Leprosy, susceptibility to, 1
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Also known as leprosy, paucibacillary type, susceptibility toLPRS1
Summary
Leprosy, susceptibility to, 1 (MONDO:0012358) is a disease with 13 cohort genes.
At a glance
- Cohort genes: 13
- ClinVar variants: 20
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | leprosy, susceptibility to, 1 |
| Mondo ID | MONDO:0012358 |
| OMIM | 609888 |
| UMLS | C1835932 |
| MedGen | 332089 |
| Is cancer (heuristic) | no |
Also known as: leprosy, paucibacillary type, susceptibility to · leprosy, susceptibility to, 1 · LPRS1
Data availability: 20 ClinVar variants.
Disease family
Classification path: disease susceptibility › inherited disease susceptibility › leprosy, susceptibility to, 1
Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder
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
20 retrieved; paginated sample, class counts are floors:
10 uncertain risk allele, 4 benign, 2 confers sensitivity, 1 pathogenic, 1 protective, 1 uncertain risk allele; risk factor, 1 conflicting classifications of pathogenicity; protective
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1710531 | NC_000001.11:g.206773552T>C | IL10 | Pathogenic | criteria provided, single submitter |
| 1710528 | NM_144974.5(CCDC122):c.555+178G>T | CCDC122 | Uncertain risk allele | no assertion criteria provided |
| 1710529 | NC_000013.11:g.43904864A>G | LACC1 | Uncertain risk allele | no assertion criteria provided |
| 1710527 | NM_198578.4(LRRK2):c.4739-122T>A | LRRK2 | Uncertain risk allele | no assertion criteria provided |
| 64687 | NM_002438.4(MRC1):c.1186G>A (p.Gly396Ser) | MRC1 | Uncertain risk allele; risk factor | no assertion criteria provided |
| 1710530 | NM_001370466.1(NOD2):c.459+168G>A | NOD2 | Uncertain risk allele | no assertion criteria provided |
| 1710534 | NM_018622.7(PARL):c.511+4771C>T | PARL | Uncertain risk allele | no assertion criteria provided |
| 1710533 | NC_000001.11:g.20651565G>A | PINK1 | Uncertain risk allele | no assertion criteria provided |
| 1710536 | NC_000008.11:g.89811459A>G | RIPK2 | Uncertain risk allele | no assertion criteria provided |
| 1710537 | NM_003821.6(RIPK2):c.483+789G>A | RIPK2 | Uncertain risk allele | no assertion criteria provided |
| 1710526 | NM_005118.4(TNFSF15):c.*4960A>G | TNFSF15 | Uncertain risk allele | no assertion criteria provided |
| 1710538 | NC_000009.12:g.114776054C>T | TNFSF15 | Uncertain risk allele | no assertion criteria provided |
| 8360 | NM_003263.4(TLR1):c.1805G>T (p.Ser602Ile) | TLR1 | Conflicting classifications of pathogenicity; protective | no assertion criteria provided |
| 1710532 | NM_001370466.1(NOD2):c.460-3786A>G | NOD2 | confers sensitivity | no assertion criteria provided |
| 1710535 | NM_006068.5(TLR6):c.745T>G (p.Ser249Ala) | TLR6 | protective | no assertion criteria provided |
| 1710525 | NM_005118.4(TNFSF15):c.211-2855G>C | TNFSF15 | confers sensitivity | no assertion criteria provided |
| 1300105 | NM_153218.4(LACC1):c.760A>G (p.Ile254Val) | CCDC122 | Benign | criteria provided, multiple submitters, no conflicts |
| 319482 | NM_001370466.1(NOD2):c.*397A>C | CYLD-AS1 | Benign | criteria provided, multiple submitters, no conflicts |
| 1166836 | NC_000001.11:g.206773289A>G | IL10 | Benign | criteria provided, single submitter |
| 308647 | NM_198578.4(LRRK2):c.7190T>C (p.Met2397Thr) | LRRK2 | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TNFSF15 | Orphanet:186 | Primary biliary cholangitis |
| PINK1 | Orphanet:2828 | Young-onset Parkinson disease |
| LRRK2 | Orphanet:2828 | Young-onset Parkinson disease |
| LRRK2 | Orphanet:411602 | Hereditary late-onset Parkinson disease |
| LACC1 | Orphanet:85414 | Systemic-onset juvenile idiopathic arthritis |
| NOD2 | Orphanet:90340 | Blau syndrome |
| IL10 | Orphanet:117 | Behçet disease |
| IL10 | Orphanet:238569 | Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome |
| IL10 | Orphanet:536 | Systemic lupus erythematosus |
Cohort genes → proteins
13 cohort genes, 12 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 13 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| RIPK2 | HGNC:10020 | ENSG00000104312 | O43353 | Receptor-interacting serine/threonine-protein kinase 2 | clinvar |
| TLR1 | HGNC:11847 | ENSG00000174125 | Q15399 | Toll-like receptor 1 | clinvar |
| TNFSF15 | HGNC:11931 | ENSG00000181634 | O95150 | Tumor necrosis factor ligand superfamily member 15 | clinvar |
| PINK1 | HGNC:14581 | ENSG00000158828 | Q9BXM7 | Serine/threonine-protein kinase PINK1, mitochondrial | clinvar |
| TLR6 | HGNC:16711 | ENSG00000174130 | Q9Y2C9 | Toll-like receptor 6 | clinvar |
| PARL | HGNC:18253 | ENSG00000175193 | Q9H300 | Presenilin-associated rhomboid-like protein, mitochondrial | clinvar |
| LRRK2 | HGNC:18618 | ENSG00000188906 | Q5S007 | Leucine-rich repeat serine/threonine-protein kinase 2 | clinvar |
| CCDC122 | HGNC:26478 | ENSG00000151773 | Q5T0U0 | Coiled-coil domain-containing protein 122 | clinvar |
| LACC1 | HGNC:26789 | ENSG00000179630 | Q8IV20 | Purine nucleoside phosphorylase LACC1 | clinvar |
| NOD2 | HGNC:5331 | ENSG00000167207 | Q9HC29 | Nucleotide-binding oligomerization domain-containing protein 2 | clinvar |
| CYLD-AS1 | HGNC:55352 | ENSG00000261644 | CYLD antisense RNA 1 | clinvar | |
| IL10 | HGNC:5962 | ENSG00000136634 | P22301 | Interleukin-10 | clinvar |
| MRC1 | HGNC:7228 | ENSG00000260314 | P22897 | Macrophage mannose receptor 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| RIPK2 | Receptor-interacting serine/threonine-protein kinase 2 | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses. |
| TLR1 | Toll-like receptor 1 | Participates in the innate immune response to microbial agents. |
| TNFSF15 | Tumor necrosis factor ligand superfamily member 15 | Receptor for TNFRSF25 and TNFRSF6B. |
| PINK1 | Serine/threonine-protein kinase PINK1, mitochondrial | Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. |
| TLR6 | Toll-like receptor 6 | Participates in the innate immune response to Gram-positive bacteria and fungi. |
| PARL | Presenilin-associated rhomboid-like protein, mitochondrial | Required for the control of apoptosis during postnatal growth. |
| LRRK2 | Leucine-rich repeat serine/threonine-protein kinase 2 | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking. |
| LACC1 | Purine nucleoside phosphorylase LACC1 | Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine, guanosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine, guanine and hypoxanthine. |
| NOD2 | Nucleotide-binding oligomerization domain-containing protein 2 | Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity. |
| IL10 | Interleukin-10 | Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. |
| MRC1 | Macrophage mannose receptor 1 | Mediates the endocytosis of glycoproteins by macrophages. |
Protein-family classification
Druggable: 4 · Difficult: 0 · Unknown: 9 · Druggable fraction: 0.31
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 | 3 | 6.4× | 0.031 |
| Protease | 1 | 2.8× | 0.302 |
| Other/Unknown | 9 | 1.2× | 0.302 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| RIPK2 | Kinase | yes | 2.7.10.2 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, CARD |
| TLR1 | Other/Unknown | no | TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt | |
| TNFSF15 | Other/Unknown | no | TNF_dom, TNF, Tumour_necrosis_fac-like_dom | |
| PINK1 | Kinase | yes | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf | |
| TLR6 | Other/Unknown | no | TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt | |
| PARL | Protease | yes | 3.4.21.105 | Peptidase_S54_rhomboid_dom, Rhomboid-like_sf, Rhomboid_protease_S54 |
| LRRK2 | Kinase | yes | Prot_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp | |
| CCDC122 | Other/Unknown | no | ||
| LACC1 | Other/Unknown | no | Cu_polyphenol_OxRdtase, Cytotoxic_necrot_fac-like_cat, Cu_polyphenol_OxRdtase_sf | |
| NOD2 | Other/Unknown | no | CARD, Leu-rich_rpt, NACHT_NTPase | |
| CYLD-AS1 | Other/Unknown | no | ||
| IL10 | Other/Unknown | no | IL-10, 4_helix_cytokine-like_core, IL-10_CS | |
| MRC1 | Other/Unknown | no | FN_type2_dom, Ricin_B_lectin, C-type_lectin-like |
Expression context
Cohort genes with no expression data: 0.
12 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) | 13 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| monocyte | 7 |
| leukocyte | 6 |
| mononuclear cell | 4 |
| cartilage tissue | 3 |
| duodenum | 1 |
| jejunal mucosa | 1 |
| gastrocnemius | 1 |
| gluteal muscle | 1 |
| tendon of biceps brachii | 1 |
| olfactory segment of nasal mucosa | 1 |
| buccal mucosa cell | 1 |
| body of pancreas | 1 |
| calcaneal tendon | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| corpus callosum | 1 |
| medial globus pallidus | 1 |
| palpebral conjunctiva | 1 |
| granulocyte | 1 |
| gall bladder | 1 |
| vermiform appendix | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| RIPK2 | 249 | ubiquitous | marker | cartilage tissue, monocyte, mononuclear cell |
| TLR1 | 218 | broad | marker | monocyte, mononuclear cell, leukocyte |
| TNFSF15 | 149 | broad | marker | cartilage tissue, jejunal mucosa, duodenum |
| PINK1 | 295 | ubiquitous | marker | tendon of biceps brachii, gastrocnemius, gluteal muscle |
| TLR6 | 157 | broad | marker | monocyte, mononuclear cell, leukocyte |
| PARL | 145 | ubiquitous | marker | monocyte, leukocyte, olfactory segment of nasal mucosa |
| LRRK2 | 220 | broad | marker | buccal mucosa cell, monocyte, leukocyte |
| CCDC122 | 161 | ubiquitous | marker | calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, body of pancreas |
| LACC1 | 243 | ubiquitous | marker | palpebral conjunctiva, corpus callosum, medial globus pallidus |
| NOD2 | 189 | broad | marker | monocyte, mononuclear cell, leukocyte |
| CYLD-AS1 | 126 | yes | granulocyte, monocyte, leukocyte | |
| IL10 | 158 | broad | marker | vermiform appendix, gall bladder, cartilage tissue |
| MRC1 | 255 | broad | marker | lower lobe of lung, visceral pleura, secondary oocyte |
Protein interactions among cohort
Intra-cohort edges: 17.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LRRK2 | 7,628 |
| IL10 | 6,185 |
| PINK1 | 4,175 |
| NOD2 | 3,527 |
| RIPK2 | 3,097 |
| TLR1 | 3,071 |
| MRC1 | 2,807 |
| TLR6 | 1,940 |
| PARL | 1,818 |
| TNFSF15 | 1,452 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| CCDC122 | LACC1 | string_interaction |
| CCDC122 | LRRK2 | string_interaction |
| CCDC122 | NOD2 | string_interaction |
| CCDC122 | RIPK2 | string_interaction |
| CCDC122 | TLR1 | string_interaction |
| CCDC122 | TNFSF15 | string_interaction |
| IL10 | MRC1 | string_interaction |
| IL10 | TLR6 | string_interaction |
| LACC1 | LRRK2 | string_interaction |
| LACC1 | NOD2 | string_interaction |
| LACC1 | RIPK2 | string_interaction |
| LACC1 | TNFSF15 | string_interaction |
| LRRK2 | PINK1 | string_interaction |
| NOD2 | RIPK2 | biogrid_interaction, intact, string_interaction |
| NOD2 | TNFSF15 | string_interaction |
| PARL | PINK1 | string_interaction |
| TLR1 | TLR6 | biogrid_interaction, intact, string_interaction |
Structural data
PDB: 8 · AlphaFold-only: 4 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| LRRK2 | Q5S007 | 44 |
| RIPK2 | O43353 | 33 |
| MRC1 | P22897 | 24 |
| IL10 | P22301 | 9 |
| TNFSF15 | O95150 | 7 |
| TLR1 | Q15399 | 6 |
| PINK1 | Q9BXM7 | 6 |
| TLR6 | Q9Y2C9 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CCDC122 | Q5T0U0 | 89.26 |
| LACC1 | Q8IV20 | 88.62 |
| NOD2 | Q9HC29 | 84.76 |
| PARL | Q9H300 | 77.67 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 43. Enrichment computed across 13 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| MyD88 deficiency (TLR2/4) | 2 | 120.2× | 0.001 | TLR1, TLR6 |
| IRAK4 deficiency (TLR2/4) | 2 | 114.2× | 0.001 | TLR1, TLR6 |
| JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 | 2 | 103.8× | 0.001 | RIPK2, NOD2 |
| activated TAK1 mediates p38 MAPK activation | 2 | 99.3× | 0.001 | RIPK2, NOD2 |
| Regulation of TLR by endogenous ligand | 2 | 99.3× | 0.001 | TLR1, TLR6 |
| SARS-CoV-2 activates/modulates innate and adaptive immune responses | 3 | 26.8× | 0.001 | RIPK2, TLR1, NOD2 |
| NOD1/2 Signaling Pathway | 2 | 63.4× | 0.003 | RIPK2, NOD2 |
| TAK1-dependent IKK and NF-kappa-B activation | 2 | 60.1× | 0.003 | RIPK2, NOD2 |
| Ovarian tumor domain proteases | 2 | 55.7× | 0.003 | RIPK2, NOD2 |
| MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 2 | 30.4× | 0.008 | TLR1, TLR6 |
| ER-Phagosome pathway | 2 | 25.9× | 0.010 | TLR1, TLR6 |
| Interleukin-1 signaling | 2 | 24.8× | 0.010 | RIPK2, NOD2 |
| PTK6 promotes HIF1A stabilization | 1 | 163.1× | 0.019 | LRRK2 |
| Modulation by Mtb of host immune system | 1 | 163.1× | 0.019 | MRC1 |
| Infection with Mycobacterium tuberculosis | 1 | 114.2× | 0.023 | MRC1 |
| CD163 mediating an anti-inflammatory response | 1 | 114.2× | 0.023 | IL10 |
| p75NTR recruits signalling complexes | 1 | 87.8× | 0.029 | RIPK2 |
| FOXO-mediated transcription of cell death genes | 1 | 71.4× | 0.033 | PINK1 |
| Processing of SMDT1 | 1 | 63.4× | 0.035 | PARL |
| Signaling by PTK6 | 1 | 54.4× | 0.037 | LRRK2 |
| Signaling by Non-Receptor Tyrosine Kinases | 1 | 54.4× | 0.037 | LRRK2 |
| TNFs bind their physiological receptors | 1 | 39.4× | 0.049 | TNFSF15 |
| PINK1-PRKN Mediated Mitophagy | 1 | 35.7× | 0.052 | PINK1 |
| Bacterial Infection Pathways | 1 | 33.6× | 0.053 | MRC1 |
| Antigen processing-Cross presentation | 1 | 31.7× | 0.053 | MRC1 |
| Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation | 1 | 30.1× | 0.054 | IL10 |
| FCGR3A-mediated IL10 synthesis | 1 | 29.3× | 0.054 | IL10 |
| Beta defensins | 1 | 27.2× | 0.056 | TLR1 |
| Dengue Virus Attachment and Entry | 1 | 25.9× | 0.056 | MRC1 |
| Cross-presentation of soluble exogenous antigens (endosomes) | 1 | 25.4× | 0.056 | MRC1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| nucleotide-binding oligomerization domain containing 2 signaling pathway | 3 | 417.8× | 1e-05 | RIPK2, LACC1, NOD2 |
| regulation of reactive oxygen species metabolic process | 3 | 199.8× | 3e-05 | PINK1, PARL, LRRK2 |
| positive regulation of interleukin-6 production | 4 | 60.7× | 3e-05 | RIPK2, TLR1, TLR6, NOD2 |
| positive regulation of canonical NF-kappaB signal transduction | 5 | 33.0× | 3e-05 | RIPK2, TNFSF15, PINK1, TLR6, NOD2 |
| positive regulation of tumor necrosis factor production | 4 | 55.7× | 4e-05 | RIPK2, TLR1, LRRK2, NOD2 |
| regulation of synaptic vesicle transport | 2 | 1021.3× | 6e-05 | PINK1, LRRK2 |
| defense response to bacterium | 4 | 39.3× | 1e-04 | RIPK2, TLR6, NOD2, IL10 |
| cellular response to peptidoglycan | 2 | 510.7× | 2e-04 | RIPK2, NOD2 |
| positive regulation of protein K63-linked ubiquitination | 2 | 383.0× | 3e-04 | RIPK2, NOD2 |
| obsolete regulation of protein targeting to mitochondrion | 2 | 383.0× | 3e-04 | PINK1, PARL |
| positive regulation of interleukin-1 beta production | 3 | 70.7× | 3e-04 | RIPK2, TLR6, NOD2 |
| innate immune response | 5 | 15.3× | 3e-04 | RIPK2, TLR1, TLR6, LACC1, NOD2 |
| activation of NF-kappaB-inducing kinase activity | 2 | 306.4× | 4e-04 | TNFSF15, TLR6 |
| cellular response to muramyl dipeptide | 2 | 306.4× | 4e-04 | RIPK2, NOD2 |
| positive regulation of protein ubiquitination | 3 | 58.2× | 4e-04 | RIPK2, PINK1, LRRK2 |
| negative regulation of autophagosome assembly | 2 | 235.7× | 6e-04 | PINK1, LRRK2 |
| negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | 2 | 235.7× | 6e-04 | PINK1, IL10 |
| negative regulation of macroautophagy | 2 | 204.3× | 7e-04 | PINK1, LRRK2 |
| pattern recognition receptor signaling pathway | 2 | 180.2× | 8e-04 | LACC1, NOD2 |
| positive regulation of cytokine production involved in immune response | 2 | 180.2× | 8e-04 | LACC1, NOD2 |
| negative regulation of interleukin-8 production | 2 | 180.2× | 8e-04 | TLR6, IL10 |
| immune response | 4 | 17.1× | 9e-04 | TLR1, TNFSF15, TLR6, IL10 |
| regulation of mitochondrion organization | 2 | 153.2× | 1e-03 | PINK1, PARL |
| positive regulation of macrophage activation | 2 | 153.2× | 1e-03 | TLR6, IL10 |
| positive regulation of stress-activated MAPK cascade | 2 | 145.9× | 0.001 | RIPK2, NOD2 |
| negative regulation of intrinsic apoptotic signaling pathway | 2 | 139.3× | 0.001 | PINK1, PARL |
| microglial cell activation | 2 | 113.5× | 0.002 | TLR1, TLR6 |
| inflammatory response | 4 | 13.7× | 0.002 | RIPK2, TLR1, TLR6, LACC1 |
| toll-like receptor signaling pathway | 2 | 109.4× | 0.002 | TLR1, TLR6 |
| cellular response to lipopolysaccharide | 3 | 26.7× | 0.002 | NOD2, IL10, MRC1 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 10
Druggability breadth: 9 of 13 evidence-associated genes (69%) 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 |
|---|---|
| RIPK2 | PONATINIB |
| LRRK2 | PONATINIB |
| NOD2 | PACLITAXEL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| RIPK2 | 64 | 4 |
| LRRK2 | 42 | 4 |
| NOD2 | 6 | 4 |
| TLR1 | 0 | 0 |
| TNFSF15 | 0 | 0 |
| PINK1 | 0 | 0 |
| TLR6 | 0 | 0 |
| PARL | 0 | 0 |
| CCDC122 | 0 | 0 |
| LACC1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| PONATINIB | 4 | LRRK2, RIPK2 |
| AFATINIB | 4 | RIPK2 |
| VEMURAFENIB | 4 | RIPK2 |
| FEDRATINIB | 4 | LRRK2, RIPK2 |
| TIVOZANIB | 4 | RIPK2 |
| LENVATINIB | 4 | RIPK2 |
| AXITINIB | 4 | LRRK2, RIPK2 |
| SORAFENIB | 4 | RIPK2 |
| IBRUTINIB | 4 | RIPK2 |
| REGORAFENIB | 4 | RIPK2 |
| DABRAFENIB | 4 | RIPK2 |
| CABOZANTINIB | 4 | RIPK2 |
| DACOMITINIB ANHYDROUS | 4 | RIPK2 |
| VANDETANIB | 4 | LRRK2, RIPK2 |
| BOSUTINIB | 4 | LRRK2, RIPK2 |
| ENCORAFENIB | 4 | RIPK2 |
| GILTERITINIB | 4 | RIPK2 |
| PAZOPANIB | 4 | RIPK2 |
| DASATINIB | 4 | RIPK2 |
| ERLOTINIB | 4 | LRRK2, RIPK2 |
| LAPATINIB | 4 | RIPK2 |
| QUIZARTINIB | 4 | RIPK2 |
| CRIZOTINIB | 4 | RIPK2 |
| GEFITINIB | 4 | NOD2, RIPK2 |
| RUXOLITINIB | 4 | LRRK2 |
| PALBOCICLIB | 4 | LRRK2 |
| ENTRECTINIB | 4 | LRRK2 |
| TOFACITINIB CITRATE | 4 | LRRK2 |
| TOFACITINIB | 4 | LRRK2 |
| BRIGATINIB | 4 | LRRK2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| LRRK2 | 809 | Binding:799, ADMET:7, Functional:3 |
| RIPK2 | 455 | Binding:452, ADMET:3 |
| NOD2 | 126 | Binding:121, Functional:5 |
| TLR1 | 59 | Binding:59 |
| TLR6 | 28 | Binding:28 |
| PARL | 27 | Binding:27 |
| PINK1 | 24 | Binding:24 |
| MRC1 | 3 | Binding:3 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| RIPK2 | 2.7.10.2, 2.7.11.30 | non-specific protein-tyrosine kinase, receptor protein serine/threonine kinase |
| PARL | 3.4.21.105 | rhomboid protease |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| RIPK2 | 455 |
| LRRK2 | 809 |
| NOD2 | 126 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 12; 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 | LRRK2, RIPK2 |
| AFATINIB | 4 | RIPK2 |
| VEMURAFENIB | 4 | RIPK2 |
| FEDRATINIB | 4 | LRRK2, RIPK2 |
| TIVOZANIB | 4 | RIPK2 |
| LENVATINIB | 4 | RIPK2 |
| AXITINIB | 4 | LRRK2, RIPK2 |
| SORAFENIB | 4 | RIPK2 |
| IBRUTINIB | 4 | RIPK2 |
| REGORAFENIB | 4 | RIPK2 |
| DABRAFENIB | 4 | RIPK2 |
| CABOZANTINIB | 4 | RIPK2 |
| DACOMITINIB ANHYDROUS | 4 | RIPK2 |
| VANDETANIB | 4 | LRRK2, RIPK2 |
| BOSUTINIB | 4 | LRRK2, RIPK2 |
| ENCORAFENIB | 4 | RIPK2 |
| GILTERITINIB | 4 | RIPK2 |
| PAZOPANIB | 4 | RIPK2 |
| DASATINIB | 4 | RIPK2 |
| ERLOTINIB | 4 | LRRK2, RIPK2 |
| LAPATINIB | 4 | RIPK2 |
| QUIZARTINIB | 4 | RIPK2 |
| CRIZOTINIB | 4 | RIPK2 |
| GEFITINIB | 4 | NOD2, RIPK2 |
| RUXOLITINIB | 4 | LRRK2 |
| PALBOCICLIB | 4 | LRRK2 |
| ENTRECTINIB | 4 | LRRK2 |
| TOFACITINIB CITRATE | 4 | LRRK2 |
| TOFACITINIB | 4 | LRRK2 |
| BRIGATINIB | 4 | LRRK2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | RIPK2, LRRK2, NOD2 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | PINK1 |
| D | Druggable family + AlphaFold only, no drug | 1 | PARL |
| E | Difficult family or no structure, no drug | 8 | TLR1, TNFSF15, TLR6, CCDC122, LACC1, CYLD-AS1, IL10, MRC1 |
Undrugged target profiles
10 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CCDC122 | 0 | RIPK2, LRRK2, NOD2 |
| LACC1 | 0 | RIPK2, NOD2 |
| TLR1 | 59 | — |
| TNFSF15 | 0 | — |
| PINK1 | 24 | — |
| TLR6 | 28 | — |
| PARL | 27 | — |
| CYLD-AS1 | 0 | — |
| IL10 | 0 | — |
| MRC1 | 3 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.