STING1
stimulator of interferon response cGAMP interactor 1
Basic information
Region (hg38): 5:139475533-139482935
Previous symbols: [ "TMEM173" ]
Links
Phenotypes
GenCC
Source:
- STING-associated vasculopathy with onset in infancy (Strong), mode of inheritance: AD
- STING-associated vasculopathy with onset in infancy (Supportive), mode of inheritance: AD
- familial chilblain lupus (Supportive), mode of inheritance: AD
- STING-associated vasculopathy with onset in infancy (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| STING-associated vasculopathy, infantile-onsent (SAVI) | AD | 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 | Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Hematologic; Pulmonary | 25029335; 25401470 |
ClinVar
This is a list of variants' phenotypes submitted to
- STING-associated_vasculopathy_with_onset_in_infancy (318 variants)
- Inborn_genetic_diseases (48 variants)
- Autoinflammatory_syndrome (41 variants)
- not_provided (28 variants)
- STING1-related_disorder (7 variants)
- not_specified (5 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the STING1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198282.4. 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 | 69 | 79 | ||||
| missense | 161 | 21 | 194 | |||
| nonsense | 4 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 11 | 11 | ||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| Total | 5 | 5 | 188 | 90 | 6 |
Highest pathogenic variant AF is 0.000006814969
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| STING1 | protein_coding | protein_coding | ENST00000330794 | 6 | 7402 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00121 | 0.961 | 125729 | 0 | 17 | 125746 | 0.0000676 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.64 | 160 | 230 | 0.695 | 0.0000139 | 2408 |
| Missense in Polyphen | 44 | 78.254 | 0.56227 | 896 | ||
| Synonymous | 0.00177 | 100 | 100 | 1.00 | 0.00000552 | 827 |
| Loss of Function | 1.83 | 7 | 14.6 | 0.481 | 6.84e-7 | 161 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000551 | 0.000550 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000444 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double- stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway. Essential for the induction of IFN-beta in response to human herpes simplex virus 1 (HHV-1) infection. Exhibits 2',3' phosphodiester linkage-specific ligand recognition. Can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:26300263). {ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21074459, ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:26669264}.;
- Disease
- DISEASE: STING-associated vasculopathy, infantile-onset (SAVI) [MIM:615934]: An autoinflammatory disease characterized by early- onset systemic inflammation and cutaneous vasculopathy, resulting in severe skin lesions. Violaceous, scaling lesions of fingers, toes, nose, cheeks and ears progress to acral necrosis in most of the patients. Some patients have severe interstitial lung disease. {ECO:0000269|PubMed:25029335}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cytosolic DNA-sensing pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);RIG-I-like Receptor Signaling;Neutrophil degranulation;STING mediated induction of host immune responses;Regulation of innate immune responses to cytosolic DNA;STAT6-mediated induction of chemokines;Innate Immune System;Immune System;IRF3-mediated induction of type I IFN;Cytosolic sensors of pathogen-associated DNA
(Consensus)
Recessive Scores
- pRec
- 0.0932
Intolerance Scores
- loftool
- 0.605
- rvis_EVS
- 1.15
- rvis_percentile_EVS
- 92.52
Haploinsufficiency Scores
- pHI
- 0.273
- hipred
- Y
- hipred_score
- 0.539
- ghis
- 0.400
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.774
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Tmem173
- Phenotype
- immune system 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); hematopoietic system phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- tmem173
- Affected structure
- trunk
- Phenotype tag
- abnormal
- Phenotype quality
- shortened
Gene ontology
- Biological process
- activation of innate immune response;positive regulation of defense response to virus by host;apoptotic process;viral process;positive regulation of protein binding;regulation of type I interferon production;positive regulation of type I interferon production;interferon-beta production;obsolete positive regulation of protein import into nucleus, translocation;cellular response to interferon-beta;cytoplasmic pattern recognition receptor signaling pathway in response to virus;neutrophil degranulation;innate immune response;positive regulation of transcription by RNA polymerase II;regulation of inflammatory response;positive regulation of DNA-binding transcription factor activity;defense response to virus;cellular response to exogenous dsRNA;cellular response to organic cyclic compound
- Cellular component
- mitochondrial outer membrane;peroxisome;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;integral component of membrane;cytoplasmic vesicle membrane;secretory granule membrane;perinuclear region of cytoplasm
- Molecular function
- protein binding;transcription factor binding;protein kinase binding;ubiquitin protein ligase binding;cyclic-di-GMP binding;identical protein binding;protein homodimerization activity;cyclic-GMP-AMP binding