SRI
protein-codingsorcin, the group of EF-hand domain containing
Gene summary
This gene encodes a calcium-binding protein with multiple E-F hand domains that relocates from the cytoplasm to the sarcoplasmic reticulum in response to elevated calcium levels. In addition to regulating intracellular calcium homeostasis it also modulates excitation-contraction coupling in the heart. Alternative splicing results in multiple transcript variants encoding distinct proteins. Multiple pseudogenes exist for this gene. [provided by RefSeq, Mar 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005045
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SRI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003130.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 31 | 31 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 10 | 11 | |||
| Total | 1 | 0 | 42 | 0 | 0 | 43 |
Highest pathogenic variant AF is 6.8445615e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003121.1 | 8 | MANE Select | |
| Ensembl | ENSP00000265729.3 | 8 | MANE Select | |
| RefSeq | NP_001243820.1 | 7 | Standard | |
| RefSeq | NP_001243821.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Stimuli-sensing channels
- Ion channel transport
- Ion homeostasis
- Sodium/Calcium exchangers
- Transport of inorganic cations/anions and amino acids/oligopeptides
Biological Process
- action potential
- calcium ion transport
- intracellular sequestering of iron ion
- regulation of striated muscle contraction
- signal transduction
Molecular Function
- protease binding
- signaling receptor binding
- calcium channel regulator activity
- calcium ion binding
- protein binding
Cellular Component
- nucleoplasm
- cytoplasm
- mitochondrion
- endoplasmic reticulum membrane
- smooth endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265729
- Coding exons
- 8
- Length
- 21876
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 37
- Defined
- 125748
- p
- 0.000147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0104 | 110 | 110 | 0.997 | 0.00000568 | 1286 |
| Missense (PolyPhen) | 37 | 36.605 | 1.0108 | 433 | ||
| Synonymous | 0.652 | 35 | 40.3 | 0.869 | 0.00000211 | 375 |
| Loss of Function | 0.179 | 15 | 15.8 | 0.951 | 9.36e-7 | 155 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00043 | 0.00044 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-binding protein that modulates excitation- contraction coupling in the heart. Contributes to calcium homeostasis in the heart sarcoplasmic reticulum. Modulates the activity of RYR2 calcium channels. {ECO:0000269|PubMed:17699613}.;
Recessive Scores
- pRec
- 0.158
Intolerance Scores
- LoFtool
- 0.644
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.551
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |