Autoinflammatory disease, systemic, with vasculitis

Summary

Autoinflammatory disease, systemic, with vasculitis (MONDO:0957271) is a disease caused by LYN (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LYN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoinflammatory disease, systemic, with vasculitis
Mondo ID	MONDO:0957271
OMIM	620376
UMLS	C5830525
MedGen	1841161
GARD	0026806
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › autoinflammatory disease, systemic, with vasculitis

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 syndrome of childhood, granulomatous autoinflammatory syndrome of childhood, autoinflammatory disease, multisystem, with immune dysregulation, X-linked, PAPASH syndrome, Sharpin-related autoinflammatory 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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1895415	NM_002350.4(LYN):c.1519C>T (p.Gln507Ter)	LYN	Pathogenic	no assertion criteria provided
1895416	NM_002350.4(LYN):c.1523A>T (p.Tyr508Phe)	LYN	Pathogenic	no assertion criteria provided
1895417	NM_002350.4(LYN):c.1524C>G (p.Tyr508Ter)	LYN	Pathogenic	no assertion criteria provided
2502324	NM_002350.4(LYN):c.1522T>C (p.Tyr508His)	LYN	Pathogenic	no assertion criteria provided
3065788	NM_002350.4(LYN):c.488G>T (p.Gly163Val)	LYN	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
LYN	Strong	Autosomal dominant	autoinflammatory disease, systemic, with vasculitis	3

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
LYN	HGNC:6735	ENSG00000254087	P07948	Tyrosine-protein kinase Lyn	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LYN	Tyrosine-protein kinase Lyn	Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integr…

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LYN	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom

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
LYN	263	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LYN	5,710

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LYN	P07948	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 68. 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
CD22 mediated BCR regulation	1	2284.0×	0.006	LYN
Erythropoietin activates Phospholipase C gamma (PLCG)	1	1631.4×	0.006	LYN
Erythropoietin activates STAT5	1	1631.4×	0.006	LYN
Assembly and Release of Dengue Virus Virions	1	1427.5×	0.006	LYN
Signaling by KIT in disease	1	1142.0×	0.006	LYN
Signaling by Erythropoietin	1	1038.2×	0.006	LYN
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	951.7×	0.006	LYN
FCGR activation	1	878.5×	0.006	LYN
PECAM1 interactions	1	878.5×	0.006	LYN
Erythropoietin activates RAS	1	761.3×	0.006	LYN
Platelet Adhesion to exposed collagen	1	671.8×	0.006	LYN
Regulation of KIT signaling	1	601.0×	0.006	LYN
Role of LAT2/NTAL/LAB on calcium mobilization	1	601.0×	0.006	LYN
Signaling by CSF3 (G-CSF)	1	571.0×	0.006	LYN
Co-inhibition by CTLA4	1	519.1×	0.006	LYN
CD209 (DC-SIGN) signaling	1	519.1×	0.006	LYN
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	519.1×	0.006	LYN
Regulation of signaling by CBL	1	496.5×	0.006	LYN
Growth hormone receptor signaling	1	475.8×	0.006	LYN
Inactivation of CSF3 (G-CSF) signaling	1	439.2×	0.006	LYN
Regulation of T cell activation by CD28 family	1	423.0×	0.006	LYN
Dectin-2 family	1	423.0×	0.006	LYN
G1 Phase	1	393.8×	0.006	LYN
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.006	LYN
Leishmania parasite growth and survival	1	393.8×	0.006	LYN
Co-stimulation by CD28	1	380.7×	0.006	LYN
EPHA-mediated growth cone collapse	1	380.7×	0.006	LYN
FCERI mediated Ca+2 mobilization	1	356.9×	0.006	LYN
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.006	LYN
FCERI mediated MAPK activation	1	346.1×	0.006	LYN

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 myeloid leukocyte differentiation	1	16852.0×	0.001	LYN
C-X-C chemokine receptor CXCR4 signaling pathway	1	16852.0×	0.001	LYN
regulation of monocyte chemotaxis	1	16852.0×	0.001	LYN
Fc receptor mediated stimulatory signaling pathway	1	8426.0×	0.001	LYN
regulation of B cell apoptotic process	1	8426.0×	0.001	LYN
response to sterol depletion	1	8426.0×	0.001	LYN
positive regulation of oligodendrocyte progenitor proliferation	1	8426.0×	0.001	LYN
regulation of mast cell activation	1	5617.3×	0.002	LYN
negative regulation of mast cell proliferation	1	5617.3×	0.002	LYN
tolerance induction to self antigen	1	4213.0×	0.002	LYN
eosinophil differentiation	1	4213.0×	0.002	LYN
positive regulation of dendritic cell apoptotic process	1	4213.0×	0.002	LYN
histamine secretion by mast cell	1	3370.4×	0.002	LYN
platelet degranulation	1	3370.4×	0.002	LYN
positive regulation of Fc receptor mediated stimulatory signaling pathway	1	3370.4×	0.002	LYN
positive regulation of mast cell proliferation	1	3370.4×	0.002	LYN
Fc receptor mediated inhibitory signaling pathway	1	2808.7×	0.002	LYN
interleukin-5-mediated signaling pathway	1	2808.7×	0.002	LYN
regulation of erythrocyte differentiation	1	2808.7×	0.002	LYN
regulation of B cell receptor signaling pathway	1	2808.7×	0.002	LYN
negative regulation of toll-like receptor 2 signaling pathway	1	2407.4×	0.002	LYN
regulation of platelet aggregation	1	2407.4×	0.002	LYN
negative regulation of intracellular signal transduction	1	2106.5×	0.002	LYN
immune response-regulating cell surface receptor signaling pathway	1	1872.4×	0.002	LYN
regulation of cell adhesion mediated by integrin	1	1872.4×	0.002	LYN
regulation of mast cell degranulation	1	1872.4×	0.002	LYN
response to carbohydrate	1	1685.2×	0.002	LYN
positive regulation of amyloid precursor protein catabolic process	1	1685.2×	0.002	LYN
growth hormone receptor signaling pathway via JAK-STAT	1	1532.0×	0.002	LYN
neuroinflammatory response	1	1532.0×	0.002	LYN

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
LYN	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LYN	83	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	LYN
AFATINIB	4	LYN
FEDRATINIB	4	LYN
TIVOZANIB	4	LYN
SORAFENIB	4	LYN
DASATINIB ANHYDROUS	4	LYN
NICLOSAMIDE	4	LYN
NERATINIB	4	LYN
INFIGRATINIB PHOSPHATE	4	LYN
INFIGRATINIB	4	LYN
IBRUTINIB	4	LYN
ENTRECTINIB	4	LYN
DABRAFENIB	4	LYN
CABOZANTINIB	4	LYN
CERITINIB	4	LYN
VANDETANIB	4	LYN
NILOTINIB	4	LYN
BOSUTINIB	4	LYN
BRIGATINIB	4	LYN
PAZOPANIB	4	LYN
NINTEDANIB	4	LYN
SUNITINIB	4	LYN
DASATINIB	4	LYN
ERLOTINIB	4	LYN
TIRBANIBULIN	4	LYN
QUIZARTINIB	4	LYN
CRIZOTINIB	4	LYN
MIDOSTAURIN	4	LYN
GEFITINIB	4	LYN
IMATINIB	4	LYN

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
LYN	820	Binding:814, ADMET:4, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LYN	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
LYN	820

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

30 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)
PONATINIB	4	LYN
AFATINIB	4	LYN
FEDRATINIB	4	LYN
TIVOZANIB	4	LYN
SORAFENIB	4	LYN
DASATINIB ANHYDROUS	4	LYN
NICLOSAMIDE	4	LYN
NERATINIB	4	LYN
INFIGRATINIB PHOSPHATE	4	LYN
INFIGRATINIB	4	LYN
IBRUTINIB	4	LYN
ENTRECTINIB	4	LYN
DABRAFENIB	4	LYN
CABOZANTINIB	4	LYN
CERITINIB	4	LYN
VANDETANIB	4	LYN
NILOTINIB	4	LYN
BOSUTINIB	4	LYN
BRIGATINIB	4	LYN
PAZOPANIB	4	LYN
NINTEDANIB	4	LYN
SUNITINIB	4	LYN
DASATINIB	4	LYN
ERLOTINIB	4	LYN
TIRBANIBULIN	4	LYN
QUIZARTINIB	4	LYN
CRIZOTINIB	4	LYN
MIDOSTAURIN	4	LYN
GEFITINIB	4	LYN
IMATINIB	4	LYN

Druggability pyramid

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

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