RYR3

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

Basic information

Region (hg38): 15:33310961-33866121

Links

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

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 20	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	29498452; 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	369	42	423
missense	1		778	47	23	849
nonsense			7			7
start loss						0
frameshift			5			5
inframe indel			7		1	8
splice donor/acceptor (+/-2bp)			5	1		6
splice region			42	65	23	130
non coding			3	33	28	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 • not specified • Congenital myopathy 20	Conflicting classifications of pathogenicity (Jan 24, 2024)
15-33311058-G-A		Epileptic encephalopathy	Uncertain significance (Jun 13, 2022)
15-33311059-G-A		Epileptic encephalopathy	Uncertain significance (Jul 25, 2022)
15-33311060-A-G			Likely benign (Jan 02, 2018)
15-33311062-A-G		Epileptic encephalopathy • not specified	Conflicting classifications of pathogenicity (Apr 14, 2022)
15-33311068-G-A		not specified	Uncertain significance (Jan 02, 2024)
15-33311075-C-A		Epileptic encephalopathy	Uncertain significance (Jun 16, 2021)
15-33311091-A-C		Epileptic encephalopathy	Likely benign (Jul 15, 2018)
15-33311105-C-T		Epileptic encephalopathy	Likely benign (Jul 15, 2018)
15-33473408-TCTC-T		Epileptic encephalopathy • RYR3-related disorder	Benign (Dec 11, 2023)
15-33473424-T-C		Epileptic encephalopathy	Likely benign (Jul 11, 2022)
15-33473445-C-A		Epileptic encephalopathy	Benign (Sep 07, 2023)
15-33473445-C-T		Epileptic encephalopathy	Likely benign (Feb 05, 2022)
15-33473446-G-A		Epileptic encephalopathy	Uncertain significance (Aug 09, 2022)
15-33473447-C-A		Epileptic encephalopathy	Uncertain significance (Apr 20, 2020)
15-33473487-C-T		Epileptic encephalopathy	Likely benign (Mar 28, 2019)
15-33473503-C-T		not specified	Uncertain significance (Feb 16, 2023)
15-33473504-G-A		Epileptic encephalopathy • not specified	Uncertain significance (Feb 02, 2024)
15-33473514-C-T		Epileptic encephalopathy	Likely benign (Feb 03, 2022)
15-33473527-T-G		Epileptic encephalopathy	Uncertain significance (Mar 18, 2020)
15-33473528-C-T		Epileptic encephalopathy • Congenital myopathy 20	Uncertain significance (Nov 29, 2023)
15-33503637-C-G		Epileptic encephalopathy	Uncertain significance (May 06, 2020)
15-33503650-G-A		Epileptic encephalopathy	Uncertain significance (Feb 05, 2020)
15-33503651-C-T		Epileptic encephalopathy	Likely benign (Jul 19, 2022)
15-33503652-G-A		Epileptic encephalopathy • not specified	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RYR3	protein_coding	protein_coding	ENST00000389232	104	555141

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.706	0.294	125160	0	197	125357	0.000786

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	2401	2.67e+3	0.900	0.000155	32045
Missense in Polyphen		779	1055.6	0.738		12703
Synonymous	-1.99	1111	1.03e+3	1.08	0.0000624	9143
Loss of Function	11.4	56	251	0.223	0.0000128	3066

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000700	0.000692
Ashkenazi Jewish	0.000499	0.000496
East Asian	0.00432	0.00419
Finnish	0.000235	0.000231
European (Non-Finnish)	0.000473	0.000458
Middle Eastern	0.00432	0.00419
South Asian	0.00125	0.00124
Other	0.000166	0.000164

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

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

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