RNASEH2A-related type 1 interferonopathy

Summary

RNASEH2A-related type 1 interferonopathy (MONDO:0700259) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	RNASEH2A-related type 1 interferonopathy
Mondo ID	MONDO:0700259
GARD	0026402
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary disorder of connective tissue › RNASEH2A-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, SAMHD1-related type 1 interferonopathy, ADAR-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 (1): Aicardi-Goutieres syndrome 4

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
632305	NM_006397.3(RNASEH2A):c.206dup (p.Thr70fs)	RNASEH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNASEH2A	Orphanet:51	Aicardi-Goutières syndrome

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
RNASEH2A	HGNC:18518	ENSG00000104889	O75792	Ribonuclease H2 subunit A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNASEH2A	Ribonuclease H2 subunit A	Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids.

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)
RNASEH2A	Enzyme (other)	yes	3.1.26.4	RNase_HII/HIII, RNase_H2_suA, RNaseH-like_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
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNASEH2A	140	ubiquitous	marker	ganglionic eminence, embryo, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNASEH2A	3,129

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNASEH2A	O75792	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
DNA replication, removal of RNA primer	1	4213.0×	9e-04	RNASEH2A
mismatch repair	1	648.1×	0.003	RNASEH2A
RNA catabolic process	1	455.5×	0.003	RNASEH2A
DNA replication	1	165.2×	0.006	RNASEH2A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RNASEH2A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNASEH2A	3.1.26.4	ribonuclease H

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	RNASEH2A
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)
RNASEH2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.