COVID-19–associated multisystem inflammatory syndrome in adults

Summary

COVID-19–associated multisystem inflammatory syndrome in adults (MONDO:0100319) 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	COVID-19–associated multisystem inflammatory syndrome in adults
Mondo ID	MONDO:0100319
GARD	0026142
Is cancer (heuristic)	no

Also known as: MIS-A

Data availability: 2 ClinVar variants.

Disease family

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 › COVID-19–associated multisystem inflammatory syndrome in adults

Related subtypes (1): COVID-19–associated multisystem inflammatory syndrome in children

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:

2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3058962	NM_001318789.2(TLR2):c.1350T>C (p.Ser450=)	TLR2	Conflicting classifications of pathogenicity	no assertion criteria provided
3060911	NM_001318789.2(TLR2):c.597T>C (p.Asn199=)	TLR2	Conflicting classifications of pathogenicity	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
TLR2	HGNC:11848	ENSG00000137462	O60603	Toll-like receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TLR2	Toll-like receptor 2	Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TLR2	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TLR2	214	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TLR2	5,037

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TLR2	O60603	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Modulation by Mtb of host immune system	1	1631.4×	0.006	TLR2
MyD88 deficiency (TLR2/4)	1	601.0×	0.006	TLR2
IRAK4 deficiency (TLR2/4)	1	571.0×	0.006	TLR2
Regulation of TLR by endogenous ligand	1	496.5×	0.006	TLR2
Beta defensins	1	271.9×	0.009	TLR2
Toll Like Receptor TLR6:TLR2 Cascade	1	175.7×	0.009	TLR2
Toll Like Receptor TLR1:TLR2 Cascade	1	167.9×	0.009	TLR2
RSV-host interactions	1	156.4×	0.009	TLR2
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	152.3×	0.009	TLR2
ER-Phagosome pathway	1	129.8×	0.009	TLR2
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	TLR2
Neutrophil degranulation	1	23.1×	0.043	TLR2

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
detection of triacyl bacterial lipopeptide	1	8426.0×	9e-04	TLR2
detection of diacyl bacterial lipopeptide	1	8426.0×	9e-04	TLR2
positive regulation of cellular response to macrophage colony-stimulating factor stimulus	1	8426.0×	9e-04	TLR2
cellular response to triacyl bacterial lipopeptide	1	5617.3×	9e-04	TLR2
positive regulation of matrix metallopeptidase secretion	1	5617.3×	9e-04	TLR2
microglia development	1	4213.0×	9e-04	TLR2
toll-like receptor TLR6:TLR2 signaling pathway	1	4213.0×	9e-04	TLR2
cellular response to bacterial lipopeptide	1	4213.0×	9e-04	TLR2
cellular response to diacyl bacterial lipopeptide	1	4213.0×	9e-04	TLR2
toll-like receptor 2 signaling pathway	1	3370.4×	0.001	TLR2
negative regulation of synapse assembly	1	2407.4×	0.001	TLR2
positive regulation of interleukin-18 production	1	2106.5×	0.001	TLR2
cellular response to lipoteichoic acid	1	1532.0×	0.002	TLR2
negative regulation of phagocytosis	1	991.3×	0.003	TLR2
toll-like receptor signaling pathway	1	601.9×	0.004	TLR2
positive regulation of interferon-beta production	1	391.9×	0.005	TLR2
positive regulation of interleukin-12 production	1	391.9×	0.005	TLR2
positive regulation of Wnt signaling pathway	1	383.0×	0.005	TLR2
positive regulation of chemokine production	1	374.5×	0.005	TLR2
learning	1	280.9×	0.006	TLR2
positive regulation of interleukin-8 production	1	244.2×	0.007	TLR2
cellular response to type II interferon	1	208.1×	0.008	TLR2
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.008	TLR2
positive regulation of interleukin-6 production	1	166.8×	0.009	TLR2
positive regulation of tumor necrosis factor production	1	153.2×	0.009	TLR2
positive regulation of inflammatory response	1	145.3×	0.010	TLR2
defense response to Gram-positive bacterium	1	127.7×	0.010	TLR2
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.018	TLR2
defense response to virus	1	69.3×	0.018	TLR2
immune response	1	47.1×	0.025	TLR2

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
TLR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TLR2	225	Binding:202, Functional:23

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TLR2	225

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TLR2

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)
TLR2	225	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.