Type 1 interferonopathy of childhood

Summary

Type 1 interferonopathy of childhood (MONDO:0957408) is a disease (an umbrella term covering 12 Mondo subtypes) with 2 cohort genes.

At a glance

• Umbrella term: 12 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	type 1 interferonopathy of childhood
Mondo ID	MONDO:0957408
Orphanet	481671
UMLS	C5681250
MedGen	1843010
GARD	0021986
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 12 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › type 1 interferonopathy › type 1 interferonopathy of childhood

Related subtypes (8): 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, ADAR-related type 1 interferonopathy, IFIH1-related type 1 interferonopathy, RNU7-1-related type 1 interferonopathy

Subtypes (12): Singleton-Merten dysplasia, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, trichohepatoenteric syndrome, proteosome-associated autoinflammatory syndrome, X-linked reticulate pigmentary disorder, Spondyloenchondrodysplasia with immune dysregulation, deficiency of adenosine deaminase 2, STING-associated vasculopathy with onset in infancy, autoimmune interstitial lung disease-arthritis syndrome, familial chilblain lupus, pseudo-TORCH syndrome 2, Aicardi-Goutieres 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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4818965	NM_002827.4(PTPN1):c.409_422del (p.Asp137fs)	PTPN1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
REXO2	Moderate	Autosomal dominant	type 1 interferonopathy of childhood	2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
REXO2	HGNC:17851	ENSG00000076043	Q9Y3B8	Oligoribonuclease, mitochondrial	gencc
PTPN1	HGNC:9642	ENSG00000196396	P18031	Tyrosine-protein phosphatase non-receptor type 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
REXO2	Oligoribonuclease, mitochondrial	3’-to-5’exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides.
PTPN1	Tyrosine-protein phosphatase non-receptor type 1	Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response.

Protein-family classification

Druggable: 2 · 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
Phosphatase	1	42.0×	0.047
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
REXO2	Enzyme (other)	yes	3.1.13.3	RNaseH-like_sf, Ribonucl_H, Oligoribonuclease
PTPN1	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	1
oocyte	1
secondary oocyte	1
right lung	1
upper lobe of left lung	1
upper lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
REXO2	286	ubiquitous	marker	secondary oocyte, oocyte, decidua
PTPN1	232	ubiquitous	marker	upper lobe of left lung, right lung, upper lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN1	4,220
REXO2	1,546

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN1	P18031	439
REXO2	Q9Y3B8	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 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
PTK6 Down-Regulation	1	1427.5×	0.006	PTPN1
Mitochondrial RNA degradation	1	815.7×	0.006	REXO2
Regulation of IFNG signaling	1	407.9×	0.006	PTPN1
MECP2 regulates neuronal receptors and channels	1	300.5×	0.006	PTPN1
Negative regulation of MET activity	1	259.6×	0.006	PTPN1
Growth hormone receptor signaling	1	237.9×	0.006	PTPN1
Regulation of IFNA/IFNB signaling	1	219.6×	0.006	PTPN1
Integrin signaling	1	211.5×	0.006	PTPN1
Insulin receptor recycling	1	190.3×	0.006	PTPN1
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	178.4×	0.006	PTPN1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of hepatocyte growth factor receptor signaling pathway	1	4213.0×	0.004	PTPN1
mitochondrial RNA surveillance	1	2808.7×	0.004	REXO2
insulin receptor recycling	1	2106.5×	0.004	PTPN1
regulation of type I interferon-mediated signaling pathway	1	2106.5×	0.004	PTPN1
platelet-derived growth factor receptor-beta signaling pathway	1	1685.2×	0.004	PTPN1
vascular endothelial cell response to oscillatory fluid shear stress	1	1685.2×	0.004	PTPN1
positive regulation of receptor catabolic process	1	1685.2×	0.004	PTPN1
regulation of intracellular protein transport	1	1404.3×	0.004	PTPN1
positive regulation of IRE1-mediated unfolded protein response	1	1053.2×	0.004	PTPN1
nucleotide metabolic process	1	936.2×	0.004	REXO2
IRE1-mediated unfolded protein response	1	936.2×	0.004	PTPN1
negative regulation of vascular associated smooth muscle cell migration	1	842.6×	0.004	PTPN1
growth hormone receptor signaling pathway via JAK-STAT	1	766.0×	0.004	PTPN1
positive regulation of systemic arterial blood pressure	1	702.2×	0.004	PTPN1
negative regulation of MAP kinase activity	1	702.2×	0.004	PTPN1
negative regulation of PERK-mediated unfolded protein response	1	702.2×	0.004	PTPN1
regulation of proteolysis	1	648.1×	0.004	PTPN1
negative regulation of vascular endothelial growth factor receptor signaling pathway	1	648.1×	0.004	PTPN1
positive regulation of cardiac muscle cell apoptotic process	1	601.9×	0.004	PTPN1
negative regulation of cell-substrate adhesion	1	526.6×	0.004	PTPN1
cellular response to unfolded protein	1	495.6×	0.004	PTPN1
cellular response to nitric oxide	1	468.1×	0.004	PTPN1
cellular response to angiotensin	1	468.1×	0.004	PTPN1
peptidyl-tyrosine dephosphorylation	1	443.5×	0.004	PTPN1
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	421.3×	0.004	PTPN1
positive regulation of endothelial cell apoptotic process	1	366.4×	0.005	PTPN1
positive regulation of heart rate	1	351.1×	0.005	PTPN1
cellular response to platelet-derived growth factor stimulus	1	324.1×	0.005	PTPN1
cellular response to fibroblast growth factor stimulus	1	271.8×	0.006	PTPN1
nucleobase-containing compound metabolic process	1	263.3×	0.006	REXO2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
PTPN1	AMINOSALICYLIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTPN1	23	4
REXO2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMINOSALICYLIC ACID	4	PTPN1
EVANS BLUE	4	PTPN1
TRYPAN BLUE	4	PTPN1
ESTRAMUSTINE PHOSPHATE	4	PTPN1
BERBERINE	4	PTPN1
BENZBROMARONE	4	PTPN1
TROGLITAZONE	4	PTPN1
CANTHARIDIN	4	PTPN1
CARBENOXOLONE	4	PTPN1
PIOGLITAZONE	4	PTPN1
CAFFEIC ACID	3	PTPN1
SURAMIN	3	PTPN1
QUERCETIN	3	PTPN1
URSOLIC ACID	2	PTPN1
ERTIPROTAFIB	2	PTPN1
ENOXOLONE	2	PTPN1
CHLOROGENIC ACID	2	PTPN1
BEVIRIMAT	2	PTPN1
TRODUSQUEMINE	2	PTPN1
OSUNPROTAFIB	2	PTPN1
TEGEPROTAFIB	2	PTPN1
OLEIC ACID	2	PTPN1
BETULINIC ACID	1	PTPN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PTPN1	1,225	Binding:1210, Functional:10, ADMET:4, Toxicity:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
REXO2	3.1.13.3	oligonucleotidase
PTPN1	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PTPN1	1,225

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

23 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)
AMINOSALICYLIC ACID	4	PTPN1
EVANS BLUE	4	PTPN1
TRYPAN BLUE	4	PTPN1
ESTRAMUSTINE PHOSPHATE	4	PTPN1
BERBERINE	4	PTPN1
BENZBROMARONE	4	PTPN1
TROGLITAZONE	4	PTPN1
CANTHARIDIN	4	PTPN1
CARBENOXOLONE	4	PTPN1
PIOGLITAZONE	4	PTPN1
CAFFEIC ACID	3	PTPN1
SURAMIN	3	PTPN1
QUERCETIN	3	PTPN1
URSOLIC ACID	2	PTPN1
ERTIPROTAFIB	2	PTPN1
ENOXOLONE	2	PTPN1
CHLOROGENIC ACID	2	PTPN1
BEVIRIMAT	2	PTPN1
TRODUSQUEMINE	2	PTPN1
OSUNPROTAFIB	2	PTPN1
TEGEPROTAFIB	2	PTPN1
OLEIC ACID	2	PTPN1
BETULINIC ACID	1	PTPN1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PTPN1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	REXO2
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)
REXO2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.