STING1

stimulator of interferon response cGAMP interactor 1

Basic information

Region (hg38): 5:139475532-139482935

Previous symbols: [ "TMEM173" ]

Links

ENSG00000184584 ∙ NCBI:340061 ∙ OMIM:612374 ∙ HGNC:27962 ∙ Uniprot:Q86WV6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the STING1 gene.

• STING-associated vasculopathy with onset in infancy (242 variants)
• Autoinflammatory syndrome (43 variants)
• not provided (29 variants)
• not specified (9 variants)
• Inborn genetic diseases (4 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	48	5	57
missense	3	2	112	7	8	132
nonsense			2			2
start loss			1			1
frameshift			6			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)			4			4
splice region			11	5		16
non coding			1	24	8	33
Total	3	2	131	79	21

Highest pathogenic variant AF is 0.0000263

Variants in STING1

This is a list of pathogenic ClinVar variants found in the STING1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-139476255-TGG-T			Benign (Jul 01, 2022)
5-139476262-C-T		STING-associated vasculopathy with onset in infancy	Likely benign (Oct 06, 2019)
5-139476272-C-A		STING-associated vasculopathy with onset in infancy	Uncertain significance (Sep 17, 2023)
5-139476273-C-T		STING-associated vasculopathy with onset in infancy	Likely benign (Aug 09, 2022)
5-139476274-G-A		STING-associated vasculopathy with onset in infancy	Uncertain significance (Jul 03, 2023)
5-139476274-G-C		STING-associated vasculopathy with onset in infancy • Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
5-139476277-C-A		STING-associated vasculopathy with onset in infancy	Benign/Likely benign (Jan 02, 2024)
5-139476277-C-T		STING-associated vasculopathy with onset in infancy • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Nov 25, 2023)
5-139476278-G-A		STING-associated vasculopathy with onset in infancy	Uncertain significance (Oct 25, 2022)
5-139476290-G-T			Uncertain significance (Jan 24, 2017)
5-139476291-C-T		STING-associated vasculopathy with onset in infancy	Likely benign (Dec 18, 2023)
5-139476297-C-T		Autoinflammatory syndrome	Uncertain significance (Dec 12, 2016)
5-139476317-C-T		STING-associated vasculopathy with onset in infancy	Uncertain significance (Oct 20, 2022)
5-139476318-A-G		STING-associated vasculopathy with onset in infancy	Likely benign (Sep 29, 2022)
5-139476324-T-C		STING-associated vasculopathy with onset in infancy	Likely benign (Mar 14, 2022)
5-139476325-T-C		STING-associated vasculopathy with onset in infancy • Autoinflammatory syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 25, 2023)
5-139476333-C-T		STING-associated vasculopathy with onset in infancy	Likely benign (Jan 25, 2024)
5-139476336-G-T		STING-associated vasculopathy with onset in infancy	Likely benign (Jul 26, 2023)
5-139476340-G-A		STING-associated vasculopathy with onset in infancy	Uncertain significance (Sep 10, 2022)
5-139476340-G-T		STING-associated vasculopathy with onset in infancy	Uncertain significance (Dec 06, 2023)
5-139476347-G-A		STING-associated vasculopathy with onset in infancy	Uncertain significance (Mar 19, 2023)
5-139476352-G-A		Autoinflammatory syndrome • STING-associated vasculopathy with onset in infancy	Uncertain significance (May 23, 2023)
5-139476373-A-G		STING-associated vasculopathy with onset in infancy	Uncertain significance (Sep 21, 2023)
5-139476374-C-T		STING-associated vasculopathy with onset in infancy	Uncertain significance (May 06, 2022)
5-139476375-AG-A		STING-associated vasculopathy with onset in infancy	Uncertain significance (Oct 14, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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