Glioma susceptibility 1
diseaseOn this page
Also known as glioblastoma, somaticglioma susceptibility 1, autosomal dominant, somatic mutationglioma, susceptibility to, somaticGLM1
Summary
Glioma susceptibility 1 (MONDO:0024498) is a cancer with 6 cohort genes (4 CIViC-evidence somatic drivers; 101 ClinVar predisposition records).
At a glance
- Classification: Cancer
- Cohort genes: 6
- ClinVar variants: 101
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | glioma susceptibility 1 |
| Mondo ID | MONDO:0024498 |
| OMIM | 137800 |
| UMLS | C2750850 |
| MedGen | 413414 |
| GARD | 0027917 |
| Is cancer (heuristic) | yes |
Also known as: glioblastoma, somatic · glioma susceptibility 1 · glioma susceptibility 1, autosomal dominant, somatic mutation · glioma, susceptibility to, somatic · GLM1
Data availability: 101 ClinVar variants · 1 GenCC gene-disease record.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › glioma susceptibility › glioma susceptibility 1
Related subtypes (9): glioma susceptibility 4, glioma susceptibility 2, glioma susceptibility 3, glioma susceptibility 5, glioma susceptibility 6, glioma susceptibility 7, glioma susceptibility 8, melanoma, cutaneous malignant, susceptibility to, 9, tumor predisposition syndrome 3
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
101 retrieved; paginated sample, class counts are floors:
45 uncertain significance, 19 conflicting classifications of pathogenicity, 15 pathogenic/likely pathogenic, 12 pathogenic, 3 benign, 3 likely benign, 3 benign/likely benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13878 | NM_004448.4(ERBB2):c.2740G>A (p.Glu914Lys) | ERBB2 | Pathogenic | no assertion criteria provided |
| 156444 | NM_005896.4(IDH1):c.395G>A (p.Arg132His) | IDH1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 375891 | NM_005896.4(IDH1):c.394C>T (p.Arg132Cys) | IDH1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 12356 | NM_000546.6(TP53):c.743G>A (p.Arg248Gln) | TP53 | Pathogenic | reviewed by expert panel |
| 12359 | NM_000546.6(TP53):c.722C>T (p.Ser241Phe) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 12365 | NM_000546.6(TP53):c.733G>A (p.Gly245Ser) | TP53 | Pathogenic | reviewed by expert panel |
| 12366 | NM_000546.6(TP53):c.818G>A (p.Arg273His) | TP53 | Pathogenic | reviewed by expert panel |
| 12374 | NM_000546.6(TP53):c.524G>A (p.Arg175His) | TP53 | Pathogenic | reviewed by expert panel |
| 12379 | NM_000546.6(TP53):c.1010G>A (p.Arg337His) | TP53 | Pathogenic/Likely pathogenic/Pathogenic, low penetrance | criteria provided, multiple submitters, no conflicts |
| 127819 | NM_000546.6(TP53):c.659A>G (p.Tyr220Cys) | TP53 | Pathogenic | reviewed by expert panel |
| 1341341 | NM_000546.6(TP53):c.72dup (p.Leu25fs) | TP53 | Pathogenic | criteria provided, single submitter |
| 141764 | NM_000546.6(TP53):c.799C>T (p.Arg267Trp) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 141963 | NM_000546.6(TP53):c.473G>A (p.Arg158His) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 142657 | NM_000546.6(TP53):c.427G>A (p.Val143Met) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 177825 | NM_000546.6(TP53):c.375G>A (p.Thr125=) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 182968 | NM_000546.6(TP53):c.842A>T (p.Asp281Val) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 182970 | NM_000546.6(TP53):c.1024C>T (p.Arg342Ter) | TP53 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 231146 | NM_000546.6(TP53):c.1101-1G>A | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 376615 | NM_000546.6(TP53):c.641A>G (p.His214Arg) | TP53 | Pathogenic | reviewed by expert panel |
| 376625 | NM_000546.6(TP53):c.395A>G (p.Lys132Arg) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 376655 | NM_000546.6(TP53):c.818G>T (p.Arg273Leu) | TP53 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 376659 | NM_000546.6(TP53):c.845G>C (p.Arg282Pro) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3892955 | NC_000017.10:g.7578466_7590809del | TP53 | Pathogenic | criteria provided, single submitter |
| 428873 | NM_000546.6(TP53):c.389T>C (p.Leu130Pro) | TP53 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 428908 | NM_000546.6(TP53):c.559+1G>A | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 482212 | NM_000546.6(TP53):c.96+1G>T | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 634674 | NM_000546.6(TP53):c.298del (p.Gln100fs) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 634682 | NM_000546.6(TP53):c.817C>G (p.Arg273Gly) | TP53 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1587981 | NM_004448.4(ERBB2):c.1179G>A (p.Gln393=) | ERBB2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2171330 | NM_004448.4(ERBB2):c.3573G>A (p.Val1191=) | ERBB2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 41 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Somatic driver evidence (intOGen + CIViC, cohort fanout)
| Gene | intOGen role | Cancer types | CIViC |
|---|---|---|---|
| ERBB2 | Act | BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC | CIViC #20 |
| TP53 | LoF | ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT | CIViC #45 |
| POT1 | Act | ANGS,CLLSLL,LGGNOS,MEL,SOFT_TISSUE | CIViC #9935 |
| IDH1 | Act | AML,CHOL,GB,GBM,HCC,HGGNOS,LGGNOS,MBL,MEL,MT,OS,PAST,PCM,PRAD,SKCM | CIViC #26 |
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 |
|---|---|---|---|---|
| ERBB2 | Limited | Unknown | glioma susceptibility 1 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ERBB2 | Orphanet:213726 | Serous carcinoma of the corpus uteri |
| ERBB2 | Orphanet:2800 | Extramammary Paget disease |
| ERBB2 | Orphanet:388 | Hirschsprung disease |
| ERBB2 | Orphanet:99976 | Adenocarcinoma of the oesophagus and oesophagogastric junction |
| TP53 | Orphanet:1333 | Familial pancreatic carcinoma |
| TP53 | Orphanet:145 | Hereditary breast and/or ovarian cancer syndrome |
| TP53 | Orphanet:1501 | Adrenocortical carcinoma |
| TP53 | Orphanet:210159 | Adult hepatocellular carcinoma |
| TP53 | Orphanet:251576 | Gliosarcoma |
| TP53 | Orphanet:251579 | Giant cell glioblastoma |
| TP53 | Orphanet:251899 | Choroid plexus carcinoma |
| TP53 | Orphanet:2807 | Papilloma of choroid plexus |
| TP53 | Orphanet:293199 | Pleomorphic rhabdomyosarcoma |
| TP53 | Orphanet:3318 | Essential thrombocythemia |
| TP53 | Orphanet:524 | Li-Fraumeni syndrome |
| TP53 | Orphanet:52688 | Myelodysplastic syndrome |
| TP53 | Orphanet:585909 | B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2) |
| TP53 | Orphanet:667662 | Breast implant-associated anaplastic large cell lymphoma |
| TP53 | Orphanet:668 | Osteosarcoma |
| TP53 | Orphanet:67038 | B-cell chronic lymphocytic leukemia |
| TP53 | Orphanet:70573 | Small cell lung cancer |
| TP53 | Orphanet:96253 | Cushing disease |
| TP53 | Orphanet:99756 | Alveolar rhabdomyosarcoma |
| TP53 | Orphanet:99757 | Embryonal rhabdomyosarcoma |
| POT1 | Orphanet:251627 | Oligodendroglioma |
| POT1 | Orphanet:251630 | Anaplastic oligodendroglioma |
| POT1 | Orphanet:618 | Familial melanoma |
| POT1 | Orphanet:67038 | B-cell chronic lymphocytic leukemia |
| FANCB | Orphanet:3412 | VACTERL with hydrocephalus |
| FANCB | Orphanet:84 | Fanconi anemia |
| IDH1 | Orphanet:163634 | Maffucci syndrome |
| IDH1 | Orphanet:251576 | Gliosarcoma |
| IDH1 | Orphanet:251579 | Giant cell glioblastoma |
| IDH1 | Orphanet:296 | Ollier disease |
| IDH1 | Orphanet:86845 | Acute myeloid leukaemia with myelodysplasia-related features |
| IDH1 | Orphanet:99646 | Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria |
| PPARG | Orphanet:146 | Differentiated thyroid carcinoma |
| PPARG | Orphanet:251576 | Gliosarcoma |
| PPARG | Orphanet:251579 | Giant cell glioblastoma |
| PPARG | Orphanet:696242 | PPARG-associated congenital generalized lipodystrophy |
| PPARG | Orphanet:79083 | PPARG-related familial partial lipodystrophy |
Cohort genes → proteins
6 cohort genes, 6 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 6 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| ERBB2 | HGNC:3430 | ENSG00000141736 | P04626 | Receptor tyrosine-protein kinase erbB-2 | gencc,clinvar |
| TP53 | HGNC:11998 | ENSG00000141510 | P04637 | Cellular tumor antigen p53 | clinvar |
| POT1 | HGNC:17284 | ENSG00000128513 | Q9NUX5 | Protection of telomeres protein 1 | clinvar |
| FANCB | HGNC:3583 | ENSG00000181544 | Q8NB91 | Fanconi anemia group B protein | clinvar |
| IDH1 | HGNC:5382 | ENSG00000138413 | O75874 | Isocitrate dehydrogenase [NADP] cytoplasmic | clinvar |
| PPARG | HGNC:9236 | ENSG00000132170 | P37231 | Peroxisome proliferator-activated receptor gamma | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ERBB2 | Receptor tyrosine-protein kinase erbB-2 | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. |
| TP53 | Cellular tumor antigen p53 | Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| POT1 | Protection of telomeres protein 1 | Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. |
| FANCB | Fanconi anemia group B protein | DNA repair protein required for FANCD2 ubiquitination. |
| IDH1 | Isocitrate dehydrogenase [NADP] cytoplasmic | Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase. |
| PPARG | Peroxisome proliferator-activated receptor gamma | Ligand-activated transcription factor that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-o… |
Protein-family classification
Druggable: 3 · Difficult: 1 · Unknown: 2 · 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.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Nuclear receptor | 1 | 64.3× | 0.077 |
| Kinase | 1 | 4.6× | 0.495 |
| Enzyme (other) | 1 | 2.0× | 0.674 |
| Transcription factor | 1 | 1.4× | 0.674 |
| Other/Unknown | 2 | 0.6× | 0.936 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ERBB2 | Kinase | yes | 2.7.10.1 | Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom |
| TP53 | Transcription factor | no | p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn | |
| POT1 | Other/Unknown | no | Telomer_end-bd_POT1/Cdc13, NA-bd_OB-fold, POT1 | |
| FANCB | Other/Unknown | no | FANCB | |
| IDH1 | Enzyme (other) | yes | 1.1.1.42 | Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom |
| PPARG | Nuclear receptor | yes | Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt |
Expression context
Cohort genes with no expression data: 0.
6 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) | 6 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| lower esophagus mucosa | 1 |
| right uterine tube | 1 |
| sural nerve | 1 |
| ganglionic eminence | 1 |
| tendon of biceps brachii | 1 |
| ventricular zone | 1 |
| calcaneal tendon | 1 |
| germinal epithelium of ovary | 1 |
| secondary oocyte | 1 |
| buccal mucosa cell | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| primordial germ cell in gonad | 1 |
| adrenal tissue | 1 |
| corpus epididymis | 1 |
| jejunal mucosa | 1 |
| adipose tissue of abdominal region | 1 |
| omental fat pad | 1 |
| peritoneum | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ERBB2 | 276 | ubiquitous | marker | lower esophagus mucosa, right uterine tube, sural nerve |
| TP53 | 223 | ubiquitous | marker | ventricular zone, ganglionic eminence, tendon of biceps brachii |
| POT1 | 279 | ubiquitous | marker | secondary oocyte, germinal epithelium of ovary, calcaneal tendon |
| FANCB | 160 | ubiquitous | marker | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, buccal mucosa cell |
| IDH1 | 294 | ubiquitous | marker | corpus epididymis, jejunal mucosa, adrenal tissue |
| PPARG | 194 | ubiquitous | marker | omental fat pad, peritoneum, adipose tissue of abdominal region |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TP53 | 22,736 |
| ERBB2 | 9,659 |
| PPARG | 7,747 |
| IDH1 | 5,464 |
| POT1 | 1,842 |
| FANCB | 1,097 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| IDH1 | TP53 | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PPARG | P37231 | 380 |
| TP53 | P04637 | 313 |
| ERBB2 | P04626 | 63 |
| IDH1 | O75874 | 61 |
| POT1 | Q9NUX5 | 14 |
| FANCB | Q8NB91 | 6 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 105. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate | 1 | 1903.3× | 0.011 | IDH1 |
| Loss of function of TP53 in cancer due to loss of tetramerization ability | 1 | 1903.3× | 0.011 | TP53 |
| NADPH regeneration | 1 | 951.7× | 0.011 | IDH1 |
| Regulation of TP53 Expression | 1 | 951.7× | 0.011 | TP53 |
| NFE2L2 regulating TCA cycle genes | 1 | 634.4× | 0.011 | IDH1 |
| PLCG1 events in ERBB2 signaling | 1 | 475.8× | 0.011 | ERBB2 |
| Transcriptional activation of cell cycle inhibitor p21 | 1 | 475.8× | 0.011 | TP53 |
| Drug-mediated inhibition of ERBB2 signaling | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to trastuzumab | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to sapitinib | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to tesevatinib | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to neratinib | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to osimertinib | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to afatinib | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to AEE788 | 1 | 475.8× | 0.011 | ERBB2 |
| Resistance of ERBB2 KD mutants to lapatinib | 1 | 475.8× | 0.011 | ERBB2 |
| Drug resistance in ERBB2 TMD/JMD mutants | 1 | 475.8× | 0.011 | ERBB2 |
| Regulation of PTEN gene transcription | 2 | 59.5× | 0.011 | TP53, PPARG |
| DNA Damage/Telomere Stress Induced Senescence | 2 | 54.4× | 0.011 | TP53, POT1 |
| PKR-mediated signaling | 2 | 47.0× | 0.011 | TP53, FANCB |
| MECP2 regulates transcription factors | 1 | 380.7× | 0.013 | PPARG |
| Activation of NOXA and translocation to mitochondria | 1 | 317.2× | 0.014 | TP53 |
| GRB7 events in ERBB2 signaling | 1 | 317.2× | 0.014 | ERBB2 |
| RUNX3 regulates CDKN1A transcription | 1 | 271.9× | 0.016 | TP53 |
| PI5P Regulates TP53 Acetylation | 1 | 211.5× | 0.020 | TP53 |
| Activation of PUMA and translocation to mitochondria | 1 | 190.3× | 0.020 | TP53 |
| TP53 Regulates Transcription of Caspase Activators and Caspases | 1 | 158.6× | 0.020 | TP53 |
| TP53 Regulates Transcription of Death Receptors and Ligands | 1 | 158.6× | 0.020 | TP53 |
| Constitutive Signaling by Overexpressed ERBB2 | 1 | 158.6× | 0.020 | ERBB2 |
| Urea cycle | 1 | 146.4× | 0.020 | TP53 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| negative regulation of telomere maintenance via telomerase | 2 | 244.2× | 0.007 | TP53, POT1 |
| negative regulation of helicase activity | 1 | 2808.7× | 0.009 | TP53 |
| positive regulation of DNA strand elongation | 1 | 2808.7× | 0.009 | POT1 |
| regulation of phospholipid catabolic process | 1 | 2808.7× | 0.009 | IDH1 |
| cellular response to actinomycin D | 1 | 2808.7× | 0.009 | TP53 |
| regulation of intrinsic apoptotic signaling pathway by p53 class mediator | 1 | 2808.7× | 0.009 | TP53 |
| negative regulation of G1 to G0 transition | 1 | 2808.7× | 0.009 | TP53 |
| positive regulation of telomeric D-loop disassembly | 1 | 2808.7× | 0.009 | POT1 |
| glyoxylate cycle | 1 | 1404.3× | 0.009 | IDH1 |
| positive regulation of mitochondrial membrane permeability | 1 | 1404.3× | 0.009 | TP53 |
| regulation of phospholipid biosynthetic process | 1 | 1404.3× | 0.009 | IDH1 |
| oligodendrocyte apoptotic process | 1 | 1404.3× | 0.009 | TP53 |
| negative regulation of glucose catabolic process to lactate via pyruvate | 1 | 1404.3× | 0.009 | TP53 |
| negative regulation of connective tissue replacement involved in inflammatory response wound healing | 1 | 1404.3× | 0.009 | PPARG |
| negative regulation of pentose-phosphate shunt | 1 | 1404.3× | 0.009 | TP53 |
| obsolete homolactic fermentation | 1 | 936.2× | 0.009 | TP53 |
| positive regulation of adiponectin secretion | 1 | 936.2× | 0.009 | PPARG |
| signal transduction by p53 class mediator | 1 | 936.2× | 0.009 | TP53 |
| beige fat cell differentiation | 1 | 936.2× | 0.009 | PPARG |
| negative regulation of miRNA processing | 1 | 936.2× | 0.009 | TP53 |
| intrinsic apoptotic signaling pathway in response to hypoxia | 1 | 936.2× | 0.009 | TP53 |
| regulation of fibroblast apoptotic process | 1 | 936.2× | 0.009 | TP53 |
| T cell proliferation involved in immune response | 1 | 702.2× | 0.009 | TP53 |
| telomere assembly | 1 | 702.2× | 0.009 | POT1 |
| positive regulation of programmed necrotic cell death | 1 | 702.2× | 0.009 | TP53 |
| oxidative stress-induced premature senescence | 1 | 702.2× | 0.009 | TP53 |
| negative regulation of extracellular matrix assembly | 1 | 702.2× | 0.009 | PPARG |
| negative regulation of cellular response to transforming growth factor beta stimulus | 1 | 702.2× | 0.009 | PPARG |
| B cell lineage commitment | 1 | 561.7× | 0.009 | TP53 |
| T cell lineage commitment | 1 | 561.7× | 0.009 | TP53 |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 2
Druggability breadth: 5 of 6 evidence-associated genes (83%) 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 |
|---|---|
| ERBB2 | CLOTRIMAZOLE |
| TP53 | NITROFURANTOIN |
| IDH1 | ENASIDENIB |
| PPARG | METHYLENE BLUE ANHYDROUS |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TP53 | 196 | 4 |
| ERBB2 | 83 | 4 |
| PPARG | 83 | 4 |
| IDH1 | 10 | 4 |
| POT1 | 0 | 0 |
| FANCB | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| CLOTRIMAZOLE | 4 | ERBB2, TP53 |
| ERLOTINIB HYDROCHLORIDE | 4 | ERBB2 |
| PONATINIB | 4 | ERBB2 |
| AFATINIB | 4 | ERBB2 |
| LAPATINIB DITOSYLATE | 4 | ERBB2 |
| SORAFENIB | 4 | ERBB2 |
| NERATINIB | 4 | ERBB2 |
| IBRUTINIB | 4 | ERBB2 |
| AFATINIB DIMALEATE | 4 | ERBB2 |
| CABOZANTINIB | 4 | ERBB2 |
| DACOMITINIB | 4 | ERBB2 |
| DACOMITINIB ANHYDROUS | 4 | ERBB2 |
| VANDETANIB | 4 | ERBB2 |
| TRIBROMSALAN | 4 | ERBB2 |
| BOSUTINIB | 4 | ERBB2 |
| BITHIONOL | 4 | ERBB2 |
| ASTEMIZOLE | 4 | ERBB2, TP53 |
| EBASTINE | 4 | ERBB2 |
| OSIMERTINIB | 4 | ERBB2 |
| BRIGATINIB | 4 | ERBB2 |
| ACALABRUTINIB | 4 | ERBB2 |
| ZANUBRUTINIB | 4 | ERBB2 |
| TUCATINIB | 4 | ERBB2 |
| TIRABRUTINIB | 4 | ERBB2 |
| PACLITAXEL | 4 | ERBB2, TP53 |
| LAZERTINIB | 4 | ERBB2 |
| HEXACHLOROPHENE | 4 | ERBB2 |
| DOXORUBICIN | 4 | ERBB2 |
| DASATINIB | 4 | ERBB2 |
| ERLOTINIB | 4 | ERBB2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PPARG | 2,033 | Binding:1593, Functional:380, ADMET:56, Toxicity:3, Unclassified:1 |
| ERBB2 | 1,221 | Binding:1136, Functional:79, ADMET:6 |
| TP53 | 869 | Binding:775, ADMET:83, Functional:10, Toxicity:1 |
| IDH1 | 488 | Binding:475, Functional:12, ADMET:1 |
| POT1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ERBB2 | 2.7.10.1 | receptor protein-tyrosine kinase |
| IDH1 | 1.1.1.42 | isocitrate dehydrogenase (NADP+) |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| ERBB2 | 1,221 |
| TP53 | 869 |
| IDH1 | 488 |
| PPARG | 2,033 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Drug repurposing candidates
30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| CLOTRIMAZOLE | 4 | ERBB2, TP53 |
| ERLOTINIB HYDROCHLORIDE | 4 | ERBB2 |
| PONATINIB | 4 | ERBB2 |
| AFATINIB | 4 | ERBB2 |
| LAPATINIB DITOSYLATE | 4 | ERBB2 |
| SORAFENIB | 4 | ERBB2 |
| NERATINIB | 4 | ERBB2 |
| IBRUTINIB | 4 | ERBB2 |
| AFATINIB DIMALEATE | 4 | ERBB2 |
| CABOZANTINIB | 4 | ERBB2 |
| DACOMITINIB | 4 | ERBB2 |
| DACOMITINIB ANHYDROUS | 4 | ERBB2 |
| VANDETANIB | 4 | ERBB2 |
| TRIBROMSALAN | 4 | ERBB2 |
| BOSUTINIB | 4 | ERBB2 |
| BITHIONOL | 4 | ERBB2 |
| ASTEMIZOLE | 4 | ERBB2, TP53 |
| EBASTINE | 4 | ERBB2 |
| OSIMERTINIB | 4 | ERBB2 |
| BRIGATINIB | 4 | ERBB2 |
| ACALABRUTINIB | 4 | ERBB2 |
| ZANUBRUTINIB | 4 | ERBB2 |
| TUCATINIB | 4 | ERBB2 |
| TIRABRUTINIB | 4 | ERBB2 |
| PACLITAXEL | 4 | ERBB2, TP53 |
| LAZERTINIB | 4 | ERBB2 |
| HEXACHLOROPHENE | 4 | ERBB2 |
| DOXORUBICIN | 4 | ERBB2 |
| DASATINIB | 4 | ERBB2 |
| ERLOTINIB | 4 | ERBB2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 4 | ERBB2, TP53, IDH1, PPARG |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | POT1, FANCB |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| POT1 | 1 | — |
| FANCB | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.