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GeneBe

RYR3

ryanodine receptor 3, the group of Ryanodine receptors|EF-hand domain containing

Basic information

Region (hg38): 15:33310961-33866121

Links

ENSG00000198838NCBI:6263OMIM:180903HGNC:10485Uniprot:Q15413AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • developmental and epileptic encephalopathy (Limited), mode of inheritance: AD
  • congenital myopathy (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Congenital myopathy 20ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic29498452; 31230720

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RYR3 gene.

  • Epileptic encephalopathy (1338 variants)
  • Inborn genetic diseases (205 variants)
  • not provided (122 variants)
  • not specified (8 variants)
  • Congenital myopathy 20 (8 variants)
  • RYR3-related Epileptic encephalopathy (7 variants)
  • See cases (7 variants)
  • RYR3-related condition (6 variants)
  • Seizure (4 variants)
  • Flexion contracture (3 variants)
  • Premature ovarian failure (3 variants)
  • Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
  • Monomelic amyotrophy (1 variants)
  • Arthrogryposis multiplex congenita (1 variants)
  • Hydrops fetalis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RYR3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
12
clinvar
369
clinvar
42
clinvar
423
missense
1
clinvar
778
clinvar
47
clinvar
23
clinvar
849
nonsense
7
clinvar
7
start loss
0
frameshift
5
clinvar
5
inframe indel
7
clinvar
1
clinvar
8
splice donor/acceptor (+/-2bp)
5
clinvar
1
clinvar
6
splice region
42
65
23
130
non coding
3
clinvar
33
clinvar
28
clinvar
64
Total 1 0 817 450 94

Variants in RYR3

This is a list of pathogenic ClinVar variants found in the RYR3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
15-33311056-G-C Epileptic encephalopathy • Congenital myopathy 20 Conflicting classifications of pathogenicity (Jul 11, 2022)857441
15-33311058-G-A Epileptic encephalopathy Uncertain significance (Jun 13, 2022)531023
15-33311059-G-A Epileptic encephalopathy Uncertain significance (Jul 25, 2022)1006560
15-33311060-A-G Likely benign (Jan 02, 2018)747459
15-33311062-A-G Epileptic encephalopathy • Inborn genetic diseases Conflicting classifications of pathogenicity (Apr 14, 2022)531143
15-33311075-C-A Epileptic encephalopathy Uncertain significance (Jun 16, 2021)646212
15-33311091-A-C Epileptic encephalopathy Likely benign (Jul 15, 2018)763006
15-33311105-C-T Epileptic encephalopathy Likely benign (Jul 15, 2018)763007
15-33473408-TCTC-T Epileptic encephalopathy • RYR3-related condition Benign (Dec 11, 2023)461924
15-33473424-T-C Epileptic encephalopathy Likely benign (Jul 11, 2022)1150256
15-33473445-C-A Epileptic encephalopathy Benign (Sep 07, 2023)461962
15-33473445-C-T Epileptic encephalopathy Likely benign (Feb 05, 2022)1152243
15-33473446-G-A Epileptic encephalopathy Uncertain significance (Aug 09, 2022)1052415
15-33473447-C-A Epileptic encephalopathy Uncertain significance (Apr 20, 2020)962923
15-33473487-C-T Epileptic encephalopathy Likely benign (Mar 28, 2019)730338
15-33473503-C-T Inborn genetic diseases Uncertain significance (Feb 16, 2023)2457360
15-33473504-G-A Epileptic encephalopathy Uncertain significance (Nov 03, 2020)1395319
15-33473514-C-T Epileptic encephalopathy Likely benign (Feb 03, 2022)461880
15-33473527-T-G Epileptic encephalopathy Uncertain significance (Mar 18, 2020)566963
15-33473528-C-T Epileptic encephalopathy • Congenital myopathy 20 Uncertain significance (Nov 29, 2023)1053470
15-33503637-C-G Epileptic encephalopathy Uncertain significance (May 06, 2020)1062277
15-33503650-G-A Epileptic encephalopathy Uncertain significance (Feb 05, 2020)864076
15-33503651-C-T Epileptic encephalopathy Likely benign (Jul 19, 2022)1101119
15-33503652-G-A Epileptic encephalopathy • Inborn genetic diseases Uncertain significance (Aug 12, 2021)1002099
15-33503681-A-G Epileptic encephalopathy Likely benign (Oct 07, 2020)1126551

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RYR3protein_codingprotein_codingENST00000389232 104555141
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.7060.29412516001971253570.000786
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.8424012.67e+30.9000.00015532045
Missense in Polyphen7791055.60.73812703
Synonymous-1.9911111.03e+31.080.00006249143
Loss of Function11.4562510.2230.00001283066

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007000.000692
Ashkenazi Jewish0.0004990.000496
East Asian0.004320.00419
Finnish0.0002350.000231
European (Non-Finnish)0.0004730.000458
Middle Eastern0.004320.00419
South Asian0.001250.00124
Other0.0001660.000164

dbNSFP

Source: dbNSFP

Function
FUNCTION: Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction. May regulate Ca(2+) release by other calcium channels. Calcium channel that mediates Ca(2+)-induced Ca(2+) release from the endoplasmic reticulum in non-muscle cells. Contributes to cellular calcium ion homeostasis (By similarity). Plays a role in cellular calcium signaling. {ECO:0000250, ECO:0000269|PubMed:12354756}.;
Pathway
Oxytocin signaling pathway - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Alzheimers Disease;Myometrial Relaxation and Contraction Pathways;MFAP5-mediated ovarian cancer cell motility and invasiveness;Cell-type Dependent Selectivity of CCK2R Signaling;Calcium Regulation in the Cardiac Cell;Stimuli-sensing channels;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

pRec
0.170

Intolerance Scores

loftool
0.0351
rvis_EVS
-5.87
rvis_percentile_EVS
0.06

Haploinsufficiency Scores

pHI
0.325
hipred
N
hipred_score
0.463
ghis
0.549

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.746

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Ryr3
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype;

Zebrafish Information Network

Gene name
ryr3
Affected structure
slow muscle cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
calcium ion transport;ion transmembrane transport;release of sequestered calcium ion into cytosol;protein homotetramerization;negative regulation of cytosolic calcium ion concentration;calcium ion transmembrane transport;cellular response to calcium ion;cellular response to magnesium ion;cellular response to caffeine;cellular response to ATP;regulation of cardiac conduction
Cellular component
smooth endoplasmic reticulum;plasma membrane;integral component of membrane;sarcoplasmic reticulum;Z disc;cytoplasmic vesicle membrane;sarcoplasmic reticulum membrane;calcium channel complex;sarcolemma;perinuclear region of cytoplasm
Molecular function
ryanodine-sensitive calcium-release channel activity;calcium ion binding;calmodulin binding;calcium-release channel activity;calcium-induced calcium release activity