TISIDB

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm. Cytoplasm, perinuclear region. Note=Perinuclear distribution in response to stress signals such as UV radiation.; SUBCELLULAR LOCATION: Isoform 5: Cytoplasmic vesicle, secretory vesicle, acrosome. Note=Associated with the plasma membrane of the acrosomal compartment and also localizes in the acrosome matrix.
Domain	PF16471 JNK-interacting protein leucine zipper II PF09744 JNK_SAPK-associated protein-1
Function	The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Isoform 5 may play a role in spermatozoa-egg-interaction.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0007034 vacuolar transport GO:0007254 JNK cascade GO:0007257 activation of JUN kinase activity GO:0007283 spermatogenesis GO:0010720 positive regulation of cell development GO:0016197 endosomal transport GO:0016482 cytosolic transport GO:0030335 positive regulation of cell migration GO:0031098 stress-activated protein kinase signaling cascade GO:0032091 negative regulation of protein binding GO:0032147 activation of protein kinase activity GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0033674 positive regulation of kinase activity GO:0040017 positive regulation of locomotion GO:0042147 retrograde transport, endosome to Golgi GO:0042692 muscle cell differentiation GO:0043393 regulation of protein binding GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043496 regulation of protein homodimerization activity GO:0043506 regulation of JUN kinase activity GO:0043507 positive regulation of JUN kinase activity GO:0045666 positive regulation of neuron differentiation GO:0045860 positive regulation of protein kinase activity GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0048232 male gamete generation GO:0050769 positive regulation of neurogenesis GO:0051098 regulation of binding GO:0051100 negative regulation of binding GO:0051146 striated muscle cell differentiation GO:0051147 regulation of muscle cell differentiation GO:0051149 positive regulation of muscle cell differentiation GO:0051259 protein oligomerization GO:0051260 protein homooligomerization GO:0051272 positive regulation of cellular component movement GO:0051403 stress-activated MAPK cascade GO:0051962 positive regulation of nervous system development GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090074 negative regulation of protein homodimerization activity GO:2000147 positive regulation of cell motility
Molecular Function	GO:0005078 MAP-kinase scaffold activity GO:0008432 JUN kinase binding GO:0019894 kinesin binding GO:0030159 receptor signaling complex scaffold activity GO:0032947 protein complex scaffold GO:0035591 signaling adaptor activity GO:0048273 mitogen-activated protein kinase p38 binding GO:0051019 mitogen-activated protein kinase binding GO:0060090 binding, bridging
Cellular Component	GO:0001669 acrosomal vesicle GO:0030141 secretory granule GO:0097223 sperm part GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-375170: CDO in myogenesis R-HSA-1266738: Developmental Biology R-HSA-525793: Myogenesis

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SPAG9 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between SPAG9 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19326449	Cervical carcinoma	Promote immunity	The aim of the current study was to evaluate the clinical utility of SPAG9 expression and humoral immune response in cervical carcinomas. The current study findings revealed that in early stage cervical cancer, a substantial number of patients exhibited SPAG9 expression and generated SPAG9 antibodies, supporting its potential role in early detection and diagnosis in cervical cancer management.
19820019	Thyroid Gland Carcinoma	Inhibit immunity (T cell function)	It is interesting to note that majority of early-stage (T1) thyroid cancer patients exhibited higher antibody response against SPAG9. Small interfering RNA-mediated knockdown of SPAG9 expression in thyroid cancer cell significantly reduced cellular growth and colony formation.
19190149	Breast Carcinoma	Inhibit immunity	Our reverse transcription-PCR and immunohistochemical analyses revealed SPAG9 expression in 88% breast cancer specimens independent of tumor stages and grades. Further, the humoral immune response against SPAG9 was detected in 80% breast cancer patients with SPAG9-expressing tumors. The linear regression modeling predicted a direct relationship between presence of lymphovascular invasion and high SPAG9 IRS, whereas the univariate and multivariate logistic regression models predicted a strong association of SPAG9 IRS with tumor grade.
18922895	Renal Cell Carcinoma	Inhibit immunity	Sperm-associated antigen 9 is associated with tumor growth, migration, and invasion in renal cell carcinoma. Consistent with the clinical findings, knockdown of SPAG9 expression in RCC cells with specific siRNA significantly reduced cell growth and colony formation. In conclusion, SPAG9 expression is associated with clinicopathologic features of tumors, suggesting that SPAG9 could contribute to the early spread of cancer.

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of SPAG9 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of SPAG9 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.209	0.402
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.265	0.895
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.171	0.905
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.113	0.622
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.183	0.942
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.026	0.994
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.032	0.94
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.141	0.946
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.081	0.972
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.041	0.98
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.826	0.716
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.035	0.49

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SPAG9 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	15.4	-15.4	0.482
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	16.7	-16.7	1

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPAG9. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPAG9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPAG9. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPAG9. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SPAG9 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SPAG9 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SPAG9
Name	sperm associated antigen 9
Aliases	SYD1; KIAA0516; MGC14967; MGC74461; MGC117291; JLP; PHET; HLC4; FLJ13450; FLJ14006; FLJ26141; FLJ34602; CT89 ......
Chromosomal Location	17q21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SPAG9 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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