Molecules

All signalling molecules tracked across rare diseases on Kipine, with evidence-linked profiles and cross-disease expression data.

70 molecules tracked

Molecule6 diseases

IL-1β

Central pro-inflammatory cytokine driving systemic inflammation

Adult-Onset Still's Disease · ElevatedCryopyrin-Associated Periodic Syndromes · elevatedCryopyrin-Associated Periodic Syndromes · elevatedFamilial Mediterranean Fever · ElevatedSchnitzler Syndrome · ElevatedTNF Receptor-Associated Periodic Syndrome · Elevated
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Molecule4 diseases

Caspase-1

Effector protease of the inflammasome; cleaves pro-IL-1β and pro-IL-18

Adult-Onset Still's Disease · UpregulatedCryopyrin-Associated Periodic Syndromes · elevatedFamilial Mediterranean Fever · Constitutively activatedSchnitzler Syndrome · Constitutively active
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Molecule4 diseases

IL-18

Key cytokine uniquely elevated in AOSD; drives MAS and IFN-γ production

Adult-Onset Still's Disease · Markedly elevated (up to 1000-fold)Cryopyrin-Associated Periodic Syndromes · elevatedFamilial Mediterranean Fever · ElevatedSchnitzler Syndrome · Elevated
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Molecule4 diseases

IL-6

Pleiotropic cytokine driving acute-phase response and joint destruction

Adult-Onset Still's Disease · ElevatedCryopyrin-Associated Periodic Syndromes · elevatedSchnitzler Syndrome · ElevatedTNF Receptor-Associated Periodic Syndrome · Elevated
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Molecule3 diseases

Gasdermin D

Pore-forming protein

Cryopyrin-Associated Periodic Syndromes · dysregulatedFamilial Mediterranean Fever · Cleaved/activatedSchnitzler Syndrome · Active
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Molecule3 diseases

NF-κB

Transcription factor

Cryopyrin-Associated Periodic Syndromes · elevatedSchnitzler Syndrome · Persistently activeTNF Receptor-Associated Periodic Syndrome · Constitutively activated
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Molecule3 diseases

TNF-α

Pro-inflammatory cytokine contributing to systemic inflammation

Adult-Onset Still's Disease · ElevatedSchnitzler Syndrome · ElevatedTNF Receptor-Associated Periodic Syndrome · Elevated during attacks
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Molecule2 diseases

ASC (PYCARD)

Inflammasome adaptor protein

Cryopyrin-Associated Periodic Syndromes · dysregulatedFamilial Mediterranean Fever · Essential for pyrin inflammasome
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Molecule2 diseases

MYD88

TLR signalling adaptor

Schnitzler Syndrome · L265P in ~30%Waldenström's Macroglobulinemia · L265P gain-of-function in >90%
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Molecule2 diseases

NF-kB

Transcription factor driving inflammatory gene expression

Systemic Mastocytosis · Constitutively activatedWaldenström's Macroglobulinemia · Constitutively activated
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Molecule2 diseases

NLRP3 inflammasome

Central innate immune sensor driving caspase-1 activation and IL-1β/IL-18 maturation

Adult-Onset Still's Disease · Overexpressed and hyperactivatedTNF Receptor-Associated Periodic Syndrome · Hyperactivated
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Molecule2 diseases

Serum Amyloid A (SAA)

Acute-phase reactant and amyloid precursor

Familial Mediterranean Fever · ElevatedTNF Receptor-Associated Periodic Syndrome · Markedly elevated
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14-3-3 proteins

Pyrin inhibitory chaperones

Familial Mediterranean Fever · Reduced binding to mutant pyrin
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AKT / mTOR

Downstream effectors promoting MC proliferation and survival

Systemic Mastocytosis · Constitutively activated
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Anti-C1q IgG autoantibodies

Pathogenic autoantibody

Hypocomplementemic Urticarial Vasculitis Syndrome · Elevated (90-100% of patients)
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BTK

B-cell receptor kinase

Schnitzler Syndrome · Active
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BTK (Bruton's Tyrosine Kinase)

Key signaling kinase downstream of MYD88

Waldenström's Macroglobulinemia · Constitutively activated
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C1q

Central autoantigen and complement initiator

Hypocomplementemic Urticarial Vasculitis Syndrome · Depleted (consumed)
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C3

Central complement component

Hypocomplementemic Urticarial Vasculitis Syndrome · Depleted (consumed)
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C4

Classical pathway component

Hypocomplementemic Urticarial Vasculitis Syndrome · Depleted (consumed)
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C5a

Anaphylatoxin and neutrophil chemoattractant

Hypocomplementemic Urticarial Vasculitis Syndrome · Generated during activation
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CCL2

Monocyte chemoattractant

Schnitzler Syndrome · Elevated
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CRP

Acute phase protein

Cryopyrin-Associated Periodic Syndromes · elevated
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CXCR4

Chemokine receptor driving bone marrow homing

Waldenström's Macroglobulinemia · WHIM-like mutations in ~30-40%
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DNASE1L3

Extracellular DNA clearance enzyme

Hypocomplementemic Urticarial Vasculitis Syndrome · Lost (in familial HUVS)
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Eosinophils

Effector granulocytes

Chronic Rhinosinusitis with Nasal Polyps · Massively infiltrated in tissue
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Eotaxin-3 (CCL26)

Eosinophil chemoattractant

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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Ferritin

Acute-phase reactant and hallmark biomarker; synthesis driven by multiple cytokines

Adult-Onset Still's Disease · Markedly elevated
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HCK

SRC family kinase transactivated by mutated MYD88

Waldenström's Macroglobulinemia · Upregulated
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Histamine

Primary vasoactive mediator causing flushing, pruritus, GI symptoms

Systemic Mastocytosis · Elevated (released during degranulation)
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IFN-γ

Th1 cytokine linking innate and adaptive immunity; drives macrophage activation

Adult-Onset Still's Disease · Elevated
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IgE

Allergic effector immunoglobulin

Chronic Rhinosinusitis with Nasal Polyps · Elevated (local and systemic)
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IgM (Immunoglobulin M)

Pathogenic paraprotein causing end-organ damage

Waldenström's Macroglobulinemia · Elevated (monoclonal)
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IgM (monoclonal)

Diagnostic paraprotein

Schnitzler Syndrome · Present (obligate)
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IL-12 (Interleukin-12)

Novel biomarker — consistently elevated and correlates with disease activity

POEMS Syndrome · Markedly elevated
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IL-13

Effector cytokine / tissue remodeller

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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IL-1beta (Interleukin-1 beta)

Pro-inflammatory cytokine elevated in POEMS

POEMS Syndrome · Elevated
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IL-25

Epithelial alarmin

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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IL-33

Epithelial alarmin

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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IL-4

Type 2 master cytokine

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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IL-5

Eosinophil survival factor

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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IL-6 (Interleukin-6)

Upstream inducer of VEGF — overexpressed by clonal plasma cells

POEMS Syndrome · Elevated
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ILC2s

Innate type 2 lymphoid cells

Chronic Rhinosinusitis with Nasal Polyps · Expanded in polyp tissue
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Immunoglobulin Lambda Light Chain (IGLV1-44/IGLV1-40)

Monoclonal protein produced by clonal plasma cells — near-universal lambda restriction

POEMS Syndrome · Monoclonal overproduction
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IRAK4

Myddosome kinase component

Waldenström's Macroglobulinemia · Constitutively activated
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KIT (CD117)

Central oncogenic driver — mutated receptor tyrosine kinase

Systemic Mastocytosis · Constitutively activated (D816V mutation)
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MAPK pathway

Signalling cascade — enhanced by mutant TNFR1

TNF Receptor-Associated Periodic Syndrome · Hyperactivated
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Mitochondrial ROS

Oxidative stress mediator — inflammasome activator

TNF Receptor-Associated Periodic Syndrome · Elevated
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MRP8/14 (S100A8/A9)

Neutrophil inflammatory markers

Schnitzler Syndrome · Elevated
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MUC5AC

Gel-forming mucin

Chronic Rhinosinusitis with Nasal Polyps · Upregulated
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NLRP3

Inflammasome sensor

Schnitzler Syndrome · Dysregulated
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NLRP3 (Cryopyrin)

Inflammasome sensor and scaffold

Cryopyrin-Associated Periodic Syndromes · mutated
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Periostin

Extracellular matrix protein

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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PI3K

Central kinase in mast cell survival signaling

Systemic Mastocytosis · Constitutively activated
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PKN1/PKN2

Pyrin phosphorylating kinases

Familial Mediterranean Fever · Normal (regulatory)
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Pyrin (MEFV)

Inflammasome sensor protein (mutated in FMF)

Familial Mediterranean Fever · Gain-of-function mutations
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RhoA GTPase

Upstream guard target

Familial Mediterranean Fever · Normal (sensor target)
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S. aureus enterotoxins

Superantigen / disease perpetuator

Chronic Rhinosinusitis with Nasal Polyps · Present in polyp tissue
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S100A8/A9 (Calprotectin)

Alarmin and DAMP released by activated phagocytes; amplifies TLR4 signaling

Adult-Onset Still's Disease · Elevated
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SAA (Serum Amyloid A)

Acute phase protein

Cryopyrin-Associated Periodic Syndromes · elevated
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SCF (Stem Cell Factor / KIT Ligand)

Normal KIT ligand — bypassed in D816V+ disease

Systemic Mastocytosis · Normal
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STAT5

Key transcription factor in KIT D816V signaling

Systemic Mastocytosis · Constitutively phosphorylated
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TGF-beta1 (Transforming Growth Factor beta 1)

Anti-inflammatory cytokine — paradoxically decreased in POEMS

POEMS Syndrome · Decreased
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TNF-alpha

Pro-inflammatory cytokine

Hypocomplementemic Urticarial Vasculitis Syndrome · Elevated
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TNF-alpha (Tumor Necrosis Factor alpha)

Pro-inflammatory cytokine elevated in POEMS

POEMS Syndrome · Elevated
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TNFAIP3 (A20)

NF-kB negative regulator (tumour suppressor)

Waldenström's Macroglobulinemia · Deleted in ~50% (6q deletion)
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TNFR1 (TNFRSF1A)

Mutated receptor — primary disease gene product

TNF Receptor-Associated Periodic Syndrome · Misfolded / ER-retained
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Tryptase

Key diagnostic biomarker and mast cell mediator

Systemic Mastocytosis · Elevated
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TSLP

Epithelial alarmin

Chronic Rhinosinusitis with Nasal Polyps · Elevated
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VEGF (Vascular Endothelial Growth Factor)

Central pathogenic driver — mediates vascular permeability, edema, organomegaly, neuropathy

POEMS Syndrome · Markedly elevated (5-10x normal)
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