Summary
Esophageal squamous cell carcinoma (MONDO:0005580) is a cancer with 19 cohort genes (50 GWAS associations across 5 studies; 11 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 503 clinical trials. The dominant Reactome pathway is Stabilization of p53 (4 cohort genes). Molecularly, AURKA EXPRESSION confers sensitivity to Radiation Therapy + Fluorouracil + Cisplatin in Esophagus Squamous Cell Carcinoma (CIViC Level B); 6 further subtype–drug associations are mapped below. Top therapeutic interventions include cisplatin, tislelizumab, and levoleucovorin.
At a glance
- Classification: Cancer
- Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
- Cohort genes: 19
- GWAS associations: 50
- ClinVar variants: 2
- Phenotypes (HPO): 8
- Clinical trials: 503
- Precision-medicine evidence (CIViC): 7 subtype–drug associations
Clinical features
Epidemiology
Prevalence records
28 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):
| Type | Class | Value | Geography | Validation |
|---|
| Annual incidence | 1-9 / 100 000 | 5.2 | Worldwide | Validated |
| Annual incidence | 1-9 / 100 000 | 3.357 | Europe | Validated |
| Lifetime Prevalence | 1-9 / 100 000 | 5.42 | Europe | Validated |
| Point prevalence | 1-9 / 100 000 | | Europe | Validated |
| Annual incidence | 1-9 / 100 000 | 2.026 | Austria | Validated |
| Annual incidence | 1-9 / 100 000 | 3.881 | Belgium | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.801 | Bulgaria | Validated |
| Annual incidence | 1-9 / 100 000 | 2.79 | Croatia | Validated |
| Annual incidence | 1-9 / 100 000 | 2.315 | Czech Republic | Validated |
| Annual incidence | 1-9 / 100 000 | 3.122 | Estonia | Validated |
| Annual incidence | 1-9 / 100 000 | 2.325 | Finland | Validated |
| Annual incidence | 1-9 / 100 000 | 5.069 | France | Validated |
| Annual incidence | 1-9 / 100 000 | 4.172 | Germany | Validated |
| Annual incidence | 1-9 / 100 000 | 2.215 | Iceland | Validated |
| Annual incidence | 1-9 / 100 000 | 3.443 | Ireland | Validated |
| Annual incidence | 1-9 / 100 000 | 2.623 | Italy | Validated |
| Annual incidence | 1-9 / 100 000 | 2.896 | Latvia | Validated |
| Annual incidence | 1-9 / 100 000 | 2.922 | Lithuania | Validated |
| Annual incidence | 1-9 / 100 000 | 1.256 | Malta | Validated |
| Annual incidence | 1-9 / 100 000 | 1.706 | Norway | Validated |
Signs & symptoms
Clinical features (HPO)
8 HPO clinical features (Orphanet curated; top 8 by frequency):
| HPO ID | Term | Frequency |
|---|
| HP:0001864 | Clinodactyly of the 5th toe | Very frequent (80-99%) |
| HP:0008872 | Feeding difficulties in infancy | Very frequent (80-99%) |
| HP:0011459 | Esophageal carcinoma | Very frequent (80-99%) |
| HP:0001608 | Abnormality of the voice | Frequent (30-79%) |
| HP:0002017 | Nausea and vomiting | Frequent (30-79%) |
| HP:0012735 | Cough | Frequent (30-79%) |
| HP:0100749 | Chest pain | Frequent (30-79%) |
| HP:0002716 | Lymphadenopathy | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|
| Canonical name | esophageal squamous cell carcinoma |
| Mondo ID | MONDO:0005580 |
| EFO | EFO:0005922 |
| MeSH | C562729, D000077277 |
| Orphanet | 99977 |
| DOID | DOID:3748 |
| ICD-11 | 1417891145 |
| NCIT | C4024 |
| SNOMED CT | 276804009 |
| UMLS | C0279626 |
| MedGen | 124635 |
| GARD | 0018901 |
| Anatomy (UBERON) | UBERON:0001043 |
| Is cancer (heuristic) | yes |
Also known as: ESCC · esophageal epidermoid carcinoma · esophageal scc · esophageal squamous cell cancer · esophageal squamous cell carcinoma · esophagus scc · esophagus squamous cell carcinoma · oesophagus scc · scc of esophagus · scc of the esophagus · scc of the oesophagus · squamous cell car. - esophagus · squamous cell car. - oesophagus · squamous cell carcinoma of esophagus · squamous cell carcinoma of oesophagus · squamous cell carcinoma of the esophagus · squamous cell carcinoma of the oesophagus
Data availability: 2 ClinVar variants · 50 GWAS associations (5 studies) · 261 cell lines · 22 intOGen driver records.
Disease family
An umbrella term covering 4 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › squamous cell neoplasm › squamous cell carcinoma › esophageal squamous cell carcinoma
Related subtypes (38): bone squamous cell carcinoma, prostate squamous cell carcinoma, trachea squamous cell carcinoma, scrotum squamous cell carcinoma, skin squamous cell carcinoma, bladder squamous cell carcinoma, urethra squamous cell carcinoma, papillary squamous carcinoma, basaloid squamous cell carcinoma, pseudoglandular squamous cell carcinoma, thymus squamous cell carcinoma, ovarian squamous cell carcinoma, renal pelvis squamous cell carcinoma, ureter squamous cell carcinoma, fallopian tube squamous cell carcinoma, squamous carcinoma in situ, keratinizing squamous cell carcinoma, squamous cell lung carcinoma, squamous cell breast carcinoma, adenosquamous carcinoma, cervical squamous cell carcinoma, colorectal squamous cell carcinoma, endometrial squamous cell carcinoma, gallbladder squamous cell carcinoma, gastric squamous cell carcinoma, thyroid gland squamous cell carcinoma, vaginal squamous cell carcinoma, head and neck squamous cell carcinoma, squamous cell carcinoma of the corpus uteri, squamous cell carcinoma of penis, squamous cell carcinoma of the small intestine, squamous cell carcinoma of pancreas, squamous cell carcinoma of liver and intrahepatic biliary tract, human papillomavirus-related squamous cell carcinoma, sarcomatoid squamous cell carcinoma, vulvar squamous cell carcinoma, metastatic squamous cell carcinoma, pure squamous carcinoma of the urothelial tract
Subtypes (4): esophagus verrucous carcinoma, esophageal adenosquamous carcinoma, esophageal basaloid carcinoma, undifferentiated carcinoma of esophagus
Genetics & variants
GWAS landscape
50 GWAS associations across 5 studies. Top hits map to 33 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|
| rs7447927 | 8e-20 | STING1 | C | 1.18 |
| rs12263737 | 1e-19 | PLCE1, PLCE1-AS1 | A | 1.44 |
| rs2274223 | 4e-18 | PLCE1 | G | 1.35 |
| rs1642764 | 3e-13 | ATP1B2 | C | 1.14 |
| rs13016963 | 4e-13 | CASP8, FLACC1 | A | 1.27 |
| rs738722 | 8e-10 | CHEK2 | C | 1.26 |
| rs12379660 | 9e-10 | Y_RNA - FAM120AOS | A | 1.51 |
| rs1033667 | 1e-09 | CHEK2 | T | 1.84 |
| rs2014300 | 8e-09 | RUNX1 | G | 1.28 |
| rs7099485 | 1e-08 | PLCE1 | C | 1.94 |
| rs4086889 | 3e-08 | ANKRD36B | A | 1.22 |
| rs142741123 | 5e-08 | MYO1B | C | 2.66 |
| rs35597309 | 1e-07 | HLA-DRB1 - HLA-DQA1 | A | 1.19 |
| rs34115901 | 1e-07 | SLC16A14 - SP110 | A | 1.86 |
| rs144188626 | 2e-07 | PCM1 | A | 1.82 |
| rs11205513 | 3e-07 | AGBL4 | G | 1.26 |
| rs112854191 | 3e-07 | GSE1 | A | 1.4 |
| rs114448224 | 3e-07 | CCDC71L - LINC02577 | T | 0.54 |
| rs148725713 | 3e-07 | MUC7 - AMTN | G | 2.18 |
| rs7806956 | 3e-07 | ABHD11 - CLDN3 | T | 0.79 |
| rs2239815 | 4e-07 | XBP1 | T | 1.16 |
| rs62093212 | 4e-07 | RBBP8, RBBP8-AS1 | T | 0.81 |
| rs61271866 | 7e-07 | CDKN2B-AS1 | A | 1.11 |
| rs531841075 | 9e-07 | TNFRSF10C - TNFRSF10D | A | 1.96 |
| rs113702517 | 9e-07 | STAT4 | C | 0.68 |
| rs10052657 | 1e-06 | PDE4D | C | 1.25 |
| rs4744456 | 1e-06 | FANCC | C | 0.83 |
| rs73365656 | 1e-06 | MIR99AHG | G | 1.74 |
| rs115523423 | 1e-06 | LINC02127 | G | 1.6 |
| rs78048962 | 2e-06 | TWSG1 | A | 0.75 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|
| GCST90435238 | Niu S | 2024 | 9,728 | 10,977 | PTPN23[Thr] variant reduces susceptibility and tumorigenesis in esophageal squamous cell carcinoma through dephosphorylation of EGFR. |
| GCST002568 | Wu C | 2014 | 5,337 | 5,787 | Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. |
| GCST90271955 | Chen WC | 2023 | 1,686 | 3,217 | Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations. |
| GCST90271956 | Chen WC | 2023 | 1,686 | 3,217 | Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations. |
| GCST90841197 | He F | 2026 | 1,050 | 4,506 | Genome wide association analysis and association of genetic risk and lifestyle with upper gastrointestinal cancer among an endoscopy-screened cohort in China. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 1 |
| Tier 4: intronic/intergenic | 45 |
MAF distribution
| Bucket | Variants |
|---|
| common (>=0.05) | 33 |
| low_freq (0.01-0.05) | 11 |
| rare (<0.01) | 3 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|
| intron_variant | 32 |
| intergenic_variant | 10 |
| synonymous_variant | 2 |
| missense_variant | 1 |
| regulatory_region_variant | 1 |
| unknown | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|
| rs7447927 | 5 | 139481561 | C>G,T | 0.46 | synonymous_variant | STING1 | 8e-20 | Tier 4: intronic/intergenic |
| rs12263737 | 10 | 94285156 | G>A | 0.05 | intron_variant | PLCE1, PLCE1-AS1 | 1e-19 | Tier 4: intronic/intergenic |
| rs2274223 | 10 | 94306584 | A>C,G,T | 0.209 | missense_variant | PLCE1 | 4e-18 | Tier 1: coding |
| rs1642764 | 17 | 7654516 | C>A,G,T | 0.499 | synonymous_variant | ATP1B2 | 3e-13 | Tier 4: intronic/intergenic |
| rs13016963 | 2 | 201298088 | A>C,G,T | 0.283 | intron_variant | CASP8, FLACC1 | 4e-13 | Tier 4: intronic/intergenic |
| rs738722 | 22 | 28734024 | T>C,G | 0.05 | intron_variant | CHEK2 | 8e-10 | Tier 4: intronic/intergenic |
| rs12379660 | 9 | 93420205 | G>A | 0.05 | intergenic_variant | Y_RNA - FAM120AOS | 9e-10 | Tier 4: intronic/intergenic |
| rs1033667 | 22 | 28734312 | C>T | 0.05 | intron_variant | CHEK2 | 1e-09 | Tier 4: intronic/intergenic |
| rs2014300 | 21 | 34985564 | A>C,G,T | 0.157 | intron_variant | RUNX1 | 8e-09 | Tier 4: intronic/intergenic |
| rs7099485 | 10 | 94305937 | T>C | 0.05 | intron_variant | PLCE1 | 1e-08 | Tier 4: intronic/intergenic |
| rs4086889 | 2 | 97567771 | C>A,G | 0.05 | intron_variant | ANKRD36B | 3e-08 | Tier 4: intronic/intergenic |
| rs142741123 | 2 | 191342389 | T>C,G | 0.007 | intron_variant | MYO1B | 5e-08 | Tier 4: intronic/intergenic |
| rs35597309 | 6 | 32621489 | G>A | 0.072 | intron_variant | HLA-DRB1 - HLA-DQA1 | 1e-07 | Tier 4: intronic/intergenic |
| rs34115901 | 2 | 230076332 | G>A,C | 0.05 | intergenic_variant | SLC16A14 - SP110 | 1e-07 | Tier 4: intronic/intergenic |
| rs144188626 | 8 | 17943536 | G>A,C | 0.023 | intron_variant | PCM1 | 2e-07 | Tier 4: intronic/intergenic |
| rs11205513 | 1 | 48590261 | G>C,T | 0.231 | intron_variant | AGBL4 | 3e-07 | Tier 4: intronic/intergenic |
| rs112854191 | 16 | 85547331 | T>A,C | 0.08 | regulatory_region_variant | GSE1 | 3e-07 | Tier 3: regulatory |
| rs114448224 | 7 | 106679607 | C>T | 0.031 | intron_variant | CCDC71L - LINC02577 | 3e-07 | Tier 4: intronic/intergenic |
| rs148725713 | 4 | 70502759 | C>G | 0.01 | intergenic_variant | MUC7 - AMTN | 3e-07 | Tier 4: intronic/intergenic |
| rs7806956 | 7 | 73741147 | T>A | 0.207 | intron_variant | ABHD11 - CLDN3 | 3e-07 | Tier 4: intronic/intergenic |
| rs2239815 | 22 | 28796682 | T>A,C,G | 0.387 | intron_variant | XBP1 | 4e-07 | Tier 4: intronic/intergenic |
| rs62093212 | 18 | 22859725 | T>C | 0.353 | intron_variant | RBBP8, RBBP8-AS1 | 4e-07 | Tier 4: intronic/intergenic |
| rs61271866 | 9 | 21997016 | T>A | 0.19 | intron_variant | CDKN2B-AS1 | 7e-07 | Tier 4: intronic/intergenic |
| rs531841075 | 8 | 23124847 | G>A | 0.013 | intergenic_variant | TNFRSF10C - TNFRSF10D | 9e-07 | Tier 4: intronic/intergenic |
| rs113702517 | 2 | 191052644 | T>C | 0.066 | intron_variant | STAT4 | 9e-07 | Tier 4: intronic/intergenic |
| rs10052657 | 5 | 59111944 | C>A | 0.12 | intron_variant | PDE4D | 1e-06 | Tier 4: intronic/intergenic |
| rs4744456 | 9 | 95344432 | C>T | 0.418 | intergenic_variant | FANCC | 1e-06 | Tier 4: intronic/intergenic |
| rs73365656 | 21 | 16256605 | C>G | 0.021 | intron_variant | MIR99AHG | 1e-06 | Tier 4: intronic/intergenic |
| rs115523423 | 16 | 51023992 | C>A,G | 0.034 | intron_variant | LINC02127 | 1e-06 | Tier 4: intronic/intergenic |
| rs78048962 | 18 | 9374238 | G>A,T | 0.118 | intron_variant | TWSG1 | 2e-06 | Tier 4: intronic/intergenic |
ClinVar germline variants
2 retrieved; paginated sample, class counts are floors:
2 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|
| 183303 | NM_016373.4(WWOX):c.606-1G>A | WWOX | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3384012 | NM_016373.3:c.410-17474_516+10296del | WWOX | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 58 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2
Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)
| Gene | HGNC | Evidence routes |
|---|
| TP53 | TP53 | GWAS, Orphanet |
| CDKN2A | CDKN2A | GWAS, Orphanet |
Somatic driver evidence (intOGen + CIViC, cohort fanout)
| Gene | intOGen role | Cancer types | CIViC |
|---|
| 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 |
| CDKN2A | LoF | ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC | CIViC #14 |
| AURKA | | | CIViC #61 |
| EGFR | Act | BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC | CIViC #19 |
| MDM2 | Act | LMS | CIViC #3465 |
| MYC | Act | AML,BL,MLYM,NHL | CIViC #3737 |
| AXL | | | CIViC #533 |
| RUNX1 | LoF | ACYC,ALL,AML,BRCA,GBM | CIViC #43 |
| CASP8 | LoF | BCC,BLCA,BRCA,CEAD,CESC,CSCC,HNSC,NHL,NPC,STAD,VULVA | CIViC #761 |
| CHEK2 | Act | BRCA | CIViC #8950 |
| CDKN2B | | | CIViC #916 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|
| 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 |
| CDKN2A | Orphanet:1333 | Familial pancreatic carcinoma |
| CDKN2A | Orphanet:1501 | Adrenocortical carcinoma |
| CDKN2A | Orphanet:252206 | Melanoma and neural system tumor syndrome |
| CDKN2A | Orphanet:404560 | Familial atypical multiple mole melanoma syndrome |
| CDKN2A | Orphanet:524 | Li-Fraumeni syndrome |
| CDKN2A | Orphanet:585909 | B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2) |
| CDKN2A | Orphanet:618 | Familial melanoma |
| CDKN2A | Orphanet:99861 | Precursor T-cell acute lymphoblastic leukemia |
| EGFR | Orphanet:251576 | Gliosarcoma |
| EGFR | Orphanet:251579 | Giant cell glioblastoma |
| MDM2 | Orphanet:524 | Li-Fraumeni syndrome |
| MDM2 | Orphanet:99970 | Dedifferentiated liposarcoma |
| MDM2 | Orphanet:99971 | Well-differentiated liposarcoma |
| MYC | Orphanet:480541 | High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement |
| MYC | Orphanet:543 | Burkitt lymphoma |
| MYC | Orphanet:99861 | Precursor T-cell acute lymphoblastic leukemia |
| RUNX1 | Orphanet:102724 | Acute myeloid leukemia with t(8;21)(q22;q22) translocation |
| RUNX1 | Orphanet:521 | Chronic myeloid leukemia |
| RUNX1 | Orphanet:71290 | Familial platelet disorder with associated myeloid malignancy |
| RUNX1 | Orphanet:98850 | Aggressive systemic mastocytosis |
| WWOX | Orphanet:251510 | 46,XY partial gonadal dysgenesis |
| WWOX | Orphanet:284282 | Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency |
| WWOX | Orphanet:708171 | Facial dysmorphism-corpus callosum hypoplasia-infantile epileptic encephalopathy |
| WWOX | Orphanet:99977 | Squamous cell carcinoma of the esophagus |
| CASP8 | Orphanet:210159 | Adult hepatocellular carcinoma |
| CASP8 | Orphanet:275517 | Autoimmune lymphoproliferative syndrome-recurrent viral infections due to CASP8 deficiency |
| CHEK2 | Orphanet:1331 | Familial prostate cancer |
| CHEK2 | Orphanet:145 | Hereditary breast and/or ovarian cancer syndrome |
| CHEK2 | Orphanet:440437 | Familial colorectal cancer Type X |
| CHEK2 | Orphanet:524 | Li-Fraumeni syndrome |
Cohort genes → proteins
19 cohort genes, 19 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|
| gwas_only | 11 |
| civic_only | 5 |
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|
| TP53 | HGNC:11998 | ENSG00000141510 | P04637 | Cellular tumor antigen p53 | gwas,civic_evidence |
| CDKN2A | HGNC:1787 | ENSG00000147889 | P42771 | Cyclin-dependent kinase inhibitor 2A | gwas,civic_evidence |
| AURKA | HGNC:11393 | ENSG00000087586 | O14965 | Aurora kinase A | civic_evidence |
| EGFR | HGNC:3236 | ENSG00000146648 | P00533 | Epidermal growth factor receptor | civic_evidence |
| MDM2 | HGNC:6973 | ENSG00000135679 | Q00987 | E3 ubiquitin-protein ligase Mdm2 | civic_evidence |
| MYC | HGNC:7553 | ENSG00000136997 | P01106 | Myc proto-oncogene protein | civic_evidence |
| AXL | HGNC:905 | ENSG00000167601 | P30530 | Tyrosine-protein kinase receptor UFO | civic_evidence |
| RUNX1 | HGNC:10471 | ENSG00000159216 | Q01196 | Runt-related transcription factor 1 | gwas |
| WWOX | HGNC:12799 | ENSG00000186153 | Q9NZC7 | WW domain-containing oxidoreductase | clinvar |
| XBP1 | HGNC:12801 | ENSG00000100219 | P17861 | X-box-binding protein 1 | gwas |
| FLACC1 | HGNC:14439 | ENSG00000155749 | Q96Q35 | Flagellum-associated coiled-coil domain-containing protein 1 | gwas |
| CASP8 | HGNC:1509 | ENSG00000064012 | Q14790 | Caspase-8 | gwas |
| CHEK2 | HGNC:16627 | ENSG00000183765 | O96017 | Serine/threonine-protein kinase Chk2 | gwas |
| PLCE1 | HGNC:17175 | ENSG00000138193 | Q9P212 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | gwas |
| CDKN2B | HGNC:1788 | ENSG00000147883 | P42772 | Cyclin-dependent kinase 4 inhibitor B | gwas |
| CCDC117 | HGNC:26599 | ENSG00000159873 | Q8IWD4 | Coiled-coil domain-containing protein 117 | gwas |
| STING1 | HGNC:27962 | ENSG00000184584 | Q86WV6 | Stimulator of interferon genes protein | gwas |
| ATP1B2 | HGNC:805 | ENSG00000129244 | P14415 | Sodium/potassium-transporting ATPase subunit beta-2 | gwas |
| PDE4D | HGNC:8783 | ENSG00000113448 | Q08499 | 3’,5’-cyclic-AMP phosphodiesterase 4D | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|
| TP53 | Cellular tumor antigen p53 | Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| CDKN2A | Cyclin-dependent kinase inhibitor 2A | Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. |
| AURKA | Aurora kinase A | Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. |
| EGFR | Epidermal growth factor receptor | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. |
| MDM2 | E3 ubiquitin-protein ligase Mdm2 | E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. |
| MYC | Myc proto-oncogene protein | Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5’-CAC[GA]TG-3'. |
| AXL | Tyrosine-protein kinase receptor UFO | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migratio… |
| RUNX1 | Runt-related transcription factor 1 | Forms the heterodimeric complex core-binding factor (CBF) with CBFB. |
| WWOX | WW domain-containing oxidoreductase | Putative oxidoreductase. |
| XBP1 | X-box-binding protein 1 | Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). |
| CASP8 | Caspase-8 | Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood. |
| CHEK2 | Serine/threonine-protein kinase Chk2 | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. |
| PLCE1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. |
| CDKN2B | Cyclin-dependent kinase 4 inhibitor B | Interacts strongly with CDK4 and CDK6. |
| CCDC117 | Coiled-coil domain-containing protein 117 | Facilitates DNA repair, cell cycle progression, and cell proliferation through its interaction with CIAO2B. |
| STING1 | Stimulator of interferon genes protein | Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). |
| ATP1B2 | Sodium/potassium-transporting ATPase subunit beta-2 | This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. |
| PDE4D | 3’,5’-cyclic-AMP phosphodiesterase 4D | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. |
Protein-family classification
Druggable: 7 · Difficult: 8 · Unknown: 4 · Druggable fraction: 0.37
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|
| Kinase | 4 | 5.8× | 0.021 |
| Scaffold/PPI | 3 | 2.7× | 0.156 |
| Transcription factor | 5 | 2.2× | 0.156 |
| Enzyme (other) | 3 | 1.9× | 0.259 |
| Other/Unknown | 4 | 0.4× | 1.000 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|
| TP53 | Transcription factor | no | | p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn |
| CDKN2A | Scaffold/PPI | no | | Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF |
| AURKA | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| EGFR | Kinase | yes | 2.7.10.1 | Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom |
| MDM2 | Transcription factor | no | 2.3.2.27 | Znf_RING, Znf_RanBP2, SWIB_MDM2_domain |
| MYC | Transcription factor | no | | Tscrpt_reg_Myc, Myc-LZ, bHLH_dom |
| AXL | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub |
| RUNX1 | Transcription factor | no | | AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf |
| WWOX | Scaffold/PPI | no | | WW_dom, SDR_fam, WW_dom_sf |
| XBP1 | Transcription factor | no | | bZIP, bZIP_sf, ER_Stress-Reg_TF |
| FLACC1 | Other/Unknown | no | | FLACC1 |
| CASP8 | Enzyme (other) | yes | 3.4.22.61 | Pept_C14_p20, DED_dom, Pept_C14_p10 |
| CHEK2 | Kinase | yes | 2.7.11.1 | FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS |
| PLCE1 | Enzyme (other) | yes | 3.1.4.11 | C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom |
| CDKN2B | Scaffold/PPI | no | | Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor |
| CCDC117 | Other/Unknown | no | | CCDC117 |
| STING1 | Other/Unknown | no | | STING, STING_C_sf, STING_C_chordates |
| ATP1B2 | Other/Unknown | no | | Na/K_ATPase_sub_beta, Na/K_ATPase_sub_beta_sf |
| PDE4D | Enzyme (other) | yes | 3.1.4.53 | PDEase_catalytic_dom, PDEase, PDEase_CS |
Expression context
Cohort genes with no expression data: 0.
19 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) | 19 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|
| ventricular zone | 4 |
| cervix squamous epithelium | 2 |
| parotid gland | 2 |
| secondary oocyte | 2 |
| olfactory segment of nasal mucosa | 2 |
| right uterine tube | 2 |
| lower esophagus mucosa | 2 |
| primordial germ cell in gonad | 2 |
| ganglionic eminence | 1 |
| tendon of biceps brachii | 1 |
| pituitary gland | 1 |
| oocyte | 1 |
| gingiva | 1 |
| gingival epithelium | 1 |
| nipple | 1 |
| adrenal tissue | 1 |
| calcaneal tendon | 1 |
| left uterine tube | 1 |
| upper leg skin | 1 |
| vena cava | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|
| TP53 | 223 | ubiquitous | marker | ventricular zone, ganglionic eminence, tendon of biceps brachii |
| CDKN2A | 220 | ubiquitous | marker | parotid gland, cervix squamous epithelium, pituitary gland |
| AURKA | 236 | ubiquitous | marker | oocyte, secondary oocyte, ventricular zone |
| EGFR | 285 | ubiquitous | marker | nipple, gingiva, gingival epithelium |
| MDM2 | 274 | ubiquitous | marker | calcaneal tendon, adrenal tissue, ventricular zone |
| MYC | 256 | ubiquitous | marker | upper leg skin, vena cava, left uterine tube |
| AXL | 290 | ubiquitous | marker | synovial joint, saphenous vein, stromal cell of endometrium |
| RUNX1 | 253 | ubiquitous | marker | olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus |
| WWOX | 286 | ubiquitous | marker | parotid gland, cervix squamous epithelium, cranial nerve II |
| XBP1 | 167 | broad | marker | body of pancreas, trachea, pancreas |
| FLACC1 | 168 | tissue_specific | marker | right uterine tube, bronchial epithelial cell, bronchus |
| CASP8 | 252 | ubiquitous | marker | monocyte, mononuclear cell, leukocyte |
| CHEK2 | 183 | ubiquitous | marker | primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis |
| PLCE1 | 271 | broad | marker | renal glomerulus, metanephric glomerulus, ventricular zone |
| CDKN2B | 219 | ubiquitous | marker | jejunal mucosa, colonic mucosa, lower esophagus mucosa |
| CCDC117 | 254 | ubiquitous | marker | buccal mucosa cell, secondary oocyte, primordial germ cell in gonad |
| STING1 | 134 | ubiquitous | marker | right uterine tube, olfactory segment of nasal mucosa, granulocyte |
| ATP1B2 | 221 | broad | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| PDE4D | 283 | ubiquitous | marker | gluteal muscle, biceps brachii, skeletal muscle tissue of rectus abdominis |
Protein interactions among cohort
Intra-cohort edges: 19.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|
| TP53 | 22,736 |
| MYC | 20,608 |
| EGFR | 18,421 |
| MDM2 | 9,892 |
| CDKN2A | 9,311 |
| AURKA | 6,376 |
| WWOX | 5,892 |
| CASP8 | 5,040 |
| RUNX1 | 4,994 |
| CHEK2 | 4,795 |
Intra-cohort edges
| A | B | Sources |
|---|
| AURKA | EGFR | intact |
| AURKA | MYC | string_interaction |
| AURKA | TP53 | string_interaction |
| AXL | EGFR | biogrid_interaction, intact |
| CASP8 | FLACC1 | string_interaction |
| CCDC117 | CHEK2 | string_interaction |
| CDKN2A | CDKN2B | biogrid_interaction |
| CDKN2A | MDM2 | biogrid_interaction, string_interaction |
| CDKN2A | MYC | string_interaction |
| CDKN2A | TP53 | string_interaction |
| CDKN2B | TP53 | string_interaction |
| CHEK2 | MDM2 | intact |
| CHEK2 | TP53 | intact, string_interaction |
| MDM2 | PLCE1 | biogrid_interaction |
| MDM2 | TP53 | biogrid_interaction, intact, string_interaction |
| MDM2 | XBP1 | biogrid_interaction |
| MYC | TP53 | string_interaction |
| PLCE1 | TP53 | biogrid_interaction |
| TP53 | WWOX | string_interaction |
Structural data
PDB: 15 · AlphaFold-only: 4 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|
| EGFR | P00533 | 388 |
| TP53 | P04637 | 313 |
| AURKA | O14965 | 193 |
| MDM2 | Q00987 | 147 |
| PDE4D | Q08499 | 122 |
| STING1 | Q86WV6 | 119 |
| CHEK2 | O96017 | 38 |
| CASP8 | Q14790 | 36 |
| MYC | P01106 | 25 |
| CDKN2A | P42771 | 5 |
| RUNX1 | Q01196 | 5 |
| XBP1 | P17861 | 5 |
| AXL | P30530 | 4 |
| PLCE1 | Q9P212 | 3 |
| WWOX | Q9NZC7 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|
| CDKN2B | P42772 | 90.12 |
| ATP1B2 | P14415 | 90.04 |
| FLACC1 | Q96Q35 | 75.95 |
| CCDC117 | Q8IWD4 | 60.99 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 315. Enrichment computed across 19 evidence-associated genes (17 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 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| Stabilization of p53 | 4 | 179.1× | 1e-06 | TP53, CDKN2A, CHEK2, MDM2 |
| Oncogene Induced Senescence | 4 | 79.0× | 2e-05 | TP53, CDKN2A, CDKN2B, MDM2 |
| Regulation of TP53 Degradation | 4 | 68.9× | 3e-05 | TP53, CDKN2A, CHEK2, MDM2 |
| Transcriptional regulation by RUNX3 | 4 | 64.0× | 3e-05 | CDKN2A, RUNX1, MDM2, MYC |
| SUMOylation of transcription factors | 3 | 100.8× | 2e-04 | TP53, CDKN2A, MDM2 |
| Regulation of TP53 Activity through Methylation | 3 | 96.0× | 2e-04 | TP53, CHEK2, MDM2 |
| Regulation of TP53 Activity through Phosphorylation | 4 | 27.7× | 5e-04 | TP53, AURKA, CHEK2, MDM2 |
| Oxidative Stress Induced Senescence | 4 | 21.3× | 0.001 | TP53, CDKN2A, CDKN2B, MDM2 |
| RNA Polymerase II Transcription | 6 | 8.0× | 0.002 | CDKN2A, RUNX1, AURKA, CDKN2B, MDM2, MYC |
| Cell Cycle | 5 | 10.6× | 0.002 | CDKN2A, AURKA, CDKN2B, MDM2, MYC |
| RUNX3 regulates p14-ARF | 2 | 134.3× | 0.003 | CDKN2A, RUNX1 |
| Mitotic G1 phase and G1/S transition | 3 | 32.5× | 0.003 | CDKN2A, CDKN2B, MYC |
| SUMO E3 ligases SUMOylate target proteins | 3 | 31.5× | 0.003 | CDKN2A, AURKA, MDM2 |
| SUMOylation | 3 | 28.8× | 0.003 | CDKN2A, AURKA, MDM2 |
| Disease | 7 | 5.4× | 0.003 | CDKN2A, RUNX1, CASP8, STING1, MDM2, MYC, ATP1B2 |
| p53-Dependent G1 DNA Damage Response | 2 | 84.0× | 0.004 | CDKN2A, MDM2 |
| p53-Dependent G1/S DNA damage checkpoint | 2 | 84.0× | 0.004 | CDKN2A, MDM2 |
| Cellular Senescence | 3 | 24.3× | 0.004 | CDKN2A, CDKN2B, MDM2 |
| Regulation of TP53 Activity | 3 | 23.4× | 0.004 | CDKN2A, AURKA, MDM2 |
| Gene expression (Transcription) | 6 | 6.3× | 0.004 | CDKN2A, RUNX1, AURKA, CDKN2B, MDM2, MYC |
| G1/S DNA Damage Checkpoints | 2 | 79.0× | 0.004 | CDKN2A, MDM2 |
| Diseases of programmed cell death | 2 | 74.6× | 0.004 | CDKN2A, CASP8 |
| Regulation of NF-kappa B signaling | 2 | 74.6× | 0.004 | TP53, CASP8 |
| TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 2 | 70.7× | 0.004 | TP53, AURKA |
| Cell Cycle, Mitotic | 4 | 11.3× | 0.004 | CDKN2A, AURKA, CDKN2B, MYC |
| Regulation of TP53 Expression and Degradation | 2 | 61.1× | 0.006 | CDKN2A, MDM2 |
| Generic Transcription Pathway | 6 | 5.3× | 0.006 | CDKN2A, RUNX1, AURKA, CDKN2B, MDM2, MYC |
| G1 Phase | 2 | 46.3× | 0.009 | CDKN2A, CDKN2B |
| Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 2 | 43.3× | 0.010 | CDKN2B, MYC |
| Cellular responses to stress | 4 | 8.7× | 0.010 | CDKN2A, CDKN2B, MDM2, MYC |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| replicative senescence | 3 | 165.2× | 2e-04 | TP53, CDKN2A, CHEK2 |
| negative regulation of apoptotic process | 7 | 13.5× | 2e-04 | TP53, AURKA, XBP1, EGFR, MDM2, MYC, AXL |
| cellular response to gamma radiation | 3 | 100.3× | 6e-04 | TP53, CHEK2, MDM2 |
| cellular response to UV-C | 2 | 374.5× | 0.001 | TP53, MDM2 |
| positive regulation of transcription by RNA polymerase II | 8 | 6.6× | 0.001 | TP53, CDKN2A, RUNX1, WWOX, XBP1, STING1, EGFR, MYC |
| DNA damage response, signal transduction by p53 class mediator | 3 | 59.8× | 0.001 | TP53, CHEK2, MDM2 |
| cellular response to nutrient | 2 | 234.1× | 0.002 | XBP1, CDKN2B |
| cellular senescence | 3 | 49.3× | 0.002 | TP53, CDKN2A, CDKN2B |
| protein destabilization | 3 | 48.4× | 0.002 | CDKN2A, XBP1, MDM2 |
| positive regulation of miRNA transcription | 3 | 48.4× | 0.002 | TP53, EGFR, MYC |
| cellular response to xenobiotic stimulus | 3 | 40.1× | 0.003 | TP53, CHEK2, MYC |
| cellular response to interferon-alpha | 2 | 170.2× | 0.003 | MYC, AXL |
| thymocyte apoptotic process | 2 | 156.0× | 0.003 | TP53, CHEK2 |
| Ras protein signal transduction | 3 | 34.2× | 0.003 | TP53, CDKN2A, PLCE1 |
| cardiac septum morphogenesis | 2 | 133.8× | 0.004 | TP53, MDM2 |
| rRNA transcription | 2 | 110.1× | 0.004 | TP53, CDKN2A |
| positive regulation of vascular associated smooth muscle cell migration | 2 | 110.1× | 0.004 | XBP1, MDM2 |
| protein stabilization | 4 | 14.9× | 0.004 | TP53, CDKN2A, CHEK2, ATP1B2 |
| positive regulation of cell population proliferation | 5 | 9.3× | 0.004 | XBP1, CCDC117, EGFR, MDM2, MYC |
| regulation of protein catabolic process | 2 | 93.6× | 0.005 | CHEK2, MDM2 |
| cellular response to peptide hormone stimulus | 2 | 93.6× | 0.005 | XBP1, MDM2 |
| positive regulation of execution phase of apoptosis | 2 | 93.6× | 0.005 | TP53, CASP8 |
| response to antibiotic | 2 | 78.0× | 0.007 | TP53, MDM2 |
| positive regulation of DNA-templated transcription | 5 | 7.8× | 0.007 | TP53, CDKN2A, RUNX1, CHEK2, MYC |
| negative regulation of transcription by RNA polymerase II | 6 | 5.9× | 0.007 | TP53, CDKN2A, RUNX1, XBP1, MDM2, MYC |
| regulation of protein stability | 3 | 21.0× | 0.008 | CDKN2A, AURKA, XBP1 |
| amyloid fibril formation | 2 | 66.9× | 0.008 | CDKN2A, MDM2 |
| chromosome organization | 2 | 64.6× | 0.008 | TP53, MYC |
| intrinsic apoptotic signaling pathway by p53 class mediator | 2 | 64.6× | 0.008 | TP53, WWOX |
| cellular response to hypoxia | 3 | 20.2× | 0.008 | TP53, MDM2, MYC |
Therapeutics
Drugs indicated for this disease
1 approved, 28 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adebrelimab, Afatinib, Albumin Human, Avelumab, Benmelstobart, Cadonilimab, Catequentinib, Dalpiciclib, Decitabine, Endostatin, N-Terminal-Mggshhhhh, Envafolimab, Erfonrilimab, Famitinib, Fluzoparib, Fruquintinib, Icotinib, Izalontamab, Lapatinib, Metformin, Ociperlimab, Palbociclib, Panitumumab, Penpulimab, Poziotinib, Raltitrexed, Ramucirumab, Rigosertib, Sacituzumab Govitecan, Sitravatinib, Spartalizumab, Tucidinostat.
Drug target analysis
Approved (phase 4): 12 · Phase ≥3: 13 · Phased (≥1): 13 · Undrugged: 6
Druggability breadth: 14 of 19 evidence-associated genes (74%) 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.
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|
| PDE4D | 269 | 4 |
| TP53 | 196 | 4 |
| EGFR | 175 | 4 |
| AURKA | 65 | 4 |
| AXL | 59 | 4 |
| CHEK2 | 30 | 4 |
| MDM2 | 14 | 4 |
| ATP1B2 | 5 | 4 |
| XBP1 | 4 | 4 |
| MYC | 3 | 3 |
Drugs targeting cohort genes (top 30)
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 8.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|
| EGFR | 6,531 | Binding:6211, Functional:173, ADMET:138, Toxicity:9 |
| AURKA | 1,500 | Binding:1483, Functional:10, ADMET:7 |
| MDM2 | 1,007 | Binding:979, Functional:28 |
| STING1 | 890 | Binding:890 |
| TP53 | 869 | Binding:775, ADMET:83, Functional:10, Toxicity:1 |
| PDE4D | 863 | Binding:805, Functional:33, ADMET:23, Toxicity:2 |
| AXL | 701 | Binding:698, Functional:3 |
| CHEK2 | 690 | Binding:687, Functional:2, ADMET:1 |
| MYC | 202 | Binding:202 |
| CASP8 | 116 | Binding:106, Functional:10 |
| ATP1B2 | 46 | Binding:46 |
| RUNX1 | 20 | Binding:17, Functional:3 |
| XBP1 | 7 | Binding:6, Functional:1 |
| CDKN2A | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|
| AURKA | 2.7.11.1 | non-specific serine/threonine protein kinase |
| EGFR | 2.7.10.1 | receptor protein-tyrosine kinase |
| MDM2 | 2.3.2.27 | RING-type E3 ubiquitin transferase |
| AXL | 2.7.10.1 | receptor protein-tyrosine kinase |
| CASP8 | 3.4.22.61 | caspase-8 |
| CHEK2 | 2.7.11.1 | non-specific serine/threonine protein kinase |
| PLCE1 | 3.1.4.11 | phosphoinositide phospholipase C |
| PDE4D | 3.1.4.53 | 3’,5’-cyclic-AMP phosphodiesterase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|
| TP53 | 869 |
| AURKA | 1,500 |
| EGFR | 6,531 |
| MDM2 | 1,007 |
| MYC | 202 |
| AXL | 701 |
| CASP8 | 116 |
| CHEK2 | 690 |
| STING1 | 890 |
| PDE4D | 863 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 19; 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) |
|---|
| NITROFURANTOIN | 4 | MDM2, TP53 |
| DIOSMIN | 4 | TP53 |
| VERTEPORFIN | 4 | TP53 |
| CANDESARTAN CILEXETIL | 4 | PDE4D, TP53 |
| DIENESTROL | 4 | TP53 |
| CLOTRIMAZOLE | 4 | EGFR, TP53 |
| COLCHICINE | 4 | TP53 |
| NABUMETONE | 4 | TP53 |
| SALMETEROL XINAFOATE | 4 | TP53 |
| AMIODARONE HYDROCHLORIDE | 4 | TP53 |
| FURAZOLIDONE | 4 | TP53 |
| AMOXAPINE | 4 | PDE4D, TP53 |
| RALOXIFENE HYDROCHLORIDE | 4 | TP53 |
| NICARDIPINE HYDROCHLORIDE | 4 | TP53 |
| SULCONAZOLE NITRATE | 4 | TP53 |
| PYRITHIONE ZINC | 4 | TP53 |
| LACTIC ACID | 4 | TP53 |
| OXYMETHOLONE | 4 | TP53 |
| CHLOROXINE | 4 | TP53 |
| PROPIOLACTONE | 4 | TP53 |
| CLOMIPRAMINE HYDROCHLORIDE | 4 | TP53 |
| PHENYL AMINOSALICYLATE | 4 | TP53 |
| THIORIDAZINE HYDROCHLORIDE | 4 | TP53 |
| AMITRIPTYLINE HYDROCHLORIDE | 4 | TP53 |
| ETHOPROPAZINE HYDROCHLORIDE | 4 | TP53 |
| MECHLORETHAMINE HYDROCHLORIDE | 4 | TP53 |
| ECONAZOLE NITRATE | 4 | TP53 |
| TRIFLUPROMAZINE HYDROCHLORIDE | 4 | TP53 |
| PROCHLORPERAZINE EDISYLATE | 4 | TP53 |
| DEQUALINIUM CHLORIDE | 4 | TP53 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|
| A | Approved (phase 4 drug) | 12 | TP53, AURKA, EGFR, MDM2, AXL, RUNX1, XBP1, CASP8, CHEK2, STING1 (+2 more) |
| B | Phased (≥1) drug, not yet approved | 1 | MYC |
| C | Druggable family + PDB, no drug | 1 | PLCE1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 5 | CDKN2A, WWOX, FLACC1, CDKN2B, CCDC117 |
Undrugged target profiles
6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|
| CDKN2A | 2 | MDM2 |
| CDKN2B | 0 | TP53 |
| WWOX | 0 | — |
| FLACC1 | 0 | — |
| PLCE1 | 0 | — |
| CCDC117 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 503.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|
| PHASE2 | 237 |
| Not specified | 113 |
| PHASE1 | 52 |
| PHASE3 | 49 |
| PHASE1/PHASE2 | 36 |
| PHASE2/PHASE3 | 12 |
| PHASE4 | 2 |
| EARLY_PHASE1 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|
| NCT06388135 | PHASE4 | NOT_YET_RECRUITING | Serplulimab Combined With Nab-paclitaxel and Cisplatin in Neoadjuvant Therapy for Resectable Esophageal Squamous Cell Carcinoma |
| NCT05603065 | PHASE4 | UNKNOWN | Tislelizumab With Chemotherapy or Radiation for Neoadjuvant Therapy of Esophageal Squamous Cell Carcinoma (TINES) |
| NCT04009265 | PHASE3 | RECRUITING | Study Compare Adjuvant Chemotherapy, Chemoradiotherapy and Surgery Alone for pN1-2(pT1b-3N1-2M0) Esophageal Carcinoma |
| NCT04138212 | PHASE3 | RECRUITING | Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy for Resectable Locally Advanced Esophageal Cancer (HCHTOG1903) |
| NCT04210115 | PHASE3 | ACTIVE_NOT_RECRUITING | Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975) |
| NCT04328948 | PHASE3 | RECRUITING | A Randomized Controlled Trial Evaluating of Prophylactic Irradiation in CRT for cT1bN0M0 ESCC |
| NCT04460352 | PHASE3 | RECRUITING | Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Oesophageal Cancer |
| NCT04543617 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy |
| NCT04550260 | PHASE3 | ACTIVE_NOT_RECRUITING | Study of Durvalumab Versus Placebo in Combination With Definitive Chemoradiation Therapy in Patient With ESCC |
| NCT04807673 | PHASE3 | RECRUITING | Pembrolizumab Plus Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Locally Advanced ESCC (KEYSTONE-002) |
| NCT04949256 | PHASE3 | ACTIVE_NOT_RECRUITING | Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014) |
| NCT04973306 | PHASE2/PHASE3 | RECRUITING | Neoadjuvant Immunotherapy Plus CRT Versus Neoadjuvant CRT for Locally Advanced Resectable ESCC |
| NCT05078047 | PHASE3 | RECRUITING | Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO |
| NCT05244798 | PHASE3 | NOT_YET_RECRUITING | Sintilimab Plus NCT or NCRT Versus NCRT for ESCC |
| NCT05495152 | PHASE3 | RECRUITING | Adjuvant Sintilimab for Locally Advanced Esophageal Squamous Cell Carcinoma |
| NCT05919030 | PHASE3 | RECRUITING | A Study of Chemoradiation in Combination with Tislelizumab As First Line Treatment in Participants with Advanced Esophageal Squamous Cell Carcinoma |
| NCT06022861 | PHASE3 | RECRUITING | A Study to Compare the Efficacy and Safety of LY01015 and Opdivo® Combined Respectively With Chemotherapy in Advanced or Metastatic Esophageal Squamous Cell Carcinoma |
| NCT06138028 | PHASE2/PHASE3 | RECRUITING | Sintilimab and Chemotherapy Sequential Radiotherapy in Advanced Esophageal Cancer |
| NCT06190782 | PHASE3 | RECRUITING | Local Therapy for Oligometastatic ESCC Patients Treated With PD-1 Inhibitor |
| NCT06194734 | PHASE3 | RECRUITING | A Study of KC1036 Versus Investigator’s Choice of Chemotherapy in Patients With Advanced Esophageal Cancer |
| NCT06304974 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study Comparing BL-B01D1 With Chemotherapy of Physician’s Choice in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma(PANKU-Esophagus01) |
| NCT06354530 | PHASE2/PHASE3 | RECRUITING | A Study of Neoadjuvant Therapy for the Treatment of Patients With Locally Advanced Esophageal Squamous Cell Carcinoma |
| NCT06563869 | PHASE3 | RECRUITING | Sintilimab With Chemotherapy Plus PEG-rhG-GSF for Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma |
| NCT06644781 | PHASE3 | RECRUITING | A Study of Ifinatamab Deruxtecan in Subjects With Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) (IDeate-Esophageal01) |
| NCT06861777 | PHASE2/PHASE3 | NOT_YET_RECRUITING | Total Neoadjuvant Therapy Combined With Adebrelimab in Locally Advanced Resectable ESCC |
| NCT06907602 | PHASE2/PHASE3 | RECRUITING | Optimizing Neoadjuvant Treatment Regimens for Locally Advanced Esophageal Squamous Cell Carcinoma |
| NCT06952621 | PHASE3 | NOT_YET_RECRUITING | Neoadjuvant Treatment of Toripalimab Combined With Nab-paclitaxel and Platinum Versus Neoadjuvant Docetaxel Combined With Cisplatin and 5-fluorouracil (DCF) in Esophageal Squamous Cell Carcinoma |
| NCT07016737 | PHASE3 | ENROLLING_BY_INVITATION | Immunochemotherapy ± Salvage Chemoradiation for Local Recurrence of Esophageal Squamous Cell Carcinoma After Definitive Chemoradiotherapy |
| NCT07246330 | PHASE3 | NOT_YET_RECRUITING | Stratified Treatment in Unresectable Locally Advanced ESCC Without Progression After Chemoimmunotherapy Induction Plus CCRT: Toripalimab Consolidation vs observation–a Prospective, Randomized, Controlled Phase III Multicenter Study |
| NCT07251062 | PHASE2/PHASE3 | NOT_YET_RECRUITING | A Study of SYS6010, Enlonstobart, and Chemotherapy for First-Line Treatment of Esophageal Squamous Cell Carcinoma. |
| NCT07446335 | PHASE3 | NOT_YET_RECRUITING | A Phase III Study of First-line Anlotinib Combined With Benmelstobart in Patients With Advanced Esophageal Squamous Cell Carcinoma |
| NCT07463573 | PHASE3 | RECRUITING | QLC5508 vs. Chemotherapy in Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma |
| NCT07487896 | PHASE3 | NOT_YET_RECRUITING | A Study of YL201 Versus Investigator’s Choice of Chemotherapy in Participants With Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma After Failure of First-Line Therapy |
| NCT07554456 | PHASE2/PHASE3 | NOT_YET_RECRUITING | A Study of BL-B01D1 in Combination With Tislelizumab ±5-Fluorouracil Versus Platinum-Based Chemotherapy Plus Tislelizumab as First-line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma(PANKU-Esophagus02) |
| NCT01398449 | PHASE3 | UNKNOWN | Is ENI Necessary For Patients With Thoracic Esophageal Cancer After Esophagectomy And With Pathological Stage Of T1-2,N+,M0 |
| NCT01402180 | PHASE2/PHASE3 | UNKNOWN | Chemoradiation With or Without Nimotuzumab in Treating Esophageal Cancer Patients Who Suffer With Recurrence in Regional Lymph Nodes After Esophagectomy |
| NCT01591135 | PHASE3 | COMPLETED | A Phase III Study of Comparing Paclitaxel Plus 5-Fluorouracil Versus Cisplatin Plus 5-Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Carcinoma |
| NCT01627379 | PHASE3 | TERMINATED | Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable,Advanced or Metastatic Esophageal Squamous Cell Cancer |
| NCT01740375 | PHASE3 | TERMINATED | Role of Esophagectomy in Complete Responders to CCRT |
| NCT02025036 | PHASE3 | UNKNOWN | Chemoradiotherapy of Capecitabine With or Without Oxaliplatin Versus Cisplatin-5-FU for Esophageal Squamous Cancer |
Drugs tested across these trials (top 30)
Precision-medicine subtype map (CIViC)
Drug × molecular subtype: 7 predictive associations from 7 curated evidence items; also 5 prognostic, 1 oncogenic, 1 predisposing.
| Molecular subtype | Therapy | Effect | Level | CIViC |
|---|
| AURKA EXPRESSION | Radiation Therapy + Fluorouracil + Cisplatin | Sensitivity/Response | CIViC B | EID1653 |
| EGFR Overexpression | Nimotuzumab | Sensitivity/Response | CIViC B | EID783 |
| EGFR L861Q | Afatinib | Sensitivity/Response | CIViC D | EID9679 |
| ERBB3 D297Y | Cetuximab + Afatinib + Erlotinib | Sensitivity/Response | CIViC D | EID9675 |
| MYC Overexpression | Ganetespib | Sensitivity/Response | CIViC D | EID10151 |
| WEE1 Overexpression | Adavosertib | Sensitivity/Response | CIViC D | EID9232 |
| EGFR Y69FS*11 | Erlotinib | Resistance | CIViC D | EID4808 |
- Cohort genes: TP53, CDKN2A, AURKA, EGFR, MDM2, MYC, AXL, RUNX1, CASP8, CHEK2, CDKN2B, WWOX, XBP1, FLACC1, PLCE1, CCDC117, STING1, ATP1B2, PDE4D
- Drugs: Cisplatin, Tislelizumab, Levoleucovorin, Toripalimab, Afatinib, Irinotecan, Pralatrexate, Atezolizumab, Durvalumab, Erlotinib, FLUDEOXYGLUCOSE F 18, Lenvatinib, Paclitaxel, Panitumumab, Vinorelbine, Nimotuzumab, Nedaplatin, Sintilimab, Catequentinib, Endostatin, N-Terminal-Mggshhhhh, Rigosertib, Tiragolumab, Enlonstobart, Ifinatamab Deruxtecan, Oblimersen, Icotinib, Ganetespib