SSX2B

Summary

SSX2B (SSX family member 2B, HGNC:22263) is a protein-coding gene on chromosome Xp11.22, encoding Protein SSX2 (Q16385). Could act as a modulator of transcription.

The product of this gene belongs to the family of highly homologous synovial sarcoma X (SSX) breakpoint proteins. These proteins may function as transcriptional repressors. They are also capable of eliciting spontaneous humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. This gene, and also the SSX1 and SSX4 family members, have been involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas. This translocation results in the fusion of the synovial sarcoma translocation gene on chromosome 18 to one of the SSX genes on chromosome X. The encoded hybrid proteins are likely responsible for transforming activity. Alternative splicing of this gene results in multiple transcript variants. This gene also has an identical duplicate, GeneID: 6757, located about 45 kb upstream in the opposite orientation on chromosome X.

Source: NCBI Gene 727837 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001164417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22263
Approved symbol	SSX2B
Name	SSX family member 2B
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	CT5.2b
Ensembl gene	ENSG00000268447
Ensembl biotype	protein_coding
Entrez	727837

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000288839, ENST00000596480, ENST00000612490, ENST00000616191

RefSeq mRNA: 3 — MANE Select: NM_001164417 NM_001164417, NM_001278701, NM_001278702

CCDS: CCDS48129, CCDS65267

Canonical transcript exons

ENST00000596480 — 8 exons

Exon	Start	End
ENSE00003047992	52753838	52753933
ENSE00003064275	52760344	52760448
ENSE00003098861	52752661	52752749
ENSE00003167746	52755800	52755849
ENSE00003171810	52757854	52757989
ENSE00003176605	52751252	52751318
ENSE00003202681	52753188	52753302
ENSE00003902963	52760914	52761536

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 93.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2111 / max 26.1228, expressed in 57 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209704	0.2111	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.83	gold quality
right testis	UBERON:0004534	87.70	gold quality
testis	UBERON:0000473	87.29	gold quality
left testis	UBERON:0004533	86.60	gold quality
sural nerve	UBERON:0015488	57.45	silver quality
right lobe of thyroid gland	UBERON:0001119	53.68	gold quality
left lobe of thyroid gland	UBERON:0001120	53.11	gold quality
thyroid gland	UBERON:0002046	53.09	gold quality
colonic epithelium	UBERON:0000397	41.53	gold quality
stromal cell of endometrium	CL:0002255	39.55	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
apex of heart	UBERON:0002098	36.39	gold quality
skeletal muscle tissue	UBERON:0001134	36.31	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	34.42	gold quality
mucosa of stomach	UBERON:0001199	33.80	gold quality
blood	UBERON:0000178	32.40	gold quality
cortex of kidney	UBERON:0001225	32.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
liver	UBERON:0002107	30.63	gold quality
lymph node	UBERON:0000029	30.39	gold quality
vermiform appendix	UBERON:0001154	29.59	gold quality
placenta	UBERON:0001987	29.57	gold quality
muscle of leg	UBERON:0001383	29.31	gold quality
multicellular organism	UBERON:0000468	29.08	gold quality
gastrocnemius	UBERON:0001388	28.91	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	690.34
E-GEOD-124263	yes	527.49
E-ANND-3	no	1.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting SSX2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-549A-5P	96.35	68.08	587
HSA-MIR-6738-5P	96.33	63.61	815

Literature-anchored findings (GeneRIF, showing 1)

• SS18-SSX Expression in a Contemporary Cohort of Primary Renal Synovial Sarcoma: A Multi-Institutional Experience of Fourteen Patients. (PMID:36591871)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ssxb2	ENSMUSG00000023165
mus_musculus	Ssxb13	ENSMUSG00000035371
mus_musculus	Ssxa1	ENSMUSG00000062814
mus_musculus	Ssxb9	ENSMUSG00000068218
mus_musculus	Ssxb10	ENSMUSG00000068219
mus_musculus	Ssxb5	ENSMUSG00000071816
mus_musculus	Ssxb16	ENSMUSG00000079697
mus_musculus	Ssxb14	ENSMUSG00000079699
mus_musculus	Ssxb3	ENSMUSG00000079701
mus_musculus	Ssxb6	ENSMUSG00000079702
mus_musculus	Ssxb8	ENSMUSG00000079703
mus_musculus	Ssxb15	ENSMUSG00000079704
mus_musculus	Ssxb1	ENSMUSG00000079705
rattus_norvegicus	Ssx1	ENSRNOG00000027850
rattus_norvegicus	Ssx2	ENSRNOG00000049427

Paralogs (7): SSX1 (ENSG00000126752), SSX5 (ENSG00000165583), SSX3 (ENSG00000165584), SSX7 (ENSG00000187754), SSX2 (ENSG00000241476), SSX4 (ENSG00000268009), SSX4B (ENSG00000269791)

Protein

Protein identifiers

Protein SSX2 — Q16385 (reviewed: Q16385)

Alternative names: Cancer/testis antigen 5.2, Synovial sarcoma, X breakpoint 2, Tumor antigen HOM-MEL-40

All UniProt accessions (1): Q16385

UniProt curated annotations — full annotation on UniProt →

Function. Could act as a modulator of transcription.

Subunit / interactions. Interacts via its N-terminal region with RAB3IP and SSX2IP.

Subcellular location. Nucleus.

Tissue specificity. Expressed at high level in the testis. Expressed at low level in thyroid. Not detected in tonsil, colon, lung, spleen, prostate, kidney, striated and smooth muscles. Detected in rhabdomyosarcoma and fibrosarcoma cell lines. Not detected in mesenchymal and epithelial cell lines.

Disease relevance. A chromosomal aberration involving SSX2 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 SSX family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16385-1	1	yes
Q16385-2	2

RefSeq proteins (3): NP_001157889, NP_001265630, NP_001265631 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR003655	aKRAB	Domain
IPR019041	SSXRD_motif	Conserved_site
IPR036051	KRAB_dom_sf	Homologous_superfamily

Pfam: PF01352, PF09514

UniProt features (14 total): region of interest 3, modified residue 2, compositionally biased region 2, site 2, chain 1, domain 1, splice variant 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8HQY	ELECTRON MICROSCOPY	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16385-F1	69.63	0.28

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): 68–69 (breakpoint for translocation to form the ssxt-ssx2 fusion protein (rare)); 110–111 (breakpoint for translocation to form the ssxt-ssx2 fusion protein)

Post-translational modifications (2): 123, 108

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 6 (showing top): chrXp11, MIR6867_5P, MIR5581_3P, MIR2467_3P, MIR549A_5P, MIR1282

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

51 interactions, top by confidence:

A	B	Type	Score
SSX2IP	SSX2	psi-mi:“MI:0915”(physical association)	0.720
SSX2	SSX2IP	psi-mi:“MI:0407”(direct interaction)	0.720
SSX2	SSX2IP	psi-mi:“MI:0915”(physical association)	0.720
SSX2	SSX2IP	psi-mi:“MI:0403”(colocalization)	0.720
SSX2	RAB3IP	psi-mi:“MI:0915”(physical association)	0.670
AKAP9	SSX2	psi-mi:“MI:0915”(physical association)	0.670
SSX2	AKAP9	psi-mi:“MI:0915”(physical association)	0.670
RAB3IP	SSX2	psi-mi:“MI:0915”(physical association)	0.670
SSX2	ZBED1	psi-mi:“MI:0915”(physical association)	0.560
SSX2	KRT40	psi-mi:“MI:0915”(physical association)	0.560
TAX1BP1	SSX2	psi-mi:“MI:0915”(physical association)	0.560
SSX2	SYCE1	psi-mi:“MI:0915”(physical association)	0.560
ZMIZ2	SSX2	psi-mi:“MI:0915”(physical association)	0.560
BLZF1	SSX2	psi-mi:“MI:0915”(physical association)	0.560
MAGEC2	SSX2	psi-mi:“MI:0915”(physical association)	0.560
KRT40	SSX2	psi-mi:“MI:0915”(physical association)	0.560
SYCE1	SSX2	psi-mi:“MI:0915”(physical association)	0.560
SSX2	ZMIZ2	psi-mi:“MI:0915”(physical association)	0.560
ZBED1	SSX2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (67): BLZF1 (Two-hybrid), TAX1BP1 (Two-hybrid), ZBED1 (Two-hybrid), AKAP9 (Two-hybrid), MAGEC2 (Two-hybrid), ZMIZ2 (Two-hybrid), SYCE1 (Two-hybrid), RAB3IP (Two-hybrid), SSX2IP (Two-hybrid), KRT40 (Two-hybrid), SSX2B (Affinity Capture-MS), SSX3 (Affinity Capture-MS), SSX7 (Affinity Capture-MS), SSX3 (Affinity Capture-MS), SSX5 (Affinity Capture-MS)

ESM2 similar proteins: A6H5X4, B1AUS7, D0QMC3, O35368, O60224, O60225, P0C6Y7, P0DOV1, P0DOV2, P23497, P41218, Q15361, Q16384, Q16385, Q16666, Q2KIN0, Q3U827, Q3ZCI6, Q4R7Q1, Q504N7, Q5H9L4, Q5I0E2, Q5I0J8, Q5RAK3, Q5RCZ8, Q5RD14, Q5W0A0, Q62187, Q6K0P9, Q71F23, Q7RTT3, Q7RTT4, Q7RTT5, Q7RTT6, Q86T96, Q8BV49, Q8BVM9, Q8C0V1, Q8C6C7, Q8CGE8

Diamond homologs: B1AUS7, O60224, O60225, P0C6Y7, Q16384, Q16385, Q7RTT3, Q7RTT4, Q7RTT5, Q7RTT6, Q8BFS8, Q96EQ9, Q99909, Q9NQV7, Q9NQW5, Q6ZMS7, A0A163UT06, A2AGX3, A6QPM3, E9Q3T6, O75626, P52736, Q13029, Q3UZD5, Q5R5M1, Q60636, Q63755, Q6P2A1, Q6PGE4, Q80V63, Q86UQ0, Q8BZ97, Q8TD17, Q9GZV8, Q9NQV5, Q9NQV8, Q9NQX0, Q9QZP2, Q9UDV7, Q9UKN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2002 predictions. Top by Δscore:

Variant	Effect	Δscore
X:52751317:GA:G	donor_gain	1.0000
X:52751319:G:GG	donor_gain	1.0000
X:52752657:GCAGG:G	acceptor_loss	1.0000
X:52752658:CA:C	acceptor_loss	1.0000
X:52752659:A:G	acceptor_loss	1.0000
X:52752660:G:GT	acceptor_loss	1.0000
X:52752746:AAAG:A	donor_loss	1.0000
X:52752750:G:A	donor_loss	1.0000
X:52753182:TTGTA:T	acceptor_loss	1.0000
X:52753183:TGTAG:T	acceptor_loss	1.0000
X:52753184:GTA:G	acceptor_loss	1.0000
X:52753185:TAGGC:T	acceptor_loss	1.0000
X:52753186:A:AG	acceptor_gain	1.0000
X:52753186:AGGC:A	acceptor_loss	1.0000
X:52753187:G:GG	acceptor_gain	1.0000
X:52753276:GAAA:G	donor_gain	1.0000
X:52753277:A:T	donor_gain	1.0000
X:52753280:G:GG	donor_gain	1.0000
X:52753287:GC:G	donor_gain	1.0000
X:52753299:C:G	donor_gain	1.0000
X:52753834:CTA:C	acceptor_loss	1.0000
X:52753835:TA:T	acceptor_loss	1.0000
X:52753836:A:AG	acceptor_gain	1.0000
X:52753836:A:AT	acceptor_loss	1.0000
X:52753837:G:GG	acceptor_gain	1.0000
X:52753929:TCAGG:T	donor_gain	1.0000
X:52753930:CAGGG:C	donor_loss	1.0000
X:52753932:GG:G	donor_gain	1.0000
X:52753933:GG:G	donor_gain	1.0000
X:52753934:G:GG	donor_gain	1.0000

AlphaMissense

1261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:52753212:T:C	F32L	0.937
X:52753214:C:A	F32L	0.937
X:52753214:C:G	F32L	0.937
X:52753861:T:C	F70L	0.931
X:52753863:C:A	F70L	0.931
X:52753863:C:G	F70L	0.931
X:52753229:G:C	W37C	0.906
X:52753229:G:T	W37C	0.906
X:52753191:T:C	F25L	0.899
X:52753193:C:A	F25L	0.899
X:52753193:C:G	F25L	0.899
X:52753274:G:C	K52N	0.898
X:52753274:G:T	K52N	0.898
X:52760390:A:C	R171S	0.878
X:52760390:A:T	R171S	0.878
X:52753227:T:A	W37R	0.875
X:52753227:T:C	W37R	0.875
X:52760418:A:C	S181R	0.842
X:52760420:C:A	S181R	0.842
X:52760420:C:G	S181R	0.842
X:52753287:G:C	A57P	0.808
X:52753228:G:C	W37S	0.790
X:52760369:G:C	W164C	0.789
X:52760369:G:T	W164C	0.789
X:52760416:T:C	I180T	0.784
X:52753253:A:C	K45N	0.783
X:52753253:A:T	K45N	0.783
X:52760416:T:G	I180S	0.783
X:52753213:T:C	F32S	0.781
X:52753281:T:G	Y55D	0.778

dbSNP variants (sampled 205 via entrez): RS111728628 (X:52759783 C>A), RS112024130 (X:52751209 G>C), RS112365460 (X:52749490 C>T), RS1163968986 (X:52757185 A>G), RS1177275355 (X:52757104 T>A,C), RS1186911454 (X:52756773 G>T), RS1192386993 (X:52757201 GA>G,GAAAA), RS1212284536 (X:52757336 C>T), RS1223251502 (X:52755235 G>GCCAACTA), RS1224396195 (X:52757118 G>A), RS1231790155 (X:52757139 G>A,T), RS1238564053 (X:52760826 A>G), RS1250182037 (X:52757110 G>A), RS1252855379 (X:52757323 A>G), RS1253458956 (X:52757101 C>T)

Disease associations

OMIM: gene `` | 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: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Temozolomide	increases expression	1

Clinical trials (associated diseases)

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