TISIDB

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
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	Cell membrane Single-pass type I membrane protein
Domain	PF02038 ATP1G1/PLM/MAT8 family
Function	Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell (PubMed:17077088). Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1 (PubMed:21454534). Induces a hyperpolarization-activated chloride current when expressed in Xenopus oocytes (PubMed:7836447). ; FUNCTION: Isoform 1: Decreases the apparent K+ and Na+ affinity of the sodium/potassium-transporting ATPase over a large range of membrane potentials. ; FUNCTION: Isoform 2: Decreases the apparent K+ affinity of the sodium/potassium-transporting ATPase only at slightly negative and positive membrane potentials and increases the apparent Na+ affinity over a large range of membrane potentials.

> Gene Ontology [ TOP ]
Biological Process	GO:0002028 regulation of sodium ion transport GO:0003013 circulatory system process GO:0003015 heart process GO:0006814 sodium ion transport GO:0006820 anion transport GO:0006821 chloride transport GO:0008015 blood circulation GO:0008016 regulation of heart contraction GO:0010959 regulation of metal ion transport GO:0015672 monovalent inorganic cation transport GO:0015698 inorganic anion transport GO:0022898 regulation of transmembrane transporter activity GO:0032409 regulation of transporter activity GO:0032412 regulation of ion transmembrane transporter activity GO:0034762 regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0035637 multicellular organismal signaling GO:0035725 sodium ion transmembrane transport GO:0044057 regulation of system process GO:0060047 heart contraction GO:0061337 cardiac conduction GO:0098656 anion transmembrane transport GO:0098661 inorganic anion transmembrane transport GO:1902305 regulation of sodium ion transmembrane transport GO:1902476 chloride transmembrane transport GO:1903522 regulation of blood circulation GO:1903779 regulation of cardiac conduction GO:1904062 regulation of cation transmembrane transport GO:2000649 regulation of sodium ion transmembrane transporter activity
Molecular Function	GO:0005216 ion channel activity GO:0005253 anion channel activity GO:0005254 chloride channel activity GO:0008509 anion transmembrane transporter activity GO:0015103 inorganic anion transmembrane transporter activity GO:0015108 chloride transmembrane transporter activity GO:0015267 channel activity GO:0016247 channel regulator activity GO:0017080 sodium channel regulator activity GO:0022803 passive transmembrane transporter activity GO:0022838 substrate-specific channel activity GO:0051117 ATPase binding
Cellular Component	GO:0034702 ion channel complex GO:0034707 chloride channel complex GO:1902495 transmembrane transporter complex GO:1990351 transporter complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5576891: Cardiac conduction R-HSA-983712: Ion channel transport R-HSA-5578775: Ion homeostasis R-HSA-936837: Ion transport by P-type ATPases R-HSA-397014: Muscle contraction R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FXYD3 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 FXYD3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29686080	Prostate Carcinoma	Promote immunity	FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively.

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
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 FXYD3 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	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
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 FXYD3 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	2.459	0.0206
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	2.029	0.466
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	2.803	0.119
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.203	0.0676
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.774	0.382
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.47	0.832
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.196	0.863
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.244	0.896
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.367	0.829
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	-0.571	0.802
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.084	0.734

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of FXYD3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	7.4	0.0709
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	7.4	0.096
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FXYD3. 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	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FXYD3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FXYD3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FXYD3. 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	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FXYD3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FXYD3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FXYD3
Name	FXYD domain containing ion transport regulator 3
Aliases	MAT-8; PLML; FXYD domain-containing ion transport regulator 3; MAT8; chloride conductance inducer protein Ma ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FXYD3 collected from DrugBank database.

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

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