SMARCB1

Summary

SMARCB1 (SWI/SNF related BAF chromatin remodeling complex subunit B1, HGNC:11103) is a protein-coding gene on chromosome 22q11.23, encoding SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (Q12824). Core component of the BAF (hSWI/SNF) complex. In precision oncology, SMARCB1 Deletion confers sensitivity to Tazemetostat in Epithelioid Sarcoma (CIViC Level A); 6 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 82.0% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6598 — RefSeq curated summary.

At a glance

• Gene–disease (curated): rhabdoid tumor predisposition syndrome 1 (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 50
• Clinical variants (ClinVar): 1,369 total — 85 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 191
• Druggable target: yes
• Precision-oncology evidence (CIViC): 7 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 82.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11103
Approved symbol	SMARCB1
Name	SWI/SNF related BAF chromatin remodeling complex subunit B1
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	BAF47, Ini1, INI-1, Snr1, hSNFS, Sfh1p, RDT, PPP1R144, SNF5
Ensembl gene	ENSG00000099956
Ensembl biotype	protein_coding
OMIM	601607
Entrez	6598

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 18 protein_coding, 9 retained_intron, 4 nonsense_mediated_decay

ENST00000263121, ENST00000344921, ENST00000407082, ENST00000407422, ENST00000417137, ENST00000477836, ENST00000491967, ENST00000634926, ENST00000635578, ENST00000642275, ENST00000642727, ENST00000643421, ENST00000644036, ENST00000644462, ENST00000644467, ENST00000644619, ENST00000645799, ENST00000646421, ENST00000646723, ENST00000646911, ENST00000647057, ENST00000877791, ENST00000877792, ENST00000877793, ENST00000877794, ENST00000877795, ENST00000877796, ENST00000877797, ENST00000923808, ENST00000948392, ENST00000948393

RefSeq mRNA: 4 — MANE Select: NM_003073 NM_001007468, NM_001317946, NM_001362877, NM_003073

CCDS: CCDS13817, CCDS46671, CCDS82699

Canonical transcript exons

ENST00000618915 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 98.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.7637 / max 243.7578, expressed in 1822 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191320	56.2778	1822
191321	0.8405	531
191323	0.7619	411
191326	0.6133	283
191322	0.2703	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
embryo	UBERON:0000922	98.94	gold quality
ganglionic eminence	UBERON:0004023	98.94	gold quality
cortical plate	UBERON:0005343	98.63	gold quality
ventricular zone	UBERON:0003053	98.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.29	gold quality
cerebellar cortex	UBERON:0002129	96.19	gold quality
cerebellar hemisphere	UBERON:0002245	96.19	gold quality
stromal cell of endometrium	CL:0002255	96.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.00	gold quality
islet of Langerhans	UBERON:0000006	95.96	gold quality
left testis	UBERON:0004533	95.78	gold quality
left ovary	UBERON:0002119	95.58	gold quality
right testis	UBERON:0004534	95.58	gold quality
right ovary	UBERON:0002118	95.48	gold quality
vermiform appendix	UBERON:0001154	95.14	gold quality
cerebellum	UBERON:0002037	94.92	gold quality
adenohypophysis	UBERON:0002196	94.59	gold quality
endocervix	UBERON:0000458	94.56	gold quality
mucosa of transverse colon	UBERON:0004991	94.53	gold quality
ectocervix	UBERON:0012249	94.51	gold quality
prefrontal cortex	UBERON:0000451	94.43	gold quality
right adrenal gland	UBERON:0001233	94.36	gold quality
right adrenal gland cortex	UBERON:0035827	94.34	gold quality
right frontal lobe	UBERON:0002810	94.33	gold quality
smooth muscle tissue	UBERON:0001135	94.31	gold quality
anterior cingulate cortex	UBERON:0009835	94.31	gold quality
apex of heart	UBERON:0002098	94.23	gold quality
left adrenal gland	UBERON:0001234	94.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.09	gold quality
metanephros cortex	UBERON:0010533	93.89	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	2777.43
E-HCAD-10	yes	17.06
E-CURD-46	yes	11.08
E-CURD-114	yes	6.99
E-MTAB-10042	yes	6.02
E-CURD-112	yes	5.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CD44	Repression
CDKN2A	Activation
CSF1	Activation
GLI1	Repression
PTCH1	Repression

Upstream regulators (CollecTRI, top): CEBPB, MYB, PARP1, PHF5A, SMARCA1, SMARCC1, SMARCE1, TFAP2A

miRNA regulators (miRDB)

26 targeting SMARCB1, 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-4283	100.00	66.42	2097
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-4714-3P	96.53	67.44	452
HSA-MIR-1915-5P	95.25	65.78	571
HSA-MIR-4423-5P	95.24	64.42	454

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 82.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors (PMID:11782395)
• Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors. (PMID:11921280)
• SWI/SNF complex interacts with tumor suppressor p53 and is necessary for the activation of p53-mediated transcription (PMID:11950834)
• facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity (PMID:12016208)
• Chromatin remodeling factor encoded by ini1 induces G1 arrest and apoptosis in ini1-deficient cells. (PMID:12082626)
• The INI1 promoter is not hypermethylated in pediatric rhabdoid tumors. (PMID:12112529)
• Data suggest that one mechanism by which INI1/hSNF5 exerts its tumor suppressor function is by mediating the cell cycle arrest due to the direct recruitment of HDAC activity to the cyclin D1 promoter, causing its repression and G(0)-G(1) arrest. (PMID:12138206)
• Mutation may alter the amount of cMYC protein, but SMARCB1 is highly conserved in human solid carcinomas. (PMID:12213194)
• INI1 is a tumor suppressor gene gone awry in malignant rhabdoid tumor cells (PMID:12548550)
• germline hSNF5 mutation is associated with rhabdoid predisposition syndrome (PMID:12892231)
• alternative splicing and role implicated in interaction with HIV-1 (PMID:14526201)
• hSNF5-induced cellular senescence is mediated by the p16(INK4a)/pRb pathway (PMID:14604992)
• transdominant mutant S6, harboring the minimal integrase interaction domain of INI1/hSNF5, blocks HIV-1 particle production but not that of the other retroviruses in 293T cells (PMID:14963118)
• in human cells, SWI/SNF enzyme complex formation and the expression of many BRG1-dependent genes are independent of INI1. (PMID:14990991)
• Novel SMARCB1 germ-line deletions in neonatal congenital kidney rhabdoid tumors and brain primitive neuroectodermal tumors patients. (PMID:15101046)
• hSNF5/INI1 may modulate the cell cycle control and cytoskeleton organization through the regulation of the retinoblastoma protein-E2F and Rho pathways. (PMID:15150092)
• somatic point mutations of hSNF5/INI1 do not play a role in the pathogenesis of choroid plexus papilloma (PMID:15175083)
• Immunohistochemical analysis of hSNF5/INI1 gene distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors by assessing loss of INI1 expression in rhabdoid tumors. (PMID:15489652)
• INI1 is dispensable for retrovirus-induced cytoplasmic accumulation of PML and does not interfere with virus integration. (PMID:15589835)
• Mutated in choroid plexus carcinoma. (PMID:15642401)
• INI1 immunohistochemistry is a relatively simple, sensitive, and specific technique for distinguishing malignant rhabdoid tumor and atypical teratoid/rhabdoid tumor from composite rhabdoid tumor. (PMID:15761491)
• hSNF5 activates the mitotic checkpoint through the p16INK4a-cyclinD/CDK4-pRb-E2F pathway, whereas loss of hSNF5 function in malignant rhabdoid tumor-derived cells leads to polyploidization and chromosomal instability. (PMID:15769941)
• The tumor suppressor gene hSNF5 was lacking in the malignant rhabdoid tumor of the liver. (PMID:15796965)
• SMARCB1/INI1 inactivation to 6 of 11 cases of epithelioid sarcoma is shown by real-time quantitative PCR analysis of mRNA expression and by SMARCB1/INI1 immunohistochemistry. (PMID:15899790)
• Tumors harbored such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC) and missense mutation (C157T) together with LOH 22q or homozygous deletion. Cyclin D1 was overexpressed in the same tumors. (PMID:15981100)
• INI1hSNF5 and PARVG do not seem to be the tumor suppressor genes involved in oligodendroglioma development and progression (PMID:15993274)
• This strongly suggests that the SNF5 homology domain presents species-specific functions. (PMID:16154112)
• INI1/hSNF5/BAF47 could be recruited to the region of cellular oncogene c-fos promoter to reduce histone acetylation (PMID:16219292)
• All conserved domains of INI1/hSNF5/BAF47 are needed for CSF1 transcription and INI1/ hSNF5/BAF47 is recruited to the region of the CSF1 promoter. (PMID:16267391)
• hSNF5 binds the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes. hSNF5 loss may influence the regulation of multiple CDK inhibitors involved in replicative senescence. (PMID:16288006)
• Immunohistochemistry to assess expression of SMARCB1/INI1 may be useful in the diagnosis of rhabdoid tumors of the CNS, kidneys and soft tissue. (PMID:16528370)
• BAF155 and potentially INI1 are substrates for Akt phosphorylation (PMID:16568092)
• by interacting with IN, SNF5/Ini1 interferes with early steps of HIV-1 infection (PMID:16772295)
• While INI1 is dispensable for HIV-1 transduction, it can facilitate HIV-1 transcription by enhancing Tat function. (PMID:16889668)
• Relationship between Rb and Ini1 in tumor suppression indicate that Ini1 plays a role in maintaining the morphologic and functional differentiation of corticotrophic cells. (PMID:16912184)
• INI1 is the predisposing gene in familial schwannomatosis. (PMID:17357086)
• results demonstrate that deletions and mutations of the INI1 gene can occur in rare composite rhabdoid tumors of adulthood (PMID:17376508)
• Inactivation of the SMARCB1/INI1 gene is associated with rhabdoid tumor (PMID:17486366)
• Knockdown experiments performed in human ALL cell lines confirmed that lower SMARCB1 expression increased prednisolone resistance. (PMID:17616514)
• Gene expression profiling of the hSNF5-down-regulated cells by cDNA microarray analysis revealed that a limited number of p53-responsive genes, especially p21, were up-regulated (PMID:17669367)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	smarcb1b	ENSDARG00000011594
danio_rerio	smarcb1a	ENSDARG00000033647
mus_musculus	Smarcb1	ENSMUSG00000000902
rattus_norvegicus	Smarcb1	ENSRNOG00000028302
drosophila_melanogaster	Snr1	FBGN0011715
caenorhabditis_elegans		WBGENE00011111

Protein

Protein identifiers

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 — Q12824 (reviewed: Q12824)

Alternative names: BRG1-associated factor 47, Integrase interactor 1 protein, SNF5 homolog

All UniProt accessions (11): Q12824, A0A0G2JRV3, A0A0U1RQQ2, A0A0U1RRB8, A0A2R8Y5N5, A0A2R8Y5Z2, A0A2R8YDN6, A0A2R8YEE8, B5MCL5, C9JTA6, G5E975

UniProt curated annotations — full annotation on UniProt →

Function. Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. 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. Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1.

Subunit / interactions. Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin. Binds to double-stranded DNA. Interacts with CEBPB (when not methylated). Interacts with PIH1D1. Interacts with MYK and MAEL. Interacts with PPP1R15A. Interacts with DPF2. Interacts with YWHAZ. Interacts with ERCC6. Interacts with FOS, FOSB isoform 1 and 2, FOSL1 and FOSL2. (Microbial infection) Binds tightly to the human immunodeficiency virus-type 1 (HIV-1) integrase in vitro and stimulates its DNA-joining activity. Interacts with human papillomavirus 18 E1 protein to stimulate its viral replication. Interacts with Epstein-Barr virus protein EBNA-2.

Subcellular location. Nucleus.

Disease relevance. Rhabdoid tumor predisposition syndrome 1 (RTPS1) [MIM:609322] A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood. The disease is caused by variants affecting the gene represented in this entry. Schwannomatosis 1 (SWN1) [MIM:162091] An autosomal dominant tumor predisposition syndrome characterized by the development of multiple benign nerve sheath tumors called schwannomas on cranial, spinal, and peripheral nerves, without involvement of the vestibular nerve. Affected individuals may also have multiple meningiomas. Disease susceptibility is associated with variants affecting the gene represented in this entry. Coffin-Siris syndrome 3 (CSS3) [MIM:614608] A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal DNA-binding region is structurally similar to winged helix domains.

Similarity. Belongs to the SNF5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12824-1	A, INI1A	yes
Q12824-2	B, INI1B

RefSeq proteins (4): NP_001007469, NP_001304875, NP_001349806, NP_003064* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006939	SNF5	Family
IPR017393	Sfh1/SNF5	Family
IPR048664	INI1_DNA-bd	Domain

Pfam: PF04855, PF21459

UniProt features (54 total): helix 16, strand 14, sequence variant 5, region of interest 5, cross-link 4, sequence conflict 3, repeat 2, turn 2, chain 1, splice variant 1, modified residue 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
5GJK	X-RAY DIFFRACTION	2.05
5L7A	X-RAY DIFFRACTION	2.1
6KZ7	X-RAY DIFFRACTION	2.28
6KAG	X-RAY DIFFRACTION	2.6
6LTH	ELECTRON MICROSCOPY	3
7VDV	ELECTRON MICROSCOPY	3.4
9RL4	ELECTRON MICROSCOPY	3.5
6LTJ	ELECTRON MICROSCOPY	3.7
9RN2	ELECTRON MICROSCOPY	4.1
9RMC	ELECTRON MICROSCOPY	4.2
7Y8R	ELECTRON MICROSCOPY	4.4
9RN1	ELECTRON MICROSCOPY	5.9
5AJ1	SOLUTION NMR
5L7B	SOLUTION NMR
6AX5	SOLUTION NMR
6LZP	SOLUTION NMR
6UCH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12824-F1	80.77	0.51

Functional residue map

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

Post-translational modifications (5): 108, 124, 161, 129, 106

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9933937	Formation of the canonical BAF (cBAF) complex
R-HSA-9933939	Formation of the polybromo-BAF (pBAF) complex
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-1266738	Developmental Biology
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9842860	Regulation of endogenous retroelements
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 686 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, TGCGCANK_UNKNOWN, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GEORGES_CELL_CYCLE_MIR192_TARGETS, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM

GO Biological Process (26): RNA polymerase I preinitiation complex assembly (GO:0001188), blastocyst hatching (GO:0001835), nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), negative regulation of cell population proliferation (GO:0008285), DNA integration (GO:0015074), regulation of mitotic metaphase/anaphase transition (GO:0030071), single stranded viral RNA replication via double stranded DNA intermediate (GO:0039692), host-mediated activation of viral transcription (GO:0043923), positive regulation of T cell differentiation (GO:0045582), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of G0 to G1 transition (GO:0070316), hepatocyte differentiation (GO:0070365), positive regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901838), positive regulation of stem cell population maintenance (GO:1902459), positive regulation of glucose mediated signaling pathway (GO:1902661), 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), blastocyst development (GO:0001824), chromatin organization (GO:0006325)

GO Molecular Function (8): p53 binding (GO:0002039), DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), Tat protein binding (GO:0030957), identical protein binding (GO:0042802), RNA polymerase I core promoter sequence-specific DNA binding (GO:0001164), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (17): nuclear chromosome (GO:0000228), kinetochore (GO:0000776), chromatin (GO:0000785), fibrillar center (GO:0001650), XY body (GO:0001741), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), RSC-type complex (GO:0016586), protein-containing complex (GO:0032991), brahma complex (GO:0035060), germ cell nucleus (GO:0043073), npBAF complex (GO:0071564), nBAF complex (GO:0071565), bBAF complex (GO:0140092)

Reactome top-level categories

Rollup of top-12 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SWI/SNF superfamily-type complex	6
nuclear lumen	4
cellular anatomical structure	4
transcription by RNA polymerase II	2
positive regulation of developmental process	2
positive regulation of DNA-templated transcription	2
protein binding	2
nucleus	2
chromosome	2
intracellular membraneless organelle	2
transcription initiation at RNA polymerase I promoter	1
transcription preinitiation complex assembly	1
blastocyst development	1
hatching	1
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
regulation of DNA-templated transcription	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
DNA metabolic process	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
reverse transcription	1
viral RNA genome replication	1
DNA-templated viral transcription	1
viral genome integration into host DNA	1
host-mediated perturbation of viral transcription	1
host-mediated activation of viral process	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
myoblast differentiation	1

Protein interactions and networks

STRING

3478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMARCB1	SMARCC1	Q92922	999
SMARCB1	SMARCA4	P51532	999
SMARCB1	SMARCC2	Q8TAQ2	999
SMARCB1	SMARCE1	Q969G3	998
SMARCB1	ARID1A	O14497	997
SMARCB1	SMARCA2	P51531	997
SMARCB1	PBRM1	Q86U86	996
SMARCB1	ARID2	Q68CP9	995
SMARCB1	ACTL6A	O96019	995
SMARCB1	ARID1B	Q8NFD5	995
SMARCB1	SMARCD1	Q96GM5	995
SMARCB1	TP53	P04637	967
SMARCB1	XPC	Q01831	957
SMARCB1	PHF10	Q8WUB8	951
SMARCB1	SMARCD2	Q92925	935

IntAct

366 interactions, top by confidence:

A	B	Type	Score
SMARCA4	SMARCB1	psi-mi:“MI:0914”(association)	0.960
SMARCB1	SMARCA4	psi-mi:“MI:0914”(association)	0.960
SMARCB1	SMARCA4	psi-mi:“MI:0915”(physical association)	0.960
ARID1A	SMARCA4	psi-mi:“MI:0914”(association)	0.940
SMARCB1	SMARCC2	psi-mi:“MI:0914”(association)	0.900
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
SMARCC1	ARID1A	psi-mi:“MI:0914”(association)	0.790
DPF2	ARID1A	psi-mi:“MI:0914”(association)	0.730
SMARCB1	GFAP	psi-mi:“MI:0915”(physical association)	0.670
VIM	SMARCB1	psi-mi:“MI:0915”(physical association)	0.670
GFAP	SMARCB1	psi-mi:“MI:0915”(physical association)	0.670
SMARCD3	ARID1A	psi-mi:“MI:0914”(association)	0.640
NCOR1	SMARCA4	psi-mi:“MI:0915”(physical association)	0.630
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
SMARCB1	SMARCB1	psi-mi:“MI:0915”(physical association)	0.590
SMARCB1	H2BC12	psi-mi:“MI:0914”(association)	0.580
H2AC18	SMARCB1	psi-mi:“MI:0915”(physical association)	0.580
H2BC12	SMARCB1	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (1239): SMARCB1 (Two-hybrid), SMARCB1 (Biochemical Activity), SMARCB1 (Reconstituted Complex), SMARCB1 (Affinity Capture-MS), SMARCB1 (Affinity Capture-MS), SMARCB1 (Affinity Capture-MS), SMARCB1 (Affinity Capture-MS), SMARCB1 (Affinity Capture-MS), ACTL6A (Co-fractionation), ARID1A (Co-fractionation), ARID1B (Co-fractionation), BCL7A (Co-fractionation), BCL7B (Co-fractionation), CHMP4A (Co-fractionation), CPSF6 (Co-fractionation)

ESM2 similar proteins: A0JMA8, A6H8H2, O42467, O43150, O60152, P0C5E7, P30630, P91133, Q12824, Q20069, Q23541, Q30DN6, Q3B8D5, Q5BIN2, Q5F3R2, Q5U379, Q5VZ89, Q5XUN4, Q5ZK40, Q61T02, Q62240, Q6DFM1, Q6FN68, Q6GQ82, Q6IQX0, Q6P158, Q6P5D3, Q6VEU3, Q7SIG6, Q7XVN7, Q7YTB0, Q7Z401, Q80Y84, Q8IP99, Q8IPA1, Q8NFA0, Q92599, Q94125, Q95RG8, Q9BY66

Diamond homologs: O42467, P18480, P93045, Q06168, Q09699, Q12824, Q5BIN2, Q5U379, Q5ZK40, Q6C9N2, Q6CSR7, Q6DFM1, Q6FTV3, Q6GQ82, Q754R8, Q9USM3, Q9Z0H3, A2XKR7, Q10F25, Q55GK0, Q6Z433, Q8GXL7, Q9FH57, Q9LRH6

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
SMARCB1	“form complex”	“SWI/SNF complex”	binding
SMARCB1	“up-regulates quantity by expression”	CSF1	“transcriptional regulation”
SMARCB1	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
SMARCB1	“form complex”	“SWI/SNF ACTL6B varian”	binding
SMARCB1	“form complex”	“Neural progenitor-specific SWI/SNF”	binding
SMARCB1	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
SMARCB1	“form complex”	“Muscle cell-specific SWI/SNF ARID1B variant”	binding
SMARCB1	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
SMARCB1	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
SMARCB1	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding
SMARCB1	“up-regulates activity”	SMARCA2	binding
SMARCB1	“up-regulates activity”	SMARCA4	binding
SMARCB1	down-regulates	CCNA1
SMARCB1	down-regulates	CCNA2
SMARCB1	down-regulates	CDC6
SMARCB1	down-regulates	E2F1
SMARCB1	“form complex”	“Embryonic stem cell-specific SWI/SNF”	binding
CHFR	“down-regulates quantity by destabilization”	SMARCB1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the embryonic stem cell BAF (esBAF) complex	8	54.0×	2e-10
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	9	46.2×	4e-11
Formation of the canonical BAF (cBAF) complex	6	42.8×	2e-07
Formation of the polybromo-BAF (pBAF) complex	6	42.8×	2e-07
Formation of the non-canonical BAF (ncBAF) complex	5	37.7×	7e-06
Regulation of endogenous retroelements	7	29.0×	2e-07
Regulation of MITF-M-dependent genes involved in pigmentation	9	26.9×	5e-09
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	7	23.6×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	9	51.4×	3e-11
nucleosome disassembly	7	47.6×	1e-08
regulation of nucleotide-excision repair	9	45.9×	6e-11
regulation of mitotic metaphase/anaphase transition	10	42.0×	2e-11
positive regulation of T cell differentiation	8	30.9×	2e-08
positive regulation of myoblast differentiation	9	27.9×	6e-09
positive regulation of double-strand break repair	9	26.2×	8e-09
regulation of G1/S transition of mitotic cell cycle	9	23.4×	2e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — ATRT, MBL, NBL, PANET, PAST.

Clinical variants and AI predictions

ClinVar

1369 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	85
Likely pathogenic	37
Uncertain significance	554
Likely benign	526
Benign	61

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032872	NM_003073.5(SMARCB1):c.1062_1063del (p.Glu354fs)	Pathogenic
1071772	NM_003073.5(SMARCB1):c.153G>A (p.Trp51Ter)	Pathogenic
1073885	NM_003073.5(SMARCB1):c.141C>A (p.Tyr47Ter)	Pathogenic
1074512	NM_003073.5(SMARCB1):c.92_93del (p.Glu31fs)	Pathogenic
1076272	NM_003073.5(SMARCB1):c.364G>T (p.Glu122Ter)	Pathogenic
1192514	NM_003073.5(SMARCB1):c.500+883T>G	Pathogenic
1192515	NM_003073.5(SMARCB1):c.500+887G>A	Pathogenic
1416806	NM_003073.5(SMARCB1):c.1148del (p.Pro383fs)	Pathogenic
1455673	NC_000022.10:g.(?24143121)(24145619_?)del	Pathogenic
1458140	NC_000022.10:g.(?24158947)(24176449_?)del	Pathogenic
1459852	NM_003073.5(SMARCB1):c.778C>T (p.Gln260Ter)	Pathogenic
1686218	NM_003073.5(SMARCB1):c.307_346del (p.Asn103fs)	Pathogenic
1686219	NM_003073.5(SMARCB1):c.747dup (p.Thr250fs)	Pathogenic
1803243	NM_003073.5(SMARCB1):c.575_584dup (p.Asp196fs)	Pathogenic
2028679	NM_003073.5(SMARCB1):c.463del (p.Arg155fs)	Pathogenic
2134364	NM_003073.5(SMARCB1):c.147dup (p.Leu50fs)	Pathogenic
2424622	NC_000022.10:g.(?24143121)(24145619_?)dup	Pathogenic
2424623	NC_000022.10:g.(?24135736)(24135885_?)del	Pathogenic
2501798	NM_003073.5(SMARCB1):c.1118+2T>C	Pathogenic
2707117	NM_003073.5(SMARCB1):c.536_542del (p.Asn179fs)	Pathogenic
2743181	NM_003073.5(SMARCB1):c.214del (p.Thr72fs)	Pathogenic
2764125	NM_003073.5(SMARCB1):c.92A>G (p.Glu31Gly)	Pathogenic
2838229	NM_003073.5(SMARCB1):c.489del (p.Phe164fs)	Pathogenic
30201	NM_003073.5(SMARCB1):c.1085AGA[2] (p.Lys364del)	Pathogenic
30203	NM_003073.5(SMARCB1):c.1130G>A (p.Arg377His)	Pathogenic
3248101	NC_000022.10:g.(?24129357)(24135885_?)del	Pathogenic
3248102	NC_000022.10:g.(?24129357)(24145629_?)del	Pathogenic
3248103	NC_000022.10:g.(?24175749)(24176449_?)del	Pathogenic
3363753	NM_003073.5(SMARCB1):c.109C>T (p.Arg37Cys)	Pathogenic
3446068	NM_003073.5(SMARCB1):c.1039del (p.Asp347fs)	Pathogenic

SpliceAI

2144 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23787259:CGAG:C	donor_loss	1.0000
22:23787260:GAGG:G	donor_loss	1.0000
22:23787261:AGGTA:A	donor_loss	1.0000
22:23787262:GGTAG:G	donor_loss	1.0000
22:23787263:GTA:G	donor_loss	1.0000
22:23787264:T:A	donor_loss	1.0000
22:23791842:G:GT	donor_gain	1.0000
22:23793555:ACAGA:A	acceptor_loss	1.0000
22:23793557:A:AG	acceptor_gain	1.0000
22:23793558:G:GG	acceptor_gain	1.0000
22:23793558:GATC:G	acceptor_gain	1.0000
22:23793641:G:GT	donor_gain	1.0000
22:23793685:TCAG:T	donor_loss	1.0000
22:23793687:AGGT:A	donor_loss	1.0000
22:23793689:G:GA	donor_loss	1.0000
22:23793690:T:A	donor_loss	1.0000
22:23801061:G:GT	donor_gain	1.0000
22:23803291:TCA:T	acceptor_loss	1.0000
22:23803292:CAGC:C	acceptor_loss	1.0000
22:23803293:A:AG	acceptor_gain	1.0000
22:23803293:AG:A	acceptor_loss	1.0000
22:23803294:G:A	acceptor_loss	1.0000
22:23803294:G:GT	acceptor_gain	1.0000
22:23803294:GC:G	acceptor_gain	1.0000
22:23803294:GCT:G	acceptor_gain	1.0000
22:23803294:GCTT:G	acceptor_gain	1.0000
22:23803294:GCTTT:G	acceptor_gain	1.0000
22:23803430:G:GT	donor_gain	1.0000
22:23816932:TCAAG:T	donor_gain	1.0000
22:23816934:AAGG:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000133 (22:23834333 G>A), RS1000057908 (22:23828813 G>A), RS1000109018 (22:23793772 A>C,G,T), RS1000192186 (22:23802126 T>C), RS1000284546 (22:23813535 A>G), RS1000292541 (22:23793969 A>G), RS1000301305 (22:23795754 G>C,T), RS1000356733 (22:23789022 A>G), RS1000407943 (22:23818196 C>T), RS1000454218 (22:23790454 G>T), RS1000511207 (22:23785085 T>C), RS1000563738 (22:23785249 C>T), RS1000571913 (22:23835832 C>T), RS1000705229 (22:23813596 A>C,T), RS1000724225 (22:23813328 G>A,C)

Disease associations

OMIM: gene MIM:601607 | disease phenotypes: MIM:614608, MIM:609322, MIM:162091, MIM:135900, MIM:613325, MIM:220400, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
SMARCB1-related schwannomatosis	Definitive	Autosomal dominant
rhabdoid tumor predisposition syndrome 1	Definitive	Autosomal dominant
intellectual disability, autosomal dominant 15	Definitive	Autosomal dominant
Coffin-Siris syndrome	Supportive	Autosomal dominant
familial rhabdoid tumor	Supportive	Autosomal dominant
familial multiple meningioma	Supportive	Autosomal dominant
schwannomatosis	Supportive	Autosomal dominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
rhabdoid tumor predisposition syndrome 1	Definitive	AD
Coffin-Siris syndrome	Definitive	AD

Mondo (18): hereditary neoplastic syndrome (MONDO:0015356), intellectual disability, autosomal dominant 15 (MONDO:0013820), rhabdoid tumor predisposition syndrome 1 (MONDO:0012252), SMARCB1-related schwannomatosis (MONDO:0024517), schwannomatosis (MONDO:0008075), Coffin-Siris syndrome (MONDO:0015452), neurodevelopmental disorder (MONDO:0700092), rhabdoid tumor predisposition syndrome 2 (MONDO:0013224), schwannoma (MONDO:0002546), autism spectrum disorder (MONDO:0005258), nervous system cancer (MONDO:0005872), Jervell and Lange-Nielsen syndrome 1 (MONDO:0024540), intellectual disability (MONDO:0001071), NK-cell enteropathy (MONDO:0016996), ovarian cancer (MONDO:0008170)

Orphanet (12): Inherited cancer-predisposing syndrome (Orphanet:140162), Coffin-Siris syndrome (Orphanet:1465), Rhabdoid tumor predisposition syndrome (Orphanet:231108), Rhabdoid tumor (Orphanet:69077), Full schwannomatosis (Orphanet:93921), Benign schwannoma (Orphanet:252164), Congenital long QT syndrome (Orphanet:768), Jervell and Lange-Nielsen syndrome (Orphanet:90647), NK-cell enteropathy (Orphanet:263665), Rare ovarian cancer (Orphanet:213500), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

191 total (30 of 191 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000131	Uterine leiomyoma
HP:0000141	Amenorrhea
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000343	Long philtrum
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST001848_121	IgG glycosylation	1.000000e-16
GCST001848_126	IgG glycosylation	8.000000e-15
GCST001848_211	IgG glycosylation	9.000000e-17
GCST001848_218	IgG glycosylation	9.000000e-17
GCST001848_226	IgG glycosylation	1.000000e-12
GCST001848_241	IgG glycosylation	2.000000e-08
GCST001848_243	IgG glycosylation	1.000000e-10
GCST001848_307	IgG glycosylation	2.000000e-14
GCST001848_349	IgG glycosylation	4.000000e-09
GCST001848_357	IgG glycosylation	4.000000e-09
GCST001848_365	IgG glycosylation	2.000000e-08
GCST001848_388	IgG glycosylation	9.000000e-10
GCST001848_39	IgG glycosylation	2.000000e-07
GCST001848_424	IgG glycosylation	7.000000e-16
GCST001848_462	IgG glycosylation	5.000000e-10
GCST001848_499	IgG glycosylation	3.000000e-08
GCST001848_520	IgG glycosylation	3.000000e-13
GCST001848_579	IgG glycosylation	1.000000e-10
GCST001848_606	IgG glycosylation	4.000000e-06
GCST001848_684	IgG glycosylation	1.000000e-12
GCST001848_72	IgG glycosylation	2.000000e-08
GCST001849_4	IgG glycosylation	2.000000e-07
GCST004924_2	IgG monogalactosylation phenotypes (multivariate analysis)	1.000000e-12
GCST004925_4	IgG N-glycosylation phenotypes (multivariate analysis)	3.000000e-11
GCST004926_4	IgG digalactosylation phenotypes (multivariate analysis)	4.000000e-10
GCST004927_3	IgG galactosylation phenotypes (multivariate analysis)	3.000000e-10
GCST004928_2	IgG bisecting N-acetyl glucosamine phenotypes (multivariate analysis)	4.000000e-11
GCST004929_3	IgG fucosylation phenotypes (multivariate analysis)	3.000000e-11
GCST004930_2	IgG sialylation phenotypes (multivariate analysis)	1.000000e-06
GCST004931_1	IgG disialylation phenotypes (multivariate analysis)	1.000000e-07

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0008423	IgG monogalactosylation measurement
EFO:0008424	IgG digalactosylation measurement
EFO:0008425	IgG galactosylation measurement
EFO:0008426	IgG bisecting N-acetyl glucosamine measurement
EFO:0008427	IgG fucosylation measurement
EFO:0008428	IgG sialylation measurement
EFO:0008429	IgG disialylation measurement
EFO:0009285	fractional shortening
EFO:0004999	N-glycan measurement
EFO:0004327	electrocardiography
EFO:0008206	left ventricular systolic function measurement
EFO:0010556	Left ventricular mass to end-diastolic volume ratio
EFO:0008205	left ventricular structural measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D009423	Nervous System Neoplasms	C04.588.614; C10.551
D065886	Neurodevelopmental Disorders	F03.625
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
C536436	Coffin-Siris syndrome (supp.)
C563738	Rhabdoid Tumor Predisposition Syndrome 1 (supp.)
C567643	Rhabdoid Tumor Predisposition Syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725049 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 7 predictive associations from 8 curated evidence items; also 12 diagnostic, 1 prognostic, 1 oncogenic.

Variant	Therapy	Indication	Effect	Level	CIViC
SMARCB1 Deletion	Tazemetostat	Epithelioid Sarcoma	Sensitivity/Response	CIViC A	EID9992
SMARCB1 Loss	Tazemetostat	Atypical Teratoid Rhabdoid Tumor	Sensitivity/Response	CIViC B	EID11180
SMARCB1 Loss	Tazemetostat	Poorly Differentiated Chordoma	Sensitivity/Response	CIViC C	EID11178 +1
SMARCB1 Loss	Tazemetostat	Epithelioid Sarcoma	Sensitivity/Response	CIViC C	EID11181
SMARCB1 Deletion	Tazemetostat	Rhabdoid Cancer	Sensitivity/Response	CIViC D	EID1740
SMARCB1 Deletion	Panobinostat	Rhabdoid Cancer	Sensitivity/Response	CIViC D	EID1964
SMARCB1 Underexpression	Tazemetostat	Synovial Sarcoma	Sensitivity/Response	CIViC D	EID1739

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
8.03	Kd	9.241	nM	CHEMBL5653589
8.03	ED50	9.241	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149440: Binding affinity to human SMARCB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0092	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	decreases expression	4
Arsenic Trioxide	increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance	2
TAK-243	increases sumoylation	1
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	affects expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects expression	1
manganese chloride	increases abundance, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,2’,3’,4,4’,5-hexachlorobiphenyl	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
MK-8776	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Fulvestrant	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Cannabidiol	decreases expression	1
Clozapine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases activity	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance	1
Methotrexate	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652482	Binding	Binding affinity to human SMARCB1 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

73 cell lines: 66 cancer cell line, 3 embryonic stem cell, 2 transformed cell line, 2 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0270	G-401	Cancer cell line	Male
CVCL_1058	A-204	Cancer cell line	Female
CVCL_1326	Karpas-45	Cancer cell line	Male
CVCL_1720	SW1573	Cancer cell line	Female
CVCL_2022	DND-41	Cancer cell line	Male
CVCL_3007	KYM-1	Cancer cell line	Male
CVCL_4W35	FRTK-1	Cancer cell line	Male
CVCL_5616	KYM-1D4	Cancer cell line	Male
CVCL_5904	WT-CLS1	Cancer cell line	Female
CVCL_6D82	STA-WT-1	Cancer cell line	Male

Clinical trials (associated diseases)

272 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
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
NCT04163419	PHASE2	UNKNOWN	Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis
NCT05684692	PHASE2	RECRUITING	Screening Trial for Pain Relief in Schwannomatosis (STARFISH)
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03542773	PHASE1	COMPLETED	Targeted Imaging of Glutamate Carboxypeptidase II With DCFPyL-PET
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT01885767	Not specified	RECRUITING	Neurofibromatosis (NF) Registry Portal
NCT01951365	Not specified	COMPLETED	Assessment of Volumetric Growth Rates of Spinal Intradural Extramedullary Schwannoma
NCT02298270	Not specified	COMPLETED	Resiliency Training for Patients With Neurofibromatosis Via Videoconferencing With Skype