Systemic lupus erythematosus 17

Summary

Systemic lupus erythematosus 17 (MONDO:0859083) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	systemic lupus erythematosus 17
Mondo ID	MONDO:0859083
OMIM	301080
UMLS	C5676884
MedGen	1804329
GARD	0026655
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › rheumatic disorder › lupus erythematosus › systemic lupus erythematosus › systemic lupus erythematosus 17

Related subtypes (11): autosomal systemic lupus erythematosus type 16, neonatal lupus erythematosus, pediatric systemic lupus erythematosus, central nervous system lupus, bullous systemic lupus erythematosus, systemic lupus erythematosus related to C4A, systemic lupus erythematosus related to C1QA, systemic lupus erythematosus related to C1S, systemic lupus erythematosus 18, systemic lupus erythematosus related to C1QC, systemic lupus erythematosus related to C1QB

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1330375	NM_016562.4(TLR7):c.1521T>G (p.Phe507Leu)	TLR7	Pathogenic	no assertion criteria provided
1686934	NM_016562.4(TLR7):c.82A>G (p.Arg28Gly)	TLR7	Pathogenic	no assertion criteria provided
1341705	NM_016562.4(TLR7):c.2716G>A (p.Glu906Lys)	TLR7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1686932	NM_016562.4(TLR7):c.790T>C (p.Tyr264His)	TLR7	Uncertain significance	criteria provided, single submitter
2076929	NM_016562.4(TLR7):c.943A>C (p.Lys315Gln)	TLR7	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TLR7	Moderate	X-linked	systemic lupus erythematosus 17	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TLR7	Orphanet:536	Systemic lupus erythematosus

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
TLR7	HGNC:15631	ENSG00000196664	Q9NYK1	Toll-like receptor 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TLR7	Toll-like receptor 7	Endosomal receptor that plays a key role in innate and adaptive immunity.

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)
TLR7	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
TLR7	163	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TLR7	4,103

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TLR7	Q9NYK1	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Defective regulation of TLR7 by endogenous ligand	1	11420.0×	1e-03	TLR7
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	1	878.5×	0.004	TLR7
Trafficking and processing of endosomal TLR	1	815.7×	0.004	TLR7
Regulation of TLR by endogenous ligand	1	496.5×	0.006	TLR7
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.007	TLR7
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.007	TLR7
MyD88 dependent cascade initiated on endosome	1	190.3×	0.007	TLR7
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	184.2×	0.007	TLR7
RSV-host interactions	1	156.4×	0.008	TLR7
Potential therapeutics for SARS	1	114.2×	0.010	TLR7
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.011	TLR7

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
response to cGMP	1	8426.0×	0.002	TLR7
toll-like receptor 8 signaling pathway	1	5617.3×	0.002	TLR7
toll-like receptor 7 signaling pathway	1	3370.4×	0.002	TLR7
positive regulation of macrophage cytokine production	1	732.7×	0.006	TLR7
positive regulation of interferon-alpha production	1	648.1×	0.006	TLR7
toll-like receptor signaling pathway	1	601.9×	0.006	TLR7
positive regulation of interferon-beta production	1	391.9×	0.006	TLR7
positive regulation of chemokine production	1	374.5×	0.006	TLR7
canonical NF-kappaB signal transduction	1	366.4×	0.006	TLR7
JNK cascade	1	271.8×	0.007	TLR7
positive regulation of interleukin-8 production	1	244.2×	0.007	TLR7
positive regulation of type II interferon production	1	224.7×	0.007	TLR7
cellular response to mechanical stimulus	1	216.1×	0.007	TLR7
cellular response to virus	1	200.6×	0.007	TLR7
positive regulation of interleukin-6 production	1	166.8×	0.008	TLR7
positive regulation of inflammatory response	1	145.3×	0.009	TLR7
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.017	TLR7
defense response to virus	1	69.3×	0.017	TLR7
inflammatory response	1	37.7×	0.029	TLR7
innate immune response	1	33.6×	0.031	TLR7
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	TLR7

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

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
TLR7	IMIQUIMOD

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TLR7	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIQUIMOD	4	TLR7
HYDROXYCHLOROQUINE	4	TLR7
VESATOLIMOD	2	TLR7
RESIQUIMOD	2	TLR7
GSK-2245035	2	TLR7
AFIMETORAN	2	TLR7
MHV-370	2	TLR7
CPG-52852	2	TLR7
GURETOLIMOD	1	TLR7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TLR7	356	Binding:321, Functional:35

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TLR7	356

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

9 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)
IMIQUIMOD	4	TLR7
HYDROXYCHLOROQUINE	4	TLR7
VESATOLIMOD	2	TLR7
RESIQUIMOD	2	TLR7
GSK-2245035	2	TLR7
AFIMETORAN	2	TLR7
MHV-370	2	TLR7
CPG-52852	2	TLR7
GURETOLIMOD	1	TLR7

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TLR7
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	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.