Mediastinal germ cell tumor

Summary

Mediastinal germ cell tumor (MONDO:0021067) is a cancer with 9 cohort genes (2 CIViC-evidence somatic drivers; 9 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 9
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mediastinal germ cell tumor
Mondo ID	MONDO:0021067
NCIT	C6437
UMLS	C1334655
MedGen	233678
GARD	0025285
Anatomy (UBERON)	UBERON:0003728
Is cancer (heuristic)	yes

Also known as: germ cell neoplasm of mediastinum · germ cell neoplasm of the mediastinum · germ cell tumor of mediastinum · germ cell tumor of the mediastinum · germ cell tumour of mediastinum · germ cell tumour of the mediastinum · mediastinal germ cell neoplasm · mediastinal germ cell tumor · mediastinum germ cell tumor · mediastinum germ cell tumour · thymic germ cell tumor · thymic germ cell tumour

Data availability: 9 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › germ cell tumor › extragonadal germ cell tumor › mediastinal germ cell tumor

Related subtypes (5): central nervous system germ cell tumor, extragonadal germ cell cancer, extragonadal non-dysgerminomatous germ cell tumor, cardiac germ cell tumor, lung germ cell tumor

Subtypes (2): mediastinum teratoma, mediastinal malignant germ cell tumor

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
183726	NM_000314.8(PTEN):c.406T>C (p.Cys136Arg)	PTEN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218342	NM_000546.6(TP53):c.636del (p.Arg213fs)	TP53	Pathogenic	reviewed by expert panel
218346	NM_001099.5(ACP3):c.849CAT[1] (p.Ile284del)	ACP3	Uncertain significance	no assertion criteria provided
218341	NM_024535.5(CORO7):c.2772+50C>T	CORO7	Uncertain significance	no assertion criteria provided
218340	NM_153487.4(MDGA1):c.2674T>G (p.Phe892Val)	MDGA1	Uncertain significance	no assertion criteria provided
218344	NC_012920.1(MT-ND6):m.14372C>A	MT-ND6	Uncertain significance	no assertion criteria provided
218347	NM_001346413.3(PCF11):c.3618del (p.Phe1206fs)	PCF11	Uncertain significance	no assertion criteria provided
218343	NM_022904.3(RASAL3):c.-5C>G	RASAL3	Uncertain significance	no assertion criteria provided
218345	NM_003048.6(SLC9A2):c.2173del (p.Gln725fs)	SLC9A2	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 38 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41

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
MT-ND6	Orphanet:104	Leber hereditary optic neuropathy
MT-ND6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ND6	Orphanet:550	MELAS
MT-ND6	Orphanet:99718	Leber plus disease
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC9A2	HGNC:11072	ENSG00000115616	Q9UBY0	Sodium/hydrogen exchanger 2	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
ACP3	HGNC:125	ENSG00000014257	P15309	Prostatic acid phosphatase	clinvar
MDGA1	HGNC:19267	ENSG00000112139	Q8NFP4	MAM domain-containing glycosylphosphatidylinositol anchor protein 1	clinvar
RASAL3	HGNC:26129	ENSG00000105122	Q86YV0	RAS protein activator like-3	clinvar
CORO7	HGNC:26161	ENSG00000262246	P57737	Coronin-7	clinvar
PCF11	HGNC:30097	ENSG00000165494	O94913	Pre-mRNA cleavage complex 2 protein Pcf11	clinvar
MT-ND6	HGNC:7462	ENSG00000198695	P03923	NADH-ubiquinone oxidoreductase chain 6	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC9A2	Sodium/hydrogen exchanger 2	Plasma membrane Na(+)/H(+) antiporter.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ACP3	Prostatic acid phosphatase	A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins.
MDGA1	MAM domain-containing glycosylphosphatidylinositol anchor protein 1	Required for radial migration of cortical neurons in the superficial layer of the neocortex.
RASAL3	RAS protein activator like-3	Functions as a Ras GTPase-activating protein.
CORO7	Coronin-7	F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via ‘Lys-33’-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network,…
PCF11	Pre-mRNA cleavage complex 2 protein Pcf11	Component of pre-mRNA cleavage complex II, which promotes transcription termination by RNA polymerase II.
MT-ND6	NADH-ubiquinone oxidoreductase chain 6	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.33

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
Phosphatase	2	18.6×	0.024
Antibody/Immunoglobulin	1	3.2×	0.673
Scaffold/PPI	1	1.9×	0.692
Transcription factor	1	0.9×	0.847
Other/Unknown	4	0.8×	0.847

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC9A2	Other/Unknown	no		NHE-2/4, NaH_exchanger, Cation/H_exchanger_TM
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ACP3	Phosphatase	yes	3.1.3.2	His_Pase_clade-2, His_PPase_superfam, Acid_Pase_AS
MDGA1	Antibody/Immunoglobulin	yes		MAM_dom, Ig_sub2, Ig_sub
RASAL3	Other/Unknown	no		C2_dom, RasGAP_dom, Rho_GTPase_activation_prot
CORO7	Scaffold/PPI	no		WD40_rpt, DUF1899, Coronin
PCF11	Other/Unknown	no		CID_dom, ENTH_VHS, Pcf11_Clp1-ID
MT-ND6	Other/Unknown	no		NADH_UbQ/plastoQ_OxRdtase_su6, ComplexI_Subunit6
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

Expression context

Cohort genes with no expression data: 0.

7 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
calcaneal tendon	2
male germ line stem cell (sensu Vertebrata) in testis	1
mucosa of transverse colon	1
rectum	1
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
esophagus squamous epithelium	1
prostate gland	1
tongue squamous epithelium	1
cardiac muscle of right atrium	1
cerebellar cortex	1
cerebellar hemisphere	1
lymph node	1
spleen	1
blood	1
bone marrow	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC9A2	144	broad	marker	rectum, male germ line stem cell (sensu Vertebrata) in testis, mucosa of transverse colon
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ACP3	210	broad	marker	prostate gland, tongue squamous epithelium, esophagus squamous epithelium
MDGA1	223	broad	yes	cerebellar hemisphere, cardiac muscle of right atrium, cerebellar cortex
RASAL3	217	broad	marker	granulocyte, spleen, lymph node
CORO7	138	ubiquitous	yes	granulocyte, bone marrow, blood
PCF11	260	ubiquitous	marker	calcaneal tendon, skin of abdomen, skin of leg
MT-ND6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, right uterine tube
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
PTEN	11,626
PCF11	2,439
MDGA1	1,526
RASAL3	1,417
ACP3	1,224
MT-ND6	1,208
SLC9A2	1,115
CORO7	640

Intra-cohort edges

A	B	Sources
PTEN	TP53	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
ACP3	P15309	17
PTEN	P60484	12
MT-ND6	P03923	5
MDGA1	Q8NFP4	3
CORO7	P57737	1
PCF11	O94913	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC9A2	Q9UBY0	66.40
RASAL3	Q86YV0	66.34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 74. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	1427.5×	0.020	TP53
PTEN Loss of Function in Cancer	1	713.8×	0.020	PTEN
Regulation of TP53 Expression	1	713.8×	0.020	TP53
Ovarian tumor domain proteases	2	69.6×	0.020	TP53, PTEN
Regulation of PTEN gene transcription	2	44.6×	0.020	TP53, PTEN
TP53 Regulates Metabolic Genes	2	32.4×	0.020	TP53, PTEN
Transcriptional activation of cell cycle inhibitor p21	1	356.9×	0.030	TP53
Activation of NOXA and translocation to mitochondria	1	237.9×	0.036	TP53
RUNX3 regulates CDKN1A transcription	1	203.9×	0.036	TP53
Sodium/Proton exchangers	1	158.6×	0.036	SLC9A2
PI5P Regulates TP53 Acetylation	1	158.6×	0.036	TP53
Activation of PUMA and translocation to mitochondria	1	142.8×	0.036	TP53
Regulation of PTEN mRNA translation	1	142.8×	0.036	PTEN
Regulation of PTEN localization	1	129.8×	0.036	PTEN
TP53 Regulates Transcription of Caspase Activators and Caspases	1	119.0×	0.036	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	119.0×	0.036	TP53
Urea cycle	1	109.8×	0.036	TP53
Regulation of TP53 Activity through Association with Co-factors	1	102.0×	0.036	TP53
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	95.2×	0.036	TP53
Stabilization of p53	1	95.2×	0.036	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	89.2×	0.036	TP53
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	84.0×	0.036	TP53
Zygotic genome activation (ZGA)	1	84.0×	0.036	TP53
Regulation of NF-kappa B signaling	1	79.3×	0.036	TP53
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	75.1×	0.036	TP53
SUMOylation of transcription factors	1	71.4×	0.036	TP53
Processing of Intronless Pre-mRNAs	1	71.4×	0.036	PCF11
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	68.0×	0.036	TP53
Regulation of TP53 Activity through Methylation	1	68.0×	0.036	TP53
Ub-specific processing proteases	2	13.3×	0.036	TP53, PTEN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
prepulse inhibition	2	249.7×	0.006	MDGA1, PTEN
negative regulation of helicase activity	1	1872.4×	0.020	TP53
cellular response to actinomycin D	1	1872.4×	0.020	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	1872.4×	0.020	TP53
negative regulation of G1 to G0 transition	1	1872.4×	0.020	TP53
positive regulation of mitochondrial membrane permeability	1	936.2×	0.020	TP53
oligodendrocyte apoptotic process	1	936.2×	0.020	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	936.2×	0.020	TP53
negative regulation of pentose-phosphate shunt	1	936.2×	0.020	TP53
negative regulation of synaptic vesicle clustering	1	936.2×	0.020	PTEN
obsolete homolactic fermentation	1	624.1×	0.020	TP53
negative regulation of keratinocyte migration	1	624.1×	0.020	PTEN
positive regulation of adenosine receptor signaling pathway	1	624.1×	0.020	ACP3
signal transduction by p53 class mediator	1	624.1×	0.020	TP53
negative regulation of miRNA processing	1	624.1×	0.020	TP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	624.1×	0.020	TP53
regulation of fibroblast apoptotic process	1	624.1×	0.020	TP53
T cell proliferation involved in immune response	1	468.1×	0.020	TP53
thiamine metabolic process	1	468.1×	0.020	ACP3
rhythmic synaptic transmission	1	468.1×	0.020	PTEN
positive regulation of programmed necrotic cell death	1	468.1×	0.020	TP53
oxidative stress-induced premature senescence	1	468.1×	0.020	TP53
regulation of synaptic membrane adhesion	1	468.1×	0.020	MDGA1
B cell lineage commitment	1	374.5×	0.020	TP53
T cell lineage commitment	1	374.5×	0.020	TP53
mRNA transcription	1	374.5×	0.020	TP53
positive regulation of RNA polymerase II transcription preinitiation complex assembly	1	374.5×	0.020	TP53
positive regulation of thymocyte apoptotic process	1	374.5×	0.020	TP53
cellular response to UV-C	1	374.5×	0.020	TP53
central nervous system myelin maintenance	1	312.1×	0.020	PTEN

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 7

Druggability breadth: 5 of 9 evidence-associated genes (56%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
SLC9A2	3	2
ACP3	0	0
MDGA1	0	0
RASAL3	0	0
CORO7	0	0
PCF11	0	0
MT-ND6	0	0
PTEN	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	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): 2.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
SLC9A2	10	Binding:8, Functional:2
PTEN	8	Binding:8
ACP3	6	Binding:6
MT-ND6	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACP3	3.1.3.2	acid phosphatase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	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)	1	TP53
B	Phased (≥1) drug, not yet approved	1	SLC9A2
C	Druggable family + PDB, no drug	3	ACP3, MDGA1, PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	RASAL3, CORO7, PCF11, MT-ND6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTEN	8	TP53
ACP3	6	—
MDGA1	0	—
RASAL3	0	—
CORO7	0	—
PCF11	0	—
MT-ND6	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.