TISIDB

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
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	Mitochondrion Nucleus, nucleolus
Domain	PF00012 Hsp70 protein
Function	Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). May play a role in the control of cell proliferation and cellular aging (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0002262 myeloid cell homeostasis GO:0002683 negative regulation of immune system process GO:0006457 protein folding GO:0006611 protein export from nucleus GO:0006913 nucleocytoplasmic transport GO:0030099 myeloid cell differentiation GO:0030218 erythrocyte differentiation GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0034101 erythrocyte homeostasis GO:0045637 regulation of myeloid cell differentiation GO:0045638 negative regulation of myeloid cell differentiation GO:0045646 regulation of erythrocyte differentiation GO:0045647 negative regulation of erythrocyte differentiation GO:0048872 homeostasis of number of cells GO:0051168 nuclear export GO:0051169 nuclear transport GO:1903706 regulation of hemopoiesis GO:1903707 negative regulation of hemopoiesis
Molecular Function	GO:0031625 ubiquitin protein ligase binding GO:0044389 ubiquitin-like protein ligase binding GO:0051082 unfolded protein binding
Cellular Component	GO:0005759 mitochondrial matrix GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0009295 nucleoid GO:0030055 cell-substrate junction GO:0042645 mitochondrial nucleoid GO:0043209 myelin sheath

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03018 RNA degradation
Reactome	R-HSA-3371556: Cellular response to heat stress R-HSA-2262752: Cellular responses to stress R-HSA-392499: Metabolism of proteins R-HSA-1268020: Mitochondrial protein import R-HSA-3371453: Regulation of HSF1-mediated heat shock response

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HSPA9 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 HSPA9 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19739077	Erythroleukemia; Colorectal Carcinoma	Inhibit immunity (T cell function)	As shown here, knock down of mortalin with specific siRNA reduces MAC elimination and enhances cell sensitivity to MAC-induced cell death. Similar results were obtained with MKT-077, a cationic rhodacyanine dye that inhibits mortalin. Treatment of human erythroleukemia K562 and colorectal carcinoma HCT116 cells with MKT-077 sensitizes them to cell death mediated by MAC but not by streptolysin O.

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
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 HSPA9 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	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
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 HSPA9 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	0.031	0.892
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.145	0.962
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.057	0.98
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.13	0.667
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.164	0.942
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.504	0.864
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.06	0.906
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.17	0.942
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.314	0.905
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.231	0.913
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	0.266	0.934
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.024	0.713

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HSPA9 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	2.7	-2.7	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	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	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	2.6	0	2.6	1
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	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HSPA9. 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	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HSPA9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HSPA9. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HSPA9. 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	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HSPA9 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HSPA9 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HSPA9
Name	heat shock 70kDa protein 9 (mortalin)
Aliases	GRP75; PBP74; mot-2; mthsp75; HSPA9B; heat shock 70kDa protein 9B (mortalin-2); CRP40; GRP-75; HEL-S-124mB; ......
Chromosomal Location	5q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HSPA9 collected from DrugBank database.

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

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