Myocardial infarction, susceptibility to
diseaseOn this page
Also known as myocardial infarction, decreased susceptibility to
Summary
Myocardial infarction, susceptibility to (MONDO:0012039) is a disease with 15 cohort genes.
At a glance
- Cohort genes: 15
- ClinVar variants: 70
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | myocardial infarction, susceptibility to |
| Mondo ID | MONDO:0012039 |
| OMIM | 608446 |
| UMLS | C1832662 |
| MedGen | 318680 |
| Is cancer (heuristic) | no |
Also known as: myocardial infarction, decreased susceptibility to · myocardial infarction, susceptibility to
Data availability: 70 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease susceptibility › inherited disease susceptibility › myocardial infarction, 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, 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, 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
70 retrieved; paginated sample, class counts are floors:
16 pathogenic, 13 pathogenic/likely pathogenic, 11 uncertain significance, 9 likely pathogenic, 6 risk factor, 5 conflicting classifications of pathogenicity, 4 benign, 3 benign; risk factor, 1 benign/likely benign, 1 pathogenic/likely pathogenic; other, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13564 | NM_000212.3(ITGB3):c.2248C>T (p.Arg750Ter) | EFCAB13-DT | Pathogenic | reviewed by expert panel |
| 29694 | NM_000129.4(F13A1):c.603_606del (p.Arg202fs) | F13A1 | Pathogenic | criteria provided, single submitter |
| 3594056 | NM_000129.4(F13A1):c.523C>T (p.Arg175Ter) | F13A1 | Pathogenic | criteria provided, single submitter |
| 12076 | NM_019616.4(F7):c.995C>T (p.Ala332Val) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 12085 | NM_019616.4(F7):c.1099T>G (p.Cys367Gly) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1677255 | NM_019616.4(F7):c.868G>A (p.Val290Met) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1678759 | NM_019616.4(F7):c.505+78G>A | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1684389 | NM_019616.4(F7):c.517T>C (p.Cys173Arg) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1691295 | NM_019616.4(F7):c.225+1G>C | F7 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 265135 | NM_019616.4(F7):c.1043G>T (p.Cys348Phe) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2683442 | NM_019616.4(F7):c.739+1G>A | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3352537 | NM_019616.4(F7):c.1008G>A (p.Met336Ile) | F7 | Pathogenic | criteria provided, single submitter |
| 3382510 | NM_019616.4(F7):c.64G>A (p.Val22Ile) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3575772 | NM_019616.4(F7):c.1157A>G (p.His386Arg) | F7 | Pathogenic | criteria provided, single submitter |
| 420159 | NM_019616.4(F7):c.1025G>A (p.Arg342Gln) | F7 | Pathogenic/Likely pathogenic; other | criteria provided, multiple submitters, no conflicts |
| 420160 | NM_019616.4(F7):c.1085C>T (p.Thr362Met) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 626999 | NM_019616.4(F7):c.1325del (p.Pro442fs) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 627178 | NM_019616.4(F7):c.413A>G (p.Gln138Arg) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 627309 | NM_019616.4(F7):c.364+1G>A | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 627403 | NM_019616.4(F7):c.845C>T (p.Ala282Val) | F7 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13553 | NM_000212.3(ITGB3):c.719G>A (p.Arg240Gln) | ITGB3 | Pathogenic | reviewed by expert panel |
| 13567 | NM_000212.3(ITGB3):c.428T>G (p.Leu143Trp) | ITGB3 | Pathogenic | reviewed by expert panel |
| 1879043 | NM_000212.3(ITGB3):c.725G>A (p.Arg242Gln) | ITGB3 | Pathogenic | reviewed by expert panel |
| 812736 | NM_000212.3(ITGB3):c.565C>T (p.Pro189Ser) | ITGB3 | Pathogenic | reviewed by expert panel |
| 953028 | NM_000212.3(ITGB3):c.31T>C (p.Trp11Arg) | ITGB3 | Pathogenic | reviewed by expert panel |
| 953050 | NM_000212.3(ITGB3):c.79+1G>A | ITGB3 | Pathogenic | reviewed by expert panel |
| 996178 | NM_000212.3(ITGB3):c.709_710del (p.Ser237fs) | ITGB3 | Pathogenic | reviewed by expert panel |
| 996188 | NM_000212.3(ITGB3):c.431T>G (p.Met144Arg) | ITGB3 | Pathogenic | reviewed by expert panel |
| 996193 | NM_000212.3(ITGB3):c.100C>T (p.Arg34Ter) | ITGB3 | Pathogenic | reviewed by expert panel |
| 850886 | NM_000212.3(ITGB3):c.777+1G>A | LOC130061044 | Pathogenic | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 2 · Orphanet: 12 · 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 |
|---|---|---|---|---|
| TNFSF4 | Limited | Autosomal dominant | myocardial infarction, susceptibility to | 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TNFSF4 | Orphanet:2073 | Narcolepsy type 1 |
| TNFSF4 | Orphanet:536 | Systemic lupus erythematosus |
| ACE | Orphanet:97369 | Renal tubular dysgenesis of genetic origin |
| ESR1 | Orphanet:785 | Estrogen resistance syndrome |
| F13A1 | Orphanet:331 | Congenital factor XIII deficiency |
| F7 | Orphanet:327 | Congenital factor VII deficiency |
| GCLC | Orphanet:33574 | Glutamate-cysteine ligase deficiency |
| GCLC | Orphanet:586 | Cystic fibrosis |
| APOC3 | Orphanet:181428 | Familial Hyperalphalipoproteinemia |
| ITGB3 | Orphanet:140957 | Autosomal dominant macrothrombocytopenia |
| ITGB3 | Orphanet:849 | Glanzmann thrombasthenia |
| ITGB3 | Orphanet:853 | Fetal and neonatal alloimmune thrombocytopenia |
Cohort genes → proteins
15 cohort genes, 14 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 15 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TNFSF4 | HGNC:11934 | ENSG00000117586 | P23510 | Tumor necrosis factor ligand superfamily member 4 | gencc |
| ACE | HGNC:2707 | ENSG00000159640 | P12821 | Angiotensin-converting enzyme | clinvar |
| ESR1 | HGNC:3467 | ENSG00000091831 | P03372 | Estrogen receptor | clinvar |
| F13A1 | HGNC:3531 | ENSG00000124491 | P00488 | Coagulation factor XIII A chain | clinvar |
| F7 | HGNC:3544 | ENSG00000057593 | P08709 | Coagulation factor VII | clinvar |
| GCLC | HGNC:4311 | ENSG00000001084 | P48506 | Glutamate–cysteine ligase catalytic subunit | clinvar |
| GCLM | HGNC:4312 | ENSG00000023909 | P48507 | Glutamate–cysteine ligase regulatory subunit | clinvar |
| EFCAB13-DT | HGNC:55338 | ENSG00000263293 | EFCAB13 divergent transcript | clinvar | |
| APOC3 | HGNC:610 | ENSG00000110245 | P02656 | Apolipoprotein C-III | clinvar |
| ITGB3 | HGNC:6156 | ENSG00000259207 | P05106 | Integrin beta-3 | clinvar |
| LGALS2 | HGNC:6562 | ENSG00000100079 | P05162 | Galectin-2 | clinvar |
| LRP8 | HGNC:6700 | ENSG00000157193 | Q14114 | Low-density lipoprotein receptor-related protein 8 | clinvar |
| LTA | HGNC:6709 | ENSG00000226979 | P01374 | Lymphotoxin-alpha | clinvar |
| OLR1 | HGNC:8133 | ENSG00000173391 | P78380 | Oxidized low-density lipoprotein receptor 1 | clinvar |
| PSMA6 | HGNC:9535 | ENSG00000100902 | P60900 | Proteasome subunit alpha type-6 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TNFSF4 | Tumor necrosis factor ligand superfamily member 4 | Cytokine that binds to TNFRSF4. |
| ACE | Angiotensin-converting enzyme | Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte hom… |
| ESR1 | Estrogen receptor | Nuclear hormone receptor. |
| F13A1 | Coagulation factor XIII A chain | Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. |
| F7 | Coagulation factor VII | Initiates the extrinsic pathway of blood coagulation. |
| GCLC | Glutamate–cysteine ligase catalytic subunit | Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis. |
| APOC3 | Apolipoprotein C-III | Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma. |
| ITGB3 | Integrin beta-3 | Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. |
| LGALS2 | Galectin-2 | This protein binds beta-galactoside. |
| LRP8 | Low-density lipoprotein receptor-related protein 8 | Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. |
| LTA | Lymphotoxin-alpha | Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. |
| OLR1 | Oxidized low-density lipoprotein receptor 1 | Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. |
| PSMA6 | Proteasome subunit alpha type-6 | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. |
Protein-family classification
Druggable: 6 · Difficult: 0 · Unknown: 9 · Druggable fraction: 0.4
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 |
|---|---|---|---|
| Nuclear receptor | 1 | 25.7× | 0.155 |
| Protease | 2 | 4.9× | 0.155 |
| Antibody/Immunoglobulin | 1 | 1.9× | 0.478 |
| Enzyme (other) | 2 | 1.6× | 0.478 |
| Other/Unknown | 9 | 1.1× | 0.478 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TNFSF4 | Other/Unknown | no | TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS | |
| ACE | Protease | yes | 3.4.15.1 | Peptidase_M2 |
| ESR1 | Nuclear receptor | yes | Nucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt | |
| F13A1 | Antibody/Immunoglobulin | yes | 2.3.2.13 | Transglutaminase_N, Transglutaminase-like, Transglutaminase_C |
| F7 | Protease | yes | 3.4.21.21 | EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF |
| GCLC | Enzyme (other) | yes | 6.3.2.2 | GCS, Gln_synth/guanido_kin_cat_dom |
| GCLM | Enzyme (other) | yes | 6.3.2.2 | NADP_OxRdtase_dom, Gclm, NAD(P)_OxRdtase_dom_sf |
| EFCAB13-DT | Other/Unknown | no | ||
| APOC3 | Other/Unknown | no | Apo-CIII, Apo_CIII_sf | |
| ITGB3 | Other/Unknown | no | Integrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell | |
| LGALS2 | Other/Unknown | no | Galectin_CRD, ConA-like_dom_sf, Galectin-like | |
| LRP8 | Other/Unknown | no | LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF | |
| LTA | Other/Unknown | no | TNF_beta, TNF_dom, TNF | |
| OLR1 | Other/Unknown | no | C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold | |
| PSMA6 | Other/Unknown | no | Proteasome_asu_N, Proteasome_sua/b, Proteasome_alpha-type |
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) | 15 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| monocyte | 4 |
| mononuclear cell | 4 |
| primordial germ cell in gonad | 2 |
| left testis | 2 |
| right testis | 2 |
| liver | 2 |
| right lobe of liver | 2 |
| bronchial epithelial cell | 2 |
| islet of Langerhans | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| ileal mucosa | 1 |
| cervix epithelium | 1 |
| mammalian vulva | 1 |
| oviduct epithelium | 1 |
| pericardium | 1 |
| buccal mucosa cell | 1 |
| olfactory segment of nasal mucosa | 1 |
| right uterine tube | 1 |
| epithelium of bronchus | 1 |
| right lobe of thyroid gland | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TNFSF4 | 181 | broad | marker | primordial germ cell in gonad, monocyte, mononuclear cell |
| ACE | 177 | ubiquitous | marker | ileal mucosa, right testis, left testis |
| ESR1 | 216 | broad | marker | oviduct epithelium, cervix epithelium, mammalian vulva |
| F13A1 | 261 | broad | marker | monocyte, mononuclear cell, pericardium |
| F7 | 156 | tissue_specific | yes | right lobe of liver, liver, buccal mucosa cell |
| GCLC | 291 | ubiquitous | marker | bronchial epithelial cell, right uterine tube, olfactory segment of nasal mucosa |
| GCLM | 284 | ubiquitous | marker | bronchial epithelial cell, islet of Langerhans, epithelium of bronchus |
| EFCAB13-DT | 155 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of thyroid gland |
| APOC3 | 156 | tissue_specific | marker | jejunal mucosa, right lobe of liver, liver |
| ITGB3 | 199 | ubiquitous | marker | monocyte, mononuclear cell, leukocyte |
| LGALS2 | 197 | broad | marker | gall bladder, monocyte, mononuclear cell |
| LRP8 | 246 | ubiquitous | yes | ganglionic eminence, pigmented layer of retina, cortical plate |
| LTA | 119 | broad | marker | male germ line stem cell (sensu Vertebrata) in testis, granulocyte, lymph node |
| OLR1 | 202 | broad | marker | right lung, C1 segment of cervical spinal cord, bone marrow cell |
| PSMA6 | 137 | ubiquitous | marker | left testis, right testis, islet of Langerhans |
Protein interactions among cohort
Intra-cohort edges: 2.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ESR1 | 12,382 |
| ACE | 3,659 |
| ITGB3 | 3,274 |
| F13A1 | 2,346 |
| GCLM | 2,137 |
| GCLC | 1,928 |
| APOC3 | 1,895 |
| LTA | 1,807 |
| OLR1 | 1,742 |
| LRP8 | 1,682 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| GCLC | GCLM | biogrid_interaction, intact, string_interaction |
| LGALS2 | LTA | biogrid_interaction, intact, string_interaction |
Structural data
PDB: 12 · AlphaFold-only: 2 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ESR1 | P03372 | 478 |
| PSMA6 | P60900 | 171 |
| ITGB3 | P05106 | 123 |
| F7 | P08709 | 114 |
| ACE | P12821 | 97 |
| F13A1 | P00488 | 15 |
| OLR1 | P78380 | 13 |
| LGALS2 | P05162 | 4 |
| LRP8 | Q14114 | 4 |
| LTA | P01374 | 3 |
| TNFSF4 | P23510 | 1 |
| APOC3 | P02656 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GCLC | P48506 | 93.68 |
| GCLM | P48507 | 91.24 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 164. Enrichment computed across 15 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective GCLC causes HAGGSD | 2 | 878.5× | 2e-04 | GCLC, GCLM |
| Glutathione synthesis and recycling | 2 | 146.4× | 0.005 | GCLC, GCLM |
| Fibrin formation | 2 | 135.2× | 0.005 | F13A1, ITGB3 |
| NFE2L2 regulating anti-oxidant/detoxification enzymes | 2 | 83.7× | 0.010 | GCLC, GCLM |
| TNFs bind their physiological receptors | 2 | 60.6× | 0.014 | TNFSF4, LTA |
| Metabolism of fat-soluble vitamins | 2 | 58.6× | 0.014 | APOC3, LRP8 |
| Visual phototransduction | 2 | 39.9× | 0.025 | APOC3, LRP8 |
| Retinoid metabolism and transport | 2 | 38.2× | 0.025 | APOC3, LRP8 |
| TNFR2 non-canonical NF-kB pathway | 2 | 27.9× | 0.037 | LTA, PSMA6 |
| Regulation of RUNX2 expression and activity | 2 | 27.9× | 0.037 | ESR1, PSMA6 |
| Metabolism of vitamins and cofactors | 2 | 17.9× | 0.080 | APOC3, LRP8 |
| RUNX1 regulates estrogen receptor mediated transcription | 1 | 146.4× | 0.084 | ESR1 |
| RUNX1 regulates transcription of genes involved in WNT signaling | 1 | 146.4× | 0.084 | ESR1 |
| Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus | 1 | 97.6× | 0.084 | F7 |
| Gamma-carboxylation of protein precursors | 1 | 87.8× | 0.084 | F7 |
| Removal of aminoterminal propeptides from gamma-carboxylated proteins | 1 | 87.8× | 0.084 | F7 |
| Chylomicron assembly | 1 | 87.8× | 0.084 | APOC3 |
| Chylomicron remodeling | 1 | 87.8× | 0.084 | APOC3 |
| HDL remodeling | 1 | 87.8× | 0.084 | APOC3 |
| Cell surface interactions at the vascular wall | 2 | 14.6× | 0.084 | ITGB3, OLR1 |
| Sensory Perception | 2 | 14.6× | 0.084 | APOC3, LRP8 |
| Platelet degranulation | 2 | 13.5× | 0.084 | F13A1, ITGB3 |
| PECAM1 interactions | 1 | 67.6× | 0.103 | ITGB3 |
| p130Cas linkage to MAPK signaling for integrins | 1 | 58.6× | 0.103 | ITGB3 |
| TFAP2 (AP-2) family regulates transcription of growth factors and their receptors | 1 | 58.6× | 0.103 | ESR1 |
| GRB2:SOS provides linkage to MAPK signaling for Integrins | 1 | 54.9× | 0.103 | ITGB3 |
| Plasma lipoprotein assembly | 1 | 54.9× | 0.103 | APOC3 |
| Platelet sensitization by LDL | 1 | 51.7× | 0.103 | LRP8 |
| TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway | 1 | 51.7× | 0.103 | LTA |
| Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1 | 51.7× | 0.103 | ITGB3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| response to human chorionic gonadotropin | 2 | 1203.7× | 9e-05 | GCLC, GCLM |
| cellular response to thyroxine stimulus | 2 | 1203.7× | 9e-05 | GCLC, GCLM |
| blood vessel diameter maintenance | 3 | 133.8× | 1e-04 | ACE, GCLC, GCLM |
| obsolete cysteine metabolic process | 2 | 601.9× | 2e-04 | GCLC, GCLM |
| response to nitrosative stress | 2 | 601.9× | 2e-04 | GCLC, GCLM |
| regulation of mitochondrial depolarization | 2 | 401.2× | 4e-04 | GCLC, GCLM |
| response to activity | 3 | 69.5× | 4e-04 | GCLC, GCLM, ITGB3 |
| response to nutrient | 3 | 63.4× | 5e-04 | GCLC, GCLM, LTA |
| blood coagulation, fibrin clot formation | 2 | 240.7× | 9e-04 | F13A1, ITGB3 |
| glutathione biosynthetic process | 2 | 218.9× | 9e-04 | GCLC, GCLM |
| negative regulation of low-density lipoprotein particle clearance | 2 | 218.9× | 9e-04 | APOC3, ITGB3 |
| response to xenobiotic stimulus | 4 | 19.7× | 9e-04 | GCLC, GCLM, LRP8, LTA |
| cellular response to follicle-stimulating hormone stimulus | 2 | 200.6× | 9e-04 | GCLC, GCLM |
| glutamate metabolic process | 2 | 160.5× | 0.001 | GCLC, GCLM |
| cellular response to hepatocyte growth factor stimulus | 2 | 160.5× | 0.001 | GCLC, GCLM |
| blood coagulation | 3 | 37.2× | 0.001 | F13A1, F7, ITGB3 |
| regulation of inflammatory response | 3 | 36.1× | 0.001 | TNFSF4, ESR1, PSMA6 |
| lipoprotein metabolic process | 2 | 133.8× | 0.002 | APOC3, OLR1 |
| cellular response to fibroblast growth factor stimulus | 2 | 77.7× | 0.005 | GCLC, GCLM |
| response to carbon dioxide | 1 | 1203.7× | 0.007 | F7 |
| negative regulation of high-density lipoprotein particle clearance | 1 | 1203.7× | 0.007 | APOC3 |
| ammon gyrus development | 1 | 1203.7× | 0.007 | LRP8 |
| mononuclear cell proliferation | 1 | 1203.7× | 0.007 | ACE |
| T-helper 2 cell activation | 1 | 1203.7× | 0.007 | TNFSF4 |
| response to nitrogen dioxide | 1 | 1203.7× | 0.007 | TNFSF4 |
| regulation of serotonin uptake | 1 | 1203.7× | 0.007 | ITGB3 |
| positive regulation of CD4-positive, alpha-beta T cell costimulation | 1 | 1203.7× | 0.007 | TNFSF4 |
| positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway | 1 | 1203.7× | 0.007 | ITGB3 |
| regulation of epithelial cell apoptotic process | 1 | 1203.7× | 0.007 | ESR1 |
| response to Thyroid stimulating hormone | 1 | 1203.7× | 0.007 | F7 |
Therapeutics
Drug target analysis
Approved (phase 4): 5 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 8
Druggability breadth: 13 of 15 evidence-associated genes (87%) 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 |
|---|---|
| ACE | TELMISARTAN |
| ESR1 | CANDESARTAN CILEXETIL |
| F7 | NIACINAMIDE |
| ITGB3 | EPTIFIBATIDE |
| PSMA6 | BORTEZOMIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ESR1 | 162 | 4 |
| ACE | 31 | 4 |
| ITGB3 | 18 | 4 |
| F7 | 8 | 4 |
| PSMA6 | 6 | 4 |
| F13A1 | 1 | 3 |
| GCLC | 1 | 1 |
| TNFSF4 | 0 | 0 |
| GCLM | 0 | 0 |
| EFCAB13-DT | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| TELMISARTAN | 4 | ACE |
| MOEXIPRIL | 4 | ACE |
| RAMIPRIL | 4 | ACE |
| LISINOPRIL ANHYDROUS | 4 | ACE |
| SITAGLIPTIN | 4 | ACE |
| TRANDOLAPRIL | 4 | ACE |
| CAPTOPRIL | 4 | ACE |
| PERINDOPRIL | 4 | ACE |
| QUINAPRIL | 4 | ACE |
| LOSARTAN | 4 | ACE |
| FOSINOPRIL | 4 | ACE |
| IMIDAPRIL | 4 | ACE |
| ENALAPRILAT ANHYDROUS | 4 | ACE |
| ENALAPRIL | 4 | ACE |
| BENAZEPRIL | 4 | ACE |
| CANDESARTAN CILEXETIL | 4 | ESR1 |
| DIENESTROL | 4 | ESR1 |
| BEXAROTENE | 4 | ESR1 |
| VARENICLINE | 4 | ESR1 |
| ACETOPHENAZINE | 4 | ESR1 |
| ARIPIPRAZOLE | 4 | ESR1 |
| RALOXIFENE HYDROCHLORIDE | 4 | ESR1 |
| NORETHINDRONE | 4 | ESR1 |
| TRIMETREXATE | 4 | ESR1 |
| ESTRADIOL ACETATE | 4 | ESR1 |
| ETHYLESTRENOL | 4 | ESR1 |
| ETHYNODIOL DIACETATE | 4 | ESR1 |
| CHLOROTRIANISENE | 4 | ESR1 |
| ESTRADIOL CYPIONATE | 4 | ESR1 |
| MESTRANOL | 4 | ESR1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 5.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| ESR1 | 2,435 | Binding:2037, Functional:363, ADMET:35 |
| ITGB3 | 771 | Binding:575, Functional:183, ADMET:13 |
| ACE | 304 | Binding:288, Functional:8, ADMET:5, Unclassified:3 |
| F7 | 255 | Binding:237, Functional:17, ADMET:1 |
| PSMA6 | 175 | Binding:166, ADMET:6, Functional:3 |
| F13A1 | 42 | Binding:42 |
| GCLC | 14 | Binding:14 |
| LGALS2 | 12 | Binding:12 |
| GCLM | 3 | Binding:3 |
| LTA | 3 | Binding:3 |
| OLR1 | 2 | Binding:2 |
| APOC3 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ACE | 3.4.15.1 | peptidyl-dipeptidase A |
| F13A1 | 2.3.2.13 | protein-glutamine gamma-glutamyltransferase |
| F7 | 3.4.21.21 | coagulation factor VIIa |
| GCLC | 6.3.2.2 | glutamate-cysteine ligase |
| GCLM | 6.3.2.2 | glutamate-cysteine ligase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| ACE | 304 |
| ESR1 | 2,435 |
| F7 | 255 |
| ITGB3 | 771 |
| PSMA6 | 175 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 14; 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) |
|---|---|---|
| TELMISARTAN | 4 | ACE |
| MOEXIPRIL | 4 | ACE |
| RAMIPRIL | 4 | ACE |
| LISINOPRIL ANHYDROUS | 4 | ACE |
| SITAGLIPTIN | 4 | ACE |
| TRANDOLAPRIL | 4 | ACE |
| CAPTOPRIL | 4 | ACE |
| PERINDOPRIL | 4 | ACE |
| QUINAPRIL | 4 | ACE |
| LOSARTAN | 4 | ACE |
| FOSINOPRIL | 4 | ACE |
| IMIDAPRIL | 4 | ACE |
| ENALAPRILAT ANHYDROUS | 4 | ACE |
| ENALAPRIL | 4 | ACE |
| BENAZEPRIL | 4 | ACE |
| CANDESARTAN CILEXETIL | 4 | ESR1 |
| DIENESTROL | 4 | ESR1 |
| BEXAROTENE | 4 | ESR1 |
| VARENICLINE | 4 | ESR1 |
| ACETOPHENAZINE | 4 | ESR1 |
| ARIPIPRAZOLE | 4 | ESR1 |
| RALOXIFENE HYDROCHLORIDE | 4 | ESR1 |
| NORETHINDRONE | 4 | ESR1 |
| TRIMETREXATE | 4 | ESR1 |
| ESTRADIOL ACETATE | 4 | ESR1 |
| ETHYLESTRENOL | 4 | ESR1 |
| ETHYNODIOL DIACETATE | 4 | ESR1 |
| CHLOROTRIANISENE | 4 | ESR1 |
| ESTRADIOL CYPIONATE | 4 | ESR1 |
| MESTRANOL | 4 | ESR1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 5 | ACE, ESR1, F7, ITGB3, PSMA6 |
| B | Phased (≥1) drug, not yet approved | 2 | F13A1, GCLC |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | GCLM |
| E | Difficult family or no structure, no drug | 7 | TNFSF4, EFCAB13-DT, APOC3, LGALS2, LRP8, LTA, OLR1 |
Undrugged target profiles
8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| GCLM | 3 | GCLC |
| TNFSF4 | 0 | — |
| EFCAB13-DT | 0 | — |
| APOC3 | 1 | — |
| LGALS2 | 12 | — |
| LRP8 | 0 | — |
| LTA | 3 | — |
| OLR1 | 2 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.