Cervical carcinoma

Summary

Cervical carcinoma (MONDO:0005131) is a cancer (an umbrella term covering 9 Mondo subtypes) with 39 cohort genes (246 GWAS associations across 27 studies; 10 CIViC-evidence somatic drivers) and 1,768 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (6 cohort genes). Molecularly, XRCC1 Q399R confers sensitivity to Cisplatin + Carboplatin in Cervical Cancer (CIViC Level B); 4 further subtype–drug associations are mapped below. Top therapeutic interventions include cisplatin, human papillomavirus, l1 protein virus like particles, and topotecan.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 39
• GWAS associations: 246
• Clinical trials: 1,768
• Precision-medicine evidence (CIViC): 5 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cervical carcinoma
Mondo ID	MONDO:0005131
EFO	EFO:0001061
DOID	DOID:2893
ICD-11	1743710977
NCIT	C9039
SNOMED CT	285432005
UMLS	C0302592
MedGen	86222
Anatomy (UBERON)	UBERON:0000002
Is cancer (heuristic)	yes

Also known as: cancer of cervix · cancer of the cervix · cancer of the uterine cervix · cancer of uterine cervix · carcinoma of cervix · carcinoma of cervix uteri · carcinoma of the cervix · carcinoma of the cervix uteri · carcinoma of the uterine cervix · carcinoma of uterine cervix · cervical cancer · cervical cancer, NOS · cervical carcinoma · cervix cancer · cervix carcinoma · cervix uteri carcinoma · uterine cervix cancer · uterine cervix carcinoma

Data availability: 246 GWAS associations (27 studies) · 10 cell lines.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › reproductive system cancer › female reproductive organ cancer › uterine cancer › cervical cancer › cervical carcinoma

Related subtypes (8): cervix melanoma, uterine ligament cancer, cervical Wilms tumor, high-grade neuroendocrine carcinoma of the cervix uteri, malignant mixed epithelial and mesenchymal tumor of cervix uteri, sarcoma of cervix uteri, malignant germ cell tumor of cervix uteri, malignant neoplasm of endocervix

Subtypes (9): exocervical carcinoma, endocervical carcinoma, cervical adenocarcinoma, cervical adenoid basal carcinoma, cervical large cell neuroendocrine carcinoma, cervical small cell carcinoma, cervical squamous cell carcinoma, papillary carcinoma of the cervix uteri, uterine cervix carcinoma in situ

Genetics & variants

GWAS landscape

246 GWAS associations across 27 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9272050	1e-39	HLA-DQA1	G	1.27
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs36214159	1e-28	HLA-DQA1	T	1.71
rs4282438	5e-27	COL11A2P1	?	1.35
rs1219651	1e-25	FGFR2	?	1.09
rs2523496	4e-25	MICA	T	1.21
rs9272143	3e-22	HLA-DQA1	?	1.49
rs55986091	6e-22	HLA-DQA1 - HLA-DQB1	?	0.66
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs73730372	3e-19	HLA-DRB1 - HLA-DQA1	?	1.67
rs2516448	4e-18	MICA - LINC01149	?	1.42
rs6938453	2e-17	MICA	?	0.79
rs112149573	2e-17	TOX3	?	1.08
rs2856437	1e-15	PBX2	A	1.3
rs78540526	1e-15	LINC01488 - PNCRNA-D	?	1.13
rs35409710	2e-15	HLA-DQB1	?	1.09
rs7463708	2e-15	PCAT1, PRNCR1, CASC19	?	1.08
rs11651755	1e-14	HNF1B	?	1.06
rs10175462	8e-14	PAX8, PAX8-AS1	G	1.15
rs1485995	8e-14	LINC01488	?	0.95
rs3132461	2e-13	MICB - PPIAP9	G	1.36
rs9273736	2e-13	HLA-DQB1	?	1.12
rs2976384	3e-13	PSCA, JRK	?	1.07
rs114115115	6e-13	MUC22	T	1.35
rs2844512	1e-12	LINC01149	G	0.35
rs2585181	3e-12	PSCA - LY6K	?	1.05
HLA-DQB1*602	4e-12		?	1.44
rs59661306	2e-11	ADGRV1, LUCAT1	G	1.3
rs140668832	5e-11	HLA-E - LINC02569	?	0.14

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90011816	Rashkin SR	2020	6,563	410,350	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST90454202	Pujol Gualdo N	2025	3,408	291,883	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST004833	Leo PJ	2017	2,866	6,481	Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.
GCST007119	Takeuchi F	2018	2,609	4,712	Genome-wide association study of cervical cancer suggests a role for ARRDC3 gene in human papillomavirus infection.
GCST90041904	Jiang L	2021	1,866	245,642	A generalized linear mixed model association tool for biobank-scale data.
GCST003565	Chen D	2016	1,553	4,442	Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus.
GCST002082	Shi Y	2013	1,364	3,028	A genome-wide association study identifies two new cervical cancer susceptibility loci at 4q12 and 17q12.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	2
Tier 4: intronic/intergenic	48

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	14
non_coding_transcript_exon_variant	4
unknown	4
regulatory_region_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9272050	6	32631294	G>A	0.05	intergenic_variant	HLA-DQA1	1e-39	Tier 4: intronic/intergenic
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs36214159	6	32643982	T>G	0.05	intergenic_variant	HLA-DQA1	1e-28	Tier 4: intronic/intergenic
rs4282438	6	33104395	T>G	0.44	intron_variant	COL11A2P1	5e-27	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs2523496	6	31409942	T>A,C,G	0.05	intron_variant	MICA	4e-25	Tier 4: intronic/intergenic
rs9272143	6	32633026	T>C,G	0.05	intergenic_variant	HLA-DQA1	3e-22	Tier 4: intronic/intergenic
rs55986091	6	32655936	G>A	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	6e-22	Tier 4: intronic/intergenic
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs73730372	6	32616804	C>T	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	3e-19	Tier 4: intronic/intergenic
rs2516448	6	31422633	T>A,C,G	0.05	intron_variant	MICA - LINC01149	4e-18	Tier 4: intronic/intergenic
rs6938453	6	31410016	T>A	0.05	intron_variant	MICA	2e-17	Tier 4: intronic/intergenic
rs112149573	16	52547333	G>C,T	0.05	intron_variant	TOX3	2e-17	Tier 4: intronic/intergenic
rs2856437	6	32189587	G>A,T	0.063	intron_variant	PBX2	1e-15	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.05	regulatory_region_variant	LINC01488 - PNCRNA-D	1e-15	Tier 3: regulatory
rs35409710	6	32661126	G>A	0.05	intron_variant	HLA-DQB1	2e-15	Tier 4: intronic/intergenic
rs7463708	8	127091810	G>A,C,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	2e-15	Tier 4: intronic/intergenic
rs11651755	17	37739849	T>C	0.05	intron_variant	HNF1B	1e-14	Tier 4: intronic/intergenic
rs10175462	2	113230915	G>A,T	0.362	intron_variant	PAX8, PAX8-AS1	8e-14	Tier 4: intronic/intergenic
rs1485995	11	69492939	G>A,C	0.05	non_coding_transcript_exon_variant	LINC01488	8e-14	Tier 4: intronic/intergenic
rs3132461	6	31512891	G>A,C	0.05	intergenic_variant	MICB - PPIAP9	2e-13	Tier 4: intronic/intergenic
rs9273736	6	32661595	G>A,C	0.05	intron_variant	HLA-DQB1	2e-13	Tier 4: intronic/intergenic
rs2976384	8	142671576	T>A,C	0.05	intergenic_variant	PSCA, JRK	3e-13	Tier 4: intronic/intergenic
rs114115115	6	31021915	T>A,G	0.05	intron_variant	MUC22	6e-13	Tier 4: intronic/intergenic
rs2844512	6	31441789	C>G,T	0.424	non_coding_transcript_exon_variant	LINC01149	1e-12	Tier 4: intronic/intergenic
rs2585181	8	142690296	C>A	0.05	intergenic_variant	PSCA - LY6K	3e-12	Tier 4: intronic/intergenic
HLA-DQB1*602				0.141			4e-12	Tier 4: intronic/intergenic
rs59661306	5	91087644	A>G	0.15	intron_variant	ADGRV1, LUCAT1	2e-11	Tier 4: intronic/intergenic
rs140668832	6	30512137	A>T	0.05	intron_variant	HLA-E - LINC02569	5e-11	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 76 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SPHK1			CIViC #7041
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
XRCC1			CIViC #6144
CD44			CIViC #855
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
SOX9	LoF	COAD,COADREAD
HLA-B	LoF	CESC,DLBCLNOS,ESCA,HNSC,MLYM	CIViC #2607
HLA-C	LoF	DLBCLNOS	CIViC #2608
HLA-DQA1	Act	PLMESO
PAX8			CIViC #75

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
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly
SOX9	Orphanet:140	Campomelic dysplasia
SOX9	Orphanet:2138	46,XX ovotesticular difference of sex development
SOX9	Orphanet:242	46,XY complete gonadal dysgenesis
SOX9	Orphanet:251510	46,XY partial gonadal dysgenesis
SOX9	Orphanet:393	46,XX testicular difference of sex development
SOX9	Orphanet:718	Isolated Pierre Robin sequence
TBXAS1	Orphanet:1802	Ghosal hematodiaphyseal dysplasia
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis

Cohort genes → proteins

39 cohort genes, 35 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	34
civic_only	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPHK1	HGNC:11240	ENSG00000176170	Q9NYA1	Sphingosine kinase 1	civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
XRCC1	HGNC:12828	ENSG00000073050	P18887	DNA repair protein XRCC1	civic_evidence
CD44	HGNC:1681	ENSG00000026508	P16070	CD44 antigen	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gwas
TBXAS1	HGNC:11609	ENSG00000059377	P24557	Thromboxane-A synthase	gwas
TNF	HGNC:11892	ENSG00000232810	P01375	Tumor necrosis factor	gwas
FBXO15	HGNC:13617	ENSG00000141665	Q8NCQ5	F-box only protein 15	gwas
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	gwas
CLDN23	HGNC:17591	ENSG00000253958	Q96B33	Claudin-23	gwas
SLCO5A1	HGNC:19046	ENSG00000137571	Q9H2Y9	Solute carrier organic anion transporter family member 5A1	gwas
SULF1	HGNC:20391	ENSG00000137573	Q8IWU6	Extracellular sulfatase Sulf-1	gwas
SUGT1P3	HGNC:20513	ENSG00000239827		SUGT1 pseudogene 3	gwas
MCCD1	HGNC:20668	ENSG00000204511	P59942	Mitochondrial coiled-coil domain protein 1	gwas
ZNF804B	HGNC:21958	ENSG00000182348	A4D1E1	Zinc finger protein 804B	gwas
GSDMB	HGNC:23690	ENSG00000073605	Q8TAX9	Gasdermin-B	gwas
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	gwas
PRAG1	HGNC:25438	ENSG00000275342	Q86YV5	Inactive tyrosine-protein kinase PRAG1	gwas
LRRC28	HGNC:28355	ENSG00000168904	Q86X40	Leucine-rich repeat-containing protein 28	gwas
VSTM2A	HGNC:28499	ENSG00000170419	Q8TAG5	V-set and transmembrane domain-containing protein 2A	gwas
EXOC1	HGNC:30380	ENSG00000090989	Q9NV70	Exocyst complex component 1	gwas
ELF1	HGNC:3316	ENSG00000120690	P32519	ETS-related transcription factor Elf-1	gwas
INS-IGF2	HGNC:33527	ENSG00000129965	F8WCM5	Insulin, isoform 2	gwas
TTC34	HGNC:34297	ENSG00000215912	A8MYJ7	Tetratricopeptide repeat protein 34	gwas
GABRB1	HGNC:4081	ENSG00000163288	P18505	Gamma-aminobutyric acid receptor subunit beta-1	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
HLA-C	HGNC:4933	ENSG00000204525	P10321	HLA class I histocompatibility antigen, C alpha chain	gwas
HLA-DPB2	HGNC:4941	ENSG00000224557		major histocompatibility complex, class II, DP beta 2 (pseudogene)	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
VSTM2A-OT1	HGNC:50770	ENSG00000224223		VSTM2A overlapping transcript 1	gwas
LINC01445	HGNC:50771	ENSG00000231427		long intergenic non-protein coding RNA 1445	gwas
MEF2A	HGNC:6993	ENSG00000068305	Q02078	Myocyte-specific enhancer factor 2A	gwas
MICA	HGNC:7090	ENSG00000204520	Q29983	MHC class I polypeptide-related sequence A	gwas
MICB	HGNC:7091	ENSG00000204516	Q29980	MHC class I polypeptide-related sequence B	gwas
ACACB	HGNC:85	ENSG00000076555	O00763	Acetyl-CoA carboxylase 2	gwas
PAX8	HGNC:8622	ENSG00000125618	Q06710	Paired box protein Pax-8	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPHK1	Sphingosine kinase 1	Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
XRCC1	DNA repair protein XRCC1	Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes.
CD44	CD44 antigen	Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
TBXAS1	Thromboxane-A synthase	Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.
TNF	Tumor necrosis factor	Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
FBXO15	F-box only protein 15	Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
CLDN23	Claudin-23	Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
SULF1	Extracellular sulfatase Sulf-1	Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity.
GSDMB	Gasdermin-B	Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death.
CLPTM1L	Lipid scramblase CLPTM1L	Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to th…
PRAG1	Inactive tyrosine-protein kinase PRAG1	Catalytically inactive protein kinase that acts as a scaffold protein.
VSTM2A	V-set and transmembrane domain-containing protein 2A	Plays a role in the regulation of the early stage of white and brown preadipocyte cell differentiation.
EXOC1	Exocyst complex component 1	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
ELF1	ETS-related transcription factor Elf-1	Transcription factor that activates the LYN and BLK promoters.
GABRB1	Gamma-aminobutyric acid receptor subunit beta-1	Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
MEF2A	Myocyte-specific enhancer factor 2A	Transcriptional activator which binds specifically to the MEF2 element, 5’-YTAATTAR-3’, found in numerous muscle-specific genes.
MICA	MHC class I polypeptide-related sequence A	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8 alphabeta T-cells.
MICB	MHC class I polypeptide-related sequence B	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.
ACACB	Acetyl-CoA carboxylase 2	Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism.
PAX8	Paired box protein Pax-8	Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells.

Protein-family classification

Druggable: 15 · Difficult: 6 · Unknown: 18 · Druggable fraction: 0.38

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
Antibody/Immunoglobulin	8	6.0×	3e-04
Phosphatase	1	2.1×	0.634
Kinase	3	2.1×	0.634
Transporter	1	2.0×	0.634
Transcription factor	6	1.3×	0.634
Other/Unknown	18	0.8×	0.967
GPCR	1	0.6×	0.967
Enzyme (other)	1	0.3×	0.967

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPHK1	Kinase	yes	2.7.1.91	Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
XRCC1	Other/Unknown	no		BRCT_dom, Xrcc1_N, Galactose-bd-like_sf
CD44	Other/Unknown	no		Link_dom, CD44_antigen, C-type_lectin-like/link_sf
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
TBXAS1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
TNF	Other/Unknown	no		TNF_alpha, TNF_dom, TNF
FBXO15	Other/Unknown	no		F-box_dom, F-box-like_dom_sf
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
CLDN23	Other/Unknown	no		PMP22/EMP/MP20/Claudin, Claudin, Claudin_CS
SLCO5A1	Transporter	yes		Kazal_dom, OATP, MFS_dom
SULF1	Phosphatase	yes		Sulfatase_N, Extracellular_sulfatase, Alkaline_phosphatase_core_sf
SUGT1P3	Other/Unknown	no
MCCD1	Other/Unknown	no		MCCD1
ZNF804B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZNF804A-like/GPATCH8
GSDMB	Other/Unknown	no		Gasdermin, Gasdermin_pore, Gasdermin_PUB
CLPTM1L	Other/Unknown	no		CLPTM1
PRAG1	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS
LRRC28	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf
VSTM2A	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
EXOC1	Other/Unknown	no		Sec3_CC, Sec3-PIP2_bind, Sec3_C
ELF1	Transcription factor	no		Ets_dom, TF_Elf_N, WH-like_DNA-bd_sf
INS-IGF2	Other/Unknown	no		Insulin, Insulin-like, Insulin-like_sf
TTC34	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC34
GABRB1	Other/Unknown	no		GABAAb_rcpt, GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-C	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom
HLA-DPB2	Other/Unknown	no
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
VSTM2A-OT1	Other/Unknown	no
LINC01445	Other/Unknown	no
MEF2A	Transcription factor	no		TF_MADSbox, HJURP_C, MEF2-like_N
MICA	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
MICB	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
ACACB	Enzyme (other)	yes	6.3.4.14	Biotin_lipoyl, CPAse_ATP-bd, BC-like_N
PAX8	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C

Expression context

Cohort genes with no expression data: 0.

34 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)	1
broad (>20)	38
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	5
male germ line stem cell (sensu Vertebrata) in testis	5
monocyte	4
stromal cell of endometrium	3
tendon of biceps brachii	3
ventricular zone	3
calcaneal tendon	3
rectum	3
ileal mucosa	3
spleen	3
right lung	3
ganglionic eminence	2
adrenal tissue	2
leukocyte	2
mononuclear cell	2
right uterine tube	2
mucosa of transverse colon	2
left lobe of thyroid gland	2
thyroid gland	2
right lobe of thyroid gland	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPHK1	210	ubiquitous	marker	stromal cell of endometrium, lower esophagus mucosa, tibial nerve
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
XRCC1	276	ubiquitous	marker	ventricular zone, tendon of biceps brachii, ganglionic eminence
CD44	294	ubiquitous	marker	parotid gland, stromal cell of endometrium, mammalian vulva
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
SOX9	274	ubiquitous	marker	ventricular zone, cranial nerve II, hair follicle
TBXAS1	180	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
TNF	119	broad	marker	granulocyte, male germ line stem cell (sensu Vertebrata) in testis, bone marrow
FBXO15	197	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
CLDN23	121	broad	marker	mucosa of transverse colon, rectum, duodenum
SLCO5A1	157	broad	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, heart right ventricle
SULF1	272	ubiquitous	marker	parietal pleura, stromal cell of endometrium, pigmented layer of retina
SUGT1P3	174	broad	yes	calcaneal tendon, adrenal tissue, male germ line stem cell (sensu Vertebrata) in testis
MCCD1	67	tissue_specific	marker	adult mammalian kidney, kidney, metanephros cortex
ZNF804B	24	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, left lobe of thyroid gland, thyroid gland
GSDMB	206	tissue_specific	marker	rectum, right lobe of liver, mucosa of transverse colon
CLPTM1L	255	ubiquitous	marker	ileal mucosa, kidney epithelium, right lobe of thyroid gland
PRAG1	243	ubiquitous	yes	cerebellar vermis, pancreatic ductal cell, ileal mucosa
LRRC28	216	ubiquitous	marker	ileal mucosa, left testis, right testis
VSTM2A	140	broad	marker	middle temporal gyrus, primary visual cortex, endothelial cell
EXOC1	285	ubiquitous	marker	gingival epithelium, gingiva, esophagus squamous epithelium
ELF1	283	ubiquitous	marker	secondary oocyte, monocyte, mononuclear cell
INS-IGF2	20	broad	marker	islet of Langerhans, pancreas, body of pancreas
TTC34	109		yes	right uterine tube, left testis, right testis
GABRB1	172	tissue_specific	marker	Brodmann (1909) area 23, middle temporal gyrus, entorhinal cortex
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte
HLA-C	134	ubiquitous	marker	blood, right lung, spleen
HLA-DPB2	121	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, lymph node, granulocyte
HLA-DQA1	244	broad	marker	gall bladder, rectum, monocyte

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
TNF	11,116
CD44	6,810
PIK3CA	5,157
SOX9	4,935
HLA-DRB1	3,448
HLA-B	3,209
ACACB	2,991
MEF2A	2,903
XRCC1	2,591

Intra-cohort edges

A	B	Sources
HLA-B	HLA-C	biogrid_interaction, intact
HLA-C	HLA-DQB1	intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HLA-DRB1	TNF	string_interaction
MICA	MICB	intact
PAX8	TP53	string_interaction
SLCO5A1	SULF1	string_interaction

Structural data

PDB: 22 · AlphaFold-only: 13 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
HLA-B	P01889	237
PIK3CA	P42336	135
HLA-DRB1	P01911	108
TNF	P01375	52
HLA-DQA1	P01909	28
XRCC1	P18887	13
HLA-C	P10321	13
GSDMB	Q8TAX9	11
ACACB	O00763	11
HLA-DQB1	P01920	10
MEF2A	Q02078	10
MICA	Q29983	10
CD44	P16070	6
SPHK1	Q9NYA1	5
INS-IGF2	F8WCM5	4
GABRB1	P18505	3
PRAG1	Q86YV5	2
MICB	Q29980	2
SOX9	P48436	1
ELF1	P32519	1
PAX8	Q06710	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBXAS1	P24557	91.50
LRRC28	Q86X40	90.30
TTC34	A8MYJ7	87.36
EXOC1	Q9NV70	80.59
CLPTM1L	Q96KA5	78.54
FBXO15	Q8NCQ5	77.42
CLDN23	Q96B33	76.64
SULF1	Q8IWU6	74.27
VSTM2A	Q8TAG5	72.21
SLCO5A1	Q9H2Y9	70.91
MCCD1	P59942	66.57
ZNF804B	A4D1E1	43.04
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 240. Enrichment computed across 39 evidence-associated genes (25 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 25 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	6	30.1×	8e-06	CD44, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1
Endosomal/Vacuolar pathway	2	83.0×	0.030	HLA-B, HLA-C
Translocation of ZAP-70 to Immunological synapse	2	50.8×	0.041	HLA-DQA1, HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	2	43.5×	0.041	HLA-DQA1, HLA-DRB1
Co-inhibition by PD-1	2	41.5×	0.041	HLA-DQA1, HLA-DRB1
Downstream TCR signaling	3	15.4×	0.041	HLA-DQA1, HLA-DRB1, PIK3CA
DAP12 interactions	2	38.1×	0.042	HLA-B, HLA-C
Defective TBXAS1 causes GHDD	1	456.8×	0.051	TBXAS1
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	456.8×	0.051	TP53
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	2	31.5×	0.051	HLA-B, HLA-C
Generation of second messenger molecules	2	27.7×	0.051	HLA-DQA1, HLA-DRB1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	3	10.5×	0.056	HLA-B, HLA-C, MICB
Association of TriC/CCT with target proteins during biosynthesis	2	23.4×	0.060	SPHK1, TP53
Regulation of TP53 Expression	1	228.4×	0.075	TP53
Transcriptional activation of cell cycle inhibitor p21	1	114.2×	0.110	TP53
Resolution of AP sites via the single-nucleotide replacement pathway	1	91.4×	0.110	XRCC1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	91.4×	0.110	ELF1
Activation of NOXA and translocation to mitochondria	1	76.1×	0.110	TP53
TNFR1-mediated ceramide production	1	76.1×	0.110	TNF
MET activates PI3K/AKT signaling	1	76.1×	0.110	PIK3CA
RUNX1 regulates transcription of genes involved in BCR signaling	1	76.1×	0.110	ELF1
Activated NTRK3 signals through PI3K	1	76.1×	0.110	PIK3CA
APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway	1	65.3×	0.110	XRCC1
RUNX3 regulates CDKN1A transcription	1	65.3×	0.110	TP53
Activated NTRK2 signals through PI3K	1	65.3×	0.110	PIK3CA
Signaling by LTK in cancer	1	65.3×	0.110	PIK3CA
Formation of intermediate mesoderm	1	57.1×	0.110	PAX8
ChREBP activates metabolic gene expression	1	50.8×	0.110	ACACB
PI3K/AKT activation	1	50.8×	0.110	PIK3CA
PI5P Regulates TP53 Acetylation	1	50.8×	0.110	TP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 30 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	8	12.6×	1e-04	TNF, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1, MICA, MICB
peptide antigen assembly with MHC class II protein complex	3	105.3×	9e-04	HLA-DQA1, HLA-DQB1, HLA-DRB1
metanephric nephron tubule formation	2	224.7×	0.003	SOX9, PAX8
antigen processing and presentation of exogenous peptide antigen via MHC class II	3	54.4×	0.003	HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of T cell mediated cytotoxicity	3	51.1×	0.003	HLA-B, HLA-C, HLA-DRB1
positive regulation of immune response	3	48.1×	0.003	HLA-DQA1, HLA-DQB1, HLA-DRB1
adaptive immune response	5	14.0×	0.003	HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, MICB
positive regulation of T cell activation	3	44.4×	0.003	HLA-DQA1, HLA-DQB1, HLA-DRB1
gamma-delta T cell activation	2	140.4×	0.006	MICA, MICB
response to salt stress	2	124.8×	0.007	TNF, TP53
positive regulation of lipid storage	2	93.6×	0.009	VSTM2A, ACACB
detection of bacterium	2	93.6×	0.009	HLA-B, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	2	86.4×	0.009	HLA-B, HLA-C
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	2	86.4×	0.009	HLA-B, HLA-C
positive regulation of heterotypic cell-cell adhesion	2	86.4×	0.009	TNF, CD44
humoral immune response	3	28.1×	0.009	TNF, HLA-DQB1, HLA-DRB1
killing of cells of another organism	3	27.2×	0.009	GSDMB, MICA, MICB
cartilage development	3	25.1×	0.009	SOX9, CD44, SULF1
response to fatty acid	2	70.2×	0.013	SOX9, TBXAS1
positive regulation of branching involved in ureteric bud morphogenesis	2	53.5×	0.021	SOX9, PAX8
response to muscle inactivity	1	561.7×	0.026	PIK3CA
regulation of interleukin-4 production	1	561.7×	0.026	HLA-DRB1
positive regulation of translational initiation by iron	1	561.7×	0.026	TNF
sphingoid catabolic process	1	561.7×	0.026	SPHK1
lactic acid secretion	1	561.7×	0.026	ACACB
negative regulation of helicase activity	1	561.7×	0.026	TP53
negative regulation of branching involved in lung morphogenesis	1	561.7×	0.026	TNF
cellular response to actinomycin D	1	561.7×	0.026	TP53
intracellular aspartate homeostasis	1	561.7×	0.026	ACACB
negative regulation of bile acid secretion	1	561.7×	0.026	TNF

Therapeutics

Drugs indicated for this disease

1 approved, 14 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Approved (phase 4)
Atezolizumab	Phase 3 (in late-stage trials)
Cadonilimab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Endostatin, N-Terminal-Mggshhhhh	Phase 3 (in late-stage trials)
Epoetin Beta	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Granisetron	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Ondansetron	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Zimberelimab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Brivanib Alaninate, Camrelizumab, Cetuximab, Dostarlimab, Imiquimod, Ipilimumab, Lenvatinib, Lifileucel, Metronidazole, Niraparib, Nivolumab, Olaparib, Rivoceranib, Sintilimab.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 8 · Phased (≥1): 8 · Undrugged: 31

Druggability breadth: 16 of 39 evidence-associated genes (41%) 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
TP53	NITROFURANTOIN
PIK3CA	IDELALISIB
TBXAS1	CLOTRIMAZOLE
TNF	PREDNISOLONE
GABRB1	ENZALUTAMIDE
ACACB	BEMPEDOIC ACID
PAX8	SORAFENIB TOSYLATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
PIK3CA	67	4
TBXAS1	46	4
GABRB1	18	4
PAX8	14	4
TNF	12	4
ACACB	4	4
SPHK1	3	3
XRCC1	0	0
CD44	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TBXAS1, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
GABRB1	266	Binding:219, Functional:39, ADMET:5, Toxicity:3
SPHK1	232	Binding:228, ADMET:3, Functional:1
TBXAS1	210	Binding:138, Functional:72
TNF	193	Binding:162, Functional:31
ACACB	81	Binding:81
HLA-DRB1	17	Binding:17
CD44	9	Binding:9
SOX9	3	Binding:3
PAX8	3	Functional:3
HLA-DQA1	2	Binding:2
CLPTM1L	1	Binding:1
EXOC1	1	Binding:1
HLA-B	1	Binding:1
HLA-C	1	Binding:1
MICA	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SPHK1	2.7.1.91	sphingosine kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
ACACB	6.3.4.14, 6.4.1.2	biotin carboxylase, acetyl-CoA carboxylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SPHK1	232
TP53	869
PIK3CA	2,034
TBXAS1	210
TNF	193
GABRB1	266

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

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	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TBXAS1, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	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)	7	TP53, PIK3CA, TBXAS1, TNF, GABRB1, ACACB, PAX8
B	Phased (≥1) drug, not yet approved	1	SPHK1
C	Druggable family + PDB, no drug	8	PRAG1, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1, MICA, MICB
D	Druggable family + AlphaFold only, no drug	4	ADGRV1, SLCO5A1, SULF1, VSTM2A
E	Difficult family or no structure, no drug	19	XRCC1, CD44, SOX9, FBXO15, CLDN23, SUGT1P3, MCCD1, ZNF804B, GSDMB, CLPTM1L (+9 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
XRCC1	0	—
CD44	9	—
SOX9	3	—
FBXO15	0	—
ADGRV1	0	—
CLDN23	0	—
SLCO5A1	0	—
SULF1	0	—
SUGT1P3	0	—
MCCD1	0	—
ZNF804B	0	—
GSDMB	0	—
CLPTM1L	1	—
PRAG1	0	—
LRRC28	0	—
VSTM2A	0	—
EXOC1	1	—
ELF1	0	—
INS-IGF2	0	—
TTC34	0	—
HLA-B	1	—
HLA-C	1	—
HLA-DPB2	0	—
HLA-DQA1	2	—
HLA-DQB1	0	—
HLA-DRB1	17	—
VSTM2A-OT1	0	—
LINC01445	0	—
MEF2A	0	—
MICA	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,768.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	347
Not specified	269
PHASE1	188
PHASE3	138
PHASE1/PHASE2	96
PHASE4	30
PHASE2/PHASE3	16
EARLY_PHASE1	16

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00923702	PHASE4	ACTIVE_NOT_RECRUITING	Trial of Two Versus Three Doses of Human Papillomavirus (HPV) Vaccine in India
NCT04910802	PHASE4	RECRUITING	Concomitant HPV Vaccination and HPV Screening HPV Infection and Cervical Cancer in Sweden
NCT06536855	PHASE4	NOT_YET_RECRUITING	Faster Elimination of HPV Infection and Cervical Cancer Using Concomitant HPV Vaccination and HPV Screening: A Demonstration Project in Rwanda
NCT06786429	PHASE4	NOT_YET_RECRUITING	Managing Hepatitis B (Hep. B) and Human Papilloma Virus (HPV) Related Cancers and Mental Health.
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06952660	PHASE4	RECRUITING	Ocular Assessments in Patients Treated With Tivdak® in Recurrent or Metastatic Cervical Cancer
NCT07412873	PHASE4	NOT_YET_RECRUITING	Study on Sexual Health and Self-perceived Quality of Life (PROMs) in Patients Treated for Cervical Cancer
NCT00046969	PHASE4	COMPLETED	Epoetin Beta in Treating Anemia in Patients With Cervical Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00629993	PHASE4	TERMINATED	Dissemination of Cervical Cancer Screening to Primary Care Physicians in Underserved Communities
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00862810	PHASE4	COMPLETED	Alternate Dosing Schedules Study for HPV Vaccine
NCT01021904	PHASE4	UNKNOWN	Primary and Secondary Prevention of Human Papillomavirus (HPV) Disease in China
NCT01101750	PHASE4	COMPLETED	Does the HPV Vaccine Cause the Same Response in Adolescent Kidney and Liver Transplant Patients as in Healthy Controls?
NCT01173900	PHASE4	COMPLETED	Delivery, Uptake and Acceptability of HPV Vaccination in Tanzanian Girls
NCT01544478	PHASE4	COMPLETED	V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110)
NCT01895517	PHASE4	COMPLETED	CervIcal Cancer Screening Trial by Randomization of HPV Testing Intervention for Upcoming Screening （CITRUS Study）
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02296255	PHASE4	COMPLETED	Effect of HPV Vaccination on Women Aged 25 Years
NCT02629510	PHASE4	UNKNOWN	The Efficacy of Tachosil® for Prevention of Hemorrhage After Loop Electrosurgical Excisional Procedure (LEEP)
NCT02837926	PHASE4	COMPLETED	Comparing Health Services Interventions for the Prevention of HPV-related Cancer
NCT03206684	PHASE4	UNKNOWN	To Evaluate the Efficacy and Safety of PEG-rhG-CSF（Jinyouli®） in Reducing Neutropenia in Patients With Cervical Cancer
NCT03349463	PHASE4	UNKNOWN	Evaluation of Fluciclovine Uptake in Patients With Cervical, Ovarian Epithelial or Endometrial Cancers.
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03423082	PHASE4	TERMINATED	Pilot Study to Assess the Potential Clinical Utility of 18F Fluciclovine PET for Cervical and Endometrial Cancer.
NCT03752606	PHASE4	COMPLETED	Application of Tachosil During Lymphadenectomy
NCT04819685	PHASE4	UNKNOWN	Application of KANG FU PEN in Radical Concurrent Radiotherapy and Chemotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Rectal Injury
NCT05426148	PHASE4	COMPLETED	Lot Consistency Clinical Trial of of Recombinant HPV Bivalent Vaccine in 9 to14 Years Old Healthy Female
NCT06031493	PHASE4	UNKNOWN	A Multimodal Intervention Program to Improve Sexual Health and Self-perceived Quality of Life in Patients Treated for Cervical Cancer (PROVIDENCE)
NCT01566240	PHASE3	ACTIVE_NOT_RECRUITING	Induction Chemotherapy Plus Chemoradiation as First Line Treatment for Locally Advanced Cervical Cancer
NCT02466971	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers
NCT03755739	PHASE2/PHASE3	RECRUITING	Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors
NCT04422366	PHASE3	RECRUITING	Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females
NCT04537156	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy, Immunogenicity and Safety Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)
NCT04723875	PHASE3	ACTIVE_NOT_RECRUITING	Postoperative Adjuvant Chemotherapy in Early-stage Cervical Cancer That Not Meet Criteria of Adjuvant Therapeutic According to NCCN Guideline
NCT04733820	PHASE3	RECRUITING	Clinical Efficacy of Adjuvant Chemotherapy in Patients With Locally Advanced Cervical Cancer Who Did Not Meet the NCCN Guidelines for Adjuvant Treatment After NACT Combined With Surgery
NCT04895020	PHASE3	RECRUITING	Immunobridging Study of 9-valent Human Papillomavirus Recombinant Vaccine in Chinese Females Aged 9 to 19 Years
NCT04906993	PHASE3	ACTIVE_NOT_RECRUITING	Camrelizumab Combined With Famitinib Malate for Treatment of Recurrent/Metastatic Cervical Cancer
NCT04974346	PHASE3	RECRUITING	Para-aortic Prophylactic Irradiation for Locally Advanced Cervical Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	143
HUMAN PAPILLOMAVIRUS, L1 PROTEIN VIRUS LIKE PARTICLES	4	11
TOPOTECAN	4	9
GEMCITABINE	4	8
INDOCYANINE GREEN ACID FORM	4	6
TISOTUMAB VEDOTIN	4	6
HYDRALAZINE	4	3
VINORELBINE TARTRATE	4	3
FLUOROURACIL	4	2
IFOSFAMIDE	4	2
BLEOMYCIN SULFATE	4	1
BUPROPION HYDROCHLORIDE	4	1
DALTEPARIN SODIUM	4	1
EPOETIN ALFA	4	1
EPOETIN BETA	4	1
FERROUS FUMARATE	4	1
FLUCICLOVINE F18	4	1
GRANISETRON	4	1
MITOMYCIN	4	1
NICOTINE	4	1
OCTREOTIDE ACETATE	4	1
VINBLASTINE SULFATE	4	1
VINCRISTINE SULFATE	4	1
VINDESINE	4	1
TRIAPINE	3	4
TIRAPAZAMINE	3	3
MAGNESIUM VALPROATE	3	2
RIVOCERANIB	3	2
ARUNDINE	3	1
FENRETINIDE	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 5 predictive associations from 5 curated evidence items; also 3 prognostic, 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
XRCC1 Q399R	Cisplatin + Carboplatin	Sensitivity/Response	CIViC B	EID673
CD44 CD44v6	Cisplatin	Resistance	CIViC B	EID9481
PIK3CA E545K	Cisplatin + Pictilisib	Sensitivity/Response	CIViC D	EID2984
PIK3CA E545K	Cisplatin	Resistance	CIViC D	EID2985
PIK3CA E545K	Cisplatin + Ionizing Radiotherapy	Resistance	CIViC D	EID8112