Autoinflammatory syndrome of childhood

Summary

Autoinflammatory syndrome of childhood (MONDO:0957018) is a disease caused by PTPN2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PTPN2 (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory syndrome of childhood
Mondo ID	MONDO:0957018
Orphanet	319719
UMLS	C5680962
MedGen	1842803
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

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

Related subtypes (36): cherubism, chronic recurrent multifocal osteomyelitis, Pelger-Huet-like anomaly and episodic fever with abdominal pain, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, psoriasis 14, pustular, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, periodic fever syndrome, infantile onset panniculitis with uveitis and systemic granulomatosis, idiopathic recurrent pericarditis, pyoderma gangrenosum-acne-suppurative hidradenitis syndrome, neonatal inflammatory skin and bowel disease, magic syndrome, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, Schnitzler syndrome, PFAPA syndrome, pyoderma gangrenosum, SAPHO syndrome, sarcoidosis, adult-onset Still disease, systemic-onset juvenile idiopathic arthritis, VEXAS syndrome, autoinflammatory syndrome, familial, Behcet-like, CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome, type 1 interferonopathy, autoinflammatory disease, X-linked, autoinflammatory syndrome with immunodeficiency, early-onset pulmonary and cutaneous vasculitis, autoinflammatory syndrome due to TBK1 deficiency, F12-associated cold autoinflammatory syndrome, neonatal-onset severe multisystemic autoinflammatory disease with increased IL18, SAMD9L-associated autoinflammatory syndrome, autoinflammatory disease, systemic, with vasculitis, granulomatous autoinflammatory syndrome of childhood, autoinflammatory disease, multisystem, with immune dysregulation, X-linked, PAPASH syndrome, Sharpin-related autoinflammatory syndrome

Subtypes (1): type 1 interferonopathy of childhood

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
PTPN2	Strong	Autosomal dominant	autoinflammatory syndrome of childhood

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPN2	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN2	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis

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
PTPN2	HGNC:9650	ENSG00000175354	P17706	Tyrosine-protein phosphatase non-receptor type 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPN2	Tyrosine-protein phosphatase non-receptor type 2	Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPN2	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

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
granulocyte	1
monocyte	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPN2	296	ubiquitous	marker	tendon of biceps brachii, granulocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN2	2,705

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN2	P17706	14

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
Regulation of IFNG signaling	1	815.7×	0.003	PTPN2
Negative regulation of MET activity	1	519.1×	0.003	PTPN2
Interleukin-37 signaling	1	519.1×	0.003	PTPN2
PKR-mediated signaling	1	141.0×	0.007	PTPN2

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
negative regulation of interleukin-2-mediated signaling pathway	1	16852.0×	7e-04	PTPN2
negative regulation of positive thymic T cell selection	1	16852.0×	7e-04	PTPN2
regulation of type II interferon-mediated signaling pathway	1	8426.0×	7e-04	PTPN2
negative regulation of interleukin-6-mediated signaling pathway	1	8426.0×	7e-04	PTPN2
regulation of hepatocyte growth factor receptor signaling pathway	1	8426.0×	7e-04	PTPN2
negative regulation of interleukin-4-mediated signaling pathway	1	8426.0×	7e-04	PTPN2
negative regulation of tyrosine phosphorylation of STAT protein	1	5617.3×	7e-04	PTPN2
negative regulation of chemotaxis	1	5617.3×	7e-04	PTPN2
negative regulation of macrophage colony-stimulating factor signaling pathway	1	5617.3×	7e-04	PTPN2
insulin receptor recycling	1	4213.0×	7e-04	PTPN2
positive regulation of PERK-mediated unfolded protein response	1	4213.0×	7e-04	PTPN2
negative regulation of platelet-derived growth factor receptor-beta signaling pathway	1	4213.0×	7e-04	PTPN2
negative regulation of macrophage differentiation	1	2106.5×	0.001	PTPN2
negative regulation of type II interferon-mediated signaling pathway	1	2106.5×	0.001	PTPN2
negative regulation of lipid storage	1	1532.0×	0.001	PTPN2
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	1532.0×	0.001	PTPN2
peptidyl-tyrosine dephosphorylation	1	887.0×	0.002	PTPN2
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.002	PTPN2
negative regulation of epidermal growth factor receptor signaling pathway	1	766.0×	0.002	PTPN2
positive regulation of gluconeogenesis	1	766.0×	0.002	PTPN2
negative regulation of type I interferon-mediated signaling pathway	1	766.0×	0.002	PTPN2
negative regulation of tumor necrosis factor-mediated signaling pathway	1	455.5×	0.003	PTPN2
T cell differentiation	1	383.0×	0.004	PTPN2
negative regulation of insulin receptor signaling pathway	1	374.5×	0.004	PTPN2
negative regulation of T cell receptor signaling pathway	1	366.4×	0.004	PTPN2
erythrocyte differentiation	1	267.5×	0.005	PTPN2
insulin receptor signaling pathway	1	221.7×	0.005	PTPN2
B cell differentiation	1	218.9×	0.005	PTPN2
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.005	PTPN2
negative regulation of inflammatory response	1	137.0×	0.008	PTPN2

Therapeutics

Drug target analysis

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

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
PTPN2	4	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
URSOLIC ACID	2	PTPN2
CHLOROGENIC ACID	2	PTPN2
OSUNPROTAFIB	2	PTPN2
TEGEPROTAFIB	2	PTPN2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTPN2	250	Binding:246, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPN2	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
PTPN2	250

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

4 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)
URSOLIC ACID	2	PTPN2
CHLOROGENIC ACID	2	PTPN2
OSUNPROTAFIB	2	PTPN2
TEGEPROTAFIB	2	PTPN2

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	1	PTPN2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.