TISIDB

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
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	Sarcoplasmic reticulum membrane Multi-pass membrane protein Sarcoplasmic reticulum Note=The number of predicted transmembrane domains varies between orthologs, but the 3D-structures show the presence of six transmembrane regions. Both N-terminus and C-terminus are cytoplasmic.
Domain	PF13833 EF-hand domain pair PF08709 Inositol 1 PF00520 Ion transport protein PF02815 MIR domain PF08454 RyR and IP3R Homology associated PF06459 Ryanodine Receptor TM 4-6 PF01365 RIH domain PF02026 RyR domain PF00622 SPRY domain
Function	Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001501 skeletal system development GO:0001503 ossification GO:0001666 response to hypoxia GO:0003007 heart morphogenesis GO:0003012 muscle system process GO:0003013 circulatory system process GO:0003015 heart process GO:0003151 outflow tract morphogenesis GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006936 muscle contraction GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007507 heart development GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0008015 blood circulation GO:0008016 regulation of heart contraction GO:0014074 response to purine-containing compound GO:0014706 striated muscle tissue development GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum GO:0014902 myotube differentiation GO:0014904 myotube cell development GO:0021700 developmental maturation GO:0031000 response to caffeine GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0035637 multicellular organismal signaling GO:0036293 response to decreased oxygen levels GO:0042692 muscle cell differentiation GO:0043279 response to alkaloid GO:0043588 skin development GO:0043931 ossification involved in bone maturation GO:0044057 regulation of system process GO:0048741 skeletal muscle fiber development GO:0048747 muscle fiber development GO:0048799 animal organ maturation GO:0051146 striated muscle cell differentiation GO:0051208 sequestering of calcium ion GO:0051209 release of sequestered calcium ion into cytosol GO:0051235 maintenance of location GO:0051238 sequestering of metal ion GO:0051282 regulation of sequestering of calcium ion GO:0051283 negative regulation of sequestering of calcium ion GO:0051480 regulation of cytosolic calcium ion concentration GO:0055001 muscle cell development GO:0055002 striated muscle cell development GO:0055074 calcium ion homeostasis GO:0060047 heart contraction GO:0060348 bone development GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0061337 cardiac conduction GO:0070296 sarcoplasmic reticulum calcium ion transport GO:0070482 response to oxygen levels GO:0070509 calcium ion import GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0070977 bone maturation GO:0071312 cellular response to alkaloid GO:0071313 cellular response to caffeine GO:0071407 cellular response to organic cyclic compound GO:0071415 cellular response to purine-containing compound GO:0071417 cellular response to organonitrogen compound GO:0071695 anatomical structure maturation GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0097553 calcium ion transmembrane import into cytosol GO:1902656 calcium ion import into cytosol GO:1903514 calcium ion transport from endoplasmic reticulum to cytosol GO:1903522 regulation of blood circulation GO:1903779 regulation of cardiac conduction GO:2000021 regulation of ion homeostasis
Molecular Function	GO:0002020 protease binding GO:0005216 ion channel activity GO:0005217 intracellular ligand-gated ion channel activity GO:0005219 ryanodine-sensitive calcium-release channel activity GO:0005244 voltage-gated ion channel activity GO:0005245 voltage-gated calcium channel activity GO:0005261 cation channel activity GO:0005262 calcium channel activity GO:0005516 calmodulin binding GO:0015085 calcium ion transmembrane transporter activity GO:0015267 channel activity GO:0015276 ligand-gated ion channel activity GO:0015278 calcium-release channel activity GO:0022803 passive transmembrane transporter activity GO:0022832 voltage-gated channel activity GO:0022834 ligand-gated channel activity GO:0022836 gated channel activity GO:0022838 substrate-specific channel activity GO:0022843 voltage-gated cation channel activity GO:0046873 metal ion transmembrane transporter activity GO:0048763 calcium-induced calcium release activity GO:0072509 divalent inorganic cation transmembrane transporter activity GO:0099604 ligand-gated calcium channel activity
Cellular Component	GO:0005790 smooth endoplasmic reticulum GO:0005938 cell cortex GO:0014701 junctional sarcoplasmic reticulum membrane GO:0014802 terminal cisterna GO:0016528 sarcoplasm GO:0016529 sarcoplasmic reticulum GO:0030016 myofibril GO:0030017 sarcomere GO:0030018 Z disc GO:0030314 junctional membrane complex GO:0030315 T-tubule GO:0031674 I band GO:0031984 organelle subcompartment GO:0033017 sarcoplasmic reticulum membrane GO:0034702 ion channel complex GO:0034703 cation channel complex GO:0034704 calcium channel complex GO:0042383 sarcolemma GO:0043292 contractile fiber GO:0044449 contractile fiber part GO:0098827 endoplasmic reticulum subcompartment GO:0099568 cytoplasmic region GO:1902495 transmembrane transporter complex GO:1990351 transporter complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04020 Calcium signaling pathway hsa04713 Circadian entrainment hsa04730 Long-term depression hsa04921 Oxytocin signaling pathway
Reactome	R-HSA-5576891: Cardiac conduction R-HSA-983712: Ion channel transport R-HSA-5578775: Ion homeostasis R-HSA-397014: Muscle contraction R-HSA-2672351: Stimuli-sensing channels R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RYR1 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 [ TOP ]
There is no record.

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
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 RYR1 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	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
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 RYR1 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	-0.149	0.69
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.79	0.199
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.318	0.548
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.185	0.625
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.029	0.989
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.453	0.859
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.349	0.491
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.86	0.41
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.622	0.124
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.268	0.794
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	0.703	0.598
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.049	0.778

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RYR1 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	35.7	0	35.7	0.0118
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	50	0	50	0.0392
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	25.9	16.4	9.5	0.389
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	14.3	-14.3	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	25.9	16.9	9	0.386
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	33.3	11.8	21.5	0.148
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	46.2	18.2	28	0.211
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	33.3	18.8	14.5	0.63
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	22.2	-2.2	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	14.3	35.7	0.491
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	23.7	7.4	16.3	0.105
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	31.8	7.7	24.1	0.21
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	12.5	7.1	5.4	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	7.7	1.4	1
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	8.3	-8.3	1

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RYR1. 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	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RYR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RYR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RYR1. 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	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RYR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RYR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RYR1
Name	ryanodine receptor 1 (skeletal)
Aliases	PPP1R137; protein phosphatase 1, regulatory subunit 137; MHS; MHS1; CCO; central core disease of muscle; RYD ......
Chromosomal Location	19q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RYR1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting RYR1.

ID	Name	Drug Type	Targets	#Targets
DB00201	Caffeine	Small Molecule	ADORA1, ADORA2A, ATM, ITPR1, ITPR2, ITPR3, PDE10A, PDE11A, PDE1A, ......	33
DB01219	Dantrolene	Small Molecule	RYR1	1
DB04786	Suramin	Small Molecule	F2, FSHR, P2RY2, PLA2G2A, RYR1, SIRT5	6
DB09085	Tetracaine	Small Molecule	RYR1, RYR2	2

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