RYR3
ryanodine receptor 3, the group of Ryanodine receptors|EF-hand domain containing
Basic information
Region (hg38): 15:33310961-33866121
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy (Limited), mode of inheritance: AD
- congenital myopathy (No Known Disease Relationship), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- Epileptic encephalopathy (1335 variants)
- not provided (156 variants)
- Inborn genetic diseases (137 variants)
- RYR3-related Epileptic encephalopathy (7 variants)
- See cases (7 variants)
- Seizure (6 variants)
- Flexion contracture (4 variants)
- Premature ovarian failure (3 variants)
- not specified (2 variants)
- Arthrogryposis multiplex congenita (1 variants)
- Hydrops fetalis (1 variants)
- Arthrogryposis multiplex congenita;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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | 354 | 51 | 417 | ||
| missense | 1 | 731 | 72 | 25 | 829 | |
| nonsense | 7 | 7 | ||||
| start loss | 0 | |||||
| frameshift | 7 | 7 | ||||
| inframe indel | 6 | 1 | 7 | |||
| splice variant | 45 | 65 | 27 | 137 | ||
| non coding | 2 | 32 | 25 | 59 | ||
| Total | 1 | 0 | 810 | 523 | 129 |
Variants in RYR3
This is a list of pathogenic ClinVar variants found in the RYR3 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 15-33311056-G-C | Epileptic encephalopathy | Likely benign (Jul 11, 2022) | ||
| 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 • Inborn genetic diseases | Conflicting interpretations of pathogenicity (Apr 14, 2022) | ||
| 15-33311075-C-A | Epileptic encephalopathy | Uncertain significance (Aug 27, 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 | Benign (Oct 13, 2022) | ||
| 15-33473424-T-C | Epileptic encephalopathy | Likely benign (Jul 11, 2022) | ||
| 15-33473445-C-A | Epileptic encephalopathy | Benign (Aug 23, 2022) | ||
| 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 (Aug 28, 2021) | ||
| 15-33473487-C-T | Epileptic encephalopathy | Likely benign (Mar 28, 2019) | ||
| 15-33473503-C-T | Inborn genetic diseases | Uncertain significance (Feb 16, 2023) | ||
| 15-33473504-G-A | Epileptic encephalopathy | Uncertain significance (Sep 01, 2021) | ||
| 15-33473514-C-T | Epileptic encephalopathy | Likely benign (Feb 03, 2022) | ||
| 15-33473527-T-G | Epileptic encephalopathy | Uncertain significance (Aug 27, 2021) | ||
| 15-33473528-C-T | Epileptic encephalopathy | Uncertain significance (Sep 01, 2021) | ||
| 15-33503637-C-G | Epileptic encephalopathy | Uncertain significance (Aug 27, 2021) | ||
| 15-33503650-G-A | Epileptic encephalopathy | Uncertain significance (Aug 30, 2021) | ||
| 15-33503651-C-T | Epileptic encephalopathy | Likely benign (Jul 19, 2022) | ||
| 15-33503652-G-A | Epileptic encephalopathy • Inborn genetic diseases | Uncertain significance (Aug 24, 2021) | ||
| 15-33503681-A-G | Epileptic encephalopathy | Likely benign (Oct 07, 2020) |
GnomAD
Source:
| 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:
- 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