GeneBe

RYR3

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

Basic information

Region (hg38): 15:33310962-33866121

Links

ENSG00000198838 ∙ NCBI:6263 ∙ OMIM:180903 ∙ HGNC:10485 ∙ Uniprot:Q15413 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

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 (1307 variants)
  • not_specified (571 variants)
  • not_provided (205 variants)
  • RYR3-related_disorder (68 variants)
  • Congenital_myopathy_20 (22 variants)
  • RYR3-related_Epileptic_encephalopathy (11 variants)
  • Inborn_genetic_diseases (7 variants)
  • See_cases (7 variants)
  • Flexion_contracture (4 variants)
  • Premature_ovarian_failure (3 variants)
  • Arthrogryposis_multiplex_congenita (2 variants)
  • Hydrops_fetalis (1 variants)
  • Monomelic_amyotrophy (1 variants)
  • Fetal_akinesia_deformation_sequence_1 (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. These statistics are base on transcript: NM_000001036.6. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
11
clinvar
401
clinvar
31
clinvar
 443
missense
1
clinvar
2
clinvar
1049
clinvar
84
clinvar
15
clinvar
 1151
nonsense
8
clinvar
 8
start loss
0
frameshift
5
clinvar
 5
splice donor/acceptor (+/-2bp)
5
clinvar
1
clinvar
 6
Total 1 2 1078 486 46

Highest pathogenic variant AF is 0.00007899858

Loading clinvar variants...

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