STING-associated vasculopathy with onset in infancy

Summary

STING-associated vasculopathy with onset in infancy (MONDO:0014405) is a disease caused by STING1 (GenCC Strong), with 3 cohort genes and 2 clinical trials. Top therapeutic interventions include baricitinib.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: STING1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 356
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	STING-associated vasculopathy with onset in infancy
Mondo ID	MONDO:0014405
OMIM	615934
Orphanet	425120
DOID	DOID:0111457
SNOMED CT	711164003
UMLS	C4014722
MedGen	863159
GARD	0012357
Is cancer (heuristic)	no

Also known as: SAVI · STING-associated vasculopathy, infantile-onset

Data availability: 356 ClinVar variants · 5 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › STING-associated vasculopathy with onset in infancy

Related subtypes (59): arterial disorder, ischemic colitis, thrombotic disease, capillary disorder, angiodysplasia, hepatic vascular disorder, vascular hemostatic disease, vein disorder, ischemic disease, peripheral vascular disease, venous thromboembolism, ocular vascular disorder, cholesterol embolism, thoracic outlet syndrome, idiopathic spontaneous coronary artery dissection, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, angioosteohypertrophic syndrome, Bannayan-Riley-Ruvalcaba syndrome, arterial tortuosity syndrome, hereditary arterial and articular multiple calcification syndrome, pulmonary venoocclusive disease, multiple cutaneous and mucosal venous malformations, arterial dissection-lentiginosis syndrome, patent ductus arteriosus, multisystemic smooth muscle dysfunction syndrome, capillary malformation, Ehlers-Danlos syndrome, vascular-like type, calciphylaxis, neonatal Marfan syndrome, Ehlers-Danlos syndrome, vascular type, lethal arteriopathy syndrome due to fibulin-4 deficiency, congenital portosystemic shunt, arterial calcification of infancy, vasculitis, Loeys-Dietz syndrome, skin vascular disease, lymphatic malformation, familial thoracic aortic aneurysm and aortic dissection, congenital anomaly of superior vena cava, congenital anomaly of the inferior vena cava, congenital anomaly of hepatic vein, congenital renal artery stenosis, internal carotid agenesis, coronary sinus stenosis, coronary sinus atresia, vascular occlusion disorder, vascular insufficiency disorder, blood vessel neoplasm, vascular ectasia, vascular disorder of penis, fibrocartilaginous embolism, vascular malformation, lymphatic vessel neoplasm, neurovascular disorder, superior vena cava syndrome, coronary microvascular disorder, segmental arterial mediolysis, bleeding disorder, vascular-type, arterial tortuosity-bone fragility syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

356 retrieved; paginated sample, class counts are floors:

188 uncertain significance, 117 likely benign, 21 conflicting classifications of pathogenicity, 11 benign, 9 benign/likely benign, 5 pathogenic, 4 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
143861	NM_198282.4(STING1):c.461A>G (p.Asn154Ser)	STING1	Pathogenic	criteria provided, single submitter
143862	NM_198282.4(STING1):c.463G>A (p.Val155Met)	STING1	Pathogenic	criteria provided, multiple submitters, no conflicts
143863	NM_198282.4(STING1):c.439G>C (p.Val147Leu)	STING1	Pathogenic	no assertion criteria provided
2022271	NM_198282.4(STING1):c.851G>C (p.Arg284Thr)	STING1	Pathogenic	criteria provided, single submitter
3383481	NM_198282.4(STING1):c.852G>C (p.Arg284Ser)	STING1	Pathogenic	criteria provided, multiple submitters, no conflicts
568703	NM_198282.4(STING1):c.842G>A (p.Arg281Gln)	STING1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1299706	NM_198282.4(STING1):c.457T>A (p.Phe153Ile)	STING1	Likely pathogenic	criteria provided, single submitter
2584430	NM_198282.4(STING1):c.614A>G (p.Asp205Gly)	STING1	Likely pathogenic	criteria provided, single submitter
2982257	NM_198282.4(STING1):c.616T>G (p.Cys206Gly)	STING1	Likely pathogenic	criteria provided, single submitter
4531971	NM_198282.4(STING1):c.473G>T (p.Gly158Val)	STING1	Likely pathogenic	criteria provided, single submitter
624065	NM_198282.4(STING1):c.289G>A (p.Ala97Thr)	LOC123522803	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
661503	NM_198282.4(STING1):c.281G>A (p.Arg94His)	LOC123522803	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
746622	NM_198282.4(STING1):c.380C>T (p.Ser127Leu)	LOC123522803	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
839783	NM_198282.4(STING1):c.344C>T (p.Pro115Leu)	LOC123522803	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1063787	NM_198282.4(STING1):c.539G>A (p.Arg180Gln)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1680234	NM_198282.4(STING1):c.1124G>A (p.Arg375His)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1680240	NM_198282.4(STING1):c.946+6G>T	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1680244	NM_198282.4(STING1):c.763G>A (p.Gly255Ser)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1680257	NM_198282.4(STING1):c.430A>G (p.Ile144Val)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1680276	NM_198282.4(STING1):c.184G>A (p.Gly62Arg)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2165987	NM_198282.4(STING1):c.128C>T (p.Thr43Ile)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
475205	NM_198282.4(STING1):c.376C>A (p.Leu126Ile)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
475208	NM_198282.4(STING1):c.575G>T (p.Gly192Val)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541980	NM_198282.4(STING1):c.929G>A (p.Arg310His)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
541983	NM_198282.4(STING1):c.61G>A (p.Ala21Thr)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
636667	NM_198282.4(STING1):c.40A>C (p.Arg14=)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
641434	NM_198282.4(STING1):c.1076A>G (p.Gln359Arg)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
839824	NM_198282.4(STING1):c.841C>T (p.Arg281Trp)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
871838	NM_198282.4(STING1):c.760-3T>C	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
951442	NM_198282.4(STING1):c.758G>A (p.Arg253Gln)	STING1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
STING1	Strong	Autosomal dominant	STING-associated vasculopathy with onset in infancy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STING1	Orphanet:425120	STING-associated vasculopathy with onset in infancy
STING1	Orphanet:481662	Familial Chilblain lupus

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STING1	HGNC:27962	ENSG00000184584	Q86WV6	Stimulator of interferon genes protein	gencc,clinvar
BRD8	HGNC:19874	ENSG00000112983	Q9H0E9	Bromodomain-containing protein 8	clinvar
DNAJC18	HGNC:28429	ENSG00000170464	Q9H819	DnaJ homolog subfamily C member 18	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STING1	Stimulator of interferon genes protein	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).
BRD8	Bromodomain-containing protein 8	May act as a coactivator during transcriptional activation by hormone-activated nuclear receptors (NR).
DNAJC18	DnaJ homolog subfamily C member 18	(Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STING1	Other/Unknown	no		STING, STING_C_sf, STING_C_chordates
BRD8	Other/Unknown	no		Bromodomain, Bromodomain-like_sf, Brd8_Bromo_dom
DNAJC18	Other/Unknown	no		DnaJ_domain, DUF1977_DnaJ-like, DnaJ_domain_CS

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
granulocyte	1
olfactory segment of nasal mucosa	1
right uterine tube	1
ventricular zone	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STING1	134	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, granulocyte
BRD8	300	ubiquitous	marker	right testis, left testis, ventricular zone
DNAJC18	143	ubiquitous	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRD8	2,212
STING1	2,148
DNAJC18	2,144

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STING1	Q86WV6	119

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAJC18	Q9H819	71.31
BRD8	Q9H0E9	53.92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
STAT6-mediated induction of chemokines	1	1903.3×	0.012	STING1
STING mediated induction of host immune responses	1	519.1×	0.014	STING1
IRF3-mediated induction of type I IFN	1	407.9×	0.014	STING1
Regulation of innate immune responses to cytosolic DNA	1	380.7×	0.014	STING1
Dengue virus activates/modulates innate and adaptive immune responses	1	167.9×	0.023	STING1
Cytosolic sensors of pathogen-associated DNA	1	142.8×	0.023	STING1
SARS-CoV-1 activates/modulates innate immune responses	1	135.9×	0.023	STING1
SARS-CoV-1-host interactions	1	87.8×	0.031	STING1
SARS-CoV-1 Infection	1	71.4×	0.034	STING1
SARS-CoV-2-host interactions	1	59.5×	0.037	STING1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	44.6×	0.039	STING1
Chromatin organization	1	40.8×	0.039	BRD8
SARS-CoV-2 Infection	1	40.2×	0.039	STING1
HATs acetylate histones	1	39.6×	0.039	BRD8
Chromatin modifying enzymes	1	36.1×	0.040	BRD8
SARS-CoV Infections	1	27.7×	0.049	STING1
Viral Infection Pathways	1	15.4×	0.083	STING1
Innate Immune System	1	12.8×	0.091	STING1
Infectious disease	1	12.4×	0.091	STING1
Neutrophil degranulation	1	11.5×	0.093	STING1
Disease	1	6.5×	0.148	STING1
Immune System	1	6.5×	0.148	STING1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cGAS/STING signaling pathway	1	1123.5×	0.012	STING1
protein localization to endoplasmic reticulum	1	702.2×	0.012	STING1
cellular response to thyroid hormone stimulus	1	510.7×	0.012	BRD8
cellular response to misfolded protein	1	468.1×	0.012	DNAJC18
cellular response to exogenous dsRNA	1	351.1×	0.012	STING1
pattern recognition receptor signaling pathway	1	330.4×	0.012	STING1
cytoplasmic pattern recognition receptor signaling pathway	1	295.6×	0.012	STING1
positive regulation of type I interferon-mediated signaling pathway	1	280.9×	0.012	STING1
reticulophagy	1	234.1×	0.012	STING1
protein complex oligomerization	1	224.7×	0.012	STING1
regulation of double-strand break repair	1	193.7×	0.012	BRD8
positive regulation of defense response to virus by host	1	175.5×	0.012	STING1
positive regulation of macroautophagy	1	175.5×	0.012	STING1
cellular response to interferon-beta	1	175.5×	0.012	STING1
activation of innate immune response	1	160.5×	0.012	STING1
positive regulation of type I interferon production	1	140.4×	0.013	STING1
positive regulation of interferon-beta production	1	130.6×	0.013	STING1
positive regulation of double-strand break repair via homologous recombination	1	127.7×	0.013	BRD8
antiviral innate immune response	1	75.9×	0.018	STING1
autophagosome assembly	1	74.9×	0.018	STING1
positive regulation of transcription by RNA polymerase II	2	9.9×	0.018	STING1, BRD8
regulation of inflammatory response	1	56.2×	0.023	STING1
chromatin organization	1	33.0×	0.038	BRD8
regulation of apoptotic process	1	27.8×	0.043	BRD8
regulation of cell cycle	1	24.9×	0.046	BRD8
defense response to virus	1	23.1×	0.048	STING1
cell surface receptor signaling pathway	1	21.4×	0.050	BRD8
innate immune response	1	11.2×	0.090	STING1
positive regulation of DNA-templated transcription	1	9.3×	0.104	BRD8

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
STING1	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STING1	2	4
BRD8	0	0
DNAJC18	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	STING1
VADIMEZAN	3	STING1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
STING1	890	Binding:890
BRD8	40	Binding:40

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
STING1	890

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PALBOCICLIB	4	STING1
VADIMEZAN	3	STING1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	STING1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BRD8, DNAJC18

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BRD8	40	—
DNAJC18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2/PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04517253	PHASE2/PHASE3	TERMINATED	A Study of Baricitinib (LY3009104) in Adult and Pediatric Japanese Participants With NNS/CANDLE, SAVI, and AGS
NCT02974595	Not specified	RECRUITING	Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still’S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BARICITINIB	4	1
CHEMBL5427854	0	1