ADAR-related type 1 interferonopathy

Summary

ADAR-related type 1 interferonopathy (MONDO:0700261) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ADAR-related type 1 interferonopathy
Mondo ID	MONDO:0700261
GARD	0026404
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary disorder of connective tissue › ADAR-related type 1 interferonopathy

Related subtypes (86): Ewing sarcoma of bone, hereditary multiple osteochondromas, acroosteolysis dominant type, diaphyseal medullary stenosis-bone malignancy syndrome, cherubism, chondrocalcinosis 2, desmoid tumor, familial ossifying fibroma, hyperparathyroidism 1, hyperparathyroidism 2 with jaw tumors, uterine corpus leiomyoma, multiple symmetric lipomatosis, systemic lupus erythematosus, Ollier disease, Peyronie disease, Singleton-Merten dysplasia, Blau syndrome, inherited torticollis, arterial tortuosity syndrome, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, chondrosarcoma, trichohepatoenteric syndrome, brittle cornea syndrome, neonatal severe primary hyperparathyroidism, proteosome-associated autoinflammatory syndrome, chronic recurrent multifocal osteomyelitis, Pelger-Huet-like anomaly and episodic fever with abdominal pain, acquired polycythemia vera, autosomal recessive inherited pseudoxanthoma elasticum, X-linked reticulate pigmentary disorder, CHILD syndrome, ossification of the posterior longitudinal ligament of the spine, MASS syndrome, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, Spondyloenchondrodysplasia with immune dysregulation, sweet syndrome, chronic myeloid leukemia, hyperparathyroidism 3, bone fragility with contractures, arterial rupture, and deafness, encephalocraniocutaneous lipomatosis, psoriasis 14, pustular, Maffucci syndrome, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, deficiency of adenosine deaminase 2, STING-associated vasculopathy with onset in infancy, autoimmune interstitial lung disease-arthritis syndrome, progeroid and marfanoid aspect-lipodystrophy syndrome, thrombocytopenia 6, multiple epiphyseal dysplasia due to collagen 9 anomaly, Ehlers-Danlos syndrome, kyphoscoliotic type 1, juvenile hyaline fibromatosis, IL10-related early-onset inflammatory bowel disease, infantile myofibromatosis, Marfan and Marfan-related disorder, neonatal inflammatory skin and bowel disease, familial isolated pituitary adenoma, inherited acute myeloid leukemia, hereditary periodic fever syndrome, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, aneurysmal bone cyst, familial chilblain lupus, pseudo-TORCH syndrome 2, Aicardi-Goutieres syndrome, jugulotympanic paraganglioma, type 2 collagenopathy, hyperparathyroidism 4, VEXAS syndrome, autoinflammatory syndrome, familial, Behcet-like, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, LAMA5-related multisystemic syndrome, EMILIN-1-related connective tissue disease, TREX1-related type 1 interferonopathy, RNASEH2B-related type 1 interferonopathy, RNASEH2C-related type 1 interferonopathy, RNASEH2A-related type 1 interferonopathy, SAMHD1-related type 1 interferonopathy, IFIH1-related type 1 interferonopathy, RNU7-1-related type 1 interferonopathy, autoinflammatory disease, X-linked, autoinflammatory syndrome with immunodeficiency, autoinflammatory disease, systemic, with vasculitis, autoinflammatory disease, multisystem, with immune dysregulation, X-linked, arterial tortuosity-bone fragility syndrome, linkeropathy, hypermobility spectrum disorder, Sharpin-related autoinflammatory syndrome

Subtypes (2): dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome 6

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
521470	NM_001111.5(ADAR):c.2433_2434del (p.Ala813fs)	ADAR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126395	NM_001111.5(ADAR):c.577C>G (p.Pro193Ala)	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAR	Orphanet:225154	Familial infantile bilateral striatal necrosis
ADAR	Orphanet:41	Dyschromatosis symmetrica hereditaria
ADAR	Orphanet:51	Aicardi-Goutières syndrome
ADAR	Orphanet:694356	ADAR-related hereditary spastic paraplegia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAR	HGNC:225	ENSG00000160710	P55265	Double-stranded RNA-specific adenosine deaminase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAR	Double-stranded RNA-specific adenosine deaminase	Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAR	Enzyme (other)	yes	3.5.4.37	A_deamin, dsRBD_dom, WH-like_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
middle temporal gyrus	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAR	295	ubiquitous	marker	endothelial cell, middle temporal gyrus, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAR	3,166

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADAR	P55265	24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
C6 deamination of adenosine	1	5710.0×	4e-04	ADAR
Formation of editosomes by ADAR proteins	1	5710.0×	4e-04	ADAR
Interferon alpha/beta signaling	1	152.3×	0.007	ADAR
PKR-mediated signaling	1	141.0×	0.007	ADAR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic diversification of immune receptors via somatic mutation	1	16852.0×	8e-04	ADAR
negative regulation of post-transcriptional gene silencing by regulatory ncRNA	1	16852.0×	8e-04	ADAR
base conversion or substitution editing	1	4213.0×	0.002	ADAR
adenosine to inosine editing	1	3370.4×	0.002	ADAR
negative regulation of protein kinase activity by regulation of protein phosphorylation	1	3370.4×	0.002	ADAR
negative regulation of hepatocyte apoptotic process	1	2808.7×	0.002	ADAR
response to interferon-alpha	1	1685.2×	0.002	ADAR
RISC complex assembly	1	1532.0×	0.002	ADAR
mRNA modification	1	1296.3×	0.002	ADAR
pre-miRNA processing	1	1123.5×	0.002	ADAR
hepatocyte apoptotic process	1	1053.2×	0.002	ADAR
definitive hemopoiesis	1	936.2×	0.002	ADAR
negative regulation of type I interferon-mediated signaling pathway	1	766.0×	0.003	ADAR
positive regulation of viral genome replication	1	581.1×	0.003	ADAR
hematopoietic stem cell homeostasis	1	561.7×	0.003	ADAR
protein export from nucleus	1	510.7×	0.003	ADAR
erythrocyte differentiation	1	267.5×	0.006	ADAR
hematopoietic progenitor cell differentiation	1	237.3×	0.006	ADAR
RNA processing	1	218.9×	0.006	ADAR
cellular response to virus	1	200.6×	0.006	ADAR
protein import into nucleus	1	144.0×	0.008	ADAR
response to virus	1	144.0×	0.008	ADAR
osteoblast differentiation	1	121.2×	0.009	ADAR
mRNA processing	1	78.8×	0.014	ADAR
defense response to virus	1	69.3×	0.015	ADAR
innate immune response	1	33.6×	0.030	ADAR

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ADAR	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAR	3.5.4.37	double-stranded RNA adenine deaminase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

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

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADAR	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.