SSX5

Summary

SSX5 (SSX family member 5, HGNC:11339) is a protein-coding gene on chromosome Xp11.23, encoding Protein SSX5 (O60225). 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. Two transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 6758 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_175723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11339
Approved symbol	SSX5
Name	SSX family member 5
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165583
Ensembl biotype	protein_coding
OMIM	300327
Entrez	6758

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000311798, ENST00000347757, ENST00000403001

RefSeq mRNA: 2 — MANE Select: NM_175723 NM_021015, NM_175723

CCDS: CCDS14288, CCDS14289

Canonical transcript exons

ENST00000347757 — 8 exons

Exon	Start	End
ENSE00001185445	48186220	48186856
ENSE00001606345	48187627	48187731
ENSE00001621496	48190133	48190268
ENSE00001673963	48194129	48194224
ENSE00001696914	48192232	48192281
ENSE00001729090	48194740	48194854
ENSE00001741936	48195290	48195378
ENSE00003915234	48196731	48196795

Expression profiles

Bgee: expression breadth broad, 36 present calls, max score 87.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0099 / max 11.7504, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199150	0.0099	2

Top tissues by expression

233 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	87.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.04	silver quality
triceps brachii	UBERON:0001509	75.20	gold quality
gluteal muscle	UBERON:0002000	75.17	gold quality
vastus lateralis	UBERON:0001379	68.21	gold quality
quadriceps femoris	UBERON:0001377	67.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	67.19	gold quality
diaphragm	UBERON:0001103	65.90	gold quality
nasal cavity epithelium	UBERON:0005384	65.31	gold quality
biceps brachii	UBERON:0001507	64.77	gold quality
tongue squamous epithelium	UBERON:0006919	64.06	gold quality
cerebellar vermis	UBERON:0004720	63.43	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.41	gold quality
frontal pole	UBERON:0002795	62.85	gold quality
buccal mucosa cell	CL:0002336	62.81	gold quality
cervix squamous epithelium	UBERON:0006922	61.93	gold quality
middle frontal gyrus	UBERON:0002702	60.80	gold quality
paraflocculus	UBERON:0005351	60.36	gold quality
vena cava	UBERON:0004087	60.08	gold quality
deltoid	UBERON:0001476	58.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	58.54	gold quality
subthalamic nucleus	UBERON:0001906	57.43	gold quality
heart right ventricle	UBERON:0002080	57.40	gold quality
metanephric glomerulus	UBERON:0004736	57.38	gold quality
secondary oocyte	CL:0000655	57.29	gold quality
nephron tubule	UBERON:0001231	57.24	gold quality
mucosa of paranasal sinus	UBERON:0005030	57.17	gold quality
germinal epithelium of ovary	UBERON:0001304	57.12	gold quality
oral cavity	UBERON:0000167	56.92	gold quality
dorsal plus ventral thalamus	UBERON:0001897	56.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting SSX5, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4255	99.72	67.70	1541
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-4276	99.56	67.66	2514
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-549A-5P	96.35	68.08	587

Literature-anchored findings (GeneRIF, showing 1)

• Two kinds of cancer-testis antigen, SSX-2 and SSX-5 showed high-specific and high-frequent expression in hepatocellular carcinoma tissues, but neither of them could be detected in adjacent non-HCC tissues. (PMID:16546222)

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), SSX3 (ENSG00000165584), SSX7 (ENSG00000187754), SSX2 (ENSG00000241476), SSX4 (ENSG00000268009), SSX2B (ENSG00000268447), SSX4B (ENSG00000269791)

Protein

Protein identifiers

Protein SSX5 — O60225 (reviewed: O60225)

All UniProt accessions (1): O60225

UniProt curated annotations — full annotation on UniProt →

Function. Could act as a modulator of transcription.

Similarity. Belongs to the SSX family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60225-1	1	yes
O60225-2	2

RefSeq proteins (2): NP_066295, NP_783729* (*=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 (10 total): compositionally biased region 4, chain 1, domain 1, region of interest 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60225-F1	67.20	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MODULE_59, TGCTGAY_UNKNOWN, OCT1_06, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, MORF_IL9, EVI1_04, PARENT_MTOR_SIGNALING_UP, chrXp11, MIR6867_5P, MIR34A_5P, MIR449A, MIR2467_3P, MIR3678_3P, MIR549A_5P

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

172 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSX5	SS18	Q15532	737
SSX5	ZNF117	Q03924	688
SSX5	ZNF83	P51522	687
SSX5	IGSF22	Q8N9C0	511
SSX5	MAGEB1	P43366	423
SSX5	MAGEC2	Q9UBF1	399
SSX5	CTAG1A	P78358	398
SSX5	SSX2IP	Q9Y2D8	396
SSX5	MAGEA1	P43355	392
SSX5	MAGEA3	P43357	392
SSX5	CTAG2	O75638	391
SSX5	MAGEB2	O15479	375
SSX5	SPANXA1	Q9NS26	373
SSX5	TTC32	Q5I0X7	366
SSX5	MAGED4B	Q96JG8	360

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SSX5	AGTRAP	psi-mi:“MI:0915”(physical association)	0.740
AGTRAP	SSX5	psi-mi:“MI:0915”(physical association)	0.740
SSX5	ZSCAN1	psi-mi:“MI:0915”(physical association)	0.370
NFE2	SSX5	psi-mi:“MI:0915”(physical association)	0.370
SSX5	PCBD2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (11): AGTRAP (Two-hybrid), SSX5 (Affinity Capture-MS), SSX5 (Two-hybrid), SSX5 (Two-hybrid), CMTM5 (Two-hybrid), AGTRAP (Two-hybrid), GOLGA6L9 (Two-hybrid), SSX5 (Negative Genetic), SSX5 (Two-hybrid), PCBD2 (Two-hybrid), ZSCAN1 (Two-hybrid)

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, B8A5Y1, E9Q3T6, O75626, P10072, P52736, Q13029, Q14929, Q60636, Q63755, Q6P1L6, Q6P2A1, Q86UQ0, Q8BZ97, Q8TD17, Q9GZV8, Q9NQV5, Q9NQV8, Q9ULD5, Q9Y3M9, A2AJ77, C9JBD0, P14404

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1091 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48187620:CACT:C	donor_loss	1.0000
X:48187621:ACTT:A	donor_loss	1.0000
X:48187622:CTTAC:C	donor_loss	1.0000
X:48187623:TTACG:T	donor_loss	1.0000
X:48187624:TA:T	donor_loss	1.0000
X:48187625:A:AC	donor_gain	1.0000
X:48187626:C:CT	donor_gain	1.0000
X:48187626:CG:C	donor_gain	1.0000
X:48187626:CGG:C	donor_gain	1.0000
X:48187626:CGGA:C	donor_gain	1.0000
X:48187644:T:TA	donor_gain	1.0000
X:48187730:TCC:T	acceptor_loss	1.0000
X:48187732:C:CC	acceptor_gain	1.0000
X:48187733:T:G	acceptor_loss	1.0000
X:48190271:T:C	acceptor_gain	1.0000
X:48190271:T:TC	acceptor_gain	1.0000
X:48190273:A:C	acceptor_gain	1.0000
X:48190276:A:AC	acceptor_gain	1.0000
X:48190276:A:C	acceptor_gain	1.0000
X:48190278:G:GC	acceptor_gain	1.0000
X:48192282:C:CC	acceptor_gain	1.0000
X:48194121:CTACT:C	donor_loss	1.0000
X:48194123:ACT:A	donor_loss	1.0000
X:48194124:CTC:C	donor_loss	1.0000
X:48194125:TCACC:T	donor_loss	1.0000
X:48194126:CACC:C	donor_loss	1.0000
X:48194127:A:AC	donor_gain	1.0000
X:48194127:A:AG	donor_loss	1.0000
X:48194127:AC:A	donor_gain	1.0000
X:48194128:C:CC	donor_gain	1.0000

AlphaMissense

1258 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48194828:G:C	F32L	0.935
X:48194828:G:T	F32L	0.935
X:48194830:A:G	F32L	0.935
X:48194199:G:C	F70L	0.918
X:48194199:G:T	F70L	0.918
X:48194201:A:G	F70L	0.918
X:48194849:G:C	F25L	0.891
X:48194849:G:T	F25L	0.891
X:48194851:A:G	F25L	0.891
X:48194813:C:A	W37C	0.879
X:48194813:C:G	W37C	0.879
X:48194768:C:A	K52N	0.878
X:48194768:C:G	K52N	0.878
X:48194815:A:G	W37R	0.789
X:48194815:A:T	W37R	0.789
X:48194755:C:G	A57P	0.783
X:48194789:T:A	K45N	0.780
X:48194789:T:G	K45N	0.780
X:48194829:A:G	F32S	0.769
X:48194769:T:G	K52T	0.738
X:48194804:C:A	M40I	0.738
X:48194804:C:G	M40I	0.738
X:48194804:C:T	M40I	0.738
X:48194805:A:G	M40T	0.738
X:48194200:A:G	F70S	0.726
X:48194196:C:A	M71I	0.723
X:48194196:C:G	M71I	0.723
X:48194196:C:T	M71I	0.723
X:48194750:C:A	M58I	0.722
X:48194750:C:G	M58I	0.722

dbSNP variants (sampled 300 via entrez): RS111262473 (X:48195353 G>A,C,T), RS111366620 (X:48187132 G>C), RS111527014 (X:48190412 A>G), RS111859329 (X:48187139 G>T), RS112204202 (X:48188000 G>A,C), RS112546919 (X:48189983 G>T), RS112687457 (X:48189455 C>T), RS112762672 (X:48187965 G>A), RS112821791 (X:48186400 G>A,C,T), RS1156244500 (X:48194465 G>C), RS1156358441 (X:48195609 G>A,T), RS1156619075 (X:48197551 G>A), RS1156678013 (X:48198482 A>G,T), RS1156964466 (X:48190298 G>GT), RS1157093222 (X:48191363 A>C)

Disease associations

OMIM: gene MIM:300327 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Temozolomide	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Diethylhexyl Phthalate	increases expression	1
Endosulfan	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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