STIM1
stromal interaction molecule 1, the group of MicroRNA protein coding host genes|Sterile alpha motif domain containing
Basic information
Region (hg38): 11:3854527-4093210
Links
Phenotypes
GenCC
Source:
- myopathy, tubular aggregate, 1 (Limited), mode of inheritance: AD
- Stormorken syndrome (Supportive), mode of inheritance: AD
- tubular aggregate myopathy (Supportive), mode of inheritance: AD
- combined immunodeficiency due to STIM1 deficiency (Supportive), mode of inheritance: AR
- combined immunodeficiency due to STIM1 deficiency (Strong), mode of inheritance: AR
- myopathy, tubular aggregate, 1 (Strong), mode of inheritance: AD
- combined immunodeficiency due to STIM1 deficiency (Moderate), mode of inheritance: AR
- myopathy, tubular aggregate, 1 (Definitive), mode of inheritance: AD
- tubular aggregate myopathy (Definitive), mode of inheritance: AD
- Stormorken syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Stormorken syndrome; Immunodeficiency 10 | AD/AR | Allergy/Immunology/Infectious; Cardiovascular; Hematologic | In Stormorken syndrome, individuals may demonstrate hematologic anomalies including anemia, thrombocytopenia, and bleeding diathesis, and awareness may allow preventive measures and prompt treatment; Individuals have been described with cardiovascular anomalies (eg, intracranial aneurysms), and awareness may allow surveillance and early management; In Immunodeficiency 10, individuals may suffer early and severe (including fatal) infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic abnormalities, including autoimmune hemolytic anemia and thrombocytopenia, which have been reported as steroid-responsive; HSCT has been reported | Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 19420366; 20876309; 22190180; 23332920; 24570283; 24591628; 24619930; 25577287 |
ClinVar
This is a list of variants' phenotypes submitted to
- Combined_immunodeficiency_due_to_STIM1_deficiency (708 variants)
- Stormorken_syndrome (702 variants)
- Myopathy_with_tubular_aggregates (697 variants)
- not_provided (134 variants)
- Inborn_genetic_diseases (66 variants)
- Myopathy,_tubular_aggregate,_1 (35 variants)
- not_specified (31 variants)
- STIM1-related_disorder (30 variants)
- Immunodeficiency,_common_variable,_10 (1 variants)
- Migraine (1 variants)
- Myopathy,_autophagic_vacuolar,_infantile-onset (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the STIM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001382567.1. 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 | 173 | 182 | ||||
| missense | 10 | 394 | 11 | 429 | ||
| nonsense | 6 | |||||
| start loss | 0 | |||||
| frameshift | 9 | |||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| Total | 21 | 16 | 403 | 185 | 10 |
Highest pathogenic variant AF is 0.0000954034
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| STIM1 | protein_coding | protein_coding | ENST00000300737 | 12 | 238683 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.775 | 0.225 | 125739 | 0 | 9 | 125748 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.12 | 279 | 398 | 0.701 | 0.0000235 | 4532 |
| Missense in Polyphen | 69 | 119.06 | 0.57954 | 1386 | ||
| Synonymous | -0.363 | 158 | 152 | 1.04 | 0.00000831 | 1319 |
| Loss of Function | 4.19 | 6 | 31.3 | 0.192 | 0.00000173 | 351 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000904 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000355 | 0.0000352 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000689 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19249086, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:26322679, PubMed:25326555, PubMed:28219928). Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit ORAI1 (PubMed:16208375, PubMed:16537481). Involved in enamel formation (PubMed:24621671). Activated following interaction with STIMATE, leading to promote STIM1 conformational switch (PubMed:26322679). {ECO:0000269|PubMed:15866891, ECO:0000269|PubMed:16005298, ECO:0000269|PubMed:16208375, ECO:0000269|PubMed:16537481, ECO:0000269|PubMed:16733527, ECO:0000269|PubMed:16766533, ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:18854159, ECO:0000269|PubMed:19249086, ECO:0000269|PubMed:22464749, ECO:0000269|PubMed:24069340, ECO:0000269|PubMed:24351972, ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:24621671, ECO:0000269|PubMed:25326555, ECO:0000269|PubMed:26322679, ECO:0000269|PubMed:28219928}.;
- Disease
- DISEASE: Immunodeficiency 10 (IMD10) [MIM:612783]: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition. {ECO:0000269|PubMed:19420366, ECO:0000269|PubMed:22190180}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, tubular aggregate, 1 (TAM1) [MIM:160565]: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness. {ECO:0000269|PubMed:23332920, ECO:0000269|PubMed:24570283, ECO:0000269|PubMed:25326555, ECO:0000269|PubMed:25953320}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stormorken syndrome (STRMK) [MIM:185070]: A rare autosomal dominant disease characterized by mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis. {ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:24619930, ECO:0000269|PubMed:25577287}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Platelet activation - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signaling by the B Cell Receptor (BCR);Immune System;Adaptive Immune System;Ion homeostasis;Cardiac conduction;Muscle contraction;Hemostasis;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;Platelet homeostasis;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells
(Consensus)
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- loftool
- 0.269
- rvis_EVS
- -0.22
- rvis_percentile_EVS
- 37.54
Haploinsufficiency Scores
- pHI
- 0.245
- hipred
- Y
- hipred_score
- 0.662
- ghis
- 0.496
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.810
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Stim1
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; vision/eye 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); skeleton phenotype; immune system phenotype; respiratory system phenotype;
Gene ontology
- Biological process
- store-operated calcium entry;detection of calcium ion;cellular calcium ion homeostasis;activation of store-operated calcium channel activity;positive regulation of adenylate cyclase activity;positive regulation of angiogenesis;regulation of calcium ion transport;enamel mineralization;regulation of cardiac conduction;regulation of store-operated calcium entry
- Cellular component
- endoplasmic reticulum;endoplasmic reticulum membrane;microtubule;plasma membrane;integral component of plasma membrane;integral component of endoplasmic reticulum membrane;cortical endoplasmic reticulum;sarcoplasmic reticulum membrane;plasma membrane raft
- Molecular function
- protease binding;calcium channel regulator activity;calcium ion binding;protein binding;identical protein binding;microtubule plus-end binding