SSX1

Summary

SSX1 (SSX family member 1, HGNC:11335) is a protein-coding gene on chromosome Xp11.23, encoding Protein SSX1 (Q16384). 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 SSX2 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. A related pseudogene has been identified on chromosome X.

Source: NCBI Gene 6756 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure, X-linked, 5 (Strong, GenCC)
• Clinical variants (ClinVar): 76 total — 3 pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_005635

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11335
Approved symbol	SSX1
Name	SSX family member 1
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	CT5.1
Ensembl gene	ENSG00000126752
Ensembl biotype	protein_coding
OMIM	312820
Entrez	6756

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000376919

RefSeq mRNA: 2 — MANE Select: NM_005635 NM_001278691, NM_005635

CCDS: CCDS14290

Canonical transcript exons

ENST00000376919 — 8 exons

Exon	Start	End
ENSE00001152404	48266854	48267444
ENSE00001467402	48255392	48255432
ENSE00001650865	48257222	48257310
ENSE00001671455	48263782	48263917
ENSE00001711984	48261766	48261815
ENSE00001722509	48257746	48257860
ENSE00001730915	48258536	48258631
ENSE00001804414	48266287	48266391

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 89.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1873 / max 34.9524, expressed in 49 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196236	0.1873	49

Top tissues by expression

256 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	89.85	gold quality
buccal mucosa cell	CL:0002336	83.97	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.21	gold quality
frontal pole	UBERON:0002795	80.84	gold quality
paraflocculus	UBERON:0005351	80.68	gold quality
middle frontal gyrus	UBERON:0002702	80.09	gold quality
right testis	UBERON:0004534	71.37	gold quality
left testis	UBERON:0004533	69.73	gold quality
testis	UBERON:0000473	68.44	gold quality
endometrium epithelium	UBERON:0004811	61.86	gold quality
cervix squamous epithelium	UBERON:0006922	61.80	gold quality
lower lobe of lung	UBERON:0008949	60.31	silver quality
decidua	UBERON:0002450	56.55	gold quality
thymus	UBERON:0002370	53.14	gold quality
hair follicle	UBERON:0002073	52.75	gold quality
cerebellar vermis	UBERON:0004720	52.30	gold quality
triceps brachii	UBERON:0001509	52.19	gold quality
quadriceps femoris	UBERON:0001377	51.95	gold quality
cervix epithelium	UBERON:0004801	51.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	51.59	gold quality
vastus lateralis	UBERON:0001379	51.36	gold quality
oviduct epithelium	UBERON:0004804	50.53	gold quality
metanephric glomerulus	UBERON:0004736	49.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
renal glomerulus	UBERON:0000074	49.01	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting SSX1, 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-4697-3P	99.89	67.09	1123
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
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-183-5P	99.31	72.27	1164
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4700-5P	98.63	67.43	1915
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-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-549A-5P	96.35	68.08	587
HSA-MIR-31-3P	95.17	69.82	575

Literature-anchored findings (GeneRIF, showing 22)

• existence of fusion with SYT in synovial sarcoma (PMID:12037676)
• A synovial sarcoma of classic morphology contained a novel t(20;X) SS18L1(strong homology to SS18 on Ch20)/SSX1 fusion transcript in which nucleotide 1216 (exon 10) of SS18L1 was fused in-frame with nucleotide 422 (exon 6) of SSX1. (PMID:12696068)
• RT-PCR detection of SSX1 in paraffin-embedded tissue allowed for molecular diagnosis of synovial sarcoma. (PMID:15735574)
• demonstrate differentially expressed genes for the 2 major gene fusion variants in SS, chromosome 18 synovial sarcoma (SS18)/SSX1 and SS18/SSX2, and thereby suggest that these result in different downstream effects (PMID:16152617)
• SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells. (PMID:16247461)
• In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells. (PMID:18267106)
• siRNA targeting of SS18-SSX1 may have therapeutic potential in the treatment of synovial sarcomas. (PMID:18714179)
• We evaluated the correlations among the expression levels of NY-ESO-1, LAGE-1 and SSX-1 and clinical parameters in hepatocellular carcinoma patients (PMID:19212631)
• 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)
• Study shows that the SS18-SSX1 oncogenic fusion usurps SWI/SNF-like BAF complexes, resulting in activation of Sox2, which drives proliferation. (PMID:23540691)
• Knockdown of SS18-SSX1 in synovial sarcoma inhibits viability and induces apoptosis. (PMID:23716114)
• 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)
• The mRNA levels of SSX1 and SSX4 are associated with multiple myeloma clinical stage (PMID:24710929)
• 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)
• 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)
• In patients with Colon cancer, the expression of SSX1 gene was associated with a poor prognosis. (PMID:28631709)
• SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression (PMID:29502955)
• Synovial sarcoma (SS) is considered as high-grade tumors with a poor prognosis. Novel therapies targeted at fusion oncogene, SS18-SSX-derived peptide vaccine, epidermal growth factor receptor, and vascular endothelial growth factor are the future hope in SS. (PMID:29893303)

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): SSX5 (ENSG00000165583), SSX3 (ENSG00000165584), SSX7 (ENSG00000187754), SSX2 (ENSG00000241476), SSX4 (ENSG00000268009), SSX2B (ENSG00000268447), SSX4B (ENSG00000269791)

Protein

Protein identifiers

Protein SSX1 — Q16384 (reviewed: Q16384)

Alternative names: Cancer/testis antigen 5.1, Synovial sarcoma, X breakpoint 1

All UniProt accessions (1): Q16384

UniProt curated annotations — full annotation on UniProt →

Function. Could act as a modulator of transcription. Plays a role in spermatogenesis.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme.

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. Expressed in testis.

Disease relevance. Spermatogenic failure, X-linked, 5 (SPGFX5) [MIM:301099] A male infertility disorder characterized by reduced progressive sperm motility and multiple morphologic sperm abnormalities, resulting in asthenoteratozoospermia. The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving SSX1 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.

RefSeq proteins (2): NP_001265620, NP_005626* (*=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 (12 total): compositionally biased region 3, region of interest 2, site 2, chain 1, domain 1, sequence variant 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8HR1	ELECTRON MICROSCOPY	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16384-F1	69.32	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): 62–63 (breakpoint for translocation to form the ssxt-ssx1 fusion protein (rare)); 110–111 (breakpoint for translocation to form the ssxt-ssx1 fusion protein)

Post-translational modifications (1): 123

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GOBP_MALE_GAMETE_GENERATION, ONKEN_UVEAL_MELANOMA_UP, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, LUI_THYROID_CANCER_CLUSTER_5, MODULE_99, MODULE_123, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, MATTIOLI_MULTIPLE_MYELOMA_SUBGROUPS, GOCC_MOTILE_CILIUM, GOCC_CILIUM, MULLIGHAN_MLL_SIGNATURE_1_DN, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), spermatogenesis (GO:0007283), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (2): transcription corepressor activity (GO:0003714), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
developmental process involved in reproduction	1
male gamete generation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription coregulator activity	1
binding	1
intracellular membrane-bounded organelle	1
9+2 motile cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSX1	SS18	Q15532	969
SSX1	SS18L1	O75177	878
SSX1	TLE1	Q04724	778
SSX1	SSX2IP	Q9Y2D8	761
SSX1	ZNF117	Q03924	760
SSX1	ZNF83	P51522	760
SSX1	FTSJ1	Q9UET6	670
SSX1	SS18L2	Q9UHA2	668
SSX1	HEATR3	Q7Z4Q2	653
SSX1	SLC38A5	Q8WUX1	638
SSX1	CTAG1A	P78358	624
SSX1	CTAG2	O75638	621
SSX1	MAGEC1	O60732	610
SSX1	MAGEA1	P43355	608
SSX1	EWSR1	Q01844	608

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MAGEC2	SSX1	psi-mi:“MI:0915”(physical association)	0.560
SSX1	MAGEC2	psi-mi:“MI:0915”(physical association)	0.560
SSX1	CDCA7L	psi-mi:“MI:0915”(physical association)	0.560
SSX1	MTURN	psi-mi:“MI:0915”(physical association)	0.560
SSX1	CFL1	psi-mi:“MI:0915”(physical association)	0.400
SSX1	FUBP3	psi-mi:“MI:0915”(physical association)	0.370
SSX1	ACO1	psi-mi:“MI:0914”(association)	0.350
SSX1	NCALD	psi-mi:“MI:0914”(association)	0.350
CDCA7L	SSX1	psi-mi:“MI:0915”(physical association)	0.000
MTURN	SSX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): MAGEC2 (Two-hybrid), SSX1 (Affinity Capture-Western), CDCA7L (Two-hybrid), MTURN (Two-hybrid), SSX1 (Proximity Label-MS), CRIP2 (Affinity Capture-MS), ACO1 (Affinity Capture-MS), NCALD (Affinity Capture-MS), CPSF7 (Affinity Capture-MS), SSX1 (Affinity Capture-MS), SSX1 (Cross-Linking-MS (XL-MS)), FUBP3 (Two-hybrid), LHX4 (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, 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

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	47
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2444463	NM_005635.4(SSX1):c.185_186del (p.Gly62fs)	Pathogenic
2444464	NM_005635.4(SSX1):c.164A>G (p.Tyr55Cys)	Pathogenic
4277928	NM_005635.4(SSX1):c.330+1G>A	Pathogenic

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
X:48255430:G:GT	donor_gain	1.0000
X:48255430:GAA:G	donor_gain	1.0000
X:48255433:G:GG	donor_gain	1.0000
X:48257817:C:G	donor_gain	1.0000
X:48257857:C:G	donor_gain	1.0000
X:48261764:A:AG	acceptor_gain	1.0000
X:48261765:G:GG	acceptor_gain	1.0000
X:48263771:A:AG	acceptor_gain	1.0000
X:48263773:A:AG	acceptor_gain	1.0000
X:48266283:ATAG:A	acceptor_gain	1.0000
X:48266373:G:GT	donor_gain	1.0000
X:48266388:CTCC:C	donor_gain	1.0000
X:48266388:CTCCG:C	donor_loss	1.0000
X:48266389:TCC:T	donor_gain	1.0000
X:48266389:TCCG:T	donor_loss	1.0000
X:48266390:CC:C	donor_gain	1.0000
X:48266390:CCGT:C	donor_loss	1.0000
X:48266391:CGTAA:C	donor_loss	1.0000
X:48266392:G:GC	donor_loss	1.0000
X:48266392:G:GG	donor_gain	1.0000
X:48266393:T:A	donor_loss	1.0000
X:48266394:AAGT:A	donor_loss	1.0000
X:48257217:TGCAG:T	acceptor_loss	0.9900
X:48257220:A:G	acceptor_loss	0.9900
X:48257307:CAAGG:C	donor_loss	0.9900
X:48257309:AGGT:A	donor_loss	0.9900
X:48257310:GGTGA:G	donor_loss	0.9900
X:48257311:G:GC	donor_loss	0.9900
X:48257312:T:G	donor_loss	0.9900
X:48257740:TTTTA:T	acceptor_loss	0.9900

AlphaMissense

1276 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48257770:T:C	F32L	0.917
X:48257772:C:A	F32L	0.917
X:48257772:C:G	F32L	0.917
X:48258559:T:C	F70L	0.897
X:48258561:C:A	F70L	0.897
X:48258561:C:G	F70L	0.897
X:48257787:G:C	W37C	0.877
X:48257787:G:T	W37C	0.877
X:48266333:A:C	R171S	0.872
X:48266333:A:T	R171S	0.872
X:48257785:T:A	W37R	0.845
X:48257785:T:C	W37R	0.845
X:48266361:A:C	S181R	0.820
X:48266363:T:A	S181R	0.820
X:48266363:T:G	S181R	0.820
X:48257749:T:C	F25L	0.808
X:48257751:T:A	F25L	0.808
X:48257751:T:G	F25L	0.808
X:48257832:G:C	K52N	0.789
X:48257832:G:T	K52N	0.789
X:48257771:T:C	F32S	0.787
X:48257795:T:C	M40T	0.773
X:48266312:G:C	W164C	0.767
X:48266312:G:T	W164C	0.767
X:48257786:G:C	W37S	0.766
X:48257850:G:A	M58I	0.757
X:48257850:G:C	M58I	0.757
X:48257850:G:T	M58I	0.757
X:48257811:A:C	K45N	0.744
X:48257811:A:T	K45N	0.744

dbSNP variants (sampled 300 via entrez): RS111617084 (X:48258191 T>C), RS111623639 (X:48266818 G>A,T), RS111664227 (X:48261906 C>T), RS111695052 (X:48265354 A>T), RS111727958 (X:48257934 A>G), RS111807143 (X:48258829 G>A), RS111993872 (X:48266162 A>G), RS112130913 (X:48259098 A>C,G), RS112210405 (X:48260188 T>A), RS112217867 (X:48254342 A>C,G), RS112444645 (X:48263446 C>T), RS112696718 (X:48262257 A>G), RS112698905 (X:48261575 A>T), RS112714900 (X:48258710 T>A,C), RS112962661 (X:48263432 G>T)

Disease associations

OMIM: gene MIM:312820 | disease phenotypes: MIM:301099, MIM:300813

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure, X-linked, 5	Strong	X-linked

Mondo (3): spermatogenic failure, X-linked, 5 (MONDO:0859477), teratoma (MONDO:0002601), synovial sarcoma (MONDO:0010434)

Orphanet (1): Synovial sarcoma (Orphanet:3273)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0001417	X-linked inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0012570	Synovial sarcoma
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0033393	Irregularly shaped sperm tail
HP:0034011	Reduced progressive sperm motility

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013584	Sarcoma, Synovial	C04.557.450.565.835; C04.557.450.795.875
D013724	Teratoma	C04.557.465.910

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Decitabine	affects expression, increases expression	4
Phenylmercuric Acetate	affects cotreatment, increases expression	2
kojic acid	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases 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	increases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects binding, increases expression	1
Formaldehyde	decreases expression	1
Tretinoin	decreases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

22 cell lines: 19 cancer cell line, 3 embryonic stem cell

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_8719	HS-SY-2	Cancer cell line	Male
CVCL_A6FC	NCC-SS4-C1	Cancer cell line	Male
CVCL_A6S7	SEES3-1V human SSX1, clone1	Embryonic stem cell	Male
CVCL_A6S8	SEES3-1V human SSX1, clone2	Embryonic stem cell	Male
CVCL_A6S9	SEES3-1V human SSX1, clone3	Embryonic stem cell	Male
CVCL_B458	PDSS-26	Cancer cell line	Female
CVCL_C1GG	NCC-SS5-C1	Cancer cell line	Female
CVCL_C6LR	ICR-SS-1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00104676	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT03016819	PHASE3	RECRUITING	Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS)
NCT03520959	PHASE3	TERMINATED	A Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702)
NCT03773510	PHASE3	WITHDRAWN	Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin
NCT07174427	PHASE3	RECRUITING	Multi-center Study of TBI-1301 (INN: Mipetresgene Autoleucel; Mip-cel) in Patients With NY-ESO-1 Positive Synovial Sarcoma
NCT00002931	PHASE2	COMPLETED	Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer
NCT00301782	PHASE2	COMPLETED	Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors
NCT00432094	PHASE2	COMPLETED	Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
NCT00453232	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Men With Metastatic Germ Cell Tumors
NCT00453310	PHASE2	COMPLETED	Sunitinib in Treating Patients With Metastatic Germ Cell Tumors That Have Relapsed or Not Responded to Treatment
NCT00470366	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
NCT02300987	PHASE2	COMPLETED	A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
NCT00140855	PHASE2	TERMINATED	A Study of Anti-CTLA-4 Antibody in Patients With Advanced Synovial Sarcoma
NCT00356031	PHASE2	COMPLETED	Bevacizumab and Radiation Therapy for Sarcomas
NCT00668148	PHASE2	COMPLETED	A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma
NCT00837148	PHASE2	COMPLETED	Sorafenib and Dacarbazine in Soft Tissue Sarcoma
NCT02181829	PHASE2	COMPLETED	Whole Lung IMRT in Children and Adults With Synovial Sarcoma and Lung Metastases
NCT02452554	PHASE2	COMPLETED	Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT02584309	PHASE2	COMPLETED	Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
NCT02601950	PHASE2	COMPLETED	A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
NCT02609984	PHASE2	TERMINATED	Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
NCT03063632	PHASE2	COMPLETED	Testing the Combination of Two Experimental Drugs MK-3475 (Pembrolizumab) and Interferon-gamma for the Treatment of Mycosis Fungoides and Sézary Syndrome and Advanced Synovial Sarcoma
NCT03651375	PHASE2	UNKNOWN	Hypofractionated Radiotherapy With Sequential Chemotherapy in Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall
NCT03989596	PHASE2	UNKNOWN	Hypofractionated Radiotherapy With Hyperthermia in Unresectable or Marginally Resectable Soft Tissue Sarcomas
NCT04044768	PHASE2	ACTIVE_NOT_RECRUITING	Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
NCT04906876	PHASE2	WITHDRAWN	A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas
NCT05116800	PHASE2	WITHDRAWN	Phase 2 Study of 9-ING-41 With Chemotherapy in Sarcoma
NCT06277154	PHASE2	RECRUITING	MASCT-I Combined With Doxorubicin and Ifosfamide for First-line Treatment of Advanced Soft Tissue Sarcoma
NCT06456359	PHASE2	RECRUITING	Pasireotide as Maintenance Treatment in Synovial Sarcoma and Desmoplastic Small Round Cell Tumor
NCT07169344	PHASE2	RECRUITING	Hypofractionated, 3-week, Preoperative Proton or X-ray Radiotherapy for Patients With Localized Soft Tissue Sarcoma
NCT07173972	PHASE2	RECRUITING	Dose-escalated, Hypofractionated, Definitive Proton Radiotherapy for Patients With Inoperable Soft Tissue Sarcoma.
NCT00004853	PHASE1	COMPLETED	Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts After Intensive Chemotherapy
NCT01241162	PHASE1	COMPLETED	Decitabine Followed by a Cancer Antigen Vaccine for Patients With Neuroblastoma and Sarcoma
NCT02457650	PHASE1	UNKNOWN	T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies
NCT02601937	PHASE1	COMPLETED	EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma
NCT02683148	PHASE1	TERMINATED	DHEA in Synovial Sarcoma Patients
NCT02869217	PHASE1	ACTIVE_NOT_RECRUITING	Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors
NCT03009201	PHASE1	COMPLETED	Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery
NCT03132922	PHASE1	ACTIVE_NOT_RECRUITING	MAGE-A4ᶜ¹º³²T for Multi-Tumor