SSX3

Summary

SSX3 (SSX family member 3, HGNC:11337) is a protein-coding gene on chromosome Xp11.23, encoding Protein SSX3 (Q99909). 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. While some of the related SSX genes are involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas, this gene does not appear to be involved in such translocations.

Source: NCBI Gene 10214 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_021014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11337
Approved symbol	SSX3
Name	SSX family member 3
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	CT5.3
Ensembl gene	ENSG00000165584
Ensembl biotype	protein_coding
OMIM	300325
Entrez	10214

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000298396, ENST00000376893, ENST00000376895, ENST00000612497

RefSeq mRNA: 1 — MANE Select: NM_021014 NM_021014

CCDS: CCDS14291

Canonical transcript exons

ENST00000298396 — 8 exons

Exon	Start	End
ENSE00001289340	48346427	48347035
ENSE00001593571	48353999	48354094
ENSE00001614267	48352100	48352149
ENSE00001730639	48354632	48354746
ENSE00001775773	48355181	48355269
ENSE00001813999	48356634	48356703
ENSE00003731119	48349987	48350122
ENSE00003749105	48347500	48347604

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 89.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0215 / max 6.9336, expressed in 8 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199152	0.0215	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	89.05	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.48	gold quality
right testis	UBERON:0004534	81.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.32	gold quality
left testis	UBERON:0004533	79.46	gold quality
testis	UBERON:0000473	78.97	gold quality
adult organism	UBERON:0007023	77.11	gold quality
tendon of biceps brachii	UBERON:0008188	68.24	silver quality
periodontal ligament	UBERON:0008266	64.97	gold quality
pancreatic ductal cell	CL:0002079	64.61	silver quality
amniotic fluid	UBERON:0000173	63.15	silver quality
type B pancreatic cell	CL:0000169	62.52	gold quality
inferior olivary complex	UBERON:0002127	62.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	62.17	gold quality
olfactory bulb	UBERON:0002264	61.53	gold quality
mucosa of urinary bladder	UBERON:0001259	59.76	gold quality
cartilage tissue	UBERON:0002418	59.73	gold quality
tongue squamous epithelium	UBERON:0006919	59.60	gold quality
parotid gland	UBERON:0001831	58.57	gold quality
gluteal muscle	UBERON:0002000	58.57	gold quality
decidua	UBERON:0002450	58.52	gold quality
triceps brachii	UBERON:0001509	58.38	gold quality
tibialis anterior	UBERON:0001385	57.54	silver quality
diaphragm	UBERON:0001103	57.51	gold quality
gingival epithelium	UBERON:0001949	56.83	gold quality
squamous epithelium	UBERON:0006914	55.56	gold quality
male germ cell	CL:0000015	55.53	silver quality
esophagus squamous epithelium	UBERON:0006920	55.37	gold quality
epithelium of esophagus	UBERON:0001976	55.17	gold quality
oviduct epithelium	UBERON:0004804	54.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting SSX3, 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-4496	99.88	68.89	2236
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-4699-3P	99.71	70.15	3142
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-4261	99.59	70.30	3415
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-889-3P	99.40	69.76	2103
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-6731-5P	99.28	67.42	2375
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5087	98.01	69.09	965

Literature-anchored findings (GeneRIF, showing 1)

• SSX2, SSX3, and SSX4 are expressed only in 3.5% early-stage non-small cell lung cancer patients. (PMID:24645645)

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), SSX7 (ENSG00000187754), SSX2 (ENSG00000241476), SSX4 (ENSG00000268009), SSX2B (ENSG00000268447), SSX4B (ENSG00000269791)

Protein

Protein identifiers

Protein SSX3 — Q99909 (reviewed: Q99909)

Alternative names: Cancer/testis antigen 5.3

All UniProt accessions (2): A0A087WWQ6, Q99909

UniProt curated annotations — full annotation on UniProt →

Function. Could act as a modulator of transcription.

Subunit / interactions. Interacts with SSX2IP.

Similarity. Belongs to the SSX family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99909-1	1	yes
Q99909-2	2

RefSeq proteins (1): NP_066294* (*=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: PF09514

UniProt features (7 total): chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99909-F1	68.34	0.27

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 (1): 123

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): MODULE_205, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, OCT1_06, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, MODULE_207, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, SHEN_SMARCA2_TARGETS_DN, chrXp11, PEDRIOLI_MIR31_TARGETS_UP, ATM_DN.V1_DN, JNK_DN.V1_DN, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_UP, TGFB_UP.V1_DN, ASH1L_TARGET_GENES, ZHONG_RESPONSE_TO_AZACITIDINE_AND_TSA_UP

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

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSX3	SSX2IP	Q9Y2D8	822
SSX3	SS18	Q15532	718
SSX3	ZNF117	Q03924	645
SSX3	ZNF83	P51522	641
SSX3	RAB3IP	Q96QF0	631
SSX3	PRRG3	Q9BZD7	541
SSX3	IGSF22	Q8N9C0	447
SSX3	OR1L6	Q8NGR2	434
SSX3	AGFG2	O95081	394
SSX3	AFDN	P55196	390
SSX3	SSX1	Q16384	389
SSX3	MAGEB17	A8MXT2	374
SSX3	RFX7	Q2KHR2	371
SSX3	ZNF3	P13683	368
SSX3	GARIN5A	Q6IPT2	358

IntAct

75 interactions, top by confidence:

A	B	Type	Score
SSX3	MIPOL1	psi-mi:“MI:0915”(physical association)	0.780
MIPOL1	SSX3	psi-mi:“MI:0915”(physical association)	0.780
SSX3	MED4	psi-mi:“MI:0915”(physical association)	0.720
MED4	SSX3	psi-mi:“MI:0915”(physical association)	0.720
CEP63	SSX3	psi-mi:“MI:0915”(physical association)	0.670
SSX3	CEP63	psi-mi:“MI:0915”(physical association)	0.670
SSX3	RHOJ	psi-mi:“MI:0915”(physical association)	0.610
RHOJ	SSX3	psi-mi:“MI:0915”(physical association)	0.610
SSX3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
SSX3	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
SSX3	CEP70	psi-mi:“MI:0915”(physical association)	0.560
SSX3	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
SSX3	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	SSX3	psi-mi:“MI:0915”(physical association)	0.560
CEP70	SSX3	psi-mi:“MI:0915”(physical association)	0.560
SSX2IP	SSX3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (44): SSX3 (Two-hybrid), MED4 (Two-hybrid), AGTRAP (Two-hybrid), RHOJ (Two-hybrid), CEP63 (Two-hybrid), CEP70 (Two-hybrid), CMTM5 (Two-hybrid), SSX2IP (Two-hybrid), MIPOL1 (Two-hybrid), SSX3 (Affinity Capture-MS), SSX3 (Affinity Capture-MS), CDR2 (Affinity Capture-MS), SSX2B (Affinity Capture-MS), SSX7 (Affinity Capture-MS), KTN1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1024 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48347498:A:AC	donor_gain	1.0000
X:48347499:C:CC	donor_gain	1.0000
X:48347511:T:C	donor_gain	1.0000
X:48350130:A:AC	acceptor_gain	1.0000
X:48350132:G:GC	acceptor_gain	1.0000
X:48352145:TTGAA:T	acceptor_gain	1.0000
X:48352150:C:CC	acceptor_gain	1.0000
X:48353997:AC:A	donor_gain	1.0000
X:48353998:CC:C	donor_gain	1.0000
X:48354094:CCTA:C	acceptor_loss	1.0000
X:48354095:C:CA	acceptor_loss	1.0000
X:48354095:C:CC	acceptor_gain	1.0000
X:48354096:T:G	acceptor_loss	1.0000
X:48354653:A:AC	donor_gain	1.0000
X:48354654:C:CC	donor_gain	1.0000
X:48354654:CTTT:C	donor_gain	1.0000
X:48354657:T:A	donor_gain	1.0000
X:48354743:AGGCC:A	acceptor_loss	1.0000
X:48354744:GGCC:G	acceptor_loss	1.0000
X:48354746:CCTA:C	acceptor_loss	1.0000
X:48354747:C:CC	acceptor_gain	1.0000
X:48354747:C:G	acceptor_loss	1.0000
X:48354748:T:A	acceptor_loss	1.0000
X:48355177:TCA:T	donor_loss	1.0000
X:48355178:CAC:C	donor_loss	1.0000
X:48355179:A:T	donor_loss	1.0000
X:48355180:C:CG	donor_loss	1.0000
X:48355269:CCTG:C	acceptor_loss	1.0000
X:48355270:CTGC:C	acceptor_loss	1.0000
X:48355271:T:A	acceptor_loss	1.0000

AlphaMissense

1263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48354720:G:C	F32L	0.927
X:48354720:G:T	F32L	0.927
X:48354722:A:G	F32L	0.927
X:48354069:G:C	F70L	0.911
X:48354069:G:T	F70L	0.911
X:48354071:A:G	F70L	0.911
X:48354741:G:C	F25L	0.906
X:48354741:G:T	F25L	0.906
X:48354743:A:G	F25L	0.906
X:48354705:C:A	W37C	0.886
X:48354705:C:G	W37C	0.886
X:48354660:C:A	K52N	0.881
X:48354660:C:G	K52N	0.881
X:48354707:A:G	W37R	0.860
X:48354707:A:T	W37R	0.860
X:48347558:T:A	R171S	0.848
X:48347558:T:G	R171S	0.848
X:48354647:C:G	A57P	0.801
X:48347528:G:C	S181R	0.787
X:48347528:G:T	S181R	0.787
X:48347530:T:G	S181R	0.787
X:48354721:A:G	F32S	0.760
X:48354681:T:A	K45N	0.756
X:48354681:T:G	K45N	0.756
X:48354706:C:G	W37S	0.752
X:48354090:G:C	F63L	0.750
X:48354090:G:T	F63L	0.750
X:48354092:A:G	F63L	0.750
X:48354653:A:C	Y55D	0.739
X:48354661:T:G	K52T	0.738

dbSNP variants (sampled 300 via entrez): RS112625608 (X:48357307 G>A), RS112850154 (X:48357379 C>T), RS11323384 (X:48355579 GA>G), RS113398904 (X:48353846 A>G), RS113403735 (X:48354694 T>C), RS113583802 (X:48355366 A>C,T), RS113606582 (X:48350510 C>T), RS113618700 (X:48349395 G>A,T), RS113803892 (X:48346398 C>T), RS113865830 (X:48356814 G>A), RS1156271936 (X:48356718 C>A), RS1156518702 (X:48355764 A>G), RS1156673565 (X:48358331 C>A,T), RS1156762196 (X:48357518 C>T), RS1156986561 (X:48351976 G>T)

Disease associations

OMIM: gene MIM:300325 | 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Decitabine	decreases reaction, increases expression, decreases expression	2
sodium arsenite	increases expression	1
butylbenzyl phthalate	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, increases expression	1
Disulfiram	affects binding, increases expression	1
Silver	increases expression	1
Smoke	decreases expression, decreases reaction	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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