TISIDB

Summary
Symbol	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
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	Nucleus Nucleus, nucleolus Cell membrane Single-pass type I membrane protein Cell projection, microvillus membrane Single-pass type I membrane protein Note=Found on the surface microvilli and in the nucleus, particularly in nucleolus.
Domain	PF00194 Eukaryotic-type carbonic anhydrase
Function	Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.

> Gene Ontology [ TOP ]
Biological Process	GO:0001666 response to hypoxia GO:0006730 one-carbon metabolic process GO:0006820 anion transport GO:0015701 bicarbonate transport GO:0015711 organic anion transport GO:0033574 response to testosterone GO:0036293 response to decreased oxygen levels GO:0036294 cellular response to decreased oxygen levels GO:0042493 response to drug GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress GO:0043620 regulation of DNA-templated transcription in response to stress GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0070482 response to oxygen levels GO:0071453 cellular response to oxygen levels GO:0071456 cellular response to hypoxia GO:1901654 response to ketone
Molecular Function	GO:0004089 carbonate dehydratase activity GO:0016829 lyase activity GO:0016835 carbon-oxygen lyase activity GO:0016836 hydro-lyase activity
Cellular Component	GO:0005902 microvillus GO:0016323 basolateral plasma membrane GO:0031253 cell projection membrane GO:0031528 microvillus membrane GO:0098858 actin-based cell projection

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00910 Nitrogen metabolism
Reactome	R-HSA-2262749: Cellular response to hypoxia R-HSA-2262752: Cellular responses to stress R-HSA-1430728: Metabolism R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen R-HSA-1234158: Regulation of gene expression by Hypoxia-inducible Factor R-HSA-1475029: Reversible hydration of carbon dioxide

Summary
Symbol	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CA9 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 CA9 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26062742	Renal Cell Carcinoma	Inhibit immunity (T cell function; infiltration)	We show that anti-CAIX mAbs are capable of mediating human immune response in vivo including tumor infiltration of NK cells and activation of T cells, resulting in inhibition of CAIX(+) tumor growth.
19074859	Melanoma	Promote immunity (T cell function)	In a murine melanoma model, a complex of CA9 and gp100 generated a gp100-specific antitumor response. A soluble form of CA9 shed from tumor cells had the same chaperone-like functions, providing renal tumors and hypoxic cells with a mechanism for stimulating an immune response against extracellular antigens. Interleukin-2 treatment of patient renal tumors in short-term culture increased CA9 shedding, suggesting a strategy for augmenting the immunogenicity of renal tumors.
16931630	leukemia	Promote immunity	Specific T-cell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease. In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control.

Summary
Symbol	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
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 CA9 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	Second most enriched score: 0.54	Sensitive to T cell-mediated killing
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	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
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 CA9 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	-0.662	0.177
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.296	0.102
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.198	0.775
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.912	0.0996
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.112	0.473
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.662	0.716
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.377	0.667
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.7	0.608
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.003	0.999
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.105	0.627
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	1.731	0.62
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.636	0.137

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CA9 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	3.7	1.4	2.3	0.469
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	3.7	1.7	2	0.532
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	11.1	-11.1	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	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	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CA9. 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	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CA9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CA9. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CA9. 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	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CA9 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CA9 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CA9
Name	carbonic anhydrase IX
Aliases	CAIX; RCC-associated protein G250; CA-IX; P54/58N; RCC-associated antigen G250; carbonate dehydratase IX; me ......
Chromosomal Location	9p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CA9 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CA9.

ID	Name	Drug Type	Targets	#Targets
DB00562	Benzthiazide	Small Molecule	CA1, CA12, CA2, CA4, CA9, SLC12A3	6
DB00774	Hydroflumethiazide	Small Molecule	ATP1A1, CA1, CA12, CA2, CA4, CA9, KCNMA1, SLC12A1	8
DB00909	Zonisamide	Small Molecule	CA1, CA10, CA11, CA12, CA13, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, ......	31
DB00999	Hydrochlorothiazide	Small Molecule	CA1, CA12, CA2, CA4, CA9, KCNMA1, SLC12A3	7
DB05304	WX-G250	Small Molecule	CA9, IL2	2
DB08846	Ellagic Acid	Small Molecule	CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA9, CSNK2A1 ......	17
DB09460	Sodium carbonate	Small Molecule	CA1, CA2, CA4, CA9	4

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