SS18

Summary

SS18 (SS18 subunit of BAF chromatin remodeling complex, HGNC:11340) is a protein-coding gene on chromosome 18q11.2, encoding Protein SSXT (Q15532). Appears to function synergistically with RBM14 as a transcriptional coactivator.

Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of SWI/SNF complex. Implicated in synovial sarcoma.

Source: NCBI Gene 6760 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_001007559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11340
Approved symbol	SS18
Name	SS18 subunit of BAF chromatin remodeling complex
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SYT, SMARCL1
Ensembl gene	ENSG00000141380
Ensembl biotype	protein_coding
OMIM	600192
Entrez	6760

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 15 protein_coding, 13 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000269137, ENST00000269138, ENST00000415083, ENST00000539244, ENST00000542420, ENST00000577572, ENST00000577636, ENST00000577751, ENST00000578595, ENST00000578700, ENST00000578954, ENST00000579061, ENST00000579640, ENST00000580003, ENST00000580642, ENST00000580751, ENST00000580958, ENST00000581021, ENST00000581570, ENST00000582092, ENST00000582448, ENST00000582792, ENST00000583595, ENST00000584083, ENST00000585121, ENST00000585241, ENST00000857616, ENST00000857617, ENST00000857618, ENST00000857619, ENST00000928497, ENST00000928498, ENST00000928499, ENST00000928500, ENST00000955467

RefSeq mRNA: 3 — MANE Select: NM_001007559 NM_001007559, NM_001308201, NM_005637

CCDS: CCDS32807, CCDS54183, CCDS77168

Canonical transcript exons

ENST00000415083 — 11 exons

Exon	Start	End
ENSE00001216935	26016253	26018380
ENSE00002718148	26090501	26090613
ENSE00003467406	26078076	26078160
ENSE00003484097	26052624	26052845
ENSE00003511849	26035005	26035127
ENSE00003559040	26032399	26032532
ENSE00003605376	26039289	26039456
ENSE00003621423	26057589	26057742
ENSE00003642525	26038555	26038659
ENSE00003681021	26035831	26035923
ENSE00003759902	26087501	26087577

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.7454 / max 578.2491, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171433	60.6008	1824
171434	7.4470	1758
171435	4.6976	1434

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.65	gold quality
right adrenal gland cortex	UBERON:0035827	96.25	gold quality
right adrenal gland	UBERON:0001233	95.99	gold quality
stromal cell of endometrium	CL:0002255	95.97	gold quality
left ovary	UBERON:0002119	95.95	gold quality
calcaneal tendon	UBERON:0003701	95.88	gold quality
left adrenal gland	UBERON:0001234	95.75	gold quality
right ovary	UBERON:0002118	95.60	gold quality
left adrenal gland cortex	UBERON:0035825	95.53	gold quality
skin of abdomen	UBERON:0001416	95.48	gold quality
gall bladder	UBERON:0002110	95.46	gold quality
adrenal gland	UBERON:0002369	95.22	gold quality
nerve	UBERON:0001021	95.01	gold quality
tibial nerve	UBERON:0001323	95.01	gold quality
skin of leg	UBERON:0001511	94.96	gold quality
descending thoracic aorta	UBERON:0002345	94.96	gold quality
islet of Langerhans	UBERON:0000006	94.84	gold quality
adrenal cortex	UBERON:0001235	94.84	gold quality
left lobe of thyroid gland	UBERON:0001120	94.72	gold quality
right coronary artery	UBERON:0001625	94.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.64	gold quality
right lobe of thyroid gland	UBERON:0001119	94.61	gold quality
right uterine tube	UBERON:0001302	94.59	gold quality
popliteal artery	UBERON:0002250	94.57	gold quality
tibial artery	UBERON:0007610	94.57	gold quality
colonic epithelium	UBERON:0000397	94.42	gold quality
aorta	UBERON:0000947	94.42	gold quality
thoracic aorta	UBERON:0001515	94.41	gold quality
minor salivary gland	UBERON:0001830	94.40	gold quality
rectum	UBERON:0001052	94.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	293.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

196 targeting SS18, 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-340-5P	100.00	72.50	4437
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487

Literature-anchored findings (GeneRIF, showing 40)

• The SYT protein has a unique QPGY domain, which is also present in the largest subunits, p250 and the newly identified homolog p250R, of the corresponding SNF/SWI complexes (PMID:11734557)
• coexistence of fusions with SSX1 and SSX2 in synovial sarcomas (PMID:12037676)
• SYT may function as a general coactivator (PMID:15919756)
• demonstrate differentially expressed genes for the 2 major gene fusion variants in SS, SS18/X breakpoint 1 sarcoma (SSX1) and SS18/SSX2, and thereby suggest that these result in different downstream effects (PMID:16152617)
• SYT interacts with SYT-interacting protein/co-activator activator (PMID:16227627)
• SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells. (PMID:16247461)
• SYT-SSX2 contributes to tumor development, in part through beta-catenin signaling. (PMID:16462762)
• SS18 and SS18L1 genes map within co-linear DNA segments that may have evolved through a relatively recent genomic duplication event. (PMID:16484776)
• The SS18-SSX2 fusion protein may act as a so-called transcriptional “activator-repressor,” which induces downstream target gene deregulation through epigenetic mechanisms. (PMID:17018603)
• SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. (PMID:17101797)
• endogenous LHX4 binds to the CGA promoter and that LHX4-mediated CGA activation is enhanced by the SS18-SSX protein (PMID:17667940)
• this sarcoma showed a longer-than-expected PCR product. Direct sequencing of the product disclosed a novel SYT/SSX1 fusion transcript. (PMID:17721327)
• SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2. (PMID:18234968)
• siRNA targeting of SS18-SSX1 may have therapeutic potential in the treatment of synovial sarcomas. (PMID:18714179)
• Findings showing a complex cryptic rearrangement that gives rise to the characteristic SYT-SSX2 fusion gene in a monophasic synovial sarcoma patient. (PMID:18992642)
• SYT-SSX fusion type was not correlated with survival synovial sarcoma. (PMID:18997619)
• provides evidence that, in the appropriate context, expression of the SYT-SSX2 oncogene leads to loss of polycomb function (PMID:19337376)
• SYT-SSX1 is an adverse predictor for disease-specific survival and metastasis-free survival, but has no relation to local recurrence-free survival in synovial sarcoma. (PMID:19385976)
• findings indicate that cytoplasmic SYT isoforms interact with actin filaments and function in the ability cells to bind and react to specific extracellular matrices (PMID:19649286)
• epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects (PMID:19936258)
• siRNA targeting of SS18-SSX1 has therapeutic potential for the treatment of synovial sarcoma. (PMID:20198325)
• Rearranged SYT wasdetected in all synovial sarcomas but not in any Ewing sarcoma/primitive neuroectodermal tumors (PMID:20660338)
• the fusion gene SYT-SSX should be considered to play important role on Synovial sarcoma cell growth via ERK pathway (PMID:21234732)
• the initial events that likely occur when SYT-SSX2 is first expressed, and its dominant function in subverting the nuclear program of the stem cell, leading to its aberrant differentiation, as a first step toward transformation. (PMID:21996728)
• SS18 together with animal-specific factors defines human BAF-type SWI/SNF complexes (PMID:22442726)
• SYT-SSX2 was recruited to distinct loci across all chromosomes, and an overwhelming number of Polycomb-modified sites enriched with the trimethylated histone H3 on lysine 27 (H3K27me3) formed the main recruiting module for SYT-SSX2. (PMID:22594313)
• SS18-SSX1 and SS18-SSX2 variant translocations are associated with synovial sarcoma. (PMID:22976541)
• Studies show that in the 2 synovial sarcoma cell lines used, the fusion of SS18 with SSX leads to assembly of aberrant BAF complexes that become targeted to the Sox2 locus, with loss of repressive H3K27me3 marks, driving Sox2 expression and proliferation of these cells. (PMID:23540691)
• Knockdown of SS18-SSX1 in synovial sarcoma inhibits viability and induces apoptosis. (PMID:23716114)
• SS18-SSX fusion type is a significant prognostic factor for patients with synovial sarcoma. (PMID:24022186)
• These results suggest that the characteristic speckle localization pattern of SS18-SSX is strongly involved in the tumorigenesis through the SSX moiety of the SS18-SSX fusion protein. (PMID:24130893)
• SS18-SSX-induced Wnt/beta-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression. (PMID:24166495)
• Case Report: bronchial biphasic synovial sarcoma with SS18 gene rearrangement. (PMID:24429587)
• SYT gene split is associated with Synovial sarcoma. (PMID:24922679)
• a rare variant of the SS18-SSX1 fusion transcript, which could not be identified by routine procedures for genetic diagnosis, was detected. In addition, 8 missense mutations of cancer-related genes were confirmed (PMID:25959879)
• Data show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary synovial sarcoma. (PMID:26905812)
• Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. (PMID:26947017)
• Kidney transplant recipients’ polymorphisms of genes associated with telomere length, BICD1 and chromosome 18, but not hTERT, affect kidney allograft early and long-term function after transplantation. (PMID:27496426)
• Data indicate that the oncogene SS18-SSX1 promotes tumorigenesis by increasing the expression of SHC SH2-domain binding protein 1 (SHCBP1), which normally acts as a tumor promoting factor. (PMID:27572315)
• Thirty-four patients (20 males and 14 females, mean of 31years) with SS18-SSX fusion-positive SS-HN were identified. The parapharyngeal region of the neck was the most common site (PMID:28249647)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ss18	ENSDARG00000002970
mus_musculus	Ss18	ENSMUSG00000037013
rattus_norvegicus	Ss18	ENSRNOG00000016800
caenorhabditis_elegans	ZK973.9	WBGENE00022835

Paralogs (2): SS18L2 (ENSG00000008324), SS18L1 (ENSG00000184402)

Protein

Protein identifiers

Protein SSXT — Q15532 (reviewed: Q15532)

Alternative names: Protein SYT, Synovial sarcoma translocated to X chromosome protein

All UniProt accessions (16): B4DLD3, Q15532, F5GWN1, J3KRP6, J3KT22, J3KT74, J3QLJ7, J3QQM2, J3QQW2, J3QQW6, J3QQX5, J3QS72, J3QSB3, J3QSG1, Q4VAX0, X6R3J2

UniProt curated annotations — full annotation on UniProt →

Function. Appears to function synergistically with RBM14 as a transcriptional coactivator. Isoform 1 and isoform 2 function in nuclear receptor coactivation. Isoform 1 and isoform 2 function in general transcriptional coactivation. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.

Subunit / interactions. Interacts with MLLT10. Isoform 1 interacts with RBM14 isoform 1. Isoform 2 interacts with RBM14 isoform 1. 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 SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, the core BAF subunits, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A.

Subcellular location. Nucleus.

Tissue specificity. Fairly ubiquitously expressed. Expressed in synovial sarcomas and in other human cell lines. The fusion genes SSXT-SSX1 and SSXT-SSX2 are expressed only in synovial sarcomas.

Disease relevance. A chromosomal aberration involving SS18 may be a cause of synovial sarcoma. Translocation t(X;18)(p11.2;q11.2). The translocation is specifically found in more than 80% of synovial sarcoma. The fusion products SSXT-SSX1 or SSXT-SSX2 are probably responsible for transforming activity. Heterogeneity in the position of the breakpoint can occur (low frequency).

Similarity. Belongs to the SS18 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15532-1	1, SYTins, SYT-L	yes
Q15532-2	2

RefSeq proteins (3): NP_001007560, NP_001295130, NP_005628 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007726	SS18_N	Domain

Pfam: PF05030

UniProt features (26 total): compositionally biased region 7, short sequence motif 4, region of interest 4, helix 3, site 2, repeat 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7VRB	X-RAY DIFFRACTION	2.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15532-F1	53.54	0.11

Functional residue map

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

Catalytic / active sites (2): 366–367 (breakpoint for translocation to form the ssxt-ssx1 fusion protein (rare)); 410–411 (breakpoint for translocation to form the ssxt-ssx1 or ssxt-ssx2 fusion proteins)

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
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-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-1266738	Developmental Biology
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)
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: 0 (showing top):

GO Biological Process (13): microtubule cytoskeleton organization (GO:0000226), cell morphogenesis (GO:0000902), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), intracellular signal transduction (GO:0035556), negative regulation of cell differentiation (GO:0045596), positive regulation of transcription by RNA polymerase II (GO:0045944), ephrin receptor signaling pathway (GO:0048013), neuronal stem cell population maintenance (GO:0097150), positive regulation of stem cell population maintenance (GO:1902459), cytoskeleton organization (GO:0007010)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), microtubule cytoskeleton (GO:0015630), SWI/SNF complex (GO:0016514), npBAF complex (GO:0071564), GBAF complex (GO:0140288)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	4
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1
Gene expression (Transcription)	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	3
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
stem cell population maintenance	2
cellular anatomical structure	2
cytoskeleton organization	1
microtubule-based process	1
anatomical structure morphogenesis	1
chromatin organization	1
regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to chemical	1
intracellular anatomical structure	1
signal transduction	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
regulation of transcription by RNA polymerase II	1
cell surface receptor protein tyrosine kinase signaling pathway	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
organelle organization	1
transcription coregulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoskeleton	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SS18	SSX1	Q16384	969
SS18	SSX4	O60224	930
SS18	TLE1	Q04724	778
SS18	ZNF117	Q03924	766
SS18	ZNF83	P51522	766
SS18	SSX5	O60225	737
SS18	SSX3	Q99909	718
SS18	RBM14	Q96PK6	676
SS18	SMARCA2	P51531	630
SS18	SMARCA4	P51532	625
SS18	HEATR3	Q7Z4Q2	593
SS18	ACTL6A	O96019	590
SS18	CD99L2	Q8TCZ2	584
SS18	CD99	P14209	582
SS18	SMARCB1	Q12824	520

IntAct

94 interactions, top by confidence:

A	B	Type	Score
SMARCB1	SMARCA4	psi-mi:“MI:0914”(association)	0.960
SMARCA4	SMARCB1	psi-mi:“MI:0403”(colocalization)	0.960
SMARCA4	SMARCB1	psi-mi:“MI:0914”(association)	0.960
SMARCA4	SMARCB1	psi-mi:“MI:0915”(physical association)	0.960
SMARCA4	ARID1A	psi-mi:“MI:0914”(association)	0.940
ARID1A	SMARCA4	psi-mi:“MI:0914”(association)	0.940
SMARCC1	SMARCA4	psi-mi:“MI:0914”(association)	0.930
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760
SMARCA4	SS18	psi-mi:“MI:0914”(association)	0.760
SS18	SMARCA4	psi-mi:“MI:0914”(association)	0.760

BioGRID (242): SS18 (Two-hybrid), NFKBID (Two-hybrid), SS18 (Affinity Capture-MS), SS18 (Affinity Capture-MS), SS18 (Affinity Capture-MS), ARID1B (Affinity Capture-MS), ARID1A (Affinity Capture-MS), PHF10 (Affinity Capture-MS), SMARCC2 (Affinity Capture-MS), SMARCC1 (Affinity Capture-MS), GLTSCR1 (Affinity Capture-MS), SMARCD3 (Affinity Capture-MS), SMARCD2 (Affinity Capture-MS), SMARCD1 (Affinity Capture-MS), SMARCA2 (Affinity Capture-MS)

ESM2 similar proteins: A2AJK6, A2BH40, A5HEH4, B2RWS6, B7SBD2, G5EEL0, O14497, O15405, O42569, O74345, O75177, P02833, P32315, P34622, P47792, P49750, P79007, Q06A37, Q08E31, Q09472, Q15532, Q20870, Q21955, Q24645, Q4V3C1, Q571K4, Q5RFQ1, Q5U303, Q61L47, Q62280, Q64201, Q6AVI1, Q6DDK1, Q6LD29, Q6NVN0, Q80W03, Q8AWH1, Q8BW22, Q8BXJ2, Q8L8A5

Diamond homologs: A5HEH4, O75177, Q08E31, Q15532, Q5RFQ1, Q62280, Q6AVI1, Q6DDK1, Q8BW22, Q8L8A5, Q91XJ0, Q93VH6, Q9D174, Q9MAL9, Q9UHA2, Q86HX9, Q54HX6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SS18	“form complex”	SS18/MLLT10	binding
SS18	“form complex”	GBAF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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	12	155.4×	3e-23
Formation of the embryonic stem cell BAF (esBAF) complex	11	134.9×	2e-20
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	13	121.2×	3e-23
Formation of the polybromo-BAF (pBAF) complex	9	116.5×	9e-16
Formation of the non-canonical BAF (ncBAF) complex	8	109.7×	7e-14
Regulation of MITF-M-dependent genes involved in pigmentation	14	75.9×	9e-22
Regulation of endogenous retroelements	10	75.2×	2e-15
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	8	49.1×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	12	147.1×	1e-21
regulation of nucleotide-excision repair	12	131.3×	4e-21
regulation of mitotic metaphase/anaphase transition	12	108.1×	4e-20
nucleosome disassembly	7	102.1×	1e-11
positive regulation of double-strand break repair	12	75.0×	4e-18
regulation of G1/S transition of mitotic cell cycle	12	66.8×	2e-17
positive regulation of myoblast differentiation	10	66.6×	2e-14
positive regulation of T cell differentiation	8	66.2×	1e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2818 predictions. Top by Δscore:

Variant	Effect	Δscore
18:26032394:CTTA:C	donor_loss	1.0000
18:26032395:TTA:T	donor_loss	1.0000
18:26032396:TA:T	donor_loss	1.0000
18:26032397:A:AC	donor_gain	1.0000
18:26032397:ACCTG:A	donor_loss	1.0000
18:26032398:C:A	donor_loss	1.0000
18:26032398:C:CC	donor_gain	1.0000
18:26032398:CCTG:C	donor_gain	1.0000
18:26034994:CAAAG:C	donor_gain	1.0000
18:26034998:G:C	donor_gain	1.0000
18:26034999:CTTTA:C	donor_loss	1.0000
18:26035000:TTTA:T	donor_loss	1.0000
18:26035002:TACC:T	donor_loss	1.0000
18:26035003:A:AC	donor_gain	1.0000
18:26035003:A:AT	donor_loss	1.0000
18:26035004:C:A	donor_loss	1.0000
18:26035004:C:CC	donor_gain	1.0000
18:26035008:AG:A	donor_gain	1.0000
18:26035008:AGC:A	donor_gain	1.0000
18:26035009:G:C	donor_gain	1.0000
18:26035021:T:TA	donor_gain	1.0000
18:26035139:T:TC	acceptor_gain	1.0000
18:26035826:GATAC:G	donor_loss	1.0000
18:26035827:ATACC:A	donor_loss	1.0000
18:26035828:TAC:T	donor_loss	1.0000
18:26035829:ACCT:A	donor_gain	1.0000
18:26035830:CCTC:C	donor_gain	1.0000
18:26035832:T:TA	donor_gain	1.0000
18:26035833:C:A	donor_gain	1.0000
18:26035920:TGAC:T	acceptor_gain	1.0000

AlphaMissense

2782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:26078122:G:T	A62D	1.000
18:26078123:C:G	A62P	1.000
18:26078125:A:G	L61P	1.000
18:26078125:A:T	L61H	1.000
18:26078134:A:C	L58W	1.000
18:26078134:A:G	L58S	1.000
18:26078146:A:G	L54S	1.000
18:26087552:A:G	I32T	1.000
18:26087552:A:T	I32N	1.000
18:26087555:A:G	L31P	1.000
18:26087573:A:G	L25S	1.000
18:26078114:C:G	A65P	0.999
18:26078144:G:C	H55D	0.999
18:26078146:A:C	L54W	0.999
18:26087543:A:G	I35T	0.999
18:26087543:A:T	I35K	0.999
18:26087549:T:G	Q33P	0.999
18:26087552:A:C	I32S	0.999
18:26090505:T:G	Q22P	0.999
18:26090508:A:C	I21S	0.999
18:26090508:A:T	I21N	0.999
18:26078113:G:T	A65E	0.998
18:26078125:A:C	L61R	0.998
18:26078126:G:A	L61F	0.998
18:26078133:C:A	L58F	0.998
18:26078133:C:G	L58F	0.998
18:26078143:T:G	H55P	0.998
18:26078145:C:A	L54F	0.998
18:26078145:C:G	L54F	0.998
18:26078155:T:G	Q51P	0.998

dbSNP variants (sampled 300 via entrez): RS1000039381 (18:26075892 T>C), RS1000101965 (18:26031607 G>A), RS1000128838 (18:26088418 T>C), RS1000174779 (18:26041679 G>A), RS1000212862 (18:26076622 A>T), RS1000224451 (18:26091678 A>G), RS1000236934 (18:26063901 A>C), RS1000267687 (18:26037561 T>C), RS1000271772 (18:26046271 T>C), RS1000299423 (18:26092146 T>C), RS1000301401 (18:26058271 C>T), RS1000317822 (18:26077279 C>T), RS1000410454 (18:26071227 T>C), RS1000428460 (18:26028645 A>C), RS1000454943 (18:26033303 C>A,G,T)

Disease associations

OMIM: gene MIM:600192 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001762_313	Obesity-related traits	2.000000e-06
GCST001762_314	Obesity-related traits	5.000000e-06
GCST001762_318	Obesity-related traits	3.000000e-06
GCST001966_3	Rhegmatogenous retinal detachment	2.000000e-06
GCST002127_4	Periodontitis (Mean PAL)	5.000000e-06
GCST002671_13	Toenail selenium levels	8.000000e-06
GCST002928_4	Nickel levels	2.000000e-06
GCST004025_11	Systemic juvenile idiopathic arthritis	2.000000e-06
GCST004031_9	QT interval (sulfonylurea treatment interaction)	2.000000e-08
GCST007643_6	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	7.000000e-06
GCST010571_71	Autoimmune thyroid disease	1.000000e-09
GCST011494_77	Daytime nap	1.000000e-16
GCST90002390_549	Mean corpuscular hemoglobin	4.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004682	QT interval
EFO:0007922	response to sulfonylurea
EFO:0007828	daytime rest measurement
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
Tetrachlorodibenzodioxin	increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
tamibarotene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Formaldehyde	increases expression	1
Lead	affects expression	1
Methylcholanthrene	affects binding, increases reaction	1
Ozone	affects expression, increases abundance	1
Phenylmercuric Acetate	increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Sodium Selenite	decreases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

34 cell lines: 33 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6C43	Aska-SS	Cancer cell line	Male
CVCL_6C44	Yamato-SS	Cancer cell line	Male
CVCL_7146	SYO-1	Cancer cell line	Female
CVCL_8719	HS-SY-2	Cancer cell line	Male
CVCL_A6FC	NCC-SS4-C1	Cancer cell line	Male
CVCL_B2HD	Abcam HeLa SS18 KO	Cancer cell line	Female
CVCL_B458	PDSS-26	Cancer cell line	Female
CVCL_B8Q8	Abcam HCT 116 SS18 KO	Cancer cell line	Male
CVCL_B9BW	Abcam MCF-7 SS18 KO	Cancer cell line	Female
CVCL_B9SP	Abcam A-549 SS18 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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