RYR3
Basic information
Region (hg38): 15:33310962-33866121
Links
Phenotypes
GenCC
Source:
- 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:
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 (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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 11 | 401 | 31 | 443 | ||
missense | 1049 | 84 | 15 | 1151 | ||
nonsense | 8 | |||||
start loss | 0 | |||||
frameshift | 5 | |||||
splice donor/acceptor (+/-2bp) | 6 | |||||
Total | 1 | 2 | 1078 | 486 | 46 |
Highest pathogenic variant AF is 0.00007899858
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