Multisystem inflammatory syndrome in children and adults

Summary

Multisystem inflammatory syndrome in children and adults (MONDO:0035375) is a disease caused by OAS2 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: OAS2 (GenCC Strong)
• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multisystem inflammatory syndrome in children and adults
Mondo ID	MONDO:0035375
Orphanet	598363
UMLS	C5680268
MedGen	1842571
GARD	0022403
Is cancer (heuristic)	no

Also known as: MIS-C/A

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › post-infectious disorder › post-viral disorder › post-COVID-19 disorder › multisystem inflammatory syndrome in children and adults

Related subtypes (1): long COVID-19

Subtypes (2): COVID-19–associated multisystem inflammatory syndrome in children, COVID-19–associated multisystem inflammatory syndrome in adults

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: 4 · Orphanet: 1 · 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
OAS2	Strong	Autosomal recessive	multisystem inflammatory syndrome in children and adults
RNASEL	Moderate	Autosomal recessive	multisystem inflammatory syndrome in children and adults	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNASEL	Orphanet:1331	Familial prostate cancer

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
RNASEL	HGNC:10050	ENSG00000135828	Q05823	2-5A-dependent ribonuclease	gencc
OAS2	HGNC:8087	ENSG00000111335	P29728	2’-5’-oligoadenylate synthase 2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNASEL	2-5A-dependent ribonuclease	Endoribonuclease that functions in the interferon (IFN) antiviral response.
OAS2	2’-5’-oligoadenylate synthase 2	Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral 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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNASEL	Kinase	yes	4.6.1.19	Prot_kinase_dom, Ankyrin_rpt, KEN_dom
OAS2	Enzyme (other)	yes	2.7.7.84	Polymerase_NTP_transf_dom, NT_2-5OAS_ClassI-CCAase, 2-5OAS_C_CS

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
amniotic fluid	1
germinal epithelium of ovary	1
palpebral conjunctiva	1
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNASEL	249	ubiquitous	marker	amniotic fluid, palpebral conjunctiva, germinal epithelium of ovary
OAS2	226	ubiquitous	marker	monocyte, leukocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNASEL	6,889
OAS2	1,581

Intra-cohort edges

A	B	Sources
OAS2	RNASEL	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNASEL	Q05823	5
OAS2	P29728	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
OAS antiviral response	2	1268.9×	4e-06	RNASEL, OAS2
Interferon alpha/beta signaling	2	152.3×	2e-04	RNASEL, OAS2
Antimicrobial mechanism of IFN-stimulated genes	1	98.5×	0.022	RNASEL
RSV-host interactions	1	78.2×	0.022	OAS2
Interferon gamma signaling	1	62.8×	0.022	OAS2
Interferon Signaling	1	60.1×	0.022	RNASEL
Cytokine Signaling in Immune system	1	20.4×	0.055	RNASEL
Immune System	1	6.5×	0.148	RNASEL

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
negative regulation of viral genome replication	2	374.5×	1e-04	RNASEL, OAS2
regulation of lactation	1	8426.0×	0.001	OAS2
defense response to virus	2	69.3×	0.001	RNASEL, OAS2
interleukin-27-mediated signaling pathway	1	1203.7×	0.004	OAS2
nucleobase-containing compound metabolic process	1	263.3×	0.011	OAS2
RNA catabolic process	1	227.7×	0.011	OAS2
positive regulation of D-glucose import across plasma membrane	1	227.7×	0.011	RNASEL
regulation of mRNA stability	1	210.7×	0.011	RNASEL
positive regulation of interferon-beta production	1	195.9×	0.011	OAS2
type I interferon-mediated signaling pathway	1	172.0×	0.012	OAS2
antiviral innate immune response	1	113.9×	0.015	OAS2
RNA processing	1	109.4×	0.015	RNASEL
fat cell differentiation	1	90.6×	0.017	RNASEL
positive regulation of tumor necrosis factor production	1	76.6×	0.018	OAS2
response to virus	1	72.0×	0.018	OAS2
rRNA processing	1	70.8×	0.018	RNASEL
defense response to bacterium	1	54.0×	0.022	OAS2
mRNA processing	1	39.4×	0.028	RNASEL
protein phosphorylation	1	34.0×	0.031	RNASEL
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	RNASEL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RNASEL	0	0
OAS2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
RNASEL	43	Binding:42, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNASEL	4.6.1.19	ribonuclease T2
OAS2	2.7.7.84	2’-5’ oligoadenylate synthase

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

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	2	RNASEL, OAS2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
RNASEL	43	—
OAS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.