SS18L2

Summary

SS18L2 (SS18 like 2, HGNC:15593) is a protein-coding gene on chromosome 3p22.1, encoding SS18-like protein 2 (Q9UHA2). It is a common-essential gene (DepMap: required in 99.1% of cancer cell lines).

Synovial sarcomas occur most frequently in the extremities around large joints. More than 90% of cases have a recurrent and specific chromosomal translocation, t(X;18)(p11.2;q11.2), in which the 5-prime end of the SS18 gene (MIM 600192) is fused in-frame to the 3-prime end of the SSX1 (MIM 312820), SSX2 (MIM 300192), or SSX4 (MIM 300326) gene. The SS18L2 gene is homologous to SS18.

Source: NCBI Gene 51188 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_001370300

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15593
Approved symbol	SS18L2
Name	SS18 like 2
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA-iso
Ensembl gene	ENSG00000008324
Ensembl biotype	protein_coding
OMIM	606473
Entrez	51188

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000011691, ENST00000447630, ENST00000474941, ENST00000897957

RefSeq mRNA: 2 — MANE Select: NM_001370300 NM_001370300, NM_016305

CCDS: CCDS2701

Canonical transcript exons

ENST00000011691 — 3 exons

Exon	Start	End
ENSE00000492372	42591525	42591601
ENSE00001156879	42594422	42596934
ENSE00001156882	42590860	42590966

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 97.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8312 / max 598.5966, expressed in 1809 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36261	24.9643	1806
36258	1.2387	609
36260	0.4264	199
36259	0.2018	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.21	gold quality
oocyte	CL:0000023	97.10	gold quality
gingival epithelium	UBERON:0001949	94.01	gold quality
middle temporal gyrus	UBERON:0002771	93.24	gold quality
palpebral conjunctiva	UBERON:0001812	92.99	gold quality
gingiva	UBERON:0001828	92.74	gold quality
pancreatic ductal cell	CL:0002079	92.50	gold quality
epithelium of nasopharynx	UBERON:0001951	92.26	gold quality
germinal epithelium of ovary	UBERON:0001304	92.23	gold quality
cerebellar vermis	UBERON:0004720	92.09	gold quality
lymph node	UBERON:0000029	91.90	gold quality
jejunal mucosa	UBERON:0000399	91.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.30	gold quality
pons	UBERON:0000988	90.94	gold quality
thymus	UBERON:0002370	90.84	gold quality
leukocyte	CL:0000738	90.52	gold quality
mononuclear cell	CL:0000842	90.50	gold quality
monocyte	CL:0000576	90.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.29	gold quality
esophagus squamous epithelium	UBERON:0006920	90.26	gold quality
squamous epithelium	UBERON:0006914	90.14	gold quality
spinal cord	UBERON:0002240	89.85	gold quality
type B pancreatic cell	CL:0000169	89.80	silver quality
Brodmann (1909) area 9	UBERON:0013540	89.71	gold quality
bone marrow	UBERON:0002371	89.68	gold quality
nucleus accumbens	UBERON:0001882	89.62	gold quality
olfactory bulb	UBERON:0002264	89.58	silver quality
cortical plate	UBERON:0005343	89.43	gold quality
cervix epithelium	UBERON:0004801	89.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting SS18L2, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-411-5P	97.11	66.82	601
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-571	95.38	66.54	671

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.1% of screened cell lines, common-essential.

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ss18l2	ENSDARG00000101085
mus_musculus	Ss18l2	ENSMUSG00000032526
rattus_norvegicus	Ss18l2	ENSRNOG00000076482
caenorhabditis_elegans	ZK973.9	WBGENE00022835

Paralogs (2): SS18 (ENSG00000141380), SS18L1 (ENSG00000184402)

Protein

Protein identifiers

SS18-like protein 2 — Q9UHA2 (reviewed: Q9UHA2)

Alternative names: SYT homolog 2

All UniProt accessions (1): Q9UHA2

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the SS18 family.

RefSeq proteins (2): NP_001357229, NP_057389 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007726	SS18_N	Domain

Pfam: PF05030

UniProt features (2 total): chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHA2-F1	75.84	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, chr3p22, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, OSMAN_BLADDER_CANCER_DN, NUYTTEN_NIPP1_TARGETS_DN, WANG_TUMOR_INVASIVENESS_DN, CHEN_METABOLIC_SYNDROM_NETWORK, MARTENS_TRETINOIN_RESPONSE_DN, ARID5B_TARGET_GENES, GSE10240_IL22_VS_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, H1_6_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SS18L2	SSX4	O60224	720
SS18L2	SSX1	Q16384	668
SS18L2	SEC22C	Q9BRL7	570
SS18L2	ZNF195	O14628	516
SS18L2	VMA22	Q96NT0	440
SS18L2	MRPL51	Q4U2R6	425
SS18L2	TMEM74B	Q9NUR3	419
SS18L2	SPOUT1	Q5T280	412
SS18L2	ZNF557	Q8N988	402
SS18L2	TRAF3IP3	Q9Y228	398
SS18L2	MLF1	P58340	390
SS18L2	ZBTB47	Q9UFB7	379
SS18L2	LUC7L	Q9NQ29	377
SS18L2	CBX4	O00257	374
SS18L2	TMEM106C	Q9BVX2	374

IntAct

65 interactions, top by confidence:

A	B	Type	Score
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
YY1AP1	SS18L2	psi-mi:“MI:0915”(physical association)	0.670
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
SS18L2	GON4L	psi-mi:“MI:0914”(association)	0.610
SS18L2	SMARCA2	psi-mi:“MI:0914”(association)	0.570
SS18L2	GNG3	psi-mi:“MI:0915”(physical association)	0.560
SS18L2	EMC2	psi-mi:“MI:0915”(physical association)	0.560
EMC2	SS18L2	psi-mi:“MI:0915”(physical association)	0.560
TMEM17	SS18L2	psi-mi:“MI:0915”(physical association)	0.560
LYPD6	SS18L2	psi-mi:“MI:0915”(physical association)	0.560
GNG3	SS18L2	psi-mi:“MI:0915”(physical association)	0.560
MBD5	SS18L2	psi-mi:“MI:0915”(physical association)	0.560
RAF1	EEF1E1	psi-mi:“MI:0914”(association)	0.530
CRAMP1	NPAT	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
CLEC3A	ZZEF1	psi-mi:“MI:0914”(association)	0.530
CBFA2T3	CBFA2T2	psi-mi:“MI:0914”(association)	0.530
ZNF524	C1QBP	psi-mi:“MI:0914”(association)	0.530
SS18L2	ARID1A	psi-mi:“MI:2364”(proximity)	0.480
SS18L2	ARID1A	psi-mi:“MI:0914”(association)	0.480

BioGRID (106): SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), SS18L2 (Affinity Capture-MS)

ESM2 similar proteins: A9UL70, C5DJH5, O04211, O80877, P23923, P43273, P47805, P70302, P83093, P84903, Q0JNL3, Q0P426, Q13586, Q177A7, Q39140, Q39163, Q3SYZ9, Q41558, Q561Q8, Q561X3, Q570U6, Q58CP9, Q5M8Y7, Q5XG48, Q5Z6N9, Q612X6, Q61BU1, Q620W3, Q6BER6, Q6FTI5, Q6P7D5, Q7QH62, Q8AWD1, Q8K4I6, Q8MJK1, Q8S8F5, Q94BS8, Q9BI74, Q9CQ20, Q9CQA5

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
RMTs methylate histone arginines	6	25.1×	3e-05
FXIIa activates plasma kallikrein-kinin system	5	24.7×	2e-04
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	6	20.2×	6e-05
Negative Regulation of CDH1 Gene Transcription	5	17.2×	7e-04
CHD1 and CHD2 subfamily	5	15.5×	8e-04
Oxidative Stress Induced Senescence	5	12.9×	8e-04
Dengue Virus-Host Interactions	6	7.8×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	5	22.0×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

611 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42590963:GCGG:G	donor_gain	1.0000
3:42590964:CGGGT:C	donor_loss	1.0000
3:42590965:GG:G	donor_gain	1.0000
3:42590965:GGGT:G	donor_loss	1.0000
3:42590966:GG:G	donor_gain	1.0000
3:42590966:GGT:G	donor_loss	1.0000
3:42590967:G:C	donor_loss	1.0000
3:42590968:T:A	donor_loss	1.0000
3:42591514:T:A	acceptor_gain	1.0000
3:42591522:CAG:C	acceptor_loss	1.0000
3:42591523:A:AG	acceptor_gain	1.0000
3:42591523:A:T	acceptor_loss	1.0000
3:42591524:G:GA	acceptor_gain	1.0000
3:42591524:GC:G	acceptor_gain	1.0000
3:42591524:GCT:G	acceptor_gain	1.0000
3:42591524:GCTC:G	acceptor_gain	1.0000
3:42591524:GCTCC:G	acceptor_gain	1.0000
3:42591597:GTGCA:G	donor_gain	1.0000
3:42591598:TGCA:T	donor_gain	1.0000
3:42591599:GCA:G	donor_gain	1.0000
3:42591599:GCAG:G	donor_gain	1.0000
3:42591600:CA:C	donor_gain	1.0000
3:42591600:CAG:C	donor_loss	1.0000
3:42591601:AGTA:A	donor_loss	1.0000
3:42591602:G:GG	donor_gain	1.0000
3:42591602:GTA:G	donor_loss	1.0000
3:42591603:T:G	donor_loss	1.0000
3:42581843:CACCT:C	donor_loss	0.9900
3:42581845:C:G	donor_loss	0.9900
3:42590799:C:CA	acceptor_gain	0.9900

AlphaMissense

503 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42594457:T:C	L61S	0.997
3:42591538:A:T	N28I	0.996
3:42591547:T:C	L31P	0.996
3:42594436:T:C	L54S	0.996
3:42594448:T:C	L58P	0.995
3:42594448:T:A	L58H	0.993
3:42591526:T:C	L24P	0.992
3:42591529:T:A	L25H	0.992
3:42594445:A:T	N57I	0.992
3:42591529:T:C	L25P	0.991
3:42594459:G:C	A62P	0.991
3:42594460:C:A	A62D	0.991
3:42591537:A:T	N28Y	0.990
3:42594438:C:G	H55D	0.990
3:42594446:T:A	N57K	0.989
3:42594446:T:G	N57K	0.989
3:42594457:T:G	L61W	0.989
3:42591537:A:C	N28H	0.988
3:42591539:T:A	N28K	0.988
3:42591539:T:G	N28K	0.988
3:42590910:T:C	F5L	0.987
3:42590912:C:A	F5L	0.987
3:42590912:C:G	F5L	0.987
3:42591550:T:A	I32N	0.985
3:42591559:T:A	I35N	0.985
3:42594445:A:C	N57T	0.983
3:42594468:G:C	A65P	0.983
3:42591538:A:G	N28S	0.982
3:42594453:T:G	Y60D	0.982
3:42591537:A:G	N28D	0.981

dbSNP variants (sampled 300 via entrez): RS1000031355 (3:42587536 G>A), RS1000047793 (3:42594248 G>C), RS1000115352 (3:42589997 C>G,T), RS1000183047 (3:42591523 A>G,T), RS1000189937 (3:42581282 T>C), RS1000219315 (3:42590503 T>C), RS1000221006 (3:42581581 T>C), RS1000270115 (3:42597176 A>G,T), RS1000302596 (3:42597415 G>A,T), RS1000550899 (3:42590323 G>C), RS1000609065 (3:42595817 A>G), RS1000655698 (3:42587932 G>C,T), RS1000812492 (3:42592202 T>C), RS1001532946 (3:42582391 A>G), RS1001814491 (3:42580838 G>A)

Disease associations

OMIM: gene MIM:606473 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067352 (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
8.20	Kd	6.318	nM	CHEMBL5653589
8.20	ED50	6.318	nM	CHEMBL5653589

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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149495: Binding affinity to human SS18L2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0063	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Phenobarbital	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Selenium	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases 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
CHEMBL5652537	Binding	Binding affinity to human SS18L2 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

Clinical trials (associated diseases)

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