TISIDB

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
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	Lysosome. Melanosome. Secreted, extracellular space. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. In aortic samples, detected as an extracellular protein loosely bound to the matrix (PubMed:20551380).
Domain	PF07966 A1 Propeptide PF00026 Eukaryotic aspartyl protease
Function	Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.

> Gene Ontology [ TOP ]
Biological Process	GO:0002478 antigen processing and presentation of exogenous peptide antigen GO:0002495 antigen processing and presentation of peptide antigen via MHC class II GO:0002504 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II GO:0006914 autophagy GO:0019882 antigen processing and presentation GO:0019884 antigen processing and presentation of exogenous antigen GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0030574 collagen catabolic process GO:0032963 collagen metabolic process GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0048002 antigen processing and presentation of peptide antigen
Molecular Function	GO:0004175 endopeptidase activity GO:0004190 aspartic-type endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0008234 cysteine-type peptidase activity GO:0008236 serine-type peptidase activity GO:0017171 serine hydrolase activity GO:0070001 aspartic-type peptidase activity
Cellular Component	GO:0005775 vacuolar lumen GO:0042470 melanosome GO:0043202 lysosomal lumen GO:0045121 membrane raft GO:0048770 pigment granule GO:0098589 membrane region GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04071 Sphingolipid signaling pathway hsa04140 Regulation of autophagy hsa04142 Lysosome hsa04210 Apoptosis
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-1442490: Collagen degradation R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1474244: Extracellular matrix organization R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-2132295: MHC class II antigen presentation R-HSA-2022377: Metabolism of Angiotensinogen to Angiotensins R-HSA-392499: Metabolism of proteins R-HSA-6798695: Neutrophil degranulation R-HSA-2980736: Peptide hormone metabolism

> KEGG and Reactome Pathway

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KEGG

hsa04071 Sphingolipid signaling pathway
hsa04140 Regulation of autophagy
hsa04142 Lysosome
hsa04210 Apoptosis

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-1442490: Collagen degradation
R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-1474244: Extracellular matrix organization
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-2132295: MHC class II antigen presentation
R-HSA-2022377: Metabolism of Angiotensinogen to Angiotensins
R-HSA-392499: Metabolism of proteins
R-HSA-6798695: Neutrophil degranulation
R-HSA-2980736: Peptide hormone metabolism

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CTSD 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 CTSD and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16709808	Melanoma	Inhibit immunity	Our studies suggest that CCL20 processing in the extracellular environment of melanoma cells is exclusively mediated by cathepsin D. Thus, we propose a model where cathepsin D inactivates CCL20 and possibly prevents the establishment of an effective antitumoral immune response in melanomas.

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
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 CTSD 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	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
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 CTSD 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	0.283	0.482
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.616	0.887
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.034	0.992
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.427	0.451
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.112	0.969
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.824	0.823
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.004	0.995
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.031	0.991
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.105	0.972
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.254	0.687
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	1.231	0.799
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.023	0.832

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CTSD 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	0	0	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	0	0	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	6.2	-6.2	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	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	0	0	0	1
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	0	0	1

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CTSD. 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	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CTSD. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CTSD. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CTSD. 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	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CTSD expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CTSD and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CTSD
Name	cathepsin D
Aliases	CLN10; ceroid-lipofuscinosis, neuronal 10; CPSD; cathepsin D (lysosomal aspartyl protease); HEL-S-130P; epid ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CTSD collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CTSD.

ID	Name	Drug Type	Targets	#Targets
DB00030	Insulin Human	Biotech	CPE, CTSD, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV, PCSK1, PCSK2, RB1, ......	12
DB00071	Insulin Pork	Biotech	CPE, CTSD, HLA-DQA2, HLA-DQB1, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV ......	14
DB02216	S-Methylcysteine	Small Molecule	CTSD, MGMT	2
DB03028	1h-Benoximidazole-2-Carboxylic Acid	Small Molecule	CTSD	1
DB03096	N-Aminoethylmorpholine	Small Molecule	CTSD	1
DB07542	5-AMINO-6-CYCLOHEXYL-4-HYDROXY-2-ISOBUTYL-HEXANOIC ACID	Small Molecule	CTSD	1
DB08740	CYCLOHEXYLMETHYL-2,3-DIHYDROXY-5-METHYL-HEXYLAMIDE	Small Molecule	CTSD	1

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