Malaria, susceptibility to

disease
On this page

Also known as malaria, cerebral, reduced risk ofmalaria, cerebral, resistance tomalaria, cerebral, susceptibility tomalaria, protection againstmalaria, resistance tomalaria, Severe, resistance tomalaria, Severe, susceptibility tomalaria, vivax, protection againstresistance to malaria due to G6PD deficiency

Summary

Malaria, susceptibility to (MONDO:0021024) is a disease with 12 cohort genes.

At a glance

  • Cohort genes: 12
  • ClinVar variants: 340

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namemalaria, susceptibility to
Mondo IDMONDO:0021024
OMIM611162
UMLSC1970028
MedGen370149
Is cancer (heuristic)no

Also known as: malaria, cerebral, reduced risk of · malaria, cerebral, resistance to · malaria, cerebral, susceptibility to · malaria, protection against · malaria, resistance to · malaria, Severe, resistance to · malaria, Severe, susceptibility to · malaria, susceptibility to · malaria, vivax, protection against · resistance to malaria due to G6PD deficiency

Data availability: 340 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease susceptibility › inherited disease susceptibilitymalaria, susceptibility to

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, leprosy, susceptibility to, 1, 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, 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

Subtypes (1): malaria, mild, susceptibility to

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

340 retrieved; paginated sample, class counts are floors:

131 uncertain significance, 62 pathogenic/likely pathogenic, 56 pathogenic, 50 conflicting classifications of pathogenicity, 17 likely pathogenic, 11 benign/likely benign, 10 likely benign, 2 benign, 1 risk factor

ClinVarVariant (HGVS)GeneClassificationReview
1012319NM_001001548.3(CD36):c.1142T>G (p.Leu381Ter)CD36Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
225309NM_001001548.3(CD36):c.332_333del (p.Thr111fs)CD36Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
587500NM_001001548.3(CD36):c.784dup (p.Gln262fs)CD36Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
100057NM_000402.4(G6PD):c.653C>T (p.Ser218Phe)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
100058NM_000402.4(G6PD):c.1466G>T (p.Arg489Leu)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
100059NM_000402.4(G6PD):c.1478G>A (p.Arg493His)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
10362NM_000402.4(G6PD):c.944G>A (p.Arg315His)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10363NM_000402.4(G6PD):c.1093G>A (p.Ala365Thr)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
10367NM_000402.4(G6PD):c.577G>A (p.Gly193Ser)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10371NM_000402.4(G6PD):c.1429G>A (p.Gly477Arg)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10372NM_000402.4(G6PD):c.934G>C (p.Asp312His)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10376NM_000402.4(G6PD):c.1250G>A (p.Arg417His)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
10386NM_000402.4(G6PD):c.961G>A (p.Val321Met)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10388NM_001360016.2(G6PD):c.968T>C (p.Leu323Pro)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10391NM_000402.4(G6PD):c.682C>T (p.Arg228Cys)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
10393NM_000402.4(G6PD):c.583A>G (p.Asn195Asp)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10401NM_000402.4(G6PD):c.1039G>A (p.Glu347Lys)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10402NM_000402.4(G6PD):c.233T>C (p.Ile78Thr)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10403NM_000402.4(G6PD):c.185A>G (p.His62Arg)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10404NM_000402.4(G6PD):c.482G>T (p.Gly161Val)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10406NM_000402.4(G6PD):c.221C>G (p.Ala74Gly)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10407NM_000402.4(G6PD):c.607T>C (p.Phe203Leu)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
10411G6PD NARAG6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10417NM_000402.4(G6PD):c.683G>A (p.Arg228His)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
10422NM_000402.4(G6PD):c.1466G>C (p.Arg489Pro)G6PDPathogeniccriteria provided, multiple submitters, no conflicts
1068217NM_001360016.2(G6PD):c.1004C>A (p.Ala335Asp)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1075240NM_001360016.2(G6PD):c.406C>T (p.Arg136Cys)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1722638NM_001360016.2(G6PD):c.1387C>T (p.Arg463Cys)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1722734NM_001360016.2(G6PD):c.497G>A (p.Arg166His)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
37123NM_000402.4(G6PD):c.292G>A (p.Val98Met)G6PDPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 40 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SCN8AOrphanet:178469Autosomal dominant non-syndromic intellectual disability
SCN8AOrphanet:306Self-limited infantile epilepsy
SCN8AOrphanet:352582Familial infantile myoclonic epilepsy
SCN8AOrphanet:442835Non-specific early-onset epileptic encephalopathy
SLC4A1Orphanet:3202Dehydrated hereditary stomatocytosis
SLC4A1Orphanet:398088Hereditary cryohydrocytosis with normal stomatin
SLC4A1Orphanet:822Hereditary spherocytosis
SLC4A1Orphanet:93608Autosomal dominant distal renal tubular acidosis
SLC4A1Orphanet:93610Distal renal tubular acidosis with anemia
SLC4A1Orphanet:98868Southeast Asian ovalocytosis
G6PDOrphanet:466026Class I glucose-6-phosphate dehydrogenase deficiency
HBBOrphanet:2132Hemoglobin C disease
HBBOrphanet:2133Hemoglobin E disease
HBBOrphanet:231214Beta-thalassemia major
HBBOrphanet:231222Beta-thalassemia intermedia
HBBOrphanet:231226Unstable beta globin chain variant disease
HBBOrphanet:231237Delta-beta-thalassemia
HBBOrphanet:231242Hemoglobin C-beta-thalassemia syndrome
HBBOrphanet:231249Hemoglobin E-beta-thalassemia syndrome
HBBOrphanet:232Sickle cell anemia
HBBOrphanet:247511Autosomal dominant secondary polycythemia
HBBOrphanet:251365Sickle cell S-C disease
HBBOrphanet:251370Sickle cell S-D Punjab disease
HBBOrphanet:251375Sickle cell S-E disease
HBBOrphanet:251380Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
HBBOrphanet:330041Hemoglobin M disease
HBBOrphanet:46532Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
HBBOrphanet:695140Sickle cell-beta zero-thalassemia
HBBOrphanet:695147Sickle cell-beta plus-thalassemia
HBBOrphanet:699822Sickle cell S-Lepore disease
HBBOrphanet:700090Sickle cell S-O Arab disease
HBBOrphanet:700107Sickle cell S-other specified hemoglobin variant
HBBOrphanet:700111Homozygous hemoglobin O Arab disease
HBBOrphanet:715125Hemoglobin E-beta-thalassemia intermedia
HBBOrphanet:715128Hemoglobin E-beta-thalassemia major
HBBOrphanet:715135Hemoglobin Lepore-beta-thalassemia intermedia
HBBOrphanet:715140Hemoglobin Lepore-beta-thalassemia major
HBBOrphanet:715143Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBBOrphanet:715157Low oxygen affinity beta chain hemoglobin disease
HBBOrphanet:90039Hemoglobin D disease

Cohort genes → proteins

12 cohort genes, 12 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence12

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SCN8AHGNC:10596ENSG00000196876Q9UQD0Sodium channel protein type 8 subunit alphaclinvar
SLC4A1HGNC:11027ENSG00000004939P02730Band 3 anion transport proteinclinvar
CD36HGNC:1663ENSG00000135218P16671Platelet glycoprotein 4clinvar
TIRAPHGNC:17192ENSG00000150455P58753Toll/interleukin-1 receptor domain-containing adapter proteinclinvar
CISHHGNC:1984ENSG00000114737Q9NSE2Cytokine-inducible SH2-containing proteinclinvar
NANOS2HGNC:23292ENSG00000188425P60321Nanos homolog 2clinvar
CR1HGNC:2334ENSG00000203710P17927Complement receptor type 1clinvar
FCGR2AHGNC:3616ENSG00000143226P12318Low affinity immunoglobulin gamma Fc region receptor II-aclinvar
G6PDHGNC:4057ENSG00000160211P11413Glucose-6-phosphate 1-dehydrogenaseclinvar
HBBHGNC:4827ENSG00000244734P68871Hemoglobin subunit betaclinvar
ICAM1HGNC:5344ENSG00000090339P05362Intercellular adhesion molecule 1clinvar
NOS2HGNC:7873ENSG00000007171P35228Nitric oxide synthase, inducibleclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SCN8ASodium channel protein type 8 subunit alphaPore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively pass along their electrochemical gradie…
SLC4A1Band 3 anion transport proteinFunctions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein.
CD36Platelet glycoprotein 4Multifunctional glycoprotein that acts as a receptor for a broad range of ligands.
TIRAPToll/interleukin-1 receptor domain-containing adapter proteinAdapter involved in TLR2, TLR4 and RAGE signaling pathways in the innate immune response.
CISHCytokine-inducible SH2-containing proteinSOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction.
NANOS2Nanos homolog 2Plays a key role in the sexual differentiation of germ cells by promoting the male fate but suppressing the female fate.
CR1Complement receptor type 1Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages.
FCGR2ALow affinity immunoglobulin gamma Fc region receptor II-aBinds to the Fc region of immunoglobulins gamma.
G6PDGlucose-6-phosphate 1-dehydrogenaseCatalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.
HBBHemoglobin subunit betaInvolved in oxygen transport from the lung to the various peripheral tissues.
ICAM1Intercellular adhesion molecule 1Cell adhesion molecule that functions as a receptor ligand of the signaling receptor ITGAL:ITGB2/LFA-1 (lymphocyte-function associated (LFA) molecule 1) ensuring leukocyte cell-cell adhesion, by providing a calibrated system to namely adju…
NOS2Nitric oxide synthase, inducibleProduces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.

Protein-family classification

Druggable: 6 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.5

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.

FamilyGenesFoldFDR
Complement122.3×0.216
Antibody/Immunoglobulin24.9×0.216
Ion channel19.3×0.239
Enzyme (other)22.0×0.462
Scaffold/PPI11.4×0.715
Transcription factor10.7×0.919
Other/Unknown40.6×0.969

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SCN8AIon channelyesIQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SLC4A1Other/UnknownnoAnion_exchange, Anion_exchange_1, HCO3_transpt_euk
CD36Other/UnknownnoCD36_fam, CD36/SCARB1/SNMP1
TIRAPOther/UnknownnoTIR_dom, Tol-interleuk_rcpt_adapt_Tirap, Toll_tir_struct_dom_sf
CISHScaffold/PPInoSH2, SOCS_box, CIS_SH2
NANOS2Transcription factornoNanos/Xcar2, Znf_nanos-typ, Nanos_sf
CR1ComplementyesSushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
FCGR2AAntibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
G6PDEnzyme (other)yes1.1.1.49G6P_DH, G6P_DH_AS, G6P_DH_NAD-bd
HBBOther/UnknownnoGlobin, Hemoglobin_b, Globin-like_sf
ICAM1Antibody/ImmunoglobulinyesIg_sub, ICAM_VCAM_N, ICAM
NOS2Enzyme (other)yes1.14.13.39Flavdoxin-like, OxRdtase_FAD/NAD-bd, Flavoprot_Pyr_Nucl_cyt_Rdtase

Expression context

Cohort genes with no expression data: 0.

10 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)12
unknown0

Top tissues across cohort

TissueCohort genes
monocyte5
trabecular bone tissue2
granulocyte2
right testis2
blood2
vena cava2
Brodmann (1909) area 231
middle temporal gyrus1
postcentral gyrus1
bone marrow1
bone marrow cell1
adipose tissue of abdominal region1
omental fat pad1
buccal mucosa cell1
oviduct epithelium1
left lobe of thyroid gland1
right lobe of thyroid gland1
male germ line stem cell (sensu Vertebrata) in testis1
primordial germ cell in gonad1
mononuclear cell1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SCN8A194ubiquitousmarkerBrodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
SLC4A1161tissue_specificmarkertrabecular bone tissue, bone marrow, bone marrow cell
CD36252broadmarkeradipose tissue of abdominal region, omental fat pad, monocyte
TIRAP171ubiquitousyesoviduct epithelium, buccal mucosa cell, monocyte
CISH227ubiquitousmarkergranulocyte, left lobe of thyroid gland, right lobe of thyroid gland
NANOS232tissue_specificyesmale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right testis
CR1184broadmarkerblood, monocyte, mononuclear cell
FCGR2A144broadmarkerblood, monocyte, leukocyte
G6PD218ubiquitousmarkerstromal cell of endometrium, granulocyte, right testis
HBB284broadmarkermonocyte, trabecular bone tissue, vena cava
ICAM1256ubiquitousmarkervena cava, upper lobe of left lung, upper lobe of lung
NOS2153broadmarkercartilage tissue, olfactory segment of nasal mucosa, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CD365,268
ICAM15,248
G6PD4,226
NOS23,214
FCGR2A2,618
CISH2,453
SCN8A2,120
SLC4A11,598
TIRAP1,334
CR11,218

Intra-cohort edges

ABSources
CR1FCGR2Astring_interaction

Structural data

PDB: 10 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
HBBP68871350
SLC4A1P0273054
G6PDP1141325
ICAM1P0536214
NOS2P3522813
TIRAPP5875311
FCGR2AP123189
SCN8AQ9UQD07
CR1P179277
CD36P166711

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
NANOS2P6032176.58
CISHQ9NSE273.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 91. Enrichment computed across 12 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Erythrocytes take up oxygen and release carbon dioxide2230.7×0.003SLC4A1, HBB
Erythrocytes take up carbon dioxide and release oxygen2159.7×0.003SLC4A1, HBB
MyD88 deficiency (TLR2/4)2109.3×0.003CD36, TIRAP
IRAK4 deficiency (TLR2/4)2103.8×0.003CD36, TIRAP
Interleukin-4 and Interleukin-13 signaling328.1×0.003CD36, ICAM1, NOS2
Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA)11038.2×0.013SLC4A1
Neutrophil degranulation48.4×0.013CD36, CR1, FCGR2A, HBB
Free fatty acids regulate insulin secretion1346.1×0.022CD36
Intracellular metabolism of fatty acids regulates insulin secretion1346.1×0.022CD36
Inhibition of nitric oxide production1346.1×0.022NOS2
Heme assimilation1346.1×0.022HBB
MyD88:MAL(TIRAP) cascade initiated on plasma membrane227.7×0.022CD36, TIRAP
ER-Phagosome pathway223.6×0.022CD36, TIRAP
Cross-presentation of particulate exogenous antigens (phagosomes)1129.8×0.047CD36
NFE2L2 regulates pentose phosphate pathway genes1129.8×0.047G6PD
O2/CO2 exchange in erythrocytes1115.3×0.047SLC4A1
Bicarbonate transporters1103.8×0.047SLC4A1
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)1103.8×0.047CR1
Scavenging by Class B Receptors194.4×0.047CD36
Pentose phosphate pathway186.5×0.047G6PD
FCGR activation179.9×0.047FCGR2A
Scavenging of heme from plasma179.9×0.047HBB
Diseases of Immune System179.9×0.047CD36
Diseases associated with the TLR signaling cascade179.9×0.047CD36
Nitric oxide stimulates guanylate cyclase174.2×0.049NOS2
Binding and Uptake of Ligands by Scavenger Receptors149.4×0.070CD36
Regulation of TLR by endogenous ligand145.1×0.071CD36
Chaperone Mediated Autophagy145.1×0.071HBB
Growth hormone receptor signaling143.3×0.072CISH
Role of phospholipids in phagocytosis141.5×0.072FCGR2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cellular response to lipoteichoic acid2255.3×0.004CD36, TIRAP
positive regulation of toll-like receptor 4 signaling pathway2165.2×0.004CD36, TIRAP
positive regulation of interleukin-6 production341.7×0.004CD36, TIRAP, NOS2
positive regulation of tumor necrosis factor production338.3×0.004CD36, TIRAP, FCGR2A
regulation of leukocyte mediated cytotoxicity11404.3×0.009ICAM1
positive regulation of leukocyte mediated cytotoxicity11404.3×0.009NOS2
immune complex clearance by erythrocytes11404.3×0.009CR1
short-chain fatty acid transport11404.3×0.009CD36
response to increased oxygen levels11404.3×0.009SLC4A1
pH elevation11404.3×0.009SLC4A1
ribose phosphate biosynthetic process11404.3×0.009G6PD
oxidised low-density lipoprotein particle clearance11404.3×0.009CD36
negative regulation of serine-type endopeptidase activity11404.3×0.009CR1
erythrocyte development287.8×0.009SLC4A1, HBB
positive regulation of nitric oxide biosynthetic process275.9×0.009CD36, HBB
positive regulation of interleukin-12 production265.3×0.009CD36, TIRAP
cellular response to amyloid-beta265.3×0.009CD36, ICAM1
positive regulation of ERK1 and ERK2 cascade321.3×0.009CD36, TIRAP, ICAM1
cell surface receptor signaling pathway316.0×0.009CD36, TIRAP, FCGR2A
inflammatory response412.6×0.009CD36, TIRAP, HBB, NOS2
organ or tissue specific immune response1702.2×0.011CR1
immune complex clearance1702.2×0.011CR1
response to iron(III) ion1702.2×0.011G6PD
peptidyl-cysteine S-nitrosylation1702.2×0.011NOS2
pentose biosynthetic process1702.2×0.011G6PD
positive regulation of interleukin-15 production1702.2×0.011TIRAP
TIRAP-dependent toll-like receptor 4 signaling pathway1702.2×0.011TIRAP
negative regulation of plasma cell differentiation1702.2×0.011CR1
positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel1702.2×0.011G6PD
positive regulation of blood microparticle formation1702.2×0.011CD36

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 7

Druggability breadth: 8 of 12 evidence-associated genes (67%) 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.

SymbolExample approved molecule
SCN8AIMIPRAMINE
G6PDBREXANOLONE
HBBCANDESARTAN CILEXETIL
ICAM1LIFITEGRAST
NOS2CHLORZOXAZONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
SCN8A254
HBB234
NOS2104
G6PD84
ICAM124
SLC4A100
CD3600
TIRAP00
CISH00
NANOS200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
IMIPRAMINE4SCN8A
SERTINDOLE4SCN8A
PIMOZIDE4SCN8A
NIFEDIPINE4SCN8A
DILTIAZEM4SCN8A
MIBEFRADIL4SCN8A
HALOPERIDOL4SCN8A
MEXILETINE4SCN8A
AMITRIPTYLINE4SCN8A
AMIODARONE4SCN8A
CHLORPROMAZINE4SCN8A
TETRACAINE4SCN8A
BREXANOLONE4G6PD
APOMORPHINE HYDROCHLORIDE4G6PD
PRASTERONE4G6PD
CANDESARTAN CILEXETIL4HBB
MECHLORETHAMINE HYDROCHLORIDE4HBB
PHENAZOPYRIDINE HYDROCHLORIDE4HBB
MERCAPTOPURINE ANHYDROUS4HBB
AZACITIDINE4HBB
AZATHIOPRINE4HBB
TOPOTECAN HYDROCHLORIDE4HBB
ACYCLOVIR4HBB
FLUOROURACIL4HBB
RAUWOLFIA SERPENTINA4HBB
HYDROQUINONE4HBB
MENADIONE4HBB
THIOTEPA4HBB
THIOGUANINE4HBB
RESERPINE4HBB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
NOS2263Binding:255, Functional:5, ADMET:2, Unclassified:1
SCN8A173Binding:148, Functional:16, ADMET:7, Toxicity:2
ICAM1111Binding:73, Functional:38
HBB68Binding:50, Functional:18
G6PD49Binding:46, ADMET:2, Functional:1
CD366Binding:5, Functional:1
FCGR2A1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
G6PD1.1.1.49glucose-6-phosphate dehydrogenase (NADP+)
NOS21.14.13.39nitric-oxide synthase (NADPH)

Cohort genes with high screening signal

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

SymbolChEMBL assays
SCN8A173
ICAM1111
NOS2263

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
G6PD1

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.

CompoundMax phaseCohort target (bioactivity)
IMIPRAMINE4SCN8A
SERTINDOLE4SCN8A
PIMOZIDE4SCN8A
NIFEDIPINE4SCN8A
DILTIAZEM4SCN8A
MIBEFRADIL4SCN8A
HALOPERIDOL4SCN8A
MEXILETINE4SCN8A
AMITRIPTYLINE4SCN8A
AMIODARONE4SCN8A
CHLORPROMAZINE4SCN8A
TETRACAINE4SCN8A
BREXANOLONE4G6PD
APOMORPHINE HYDROCHLORIDE4G6PD
PRASTERONE4G6PD
CANDESARTAN CILEXETIL4HBB
MECHLORETHAMINE HYDROCHLORIDE4HBB
PHENAZOPYRIDINE HYDROCHLORIDE4HBB
MERCAPTOPURINE ANHYDROUS4HBB
AZACITIDINE4HBB
AZATHIOPRINE4HBB
TOPOTECAN HYDROCHLORIDE4HBB
ACYCLOVIR4HBB
FLUOROURACIL4HBB
RAUWOLFIA SERPENTINA4HBB
HYDROQUINONE4HBB
MENADIONE4HBB
THIOTEPA4HBB
THIOGUANINE4HBB
RESERPINE4HBB

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)5SCN8A, G6PD, HBB, ICAM1, NOS2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug2CR1, FCGR2A
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug5SLC4A1, CD36, TIRAP, CISH, NANOS2

Undrugged target profiles

7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
SLC4A10
CD366
TIRAP0
CISH0
NANOS20
CR10
FCGR2A1

Clinical trials & evidence

Clinical trials

Clinical trials: 0.