Seroatlas · Human Serome Atlas

RYR2

Ryanodine receptor 2

Also known as: ARVC2, ARVD2, RYR2_HUMAN, VTSIP

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q92736
Gene
RYR2
Ensembl
ENSG00000198626
Chromosome
1
Canonical length
4967 aa
Protein class
Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Nucleoplasm,Plasma membrane,Cytosol
Quaternary structure
Homotetramer

OverviewNCBI Gene

This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

4967 residues, UniProt reviewed canonical sequence.

>Q92736|RYR2
     1  MADGGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP
    61  DLSICTFVLE QSLSVRALQE MLANTVEKSE GQVDVEKWKF MMKTAQGGGH RTLLYGHAIL
   121  LRHSYSGMYL CCLSTSRSST DKLAFDVGLQ EDTTGEACWW TIHPASKQRS EGEKVRVGDD
   181  LILVSVSSER YLHLSYGNGS LHVDAAFQQT LWSVAPISSG SEAAQGYLIG GDVLRLLHGH
   241  MDECLTVPSG EHGEEQRRTV HYEGGAVSVH ARSLWRLETL RVAWSGSHIR WGQPFRLRHV
   301  TTGKYLSLME DKNLLLMDKE KADVKSTAFT FRSSKEKLDV GVRKEVDGMG TSEIKYGDSV
   361  CYIQHVDTGL WLTYQSVDVK SVRMGSIQRK AIMHHEGHMD DGISLSRSQH EESRTARVIR
   421  STVFLFNRFI RGLDALSKKA KASTVDLPIE SVSLSLQDLI GYFHPPDEHL EHEDKQNRLR
   481  ALKNRQNLFQ EEGMINLVLE CIDRLHVYSS AAHFADVAGR EAGESWKSIL NSLYELLAAL
   541  IRGNRKNCAQ FSGSLDWLIS RLERLEASSG ILEVLHCVLV ESPEALNIIK EGHIKSIISL
   601  LDKHGRNHKV LDVLCSLCVC HGVAVRSNQH LICDNLLPGR DLLLQTRLVN HVSSMRPNIF
   661  LGVSEGSAQY KKWYYELMVD HTEPFVTAEA THLRVGWAST EGYSPYPGGG EEWGGNGVGD
   721  DLFSYGFDGL HLWSGCIART VSSPNQHLLR TDDVISCCLD LSAPSISFRI NGQPVQGMFE
   781  NFNIDGLFFP VVSFSAGIKV RFLLGGRHGE FKFLPPPGYA PCYEAVLPKE KLKVEHSREY
   841  KQERTYTRDL LGPTVSLTQA AFTPIPVDTS QIVLPPHLER IREKLAENIH ELWVMNKIEL
   901  GWQYGPVRDD NKRQHPCLVE FSKLPEQERN YNLQMSLETL KTLLALGCHV GISDEHAEDK
   961  VKKMKLPKNY QLTSGYKPAP MDLSFIKLTP SQEAMVDKLA ENAHNVWARD RIRQGWTYGI
  1021  QQDVKNRRNP RLVPYTLLDD RTKKSNKDSL REAVRTLLGY GYNLEAPDQD HAARAEVCSG
  1081  TGERFRIFRA EKTYAVKAGR WYFEFETVTA GDMRVGWSRP GCQPDQELGS DERAFAFDGF
  1141  KAQRWHQGNE HYGRSWQAGD VVGCMVDMNE HTMMFTLNGE ILLDDSGSEL AFKDFDVGDG
  1201  FIPVCSLGVA QVGRMNFGKD VSTLKYFTIC GLQEGYEPFA VNTNRDITMW LSKRLPQFLQ
  1261  VPSNHEHIEV TRIDGTIDSS PCLKVTQKSF GSQNSNTDIM FYRLSMPIEC AEVFSKTVAG
  1321  GLPGAGLFGP KNDLEDYDAD SDFEVLMKTA HGHLVPDRVD KDKEATKPEF NNHKDYAQEK
  1381  PSRLKQRFLL RRTKPDYSTS HSARLTEDVL ADDRDDYDFL MQTSTYYYSV RIFPGQEPAN
  1441  VWVGWITSDF HQYDTGFDLD RVRTVTVTLG DEKGKVHESI KRSNCYMVCA GESMSPGQGR
  1501  NNNGLEIGCV VDAASGLLTF IANGKELSTY YQVEPSTKLF PAVFAQATSP NVFQFELGRI
  1561  KNVMPLSAGL FKSEHKNPVP QCPPRLHVQF LSHVLWSRMP NQFLKVDVSR ISERQGWLVQ
  1621  CLDPLQFMSL HIPEENRSVD ILELTEQEEL LKFHYHTLRL YSAVCALGNH RVAHALCSHV
  1681  DEPQLLYAIE NKYMPGLLRA GYYDLLIDIH LSSYATARLM MNNEYIVPMT EETKSITLFP
  1741  DENKKHGLPG IGLSTSLRPR MQFSSPSFVS ISNECYQYSP EFPLDILKSK TIQMLTEAVK
  1801  EGSLHARDPV GGTTEFLFVP LIKLFYTLLI MGIFHNEDLK HILQLIEPSV FKEAATPEEE
  1861  SDTLEKELSV DDAKLQGAGE EEAKGGKRPK EGLLQMKLPE PVKLQMCLLL QYLCDCQVRH
  1921  RIEAIVAFSD DFVAKLQDNQ RFRYNEVMQA LNMSAALTAR KTKEFRSPPQ EQINMLLNFK
  1981  DDKSECPCPE EIRDQLLDFH EDLMTHCGIE LDEDGSLDGN SDLTIRGRLL SLVEKVTYLK
  2041  KKQAEKPVES DSKKSSTLQQ LISETMVRWA QESVIEDPEL VRAMFVLLHR QYDGIGGLVR
  2101  ALPKTYTING VSVEDTINLL ASLGQIRSLL SVRMGKEEEK LMIRGLGDIM NNKVFYQHPN
  2161  LMRALGMHET VMEVMVNVLG GGESKEITFP KMVANCCRFL CYFCRISRQN QKAMFDHLSY
  2221  LLENSSVGLA SPAMRGSTPL DVAAASVMDN NELALALREP DLEKVVRYLA GCGLQSCQML
  2281  VSKGYPDIGW NPVEGERYLD FLRFAVFCNG ESVEENANVV VRLLIRRPEC FGPALRGEGG
  2341  NGLLAAMEEA IKIAEDPSRD GPSPNSGSSK TLDTEEEEDD TIHMGNAIMT FYSALIDLLG
  2401  RCAPEMHLIH AGKGEAIRIR SILRSLIPLG DLVGVISIAF QMPTIAKDGN VVEPDMSAGF
  2461  CPDHKAAMVL FLDRVYGIEV QDFLLHLLEV GFLPDLRAAA SLDTAALSAT DMALALNRYL
  2521  CTAVLPLLTR CAPLFAGTEH HASLIDSLLH TVYRLSKGCS LTKAQRDSIE VCLLSICGQL
  2581  RPSMMQHLLR RLVFDVPLLN EHAKMPLKLL TNHYERCWKY YCLPGGWGNF GAASEEELHL
  2641  SRKLFWGIFD ALSQKKYEQE LFKLALPCLS AVAGALPPDY MESNYVSMME KQSSMDSEGN
  2701  FNPQPVDTSN ITIPEKLEYF INKYAEHSHD KWSMDKLANG WIYGEIYSDS SKVQPLMKPY
  2761  KLLSEKEKEI YRWPIKESLK TMLAWGWRIE RTREGDSMAL YNRTRRISQT SQVSVDAAHG
  2821  YSPRAIDMSN VTLSRDLHAM AEMMAENYHN IWAKKKKMEL ESKGGGNHPL LVPYDTLTAK
  2881  EKAKDREKAQ DILKFLQING YAVSRGFKDL ELDTPSIEKR FAYSFLQQLI RYVDEAHQYI
  2941  LEFDGGSRGK GEHFPYEQEI KFFAKVVLPL IDQYFKNHRL YFLSAASRPL CSGGHASNKE
  3001  KEMVTSLFCK LGVLVRHRIS LFGNDATSIV NCLHILGQTL DARTVMKTGL ESVKSALRAF
  3061  LDNAAEDLEK TMENLKQGQF THTRNQPKGV TQIINYTTVA LLPMLSSLFE HIGQHQFGED
  3121  LILEDVQVSC YRILTSLYAL GTSKSIYVER QRSALGECLA AFAGAFPVAF LETHLDKHNI
  3181  YSIYNTKSSR ERAALSLPTN VEDVCPNIPS LEKLMEEIVE LAESGIRYTQ MPHVMEVILP
  3241  MLCSYMSRWW EHGPENNPER AEMCCTALNS EHMNTLLGNI LKIIYNNLGI DEGAWMKRLA
  3301  VFSQPIINKV KPQLLKTHFL PLMEKLKKKA ATVVSEEDHL KAEARGDMSE AELLILDEFT
  3361  TLARDLYAFY PLLIRFVDYN RAKWLKEPNP EAEELFRMVA EVFIYWSKSH NFKREEQNFV
  3421  VQNEINNMSF LITDTKSKMS KAAVSDQERK KMKRKGDRYS MQTSLIVAAL KRLLPIGLNI
  3481  CAPGDQELIA LAKNRFSLKD TEDEVRDIIR SNIHLQGKLE DPAIRWQMAL YKDLPNRTDD
  3541  TSDPEKTVER VLDIANVLFH LEQKSKRVGR RHYCLVEHPQ RSKKAVWHKL LSKQRKRAVV
  3601  ACFRMAPLYN LPRHRAVNLF LQGYEKSWIE TEEHYFEDKL IEDLAKPGAE PPEEDEGTKR
  3661  VDPLHQLILL FSRTALTEKC KLEEDFLYMA YADIMAKSCH DEEDDDGEEE VKSFEEKEME
  3721  KQKLLYQQAR LHDRGAAEMV LQTISASKGE TGPMVAATLK LGIAILNGGN STVQQKMLDY
  3781  LKEKKDVGFF QSLAGLMQSC SVLDLNAFER QNKAEGLGMV TEEGSGEKVL QDDEFTCDLF
  3841  RFLQLLCEGH NSDFQNYLRT QTGNNTTVNI IISTVDYLLR VQESISDFYW YYSGKDVIDE
  3901  QGQRNFSKAI QVAKQVFNTL TEYIQGPCTG NQQSLAHSRL WDAVVGFLHV FAHMQMKLSQ
  3961  DSSQIELLKE LMDLQKDMVV MLLSMLEGNV VNGTIGKQMV DMLVESSNNV EMILKFFDMF
  4021  LKLKDLTSSD TFKEYDPDGK GVISKRDFHK AMESHKHYTQ SETEFLLSCA ETDENETLDY
  4081  EEFVKRFHEP AKDIGFNVAV LLTNLSEHMP NDTRLQTFLE LAESVLNYFQ PFLGRIEIMG
  4141  SAKRIERVYF EISESSRTQW EKPQVKESKR QFIFDVVNEG GEKEKMELFV NFCEDTIFEM
  4201  QLAAQISESD LNERSANKEE SEKERPEEQG PRMAFFSILT VRSALFALRY NILTLMRMLS
  4261  LKSLKKQMKK VKKMTVKDMV TAFFSSYWSI FMTLLHFVAS VFRGFFRIIC SLLLGGSLVE
  4321  GAKKIKVAEL LANMPDPTQD EVRGDGEEGE RKPLEAALPS EDLTDLKELT EESDLLSDIF
  4381  GLDLKREGGQ YKLIPHNPNA GLSDLMSNPV PMPEVQEKFQ EQKAKEEEKE EKEETKSEPE
  4441  KAEGEDGEKE EKAKEDKGKQ KLRQLHTHRY GEPEVPESAF WKKIIAYQQK LLNYFARNFY
  4501  NMRMLALFVA FAINFILLFY KVSTSSVVEG KELPTRSSSE NAKVTSLDSS SHRIIAVHYV
  4561  LEESSGYMEP TLRILAILHT VISFFCIIGY YCLKVPLVIF KREKEVARKL EFDGLYITEQ
  4621  PSEDDIKGQW DRLVINTQSF PNNYWDKFVK RKVMDKYGEF YGRDRISELL GMDKAALDFS
  4681  DAREKKKPKK DSSLSAVLNS IDVKYQMWKL GVVFTDNSFL YLAWYMTMSV LGHYNNFFFA
  4741  AHLLDIAMGF KTLRTILSSV THNGKQLVLT VGLLAVVVYL YTVVAFNFFR KFYNKSEDGD
  4801  TPDMKCDDML TCYMFHMYVG VRAGGGIGDE IEDPAGDEYE IYRIIFDITF FFFVIVILLA
  4861  IIQGLIIDAF GELRDQQEQV KEDMETKCFI CGIGNDYFDT VPHGFETHTL QEHNLANYLF
  4921  FLMYLINKDE TEHTGQESYV WKMYQERCWE FFPAGDCFRK QYEDQLN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RYR2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Other membrane
Secreted
No
Transmembrane segments
6
Mean surface accessibility (rSASA)
0
Highest tissue expression
138 nTPM

Expression across tissuesHPA

Tissue

  • heart muscle: 138 nTPM
  • cerebellum: 17 nTPM
  • blood vessel: 12 nTPM
  • cerebral cortex: 8.6 nTPM
  • basal ganglia: 8.2 nTPM
  • pancreas: 8 nTPM

Single-cell type

  • cardiomyocytes: 30,130 nCPM
  • brain inhibitory neurons: 1,771 nCPM
  • retinal ganglion cells: 1,738 nCPM
  • gonadotrophs: 1,700 nCPM
  • brain excitatory neurons: 1,630 nCPM
  • thyrotrophs: 1,427 nCPM

Immune cell

  • MAIT T-cell: 0.4 nTPM
  • total PBMC: 0.2 nTPM
  • gdT-cell: 0.1 nTPM
  • NK-cell: 0.1 nTPM
  • T-reg: 0.1 nTPM
  • basophil: 0 nTPM

Brain region

  • cerebral cortex: 98 nTPM
  • basal ganglia: 80 nTPM
  • white matter: 75 nTPM
  • hippocampal formation: 68 nTPM
  • cerebellum: 64 nTPM
  • amygdala: 42 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RYR2.

Disease | AllUniProt

Conditions RYR2 is implicated in, by any mechanism.

  • Ventricular tachycardia, catecholaminergic polymorphic, 1, with or without atrial dysfunction and/or dilated cardiomyopathy (CPVT1) MIM:604772
  • Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome (VACRDS) MIM:115000

Disease | GeneticClinVar

255 pathogenic / likely-pathogenic of 9,939 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.25
gnomAD pLI
1
gnomAD missense Z
5.78
DepMap mean gene effect
0.01
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of RYR2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads RYR2 as an antibody target. Whether an autoantibody or antibody against RYR2 could matter depends on whether native RYR2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

RYR2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label RYR2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/RYR2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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