptor_gain	1.0000
X:129468770:AACC:A	donor_loss	1.0000
X:129468771:A:AC	donor_gain	1.0000
X:129468771:AC:A	donor_loss	1.0000
X:129468772:C:CA	donor_loss	1.0000
X:129468772:C:CC	donor_gain	1.0000
X:129468782:CCATG:C	donor_gain	1.0000
X:129468901:AAACC:A	acceptor_gain	1.0000
X:129468902:AACC:A	acceptor_gain	1.0000
X:129468903:ACC:A	acceptor_gain	1.0000
X:129468903:ACCC:A	acceptor_loss	1.0000
X:129468904:CC:C	acceptor_gain	1.0000
X:129468904:CCCTG:C	acceptor_gain	1.0000
X:129468905:CC:C	acceptor_gain	1.0000
X:129468906:C:CC	acceptor_gain	1.0000
X:129468906:C:T	acceptor_gain	1.0000
X:129468914:A:T	acceptor_gain	1.0000
X:129471202:A:AC	donor_gain	1.0000
X:129471203:C:CC	donor_gain	1.0000
X:129471220:T:TA	donor_gain	1.0000
X:129471324:AACC:A	acceptor_loss	1.0000
X:129471325:ACC:A	acceptor_loss	1.0000

AlphaMissense

7087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:129448418:A:G	L1019P	1.000
X:129448418:A:T	L1019Q	1.000
X:129448426:A:C	C1016W	1.000
X:129448427:C:T	C1016Y	1.000
X:129448428:A:G	C1016R	1.000
X:129448430:C:G	R1015P	1.000
X:129448431:G:C	R1015G	1.000
X:129448431:G:T	R1015S	1.000
X:129448432:T:A	R1014S	1.000
X:129448432:T:G	R1014S	1.000
X:129448433:C:G	R1014T	1.000
X:129448443:C:T	E1011K	1.000
X:129465529:C:A	R1007S	1.000
X:129465529:C:G	R1007S	1.000
X:129465530:C:A	R1007M	1.000
X:129465530:C:G	R1007T	1.000
X:129465534:A:G	S1006P	1.000
X:129465541:A:C	F1003L	1.000
X:129465541:A:T	F1003L	1.000
X:129465542:A:C	F1003C	1.000
X:129465543:A:G	F1003L	1.000
X:129465546:A:G	W1002R	1.000
X:129465546:A:T	W1002R	1.000
X:129465550:A:C	F1000L	1.000
X:129465550:A:T	F1000L	1.000
X:129465552:A:G	F1000L	1.000
X:129465556:A:C	F998L	1.000
X:129465556:A:T	F998L	1.000
X:129465557:A:G	F998S	1.000
X:129465558:A:G	F998L	1.000

dbSNP variants (sampled 300 via entrez): RS1000034792 (X:129446045 G>A), RS1000100117 (X:129494441 T>C), RS1000107171 (X:129510254 T>C,G), RS1000202534 (X:129524151 C>G), RS1000206257 (X:129501059 T>C), RS1000360915 (X:129491265 T>C), RS1000374521 (X:129481346 T>G), RS1000456764 (X:129509760 C>T), RS1000465013 (X:129519376 C>A,T), RS1000531960 (X:129479721 A>G,T), RS1000536954 (X:129502620 G>A), RS1000583481 (X:129449331 A>G), RS1000642893 (X:129493281 A>T), RS1000717390 (X:129491013 A>G), RS1000942293 (X:129472445 T>C)

Disease associations

OMIM: gene MIM:300012 | disease phenotypes: MIM:309530

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Definitive	X-linked
schizophrenia	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked intellectual disability	Limited	XL

Mondo (4): neurodevelopmental disorder (MONDO:0700092), X-linked intellectual disability (MONDO:0100284), non-syndromic X-linked intellectual disability (MONDO:0019181), schizophrenia (MONDO:0005090)

Orphanet (1): X-linked non-syndromic intellectual disability (Orphanet:777)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST007095_120	Systolic blood pressure	2.000000e-08
GCST007095_121	Systolic blood pressure	8.000000e-08
GCST007097_157	Pulse pressure	7.000000e-08
GCST007097_158	Pulse pressure	2.000000e-07
GCST012310_26	Schizophrenia x sex interaction	7.000000e-06
GCST012310_27	Schizophrenia x sex interaction	9.000000e-06
GCST012311_5	Schizophrenia x sex interaction	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066924 (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
8.27	Kd	5.351	nM	CHEMBL3752910
7.85	ED50	14.09	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149937: Binding affinity to human SMARCA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0054	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Valproic Acid	affects expression, decreases expression	3
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Fluorouracil	increases expression, affects response to substance	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	2
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
1-UFT protocol	decreases response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Decitabine	affects expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Choline	affects expression	1
Demecolcine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652979	Binding	Binding affinity to human SMARCA1 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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW42	K562 eGFP-SMARCA1	Cancer cell line	Female
CVCL_B8PN	Abcam HCT 116 SMARCA1 KO	Cancer cell line	Male
CVCL_B9BL	Abcam MCF-7 SMARCA1 KO	Cancer cell line	Female
CVCL_B9S3	Abcam A-549 SMARCA1 KO	Cancer cell line	Male
CVCL_D8VN	Ubigene HCT 116 SMARCA1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

300 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,
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia