Esophageal adenocarcinoma

Summary

Esophageal adenocarcinoma (MONDO:0005028) is a disease with 37 cohort genes (118 GWAS associations across 18 studies) and 210 clinical trials. Molecularly, AURKA Overexpression confers sensitivity to Alisertib + Cisplatin in Esophagus Adenocarcinoma (CIViC Level D); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include leucovorin, irinotecan, and ramucirumab.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 37
• GWAS associations: 118
• Phenotypes (HPO): 10
• Clinical trials: 210
• Precision-medicine evidence (CIViC): 2 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 / 1 000 000	0.7	Worldwide	Validated
Annual incidence	1-9 / 100 000	3.264	Europe	Validated
Lifetime Prevalence	1-9 / 100 000	5.55	Europe	Validated
Point prevalence	1-9 / 100 000		Europe	Validated
Annual incidence	1-9 / 100 000	1.235	Austria	Validated
Annual incidence	1-9 / 100 000	3.918	Belgium	Validated
Annual incidence	1-9 / 1 000 000	0.364	Bulgaria	Validated
Annual incidence	1-9 / 1 000 000	0.485	Croatia	Validated
Annual incidence	1-9 / 100 000	1.28	Czech Republic	Validated
Annual incidence	1-9 / 1 000 000	0.305	Estonia	Validated
Annual incidence	1-9 / 100 000	1.5	Finland	Validated
Annual incidence	1-9 / 100 000	1.681	France	Validated
Annual incidence	1-9 / 100 000	1.636	Germany	Validated
Annual incidence	1-9 / 100 000	2.471	Iceland	Validated
Annual incidence	1-9 / 100 000	3.736	Ireland	Validated
Annual incidence	1-9 / 1 000 000	0.947	Italy	Validated
Annual incidence	1-9 / 1 000 000	0.39	Latvia	Validated
Annual incidence	1-9 / 1 000 000	0.526	Lithuania	Validated
Annual incidence	1-9 / 100 000	1.319	Malta	Validated
Annual incidence	1-9 / 1 000 000	0.315	Poland	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0001513	Obesity	Very frequent (80-99%)
HP:0001864	Clinodactyly of the 5th toe	Very frequent (80-99%)
HP:0002020	Gastroesophageal reflux	Very frequent (80-99%)
HP:0008872	Feeding difficulties in infancy	Very frequent (80-99%)
HP:0011459	Esophageal carcinoma	Very frequent (80-99%)
HP:0100580	Barrett esophagus	Very frequent (80-99%)
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 adenocarcinoma
Mondo ID	MONDO:0005028
EFO	EFO:0000478
Orphanet	99976
DOID	DOID:4914
ICD-11	829915640
NCIT	C4025
SNOMED CT	276803003
UMLS	C0279628
MedGen	124636
GARD	0016927
Anatomy (UBERON)	UBERON:0001043
Is cancer (heuristic)	no

Also known as: adenocarcinoma - esophagus · adenocarcinoma - oesophagus · adenocarcinoma of esophagus · adenocarcinoma of oesophagus · adenocarcinoma of the esophagus · adenocarcinoma of the oesophagus · esophageal adenocarcinoma · esophagus adenocarcinoma · oesophageal adenocarcinoma · oesophagus adenocarcinoma

Data availability: 118 GWAS associations (18 studies) · 28 cell lines · 72 intOGen driver records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › esophageal adenocarcinoma

Related subtypes (63): epididymal adenocarcinoma, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, ethmoid sinus adenocarcinoma, lacrimal gland adenocarcinoma, papillary adenocarcinoma, fallopian tube adenocarcinoma, bladder adenocarcinoma, ovarian adenocarcinoma, trabecular adenocarcinoma, middle ear adenocarcinoma, bile duct adenocarcinoma, granular cell carcinoma, small intestine adenocarcinoma, urethra adenocarcinoma, villous adenocarcinoma, thymus gland adenocarcinoma, nasal cavity adenocarcinoma, ureter adenocarcinoma, adenocarcinoma in situ, gastroesophageal junction adenocarcinoma, maxillary sinus adenocarcinoma, mucinous adenocarcinoma, acinar cell carcinoma, adenoid cystic carcinoma, breast adenocarcinoma, clear cell adenocarcinoma, colorectal adenocarcinoma, endometrioid adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, prostate adenocarcinoma, renal cell carcinoma, signet ring cell carcinoma, cervical adenocarcinoma, serous adenocarcinoma, endometrium adenocarcinoma, sweat gland carcinoma, cystadenocarcinoma, tubular adenocarcinoma, mesonephric adenocarcinoma, scirrhous adenocarcinoma, pancreatic adenocarcinoma, follicular variant thyroid gland papillary carcinoma, gallbladder adenocarcinoma, hepatoid adenocarcinoma, intestinal type adenocarcinoma, micropapillary serous carcinoma, minor salivary gland adenocarcinoma, poorly differentiated thyroid gland carcinoma, salivary gland basal cell adenocarcinoma, submandibular gland adenocarcinoma, sebaceous adenocarcinoma, hepatocellular carcinoma, parathyroid gland carcinoma, pituitary adenocarcinoma, vaginal adenocarcinoma, Paget disease, diffuse type adenocarcinoma, vulvar adenocarcinoma, thyroid gland adenocarcinoma, gastroesophageal adenocarcinoma, adenoacanthoma

Subtypes (3): mucoepidermoid esophageal carcinoma, esophageal adenoid cystic carcinoma, Barrett adenocarcinoma

Genetics & variants

GWAS landscape

118 GWAS associations across 18 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs622217	3e-18	SLC22A2 - SLC22A3	T	0.13
rs9306895	2e-15	GDF7	T	0.12
rs35631104	1e-13	LINC02253	G	0.13
rs72760500	2e-13	NNT - RNU6-381P	A	0.23
rs149252763	6e-13	LINC01091	G	0.14
rs2687197	3e-12	RNU6-281P - FOXP1	T	0.11
rs2095777	3e-12	MIR4291 - BARX1	?
rs4676893	8e-12	RNU6-281P - FOXP1	?	0.11
rs10225824	2e-11	CFTR, ASZ1	?
rs4646614	3e-11	ALDH1A2	A	0.1
rs3950627	3e-11	LINC00917 - FENDRR	A	0.1
rs2188554	3e-11	ASZ1, CFTR	A	0.13
rs146917555	7e-11	PLCL1 - RNU7-147P	A	0.1
rs7255	9e-11	GDF7	T	1.14
rs60849513	1e-10	SLC66A1LP	T	0.12
rs111613945	1e-10	LINC00208	C	0.1
rs144823843	2e-10	CEP72	A	0.12
rs7045553	2e-10	TMOD1	T	0.1
rs199620551	3e-10	CRTC1	T	0.09
rs77013824	3e-10	LINC02109	T	0.09
rs10419226	4e-10	CRTC1	A	1.18
rs2464469	5e-10	ALDH1A2-AS1, ALDH1A2	G	1.12
rs17451754	5e-10	CFTR	G	1.19
rs17749155	5e-10	MSRA	A	1.18
rs12449442	8e-10	BPTF	?
rs11789015	1e-09	BARX1	A	1.2
rs7187365	1e-09	FENDRR	T	0.12
rs10108511	2e-09	LINC00208	T	1.12
rs2687202	2e-09	RNU6-281P - FOXP1	T	1.13
rs1247942	2e-09	GLULP5 - LINC02459	G	1.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90258656	Schroder J	2022	16,790	32,476	GWAS meta-analysis of 16 790 patients with Barrett’s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.
GCST008831	An J	2019	8,998	19,247	Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.
GCST011461	Dong J	2020	6,758	7,489	Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma.
GCST011462	Dong J	2020	6,758	7,489	Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma.
GCST011463	Dong J	2020	6,758	7,489	Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma.
GCST003740	Gharahkhani P	2016	6,167	17,159	Genome-wide association studies in oesophageal adenocarcinoma and Barrett’s oesophagus: a large-scale meta-analysis.
GCST90258658	Schroder J	2022	5,582	32,476	GWAS meta-analysis of 16 790 patients with Barrett’s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.
GCST003739	Gharahkhani P	2016	4,112	17,159	Genome-wide association studies in oesophageal adenocarcinoma and Barrett’s oesophagus: a large-scale meta-analysis.
GCST90473003	Schroder J	2022	4,107	12,534	GWAS meta-analysis of 16 790 patients with Barrett’s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.
GCST002231	Levine DM	2013	3,928	3,207	A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett’s esophagus.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	4
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	15
3_prime_UTR_variant	4
non_coding_transcript_exon_variant	3
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs622217	6	160345738	T>A,C	0.49	intergenic_variant	SLC22A2 - SLC22A3	3e-18	Tier 4: intronic/intergenic
rs9306895	2	20678393	T>C	0.369	3_prime_UTR_variant	GDF7	2e-15	Tier 2: splice/UTR
rs35631104	15	97014558	GA>G,GAA	0.251	intron_variant	LINC02253	1e-13	Tier 4: intronic/intergenic
rs72760500	5	43785571	G>A	0.059	intergenic_variant	NNT - RNU6-381P	2e-13	Tier 4: intronic/intergenic
rs149252763	4	123640999	GGGAAGGAA>G,GGGAA,GGGAAGGAAGGAAGGAA	0.187	intron_variant	LINC01091	6e-13	Tier 4: intronic/intergenic
rs2687197	3	70873169	T>C	0.315	intergenic_variant	RNU6-281P - FOXP1	3e-12	Tier 4: intronic/intergenic
rs2095777	9	93942240	T>A	0.05	intergenic_variant	MIR4291 - BARX1	3e-12	Tier 4: intronic/intergenic
rs4676893	3	70868488	A>T	0.05	intergenic_variant	RNU6-281P - FOXP1	8e-12	Tier 4: intronic/intergenic
rs10225824	7	117371969	G>A	0.05	intron_variant	CFTR, ASZ1	2e-11	Tier 4: intronic/intergenic
rs4646614	15	57972595	ATAGT>A,ATAGTTAGT,ATAGTTAGTTAGT	0.435	intron_variant	ALDH1A2	3e-11	Tier 4: intronic/intergenic
rs3950627	16	86402737	C>A,G	0.476	intergenic_variant	LINC00917 - FENDRR	3e-11	Tier 4: intronic/intergenic
rs2188554	7	117400063	A>G,T	0.187	intron_variant	ASZ1, CFTR	3e-11	Tier 4: intronic/intergenic
rs146917555	2	199159992		0.415	intron_variant	PLCL1 - RNU7-147P	7e-11	Tier 4: intronic/intergenic
rs7255	2	20679060	T>A,C	0.05	3_prime_UTR_variant	GDF7	9e-11	Tier 2: splice/UTR
rs60849513	3	157593634	G>C,T	0.214	intron_variant	SLC66A1LP	1e-10	Tier 4: intronic/intergenic
rs111613945	8	11576907	C>CCCGGTTT,CGGTTT	0.468	non_coding_transcript_exon_variant	LINC00208	1e-10	Tier 4: intronic/intergenic
rs144823843	5	642178	A>C,G,T	0.204	intron_variant	CEP72	2e-10	Tier 4: intronic/intergenic
rs7045553	9	97545507	C>G,T	0.396	intron_variant	TMOD1	2e-10	Tier 4: intronic/intergenic
rs199620551	19	18693485	TG>T	0.478	intron_variant	CRTC1	3e-10	Tier 4: intronic/intergenic
rs77013824	5	28954412	T>TAGG	0.444	intron_variant	LINC02109	3e-10	Tier 4: intronic/intergenic
rs10419226	19	18692362	T>A,C,G	0.456	intron_variant	CRTC1	4e-10	Tier 4: intronic/intergenic
rs2464469	15	58069827	G>A	0.05	intron_variant	ALDH1A2-AS1, ALDH1A2	5e-10	Tier 4: intronic/intergenic
rs17451754	7	117616658	G>A	0.05	intron_variant	CFTR	5e-10	Tier 4: intronic/intergenic
rs17749155	8	10210563	G>A,C	0.05	intron_variant	MSRA	5e-10	Tier 4: intronic/intergenic
rs12449442	17	67951524	G>A	0.05	non_coding_transcript_exon_variant	BPTF	8e-10	Tier 4: intronic/intergenic
rs11789015	9	93953746	A>C,G	0.283	intron_variant	BARX1	1e-09	Tier 4: intronic/intergenic
rs7187365	16	86478309	T>A,C	0.05	intron_variant	FENDRR	1e-09	Tier 4: intronic/intergenic
rs10108511	8	11578007	T>A,C	0.05	intron_variant	LINC00208	2e-09	Tier 4: intronic/intergenic
rs2687202	3	70880832	T>A,C	0.05	intergenic_variant	RNU6-281P - FOXP1	2e-09	Tier 4: intronic/intergenic
rs1247942	12	114235918	G>A,C	0.05	intergenic_variant	GLULP5 - LINC02459	2e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 21 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
TBX5	Orphanet:101016	Romano-Ward syndrome
TBX5	Orphanet:392	Holt-Oram syndrome
RP1L1	Orphanet:247834	Occult macular dystrophy
RP1L1	Orphanet:791	Retinitis pigmentosa
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
SATB2	Orphanet:251019	2q32q33 deletion syndrome
SATB2	Orphanet:251028	SATB2-associated syndrome due to a chromosomal rearrangement
SATB2	Orphanet:576283	SATB2-associated syndrome due to a pathogenic variant
DPYSL2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
FOXF1	Orphanet:210122	Congenital alveolar capillary dysplasia
FOXP1	Orphanet:391372	FOXP1 Syndrome
FOXP1	Orphanet:52417	MALT lymphoma
FOXP1	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
APOB	Orphanet:391665	Homozygous familial hypercholesterolemia

Cohort genes → proteins

37 cohort genes, 35 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	36
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AURKA	HGNC:11393	ENSG00000087586	O14965	Aurora kinase A	civic_evidence
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gwas
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	gwas
TMOD1	HGNC:11871	ENSG00000136842	P28289	Tropomodulin-1	gwas
ASZ1	HGNC:1350	ENSG00000154438	Q8WWH4	Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1	gwas
SPANXB1	HGNC:14329	ENSG00000227234	Q9NS25	Sperm protein associated with the nucleus on the X chromosome B1	gwas
ALDH1A2	HGNC:15472	ENSG00000128918	O94788	Retinal dehydrogenase 2	gwas
LINC00208	HGNC:15535	ENSG00000170983	Q96KT6	Putative uncharacterized protein encoded by LINC00208	gwas
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	gwas
CRTC1	HGNC:16062	ENSG00000105662	Q6UUV9	CREB-regulated transcription coactivator 1	gwas
ACTBL2	HGNC:17780	ENSG00000169067	Q562R1	Beta-actin-like protein 2	gwas
CDR1	HGNC:1798	ENSG00000288642	P51861	Cerebellar degeneration-related antigen 1	gwas
KHDRBS2	HGNC:18114	ENSG00000112232	Q5VWX1	KH domain-containing, RNA-binding, signal transduction-associated protein 2	gwas
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	gwas
PLK2	HGNC:19699	ENSG00000145632	Q9NYY3	Serine/threonine-protein kinase PLK2	gwas
RNF144A	HGNC:20457	ENSG00000151692	P50876	E3 ubiquitin-protein ligase RNF144A	gwas
SATB2	HGNC:21637	ENSG00000119042	Q9UPW6	DNA-binding protein SATB2	gwas
HTR3C	HGNC:24003	ENSG00000178084	Q8WXA8	5-hydroxytryptamine receptor 3C	gwas
TPPP	HGNC:24164	ENSG00000171368	O94811	Tubulin polymerization-promoting protein	gwas
RBM43	HGNC:24790	ENSG00000184898	Q6ZSC3	RNA-binding protein 43	gwas
CEP72	HGNC:25547	ENSG00000112877	Q9P209	Centrosomal protein of 72 kDa	gwas
LDAH	HGNC:26145	ENSG00000118961	Q9H6V9	Lipid droplet-associated hydrolase	gwas
DPYSL2	HGNC:3014	ENSG00000092964	Q16555	Dihydropyrimidinase-related protein 2	gwas
PTPDC1	HGNC:30184	ENSG00000158079	A2A3K4	Protein tyrosine phosphatase domain-containing protein 1	gwas
PRSS55	HGNC:30824	ENSG00000184647	Q6UWB4	Serine protease 55	gwas
SNORD114-31	HGNC:33019	ENSG00000200089		small nucleolar RNA, C/D box 114-31	gwas
MTRNR2L9	HGNC:37166		P0CJ76	Humanin-like 9	gwas
FOXF1	HGNC:3809	ENSG00000103241	Q12946	Forkhead box protein F1	gwas
FOXP1	HGNC:3823	ENSG00000114861	Q9H334	Forkhead box protein P1	gwas
LSP1P3	HGNC:39718	ENSG00000162685		LSP1 pseudogene 3	gwas
GDF7	HGNC:4222	ENSG00000143869	Q7Z4P5	Growth/differentiation factor 7	gwas
APOB	HGNC:603	ENSG00000084674	P04114	Apolipoprotein B-100	gwas
LMO3	HGNC:6643	ENSG00000048540	Q8TAP4	LIM domain only protein 3	gwas
RND3	HGNC:671	ENSG00000115963	P61587	Rho-related GTP-binding protein RhoE	gwas
MGST1	HGNC:7061	ENSG00000008394	P10620	Microsomal glutathione S-transferase 1	gwas
MSRA	HGNC:7377	ENSG00000175806	Q9UJ68	Mitochondrial peptide methionine sulfoxide reductase	gwas
BARX1	HGNC:955	ENSG00000131668	Q9HBU1	Homeobox protein BarH-like 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AURKA	Aurora kinase A	Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
TMOD1	Tropomodulin-1	Blocks the elongation and depolymerization of the actin filaments at the pointed end.
ASZ1	Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1	Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity.
ALDH1A2	Retinal dehydrogenase 2	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.
CRTC1	CREB-regulated transcription coactivator 1	Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites.
ACTBL2	Beta-actin-like protein 2	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
KHDRBS2	KH domain-containing, RNA-binding, signal transduction-associated protein 2	RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
PLK2	Serine/threonine-protein kinase PLK2	Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition.
RNF144A	E3 ubiquitin-protein ligase RNF144A	E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
SATB2	DNA-binding protein SATB2	Binds to DNA, at nuclear matrix- or scaffold-associated regions.
HTR3C	5-hydroxytryptamine receptor 3C	Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.
TPPP	Tubulin polymerization-promoting protein	Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath.
CEP72	Centrosomal protein of 72 kDa	Involved in the recruitment of key centrosomal proteins to the centrosome.
LDAH	Lipid droplet-associated hydrolase	Probable serine lipid hydrolase associated with lipid droplets.
DPYSL2	Dihydropyrimidinase-related protein 2	Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration.
PTPDC1	Protein tyrosine phosphatase domain-containing protein 1	May play roles in cilia formation and/or maintenance.
PRSS55	Serine protease 55	Probable serine protease, which plays a crucial role in the fertility of male mice including sperm migration and sperm-egg interaction.
MTRNR2L9	Humanin-like 9	Plays a role as a neuroprotective and antiapoptotic factor.
FOXF1	Forkhead box protein F1	Probable transcription activator for a number of lung-specific genes.
FOXP1	Forkhead box protein P1	Transcriptional repressor.
GDF7	Growth/differentiation factor 7	May play an active role in the motor area of the primate neocortex.
APOB	Apolipoprotein B-100	Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100).
RND3	Rho-related GTP-binding protein RhoE	Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.
MGST1	Microsomal glutathione S-transferase 1	Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
MSRA	Mitochondrial peptide methionine sulfoxide reductase	Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.
BARX1	Homeobox protein BarH-like 1	Transcription factor, which is involved in craniofacial development, in odontogenesis and in stomach organogenesis.

Protein-family classification

Druggable: 8 · Difficult: 8 · Unknown: 21 · Druggable fraction: 0.22

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	3	2.2×	0.614
Transcription factor	7	1.6×	0.614
Phosphatase	1	2.3×	0.761
Transporter	1	2.1×	0.761
Other/Unknown	21	1.0×	0.836
Protease	1	1.0×	0.855
Enzyme (other)	2	0.7×	0.890
Scaffold/PPI	1	0.5×	0.890

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AURKA	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TMOD1	Other/Unknown	no		TMOD, LRR_dom_sf
ASZ1	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf
SPANXB1	Other/Unknown	no		SPAN-X_fam
ALDH1A2	Enzyme (other)	yes	1.2.1.36	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
LINC00208	Other/Unknown	no
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf
CRTC1	Other/Unknown	no		TORC_N, TORC_M, TORC_C
ACTBL2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
CDR1	Other/Unknown	no		LED_rpt, WKTW_rpt
KHDRBS2	Other/Unknown	no		KH_dom, Sam68-YY, Qua1_dom
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
PLK2	Kinase	yes	2.7.11.21	Prot_kinase_dom, POLO_box_dom, Ser/Thr_kinase_AS
RNF144A	Transcription factor	no	2.3.2.31	Znf_RING, IBR_dom, Znf_RING/FYVE/PHD
SATB2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
HTR3C	Other/Unknown	no		Neurotrans-gated_channel_TM, Neur_channel, Neur_chan_lig-bd
TPPP	Other/Unknown	no		TPP/p25, EF-hand-dom_pair
RBM43	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
CEP72	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, U2A’_phosphoprotein32A_C
LDAH	Other/Unknown	no		LDAH, AB_hydrolase_fold
DPYSL2	Other/Unknown	no		Amidohydro-rel, Metal-dep_hydrolase_composite, Hydantoinase/dihydroPyrase
PTPDC1	Phosphatase	yes		Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Tyr_Pase_cat
PRSS55	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA
SNORD114-31	Other/Unknown	no
MTRNR2L9	Other/Unknown	no		Humanin
FOXF1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
FOXP1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
LSP1P3	Other/Unknown	no
GDF7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
APOB	Other/Unknown	no		Vitellogenin_N, Lipid_transpt_open_b-sht, Lipovitellin_superhlx_dom
LMO3	Transcription factor	no		Znf_LIM, LMO_RBTN_TF
RND3	Other/Unknown	no		Small_GTPase, Small_GTPase_Rho, Small_GTP-bd
MGST1	Other/Unknown	no		Membr-assoc_MAPEG, MAPEG-like_dom_sf, MGST1-like
MSRA	Enzyme (other)	yes	1.8.4.11	Met_Sox_Rdtase_MsrA_dom, Met_Sox_Rdtase_MsrA_sf, MsrA_MetSO_reductase
BARX1	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 1.

26 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)	2
broad (>20)	34
unknown	1

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	7
cortical plate	5
primordial germ cell in gonad	4
ventricular zone	3
islet of Langerhans	3
right testis	3
left testis	3
spleen	2
buccal mucosa cell	2
tendon of biceps brachii	2
type B pancreatic cell	2
right lung	2
Brodmann (1909) area 23	2
middle temporal gyrus	2
oviduct epithelium	2
adrenal tissue	2
mucosa of stomach	2
oocyte	1
secondary oocyte	1
lymph node	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AURKA	236	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
TBX5	129	broad	marker	tendon of biceps brachii, cardiac muscle of right atrium, buccal mucosa cell
TMOD1	265	broad	marker	type B pancreatic cell, hindlimb stylopod muscle, islet of Langerhans
ASZ1	60	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right testis
SPANXB1	65	tissue_specific	yes	left testis, right testis, male germ line stem cell (sensu Vertebrata) in testis
ALDH1A2	226	broad	marker	germinal epithelium of ovary, decidua, sperm
LINC00208	9		yes	monocyte, gastrocnemius, left testis
RP1L1	30	tissue_specific	yes	primordial germ cell in gonad, buccal mucosa cell, bone marrow cell
CRTC1	218	ubiquitous	marker	olfactory bulb, type B pancreatic cell, paraflocculus
ACTBL2	24	tissue_specific	marker	cortical plate, islet of Langerhans, olfactory segment of nasal mucosa
CDR1	167	tissue_specific	marker	tendon of biceps brachii, pons, cerebellar vermis
KHDRBS2	102	broad	marker	cortical plate, corpus callosum, male germ line stem cell (sensu Vertebrata) in testis
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas
PLK2	289	ubiquitous	marker	spleen, apex of heart, cortical plate
RNF144A	253	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, cerebellum
SATB2	235	ubiquitous	marker	periodontal ligament, cortical plate, mucosa of sigmoid colon
HTR3C	20		marker	male germ line stem cell (sensu Vertebrata) in testis, right lung, mucosa of transverse colon
TPPP	257	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
RBM43	218	ubiquitous	yes	oviduct epithelium, calcaneal tendon, fallopian tube
CEP72	173	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
LDAH	254	ubiquitous	marker	adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis, islet of Langerhans
DPYSL2	301	ubiquitous	marker	inferior vagus X ganglion, subthalamic nucleus, substantia nigra pars compacta
PTPDC1	224	ubiquitous	yes	tibial nerve, endothelial cell, sural nerve
PRSS55	49	tissue_specific	yes	primordial germ cell in gonad, right testis, left testis
SNORD114-31	70		yes	adrenal tissue, kidney, lung
MTRNR2L9
FOXF1	202	broad	marker	muscle layer of sigmoid colon, mucosa of stomach, right lung
FOXP1	256	ubiquitous	marker	pancreatic ductal cell, oviduct epithelium, cardia of stomach
LSP1P3	67	tissue_specific	yes	blood, colonic epithelium, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFTR	7,664
AURKA	6,376
APOB	5,244
ALDH1A2	4,289
ACTBL2	3,277
PLK2	3,164
DPYSL2	2,980
BLK	2,967
FOXP1	2,939
MSRA	2,363

Intra-cohort edges

A	B	Sources
ACTBL2	CFTR	intact
ALDH1A2	CFTR	intact
BARX1	FOXF1	string_interaction
CFTR	RND3	intact
FOXF1	FOXP1	biogrid_interaction
FOXF1	SATB2	biogrid_interaction
FOXP1	SATB2	biogrid_interaction, intact, string_interaction
MSRA	RP1L1	string_interaction
PRSS55	RP1L1	string_interaction

Structural data

PDB: 15 · AlphaFold-only: 20 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AURKA	O14965	193
CFTR	P13569	58
DPYSL2	Q16555	15
APOB	P04114	8
ALDH1A2	O94788	7
PLK2	Q9NYY3	7
RND3	P61587	7
TMOD1	P28289	6
TBX5	Q99593	4
CRTC1	Q6UUV9	3
SATB2	Q9UPW6	3
TPPP	O94811	3
RNF144A	P50876	2
FOXP1	Q9H334	1
BARX1	Q9HBU1	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTBL2	Q562R1	94.97
LDAH	Q9H6V9	90.59
MSRA	Q9UJ68	89.13
LMO3	Q8TAP4	88.38
BLK	P51451	81.89
HTR3C	Q8WXA8	81.38
MGST1	P10620	78.65
RBM43	Q6ZSC3	77.12
PRSS55	Q6UWB4	76.06
GDF7	Q7Z4P5	72.03
MTRNR2L9	P0CJ76	71.49
PTPDC1	A2A3K4	70.60
KHDRBS2	Q5VWX1	70.39
SPANXB1	Q9NS25	68.80
ASZ1	Q8WWH4	66.83
CEP72	Q9P209	65.74
FOXF1	Q12946	59.41
LINC00208	Q96KT6	51.52
CDR1	P51861	49.00
RP1L1	Q8IWN7	38.97

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 133. Enrichment computed across 37 evidence-associated genes (21 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 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between PHLDA1 and AURKA	1	271.9×	0.078	AURKA
RHO GTPases regulate CFTR trafficking	1	181.3×	0.078	CFTR
Scavenging by Class H Receptors	1	135.9×	0.078	APOB
PTK6 Regulates Proteins Involved in RNA Processing	1	108.8×	0.078	KHDRBS2
VLDL assembly	1	108.8×	0.078	APOB
Chylomicron clearance	1	108.8×	0.078	APOB
Formation of lateral plate mesoderm	1	108.8×	0.078	FOXF1
Scavenging by Class F Receptors	1	90.6×	0.078	APOB
Protein repair	1	90.6×	0.078	MSRA
RUNX1 regulates transcription of genes involved in BCR signaling	1	90.6×	0.078	BLK
LDL remodeling	1	90.6×	0.078	APOB
VLDL clearance	1	90.6×	0.078	APOB
Heme signaling	2	20.5×	0.078	CRTC1, APOB
SUMO E3 ligases SUMOylate target proteins	2	17.0×	0.078	AURKA, SATB2
SUMOylation	2	15.5×	0.078	AURKA, SATB2
AURKA Activation by TPX2	2	14.5×	0.078	AURKA, CEP72
Regulation of PLK1 Activity at G2/M Transition	2	12.1×	0.078	AURKA, CEP72
Mitotic G2-G2/M phases	2	12.1×	0.078	AURKA, CEP72
G2/M Transition	2	12.1×	0.078	AURKA, CEP72
Gene expression (Transcription)	5	4.2×	0.078	BLK, AURKA, TBX5, ASZ1, SATB2
RNA Polymerase II Transcription	4	4.3×	0.080	BLK, AURKA, TBX5, SATB2
Chylomicron assembly	1	54.4×	0.097	APOB
Chylomicron remodeling	1	54.4×	0.097	APOB
CD163 mediating an anti-inflammatory response	1	54.4×	0.097	PLK2
Cargo recognition for clathrin-mediated endocytosis	2	10.0×	0.097	CFTR, APOB
Scavenging by Class B Receptors	1	49.4×	0.099	APOB
Regulation of CDH11 gene transcription	1	49.4×	0.099	FOXF1
RUNX2 regulates bone development	1	38.8×	0.111	SATB2
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	36.2×	0.111	TBX5
Plasma lipoprotein assembly	1	34.0×	0.111	APOB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
midgut development	2	131.7×	0.033	ALDH1A2, FOXF1
determination of bilateral symmetry	1	526.6×	0.038	ALDH1A2
detection of wounding	1	526.6×	0.038	FOXF1
roof plate formation	1	526.6×	0.038	GDF7
embryonic ectodermal digestive tract morphogenesis	1	526.6×	0.038	FOXF1
microtubule nucleation by microtubule organizing center	1	526.6×	0.038	TPPP
right lung morphogenesis	1	526.6×	0.038	FOXF1
cell migration involved in coronary vasculogenesis	1	526.6×	0.038	TBX5
cellular response to lipid hydroperoxide	1	526.6×	0.038	MGST1
regulation of macrophage colony-stimulating factor production	1	526.6×	0.038	FOXP1
positive regulation of cardiac conduction	1	526.6×	0.038	TBX5
endocardial cushion development	2	87.8×	0.038	TBX5, FOXF1
spindle organization	2	62.0×	0.038	AURKA, CEP72
cholesterol transport	2	45.8×	0.038	CFTR, APOB
pancreas development	2	42.1×	0.038	ALDH1A2, FOXF1
embryonic forelimb morphogenesis	2	31.0×	0.038	TBX5, ALDH1A2
lung development	3	18.6×	0.038	TBX5, ALDH1A2, FOXF1
cardiac left ventricle formation	1	263.3×	0.045	TBX5
regulation of monocyte differentiation	1	263.3×	0.045	FOXP1
lateral mesodermal cell differentiation	1	263.3×	0.045	FOXF1
atrioventricular node cell fate commitment	1	263.3×	0.045	TBX5
bundle of His cell to Purkinje myocyte communication by electrical coupling	1	263.3×	0.045	TBX5
regulation of defense response to bacterium	1	263.3×	0.045	FOXP1
positive regulation of cell communication by electrical coupling involved in cardiac conduction	1	263.3×	0.045	TBX5
negative regulation of membrane hyperpolarization	1	263.3×	0.045	CRTC1
positive regulation of nuclear receptor-mediated glucocorticoid signaling pathway	1	263.3×	0.045	LMO3
positive regulation of tendon cell differentiation	1	263.3×	0.045	GDF7
blood vessel development	2	23.4×	0.045	ALDH1A2, FOXF1
somitogenesis	2	23.4×	0.045	ALDH1A2, FOXF1
atrioventricular bundle cell differentiation	1	175.5×	0.045	TBX5

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 32

Druggability breadth: 11 of 37 evidence-associated genes (30%) 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
AURKA	INAMRINONE
BLK	AFATINIB
CFTR	IVACAFTOR
PLK2	FEDRATINIB
HTR3C	ARIPIPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AURKA	65	4
BLK	62	4
HTR3C	19	4
CFTR	14	4
PLK2	12	4
TBX5	0	0
TMOD1	0	0
ASZ1	0	0
SPANXB1	0	0
ALDH1A2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INAMRINONE	4	AURKA
FEDRATINIB	4	AURKA, BLK, PLK2
AXITINIB	4	AURKA, BLK
SORAFENIB	4	AURKA, BLK
NICLOSAMIDE	4	AURKA
ENTRECTINIB	4	AURKA, BLK
FOSTAMATINIB	4	AURKA
CABOZANTINIB	4	AURKA
GILTERITINIB	4	AURKA
BRIGATINIB	4	AURKA, BLK
UPADACITINIB	4	AURKA
SULFADIAZINE	4	AURKA
PAZOPANIB	4	AURKA, BLK
DOXORUBICIN	4	AURKA
SUNITINIB	4	AURKA, BLK, PLK2
DASATINIB	4	AURKA, BLK
ERLOTINIB	4	AURKA, BLK
CRIZOTINIB	4	AURKA, BLK
MIDOSTAURIN	4	AURKA, BLK
AFATINIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK, PLK2
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
AURKA	1,500	Binding:1483, Functional:10, ADMET:7
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
BLK	483	Binding:477, ADMET:4, Functional:2
PLK2	270	Binding:268, ADMET:1, Functional:1
HTR3C	184	Binding:119, Functional:64, ADMET:1
ALDH1A2	32	Binding:32
SATB2	6	Binding:6
DPYSL2	3	Binding:3
MGST1	3	ADMET:2, Binding:1
TBX5	1	Binding:1
APOB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AURKA	2.7.11.1	non-specific serine/threonine protein kinase
BLK	2.7.10.2	non-specific protein-tyrosine kinase
ALDH1A2	1.2.1.36	retinal dehydrogenase
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase
PLK2	2.7.11.21	polo kinase
RNF144A	2.3.2.31	RBR-type E3 ubiquitin transferase
MSRA	1.8.4.11	peptide-methionine (S)-S-oxide reductase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AURKA	1,500
BLK	483
CFTR	520
PLK2	270
HTR3C	184

Pharmacogenomics

Cohort genes with a PharmGKB record: 36; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
INAMRINONE	4	AURKA
FEDRATINIB	4	AURKA, BLK, PLK2
AXITINIB	4	AURKA, BLK
SORAFENIB	4	AURKA, BLK
NICLOSAMIDE	4	AURKA
ENTRECTINIB	4	AURKA, BLK
FOSTAMATINIB	4	AURKA
GILTERITINIB	4	AURKA
BRIGATINIB	4	AURKA, BLK
UPADACITINIB	4	AURKA
SULFADIAZINE	4	AURKA
PAZOPANIB	4	AURKA, BLK
DOXORUBICIN	4	AURKA
SUNITINIB	4	AURKA, BLK, PLK2
DASATINIB	4	AURKA, BLK
ERLOTINIB	4	AURKA, BLK
CRIZOTINIB	4	AURKA, BLK
MIDOSTAURIN	4	AURKA, BLK
AFATINIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK, PLK2
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	AURKA, BLK, CFTR, PLK2, HTR3C
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ALDH1A2
D	Druggable family + AlphaFold only, no drug	3	PTPDC1, PRSS55, MSRA
E	Difficult family or no structure, no drug	28	TBX5, TMOD1, ASZ1, SPANXB1, LINC00208, RP1L1, CRTC1, ACTBL2, CDR1, KHDRBS2 (+18 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TBX5	1	—
TMOD1	0	—
ASZ1	0	—
SPANXB1	0	—
ALDH1A2	32	—
LINC00208	0	—
RP1L1	0	—
CRTC1	0	—
ACTBL2	0	—
CDR1	0	—
KHDRBS2	0	—
RNF144A	0	—
SATB2	6	—
TPPP	0	—
RBM43	0	—
CEP72	0	—
LDAH	0	—
DPYSL2	3	—
PTPDC1	0	—
PRSS55	0	—
SNORD114-31	0	—
MTRNR2L9	0	—
FOXF1	0	—
FOXP1	0	—
LSP1P3	0	—
GDF7	0	—
APOB	1	—
LMO3	0	—
RND3	0	—
MGST1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 210.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	81
Not specified	67
PHASE1	27
PHASE1/PHASE2	16
PHASE3	12
PHASE2/PHASE3	5
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02509286	PHASE3	ACTIVE_NOT_RECRUITING	Perioperative Chemotherapy Compared To Neoadjuvant Chemoradiation in Patients With Adenocarcinoma of the Esophagus
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)
NCT04248452	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body
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
NCT05152147	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers
NCT05188313	PHASE3	RECRUITING	TRAstuzumab and Pertuzumab for HER2+ Resectable Oesophageal Cancer
NCT05677490	PHASE3	RECRUITING	mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
NCT06203600	PHASE2/PHASE3	RECRUITING	Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial
NCT07221149	PHASE2/PHASE3	RECRUITING	A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Nivolumab in Combination With Chemotherapy in Participants With Previously Untreated Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (ROSETTA Gastric-204)
NCT07392892	PHASE2/PHASE3	RECRUITING	A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Gastroesophageal Cancer
NCT00487695	PHASE3	COMPLETED	Confocal Endomicroscopy for Barrett’s Esophagus
NCT01196390	PHASE3	COMPLETED	Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer
NCT01726452	PHASE3	COMPLETED	NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study (Neo-AEGIS)
NCT02628665	PHASE3	UNKNOWN	Clinical Study of Time Optimizing of Endoscopic Photodynamic Therapy on Esophageal and/or Gastric Cardiac Cancer
NCT02872116	PHASE3	COMPLETED	Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer
NCT03604991	PHASE2/PHASE3	SUSPENDED	Nivolumab and Ipilimumab in Treating Patients With Esophageal and Gastroesophageal Junction Adenocarcinoma Undergoing Surgery
NCT04499924	PHASE2/PHASE3	COMPLETED	Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer
NCT01142388	PHASE2	ACTIVE_NOT_RECRUITING	Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer
NCT02521285	PHASE2	ACTIVE_NOT_RECRUITING	Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation
NCT02678182	PHASE2	ACTIVE_NOT_RECRUITING	Planning Treatment for Oesophago-gastric Cancer: a Maintenance Therapy Trial
NCT02962063	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Durvalumab, an Anti-PDLI Antibody, and Tremelimumab, an Anti-CTLA4 Antibody, and Chemoradiation Before Surgery for Esophageal Cancer
NCT02998268	PHASE2	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab in Locally Advanced Esophageal Adenocarcinoma
NCT03161522	PHASE2	RECRUITING	Chemotherapy With or Without Radiation or Surgery in Treating Participants With Oligometastatic Esophageal or Gastric Cancer
NCT03539822	PHASE1/PHASE2	RECRUITING	Cabozantinib Plus Durvalumab With or Without Tremelimumab in Patients With Gastroesophageal Cancer and Other Gastrointestinal Malignancies
NCT04018872	PHASE2	RECRUITING	Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer
NCT04028167	PHASE2	ACTIVE_NOT_RECRUITING	Induction FLOT With CROSS CRT for Esophageal Cancer
NCT04114136	PHASE2	RECRUITING	Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies
NCT04150640	PHASE2	RECRUITING	Oxaliplatin and Liposomal Irinotecan (Plus Trastuzumab for HER2-positive Disease) in Advanced Esophageal and Gastric Adenocarcinoma
NCT04430738	PHASE2	ACTIVE_NOT_RECRUITING	Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
NCT04554771	PHASE2	ACTIVE_NOT_RECRUITING	Blood-borne Assessment of Stromal Activation in Esophageal Adenocarcinoma to Guide Tocilizumab Therapy
NCT04682158	PHASE2	RECRUITING	Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma
NCT04802876	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors
NCT04921904	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Abemaciclib Plus Ramucirumab for Esophageal/Gastroesophageal Junction Ca
NCT04929392	PHASE2	ACTIVE_NOT_RECRUITING	Chemoradiation and Pembrolizumab Followed by Pembrolizumab and Lenvatinib Before Surgery for the Treatment of Non-metastatic Esophageal or Esophageal/Gastroesophageal Junction Cancer
NCT04939051	PHASE2	RECRUITING	Obeticholic Acid for Prevention in Barrett’s Esophagus
NCT05177133	PHASE2	RECRUITING	Anti-PD-1 and CapOx for the First-line Treatment of dMMR Esophagogastric Cancer (AuspiCiOus)
NCT05476796	PHASE2	RECRUITING	Oxaliplatin ± Nivolumab in Combination With Trifluridine/Tipiracil or 5-fluorouracile in Frail Patients With Advanced, Recurrent or Metastatic Gastric, Oesophageal or Gastroesophageal Junction Cancer
NCT05480384	PHASE2	ACTIVE_NOT_RECRUITING	Adjuvant Trastuzumab Deruxtecan (Enhertu) & Nivolumab For Patients Who Are Disease Free After Completion of Trimodality Treatment For HER-2+ Cancers of Esophagus & Gastroesophageal Junction
NCT05563766	PHASE2	RECRUITING	A Phase II Trial to Evaluate the Effect of Itraconazole on Pathologic Complete Response Rates in Resectable Esophageal Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEUCOVORIN	4	11
IRINOTECAN	4	4
RAMUCIRUMAB	4	4
ITRACONAZOLE	4	3
ABEMACICLIB	4	2
FUTIBATINIB	4	2
IPILIMUMAB	4	2
LAPATINIB	4	2
LEVOLEUCOVORIN	4	2
NIVOLUMAB	4	2
PRALATREXATE	4	2
TRASTUZUMAB DERUXTECAN	4	2
TREMELIMUMAB	4	2
TUCATINIB	4	2
ZANIDATAMAB	4	2
ARSENIC TRIOXIDE	4	1
AVELUMAB	4	1
CABOZANTINIB	4	1
CAPMATINIB	4	1
CERITINIB	4	1
EPIRUBICIN	4	1
ERLOTINIB HYDROCHLORIDE	4	1
FLUDEOXYGLUCOSE F 18	4	1
FLUOROURACIL	4	1
LENVATINIB MESYLATE	4	1
OBETICHOLIC ACID	4	1
OXALIPLATIN	4	1
PANITUMUMAB	4	1
PERTUZUMAB	4	1
REGORAFENIB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
AURKA Overexpression	Alisertib + Cisplatin	Sensitivity/Response	CIViC D	EID9627
AURKA Amplification	Alisertib + Cisplatin	Sensitivity/Response	CIViC E	EID456