Summary
Upper aerodigestive tract neoplasm (MONDO:0005398) is a cancer with 7 cohort genes (180 GWAS associations across 2 studies; 1 CIViC-evidence somatic driver) and 10 clinical trials. The dominant Reactome pathway is Ethanol oxidation (4 cohort genes). Top therapeutic interventions include morphine, ketoprofen, and panitumumab.
At a glance
- Classification: Cancer
- Cohort genes: 7
- GWAS associations: 180
- Clinical trials: 10
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|
| Canonical name | upper aerodigestive tract neoplasm |
| Mondo ID | MONDO:0005398 |
| EFO | EFO:0004284 |
| SNOMED CT | 439361000 |
| UMLS | C0887900 |
| MedGen | 164664 |
| Is cancer (heuristic) | yes |
Data availability: 180 GWAS associations (2 studies).
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › upper aerodigestive tract neoplasm
Related subtypes (47): pre-malignant neoplasm, endocrine gland neoplasm, giant cell tumor, hematopoietic and lymphoid system neoplasm, skin neoplasm, mesenchymal cell neoplasm, epidural spinal canal neoplasm, skeletal muscle neoplasm, trophoblastic neoplasm, cancer, germ cell tumor, benign neoplasm, histiocytoma, embryonal neoplasm, head and neck neoplasm, epithelial neoplasm, reproductive system neoplasm, non-seminomatous lesion, odontogenic cyst, phosphaturic mesenchymal tumor, thyroglossal duct cyst, hamartoma, mesenchymoma, mesothelial neoplasm, peritoneal neoplasm, virus associated tumor, nail tumor, respiratory tract neoplasm, spindle cell neoplasm, mixed neoplasm, urinary system neoplasm, cystic neoplasm, childhood neoplasm, melanocytic neoplasm, digestive system neoplasm, nervous system neoplasm, neoplasm of thorax, connective tissue neoplasm, bronchial adenomas/carcinoids childhood, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, erythroplakia, retroperitoneal neoplasm, cardiovascular neoplasm, dermoid or epidermoid cyst of the central nervous system, connective and soft tissue neoplasm, NTRK fusion positive cancer, RET fusion positive cancer
Genetics & variants
GWAS landscape
180 GWAS associations across 2 studies. Top hits map to 40 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|
| rs55781567 | 2e-29 | CHRNA5 | G | 1.19 |
| rs11571815 | 2e-21 | BRCA2 | A | 2 |
| rs1229984 | 1e-20 | ADH1B | T | 1.56 |
| rs9267123 | 2e-19 | LINC01149 - HCP5 | C | 1.23 |
| rs139789464 | 2e-19 | APOM | G | 1.26 |
| rs115484360 | 2e-19 | WHR1 | G | 1.26 |
| rs501942 | 3e-19 | SLC44A4 | T | 1.26 |
| rs9271611 | 5e-19 | HLA-DRB1 - HLA-DQA1 | G | 1.16 |
| rs459961 | 6e-19 | CLPTM1L | A | 0.88 |
| rs1150753 | 6e-19 | TNXB | G | 1.25 |
| rs147151648 | 2e-18 | TSBP1-AS1 | G | 1.25 |
| rs114573742 | 5e-18 | HLA-DRA | G | 1.25 |
| rs971074 | 9e-17 | ADH7 | G | 1.33 |
| rs115666025 | 1e-16 | MUC21 - MUC22 | A | 1.23 |
| rs141062032 | 2e-16 | FLOT1 | A | 1.22 |
| rs114249457 | 2e-16 | DDR1 | G | 1.26 |
| rs116777428 | 5e-16 | HCG19P | A | 1.23 |
| rs17879961 | 1e-15 | CHEK2 | G | 0.43 |
| rs116073320 | 1e-15 | ZFP57 - HLA-F-AS1 | A | 1.24 |
| rs114065824 | 2e-15 | GNL1 | C | 1.22 |
| rs115390513 | 3e-15 | HCG27 | C | 1.21 |
| rs113855064 | 4e-15 | PDS5B | C | 1.85 |
| rs116480994 | 4e-15 | POLR1H, POLR1HASP, POLR1HASP | C | 1.23 |
| rs116418332 | 5e-15 | TRIM26 | A | 1.23 |
| rs114935022 | 7e-15 | HLA-G - POLR1HASP | A | 1.18 |
| rs4886579 | 1e-13 | CHRNB4 | T | 1.12 |
| rs186184919 | 1e-13 | TTC28 | T | 0.44 |
| rs7953330 | 2e-13 | WNK1 | C | 0.89 |
| rs115482250 | 3e-13 | OR11A1 | A | 1.22 |
| rs116711004 | 6e-13 | LINC01623 | T | 1.22 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|
| GCST012213 | Lesseur C | 2021 | 7,426 | 61,961 | Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers. |
| GCST001011 | McKay JD | 2011 | 2,091 | 8,334 | A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|
| Tier 1: coding | 2 |
| Tier 2: splice/UTR | 2 |
| Tier 3: regulatory | 1 |
| Tier 4: intronic/intergenic | 45 |
MAF distribution
| Bucket | Variants |
|---|
| common (>=0.05) | 45 |
| low_freq (0.01-0.05) | 5 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|
| intron_variant | 32 |
| intergenic_variant | 7 |
| non_coding_transcript_exon_variant | 4 |
| missense_variant | 2 |
| synonymous_variant | 2 |
| 5_prime_UTR_variant | 1 |
| regulatory_region_variant | 1 |
| 3_prime_UTR_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|
| rs55781567 | 15 | 78565644 | C>G | 0.36 | 5_prime_UTR_variant | CHRNA5 | 2e-29 | Tier 2: splice/UTR |
| rs11571815 | 13 | 32394413 | G>A | 0.01 | intron_variant | BRCA2 | 2e-21 | Tier 4: intronic/intergenic |
| rs1229984 | 4 | 99318162 | T>A,C,G | 0.06 | missense_variant | ADH1B | 1e-20 | Tier 1: coding |
| rs9267123 | 6 | 31459618 | G>C | 0.11 | intron_variant | LINC01149 - HCP5 | 2e-19 | Tier 4: intronic/intergenic |
| rs139789464 | 6 | 31657087 | | 0.09 | intron_variant | APOM | 2e-19 | Tier 4: intronic/intergenic |
| rs115484360 | 6 | 31973120 | | 0.09 | intron_variant | WHR1 | 2e-19 | Tier 4: intronic/intergenic |
| rs501942 | 6 | 31872700 | C>A,T | 0.09 | intron_variant | SLC44A4 | 3e-19 | Tier 4: intronic/intergenic |
| rs9271611 | 6 | 32623832 | A>G | 0.41 | regulatory_region_variant | HLA-DRB1 - HLA-DQA1 | 5e-19 | Tier 3: regulatory |
| rs459961 | 5 | 1336991 | T>A | 0.46 | intron_variant | CLPTM1L | 6e-19 | Tier 4: intronic/intergenic |
| rs1150753 | 6 | 32092090 | A>G | 0.09 | intron_variant | TNXB | 6e-19 | Tier 4: intronic/intergenic |
| rs147151648 | 6 | 32284355 | | 0.08 | intron_variant | TSBP1-AS1 | 2e-18 | Tier 4: intronic/intergenic |
| rs114573742 | 6 | 32440720 | | 0.09 | intron_variant | HLA-DRA | 5e-18 | Tier 4: intronic/intergenic |
| rs971074 | 4 | 99420704 | C>A,G,T | 0.05 | synonymous_variant | ADH7 | 9e-17 | Tier 4: intronic/intergenic |
| rs115666025 | 6 | 31009903 | | 0.09 | intergenic_variant | MUC21 - MUC22 | 1e-16 | Tier 4: intronic/intergenic |
| rs141062032 | 6 | 30731245 | | 0.1 | intron_variant | FLOT1 | 2e-16 | Tier 4: intronic/intergenic |
| rs114249457 | 6 | 30887434 | | 0.1 | intron_variant | DDR1 | 2e-16 | Tier 4: intronic/intergenic |
| rs116777428 | 6 | 30359419 | | 0.09 | non_coding_transcript_exon_variant | HCG19P | 5e-16 | Tier 4: intronic/intergenic |
| rs17879961 | 22 | 28725099 | A>C,G,T | 0.01 | missense_variant | CHEK2 | 1e-15 | Tier 1: coding |
| rs116073320 | 6 | 29693039 | | 0.08 | intron_variant | ZFP57 - HLA-F-AS1 | 1e-15 | Tier 4: intronic/intergenic |
| rs114065824 | 6 | 30547266 | | 0.09 | synonymous_variant | GNL1 | 2e-15 | Tier 4: intronic/intergenic |
| rs115390513 | 6 | 31208169 | | 0.1 | intron_variant | HCG27 | 3e-15 | Tier 4: intronic/intergenic |
| rs113855064 | 13 | 32601963 | T>C | 0.01 | intron_variant | PDS5B | 4e-15 | Tier 4: intronic/intergenic |
| rs116480994 | 6 | 30064745 | | 0.08 | 3_prime_UTR_variant | POLR1H, POLR1HASP, POLR1HASP | 4e-15 | Tier 2: splice/UTR |
| rs116418332 | 6 | 30193759 | | 0.08 | intron_variant | TRIM26 | 5e-15 | Tier 4: intronic/intergenic |
| rs114935022 | 6 | 29852225 | | 0.14 | intron_variant | HLA-G - POLR1HASP | 7e-15 | Tier 4: intronic/intergenic |
| rs4886579 | 15 | 78676914 | C>T | 0.4 | intron_variant | CHRNB4 | 1e-13 | Tier 4: intronic/intergenic |
| rs186184919 | 22 | 28612900 | C>T | 0.01 | intron_variant | TTC28 | 1e-13 | Tier 4: intronic/intergenic |
| rs7953330 | 12 | 889653 | G>C | 0.3 | intron_variant | WNK1 | 2e-13 | Tier 4: intronic/intergenic |
| rs115482250 | 6 | 29447687 | | 0.07 | intron_variant | OR11A1 | 3e-13 | Tier 4: intronic/intergenic |
| rs116711004 | 6 | 28860102 | | 0.07 | non_coding_transcript_exon_variant | LINC01623 | 6e-13 | Tier 4: intronic/intergenic |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Somatic driver evidence (intOGen + CIViC, cohort fanout)
| Gene | intOGen role | Cancer types | CIViC |
|---|
| ALDH2 | Act | OS | |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|
| AVP | Orphanet:30925 | Hereditary arginine vasopressin deficiency |
Cohort genes → proteins
7 cohort genes, 7 distinct canonical proteins.
Evidence partition
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|
| HELQ | HGNC:18536 | ENSG00000163312 | Q8TDG4 | Helicase POLQ-like | gwas |
| ADH1B | HGNC:250 | ENSG00000196616 | P00325 | All-trans-retinol dehydrogenase [NAD(+)] ADH1B | gwas |
| ADH1C | HGNC:251 | ENSG00000248144 | P00326 | Alcohol dehydrogenase 1C | gwas |
| ADH7 | HGNC:256 | ENSG00000196344 | P40394 | All-trans-retinol dehydrogenase [NAD(+)] ADH7 | gwas |
| ABRAXAS1 | HGNC:25829 | ENSG00000163322 | Q6UWZ7 | BRCA1-A complex subunit Abraxas 1 | gwas |
| ALDH2 | HGNC:404 | ENSG00000111275 | P05091 | Aldehyde dehydrogenase, mitochondrial | gwas |
| AVP | HGNC:894 | ENSG00000101200 | P01185 | Vasopressin-neurophysin 2-copeptin | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|
| HELQ | Helicase POLQ-like | Single-stranded 3’-5’ DNA helicase that plays a key role in homology-driven double-strand break (DSB) repair. |
| ADH1B | All-trans-retinol dehydrogenase [NAD(+)] ADH1B | Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism. |
| ADH1C | Alcohol dehydrogenase 1C | Alcohol dehydrogenase. |
| ADH7 | All-trans-retinol dehydrogenase [NAD(+)] ADH7 | Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, and omega-hydroxy fatty acids and their derivatives. |
| ABRAXAS1 | BRCA1-A complex subunit Abraxas 1 | Involved in DNA damage response and double-strand break (DSB) repair. |
| ALDH2 | Aldehyde dehydrogenase, mitochondrial | Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. |
| AVP | Vasopressin-neurophysin 2-copeptin | Has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels. |
Protein-family classification
Druggable: 3 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.43
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 |
|---|
| Enzyme (other) | 3 | 5.1× | 0.031 |
| Other/Unknown | 4 | 1.0× | 0.626 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|
| HELQ | Enzyme (other) | yes | 3.6.4.12 | Helicase_C-like, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd |
| ADH1B | Other/Unknown | no | | ADH_Zn_CS, GroES-like_sf, ADH-like_C |
| ADH1C | Enzyme (other) | yes | 1.1.1.1 | ADH_Zn_CS, GroES-like_sf, ADH-like_C |
| ADH7 | Other/Unknown | no | | ADH_Zn_CS, GroES-like_sf, ADH-like_C |
| ABRAXAS1 | Other/Unknown | no | | FAM175, BRISC_Abraxas1, MPN |
| ALDH2 | Enzyme (other) | yes | 1.2.1.3 | Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH |
| AVP | Other/Unknown | no | | Neurhyp_horm, Neurohypophysial_hormone_CS, Neurhyp_horm_dom_sf |
Expression context
Cohort genes with no expression data: 0.
7 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) | 7 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|
| buccal mucosa cell | 2 |
| calcaneal tendon | 2 |
| primordial germ cell in gonad | 2 |
| lower lobe of lung | 2 |
| right lobe of liver | 2 |
| right coronary artery | 1 |
| jejunal mucosa | 1 |
| mucosa of transverse colon | 1 |
| nasal cavity epithelium | 1 |
| esophagus mucosa | 1 |
| lower esophagus mucosa | 1 |
| olfactory segment of nasal mucosa | 1 |
| tendon | 1 |
| liver | 1 |
| hypothalamus | 1 |
| ileal mucosa | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|
| HELQ | 248 | ubiquitous | marker | calcaneal tendon, buccal mucosa cell, primordial germ cell in gonad |
| ADH1B | 244 | broad | marker | right lobe of liver, right coronary artery, lower lobe of lung |
| ADH1C | 199 | tissue_specific | marker | mucosa of transverse colon, jejunal mucosa, nasal cavity epithelium |
| ADH7 | 149 | tissue_specific | marker | lower esophagus mucosa, esophagus mucosa, olfactory segment of nasal mucosa |
| ABRAXAS1 | 247 | ubiquitous | marker | primordial germ cell in gonad, calcaneal tendon, tendon |
| ALDH2 | 301 | ubiquitous | marker | right lobe of liver, liver, lower lobe of lung |
| AVP | 125 | tissue_specific | marker | hypothalamus, ileal mucosa, buccal mucosa cell |
Protein interactions among cohort
Intra-cohort edges: 9.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|
| ALDH2 | 4,554 |
| ADH1B | 2,091 |
| AVP | 2,070 |
| ADH1C | 1,955 |
| HELQ | 1,879 |
| ADH7 | 1,775 |
| ABRAXAS1 | 871 |
Intra-cohort edges
| A | B | Sources |
|---|
| ABRAXAS1 | HELQ | string_interaction |
| ADH1B | ADH1C | biogrid_interaction, intact |
| ADH1B | ALDH2 | string_interaction |
| ADH1B | AVP | string_interaction |
| ADH1C | ALDH2 | string_interaction |
| ADH1C | AVP | string_interaction |
| ADH7 | ALDH2 | string_interaction |
| ADH7 | AVP | string_interaction |
| ALDH2 | AVP | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|
| ALDH2 | P05091 | 29 |
| ADH1B | P00325 | 9 |
| AVP | P01185 | 5 |
| ABRAXAS1 | Q6UWZ7 | 4 |
| ADH7 | P40394 | 3 |
| ADH1C | P00326 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|
| HELQ | Q8TDG4 | 74.30 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 7 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 |
|---|
| Ethanol oxidation | 4 | 634.4× | 6e-10 | ADH1B, ADH1C, ADH7, ALDH2 |
| Phase I - Functionalization of compounds | 4 | 146.4× | 2e-07 | ADH1B, ADH1C, ADH7, ALDH2 |
| Biological oxidations | 4 | 86.5× | 9e-07 | ADH1B, ADH1C, ADH7, ALDH2 |
| Metabolism of serotonin | 1 | 951.7× | 0.010 | ALDH2 |
| Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) | 1 | 951.7× | 0.010 | AVP |
| Metabolism | 4 | 7.7× | 0.010 | ADH1B, ADH1C, ADH7, ALDH2 |
| Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) | 1 | 634.4× | 0.013 | AVP |
| Serotonin clearance from the synaptic cleft | 1 | 475.8× | 0.015 | ALDH2 |
| Vasopressin-like receptors | 1 | 317.2× | 0.020 | AVP |
| Neurotransmitter clearance | 1 | 211.5× | 0.027 | ALDH2 |
| Organic anion transport by SLCO transporters | 1 | 173.0× | 0.030 | AVP |
| Fatty acids | 1 | 119.0× | 0.040 | ADH7 |
| RA biosynthesis pathway | 1 | 79.3× | 0.052 | ADH1C |
| DNA Double Strand Break Response | 1 | 79.3× | 0.052 | ABRAXAS1 |
| BMAL1:CLOCK,NPAS2 activates circadian expression | 1 | 70.5× | 0.053 | AVP |
| Signaling by Retinoic Acid | 1 | 68.0× | 0.053 | ADH1C |
| Aquaporin-mediated transport | 1 | 61.4× | 0.054 | AVP |
| R-HSA-400253 | 1 | 57.7× | 0.054 | AVP |
| Homology Directed Repair | 1 | 51.4× | 0.054 | ABRAXAS1 |
| HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 1 | 51.4× | 0.054 | ABRAXAS1 |
| Metalloprotease DUBs | 1 | 50.1× | 0.054 | ABRAXAS1 |
| Transport of vitamins, nucleosides, and related molecules | 1 | 45.3× | 0.054 | AVP |
| Vasopressin regulates renal water homeostasis via Aquaporins | 1 | 44.3× | 0.054 | AVP |
| Smooth Muscle Contraction | 1 | 44.3× | 0.054 | ALDH2 |
| DNA Double-Strand Break Repair | 1 | 41.4× | 0.056 | ABRAXAS1 |
| SLC transporter disorders | 1 | 34.0× | 0.065 | AVP |
| Nonhomologous End-Joining (NHEJ) | 1 | 28.0× | 0.076 | ABRAXAS1 |
| Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | 1 | 24.4× | 0.083 | ABRAXAS1 |
| Disorders of transmembrane transporters | 1 | 23.2× | 0.085 | AVP |
| G2/M Checkpoints | 1 | 22.4× | 0.085 | ABRAXAS1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| retinoic acid metabolic process | 3 | 343.9× | 4e-06 | ADH1B, ADH1C, ADH7 |
| retinol metabolic process | 3 | 212.4× | 8e-06 | ADH1B, ADH1C, ADH7 |
| retinoid metabolic process | 2 | 141.6× | 0.002 | ADH1B, ADH7 |
| nitroglycerin metabolic process | 1 | 2407.4× | 0.004 | ALDH2 |
| regulation of dopamine biosynthetic process | 1 | 2407.4× | 0.004 | ALDH2 |
| regulation of serotonin biosynthetic process | 1 | 2407.4× | 0.004 | ALDH2 |
| ethanol metabolic process | 1 | 1203.7× | 0.007 | ALDH2 |
| response to ethanol | 2 | 41.9× | 0.007 | ADH7, AVP |
| aldehyde catabolic process | 1 | 802.5× | 0.008 | ALDH2 |
| response to nerve growth factor | 1 | 802.5× | 0.008 | AVP |
| maternal aggressive behavior | 1 | 601.9× | 0.008 | AVP |
| obsolete positive regulation of cellular pH reduction | 1 | 601.9× | 0.008 | AVP |
| double-strand break repair via synthesis-dependent strand annealing | 1 | 601.9× | 0.008 | HELQ |
| negative regulation of female receptivity | 1 | 481.5× | 0.009 | AVP |
| response to 2,3,7,8-tetrachlorodibenzodioxine | 1 | 481.5× | 0.009 | AVP |
| fatty acid omega-oxidation | 1 | 401.2× | 0.009 | ADH7 |
| alcohol metabolic process | 1 | 343.9× | 0.009 | ALDH2 |
| positive regulation of glutamate secretion | 1 | 343.9× | 0.009 | AVP |
| negative regulation of transmission of nerve impulse | 1 | 343.9× | 0.009 | AVP |
| renal water absorption | 1 | 343.9× | 0.009 | AVP |
| DNA double-strand break processing involved in repair via single-strand annealing | 1 | 300.9× | 0.010 | HELQ |
| cellular detoxification of aldehyde | 1 | 300.9× | 0.010 | ALDH2 |
| response to salt stress | 1 | 267.5× | 0.010 | AVP |
| positive regulation of prostaglandin biosynthetic process | 1 | 267.5× | 0.010 | AVP |
| double-strand break repair via alternative nonhomologous end joining | 1 | 240.7× | 0.010 | HELQ |
| positive regulation of systemic arterial blood pressure | 1 | 200.6× | 0.012 | AVP |
| multicellular organismal response to stress | 1 | 185.2× | 0.013 | AVP |
| ethanol catabolic process | 1 | 172.0× | 0.013 | ALDH2 |
| grooming behavior | 1 | 160.5× | 0.013 | AVP |
| maternal behavior | 1 | 160.5× | 0.013 | AVP |
Therapeutics
Drugs indicated or in trials for this disease
12 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
25 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6
Druggability breadth: 4 of 7 evidence-associated genes (57%) 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 |
|---|
| ALDH2 | DISULFIRAM |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|
| ALDH2 | 3 | 4 |
| HELQ | 0 | 0 |
| ADH1B | 0 | 0 |
| ADH1C | 0 | 0 |
| ADH7 | 0 | 0 |
| ABRAXAS1 | 0 | 0 |
| AVP | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|
| DISULFIRAM | 4 | ALDH2 |
| THIRAM | 2 | ALDH2 |
| DAIDZEIN | 2 | ALDH2 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|
| ALDH2 | 71 | Binding:66, Functional:5 |
| ADH7 | 14 | Binding:14 |
| ADH1B | 13 | Binding:13 |
| ADH1C | 12 | Binding:12 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|
| HELQ | 3.6.4.12 | DNA helicase |
| ADH1C | 1.1.1.1 | alcohol dehydrogenase |
| ALDH2 | 1.2.1.3 | aldehyde dehydrogenase (NAD+) |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Drug repurposing candidates
3 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) |
|---|
| DISULFIRAM | 4 | ALDH2 |
| THIRAM | 2 | ALDH2 |
| DAIDZEIN | 2 | ALDH2 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|
| A | Approved (phase 4 drug) | 1 | ALDH2 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | ADH1C |
| D | Druggable family + AlphaFold only, no drug | 1 | HELQ |
| E | Difficult family or no structure, no drug | 4 | ADH1B, ADH7, ABRAXAS1, AVP |
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) |
|---|
| ADH1B | 13 | ALDH2 |
| ADH1C | 12 | ALDH2 |
| ADH7 | 14 | ALDH2 |
| HELQ | 0 | — |
| ABRAXAS1 | 0 | — |
| AVP | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 10.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|
| Not specified | 6 |
| PHASE2 | 3 |
| PHASE4 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|
| NCT02869321 | PHASE4 | COMPLETED | Analgesic Efficacy of Transmucosal Fentanyl for Breakthrough Pain Caused by Interventional Gastrostomy |
| NCT00798655 | PHASE2 | COMPLETED | Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer |
| NCT02439034 | PHASE2 | COMPLETED | Paracetamol With or Without Ketoprofen in the Management of Pain for Patients Receiving Brachytherapy (KETOCOL-1304) |
| NCT03955224 | PHASE2 | WITHDRAWN | Evaluation of Low-Level Laser Therapy Efficacy in Pain Management of Grade 2 Oral Mucositis Induced by Radiotherapy or Chemoradiotherapy: a Study in Patients With Upper Aerodigestive Tract Cancer |
| NCT07596355 | Not specified | NOT_YET_RECRUITING | AI-Assisted Endoscopy for Upper Aerodigestive Tract Lesions |
| NCT00473564 | Not specified | COMPLETED | Robotic Assisted Surgery in Upper Aerodigestive Tract Surgery |
| NCT01788878 | Not specified | UNKNOWN | Cancer of the Upper Aero-digestive Tract and Socio-professional Future |
| NCT02540174 | Not specified | COMPLETED | Alcohol and Tobacco Consumption in Patients With Head and Neck or Lung Cancer : Interest of an Addiction Treatment |
| NCT04262453 | Not specified | COMPLETED | Obstructive Sleep Apnea Syndrome In Patients Treated For Cancer Of The Upper Aerodigestive Tract |
| NCT06857396 | Not specified | COMPLETED | Tracheal Exposure Without Tracheostomy Completion in Trans-oral Robotic Oncologic Surgery |
Drugs tested across these trials (top 30)