Testicular cancer

Summary

Testicular cancer (MONDO:0005447) is a cancer (an umbrella term covering 11 Mondo subtypes) with 33 cohort genes (57 GWAS associations across 15 studies; 7 CIViC-evidence somatic drivers; 29 ClinVar predisposition records) and 105 clinical trials. Top therapeutic interventions include 2-mercaptoethanesulfonic acid, brentuximab vedotin, and brodalumab.

At a glance

• Classification: Cancer
• Umbrella term: 11 Mondo subtypes
• Cohort genes: 33
• GWAS associations: 57
• ClinVar variants: 29
• Clinical trials: 105

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	testicular cancer
Mondo ID	MONDO:0005447
EFO	EFO:0005088
MeSH	D013736
DOID	DOID:2998
ICD-10-CM	C62
NCIT	C7251
SNOMED CT	363449006
UMLS	C0153594
MedGen	56313
Anatomy (UBERON)	UBERON:0000473
Is cancer (heuristic)	yes

Also known as: cancer of testis · malignant neoplasm of testis · malignant neoplasm of the testis · malignant testicular neoplasm · malignant testicular tumor · malignant testicular tumour · malignant testis neoplasm · malignant tumor of testis · malignant tumor of the testis · malignant tumour of testis · malignant tumour of the testis · paediatric testicular neoplasm · testicular tumor · testicular tumour · testis cancer · testis neoplasm

Data availability: 29 ClinVar variants · 57 GWAS associations (15 studies).

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › reproductive system cancer › male reproductive organ cancer › testicular cancer

Related subtypes (6): epididymis cancer, penile cancer, spermatic cord cancer, carcinoma of Cowper glands, prostate cancer, scrotum cancer

Subtypes (11): malignant Sertoli-Leydig cell tumor, testicular lymphoma, malignant tumor of undescended testis, testicular leukemia, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, testicular gonadoblastoma, testis sarcoma, malignant testicular germ cell tumor, malignant testicular Leydig cell tumor, paratesticular adenocarcinoma

Genetics & variants

GWAS landscape

57 GWAS associations across 15 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs995030	2e-50	KITLG	G	2.26
rs4624820	3e-31	NDFIP1 - SPRY4	A	1.52
rs3782181	2e-26	KITLG	?	2.22
rs755383	2e-26	DMRT1	T	1.38
rs210138	2e-24	BAK1	G	1.44
rs4635969	5e-24	TERT - MIR4457	T	1.39
rs1907702	6e-24	KITLG	A	2.4
chr5:141688390	4e-16		G	1.56
rs4474514	6e-15	KITLG	A	3.07
rs2736100	8e-15	TERT	T	1.33
rs7863616	1e-14	DMRT1	C	1.58
rs2900333	1e-13	ATF7IP	C	1.32
rs36115365	2e-13	MIR4457 - CLPTM1L	C	1.54
rs9905704	4e-13	SEPTIN4-AS1	T	1.27
rs4888262	5e-12	RFWD3	C	1.26
rs7040024	1e-11	DMRT1	A	1.7
rs2720460	2e-10	CENPE	A	1.24
rs2839186	1e-09	MCM3AP, MCM3AP-AS1	T	1.26
rs10851590	1e-09	PRTG	T	1.39
rs8046148	4e-09	HEATR3 - RPL10P14	G	1.32
rs12699477	6e-09	MAD1L1	C	1.21
rs10510452	1e-08	LINC00690 - DAZL	A	1.24
rs17021463	1e-08	HPGDS	T	1.19
rs3790672	2e-08	UCK2	C	1.2
rs3805663	2e-08	PITX1	T	1.25
rs2072499	3e-08	SLC25A44	G	1.19
rs7659556	4e-08	CENPE - LINC02428	T	1.37
rs7010162	5e-08	PRDM14	G	1.22
rs111581773	1e-07	ACTL8	C	1.87
rs4699052	2e-07	CENPE - LINC02428	C	1.21

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90435613	Zhou W	2018	2,981	401,788	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90481513	Verma A	2024	1,136	415,949	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST002022	Ruark E	2013	986	4,946	Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.
GCST000701	Turnbull C	2010	979	4,947	Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer.
GCST90041906	Jiang L	2021	797	207,971	A generalized linear mixed model association tool for biobank-scale data.
GCST90077636	Backman JD	2021	769	38,845	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081622	Backman JD	2021	769	38,845	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST000414	Rapley EA	2009	730	1,435	A genome-wide association study of testicular germ cell tumor.
GCST90011805	Rashkin SR	2020	713	359,825	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST002023	Chung CC	2013	582	1,056	Meta-analysis identifies four new loci associated with testicular germ cell tumor.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	1
Tier 4: intronic/intergenic	37

MAF distribution

Bucket	Variants
common (>=0.05)	33
low_freq (0.01-0.05)	6
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	6
3_prime_UTR_variant	2
unknown	2
regulatory_region_variant	1
synonymous_variant	1
splice_polypyrimidine_tract_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs995030	12	88496894	A>G	0.2	3_prime_UTR_variant	KITLG	2e-50	Tier 2: splice/UTR
rs4624820	5	142302223	G>A	0.46	intergenic_variant	NDFIP1 - SPRY4	3e-31	Tier 4: intronic/intergenic
rs3782181	12	88559784	C>A	0.22	intron_variant	KITLG	2e-26	Tier 4: intronic/intergenic
rs755383	9	863635	C>A,T	0.37	intron_variant	DMRT1	2e-26	Tier 4: intronic/intergenic
rs210138	6	33574761	A>C,G,T	0.19	intron_variant	BAK1	2e-24	Tier 4: intronic/intergenic
rs4635969	5	1308437	G>A,C,T	0.2	intergenic_variant	TERT - MIR4457	5e-24	Tier 4: intronic/intergenic
rs1907702	12	88561692	G>A,C,T	0.05	intron_variant	KITLG	6e-24	Tier 4: intronic/intergenic
chr5:141688390							4e-16	Tier 4: intronic/intergenic
rs4474514	12	88560182	G>A,C,T	0.05	intron_variant	KITLG	6e-15	Tier 4: intronic/intergenic
rs2736100	5	1286401	C>A,G,T	0.49	intron_variant	TERT	8e-15	Tier 4: intronic/intergenic
rs7863616	9	861220	T>A,C,G	0.05	intron_variant	DMRT1	1e-14	Tier 4: intronic/intergenic
rs2900333	12	14500933	C>A,G,T	0.38	3_prime_UTR_variant	ATF7IP	1e-13	Tier 2: splice/UTR
rs36115365	5	1313127	G>A,C,T	0.05	regulatory_region_variant	MIR4457 - CLPTM1L	2e-13	Tier 3: regulatory
rs9905704	17	58555182	G>A,C,T	0.32	intron_variant	SEPTIN4-AS1	4e-13	Tier 4: intronic/intergenic
rs4888262	16	74636560	C>T	0.458	synonymous_variant	RFWD3	5e-12	Tier 4: intronic/intergenic
rs7040024	9	845516	A>C,G,T	0.05	intron_variant	DMRT1	1e-11	Tier 4: intronic/intergenic
rs2720460	4	103133529	A>G	0.39	intron_variant	CENPE	2e-10	Tier 4: intronic/intergenic
rs2839186	21	46270154	C>T	0.46	intron_variant	MCM3AP, MCM3AP-AS1	1e-09	Tier 4: intronic/intergenic
rs10851590	15	55697741	C>T	0.05	intron_variant	PRTG	1e-09	Tier 4: intronic/intergenic
rs8046148	16	50109033	A>G,T	0.21	intron_variant	HEATR3 - RPL10P14	4e-09	Tier 4: intronic/intergenic
rs12699477	7	1929317	T>A,C,G	0.38	intron_variant	MAD1L1	6e-09	Tier 4: intronic/intergenic
rs10510452	3	16583541	A>G	0.31	intergenic_variant	LINC00690 - DAZL	1e-08	Tier 4: intronic/intergenic
rs17021463	4	94303661	T>G	0.42	intron_variant	HPGDS	1e-08	Tier 4: intronic/intergenic
rs3790672	1	165904155	T>A,C,G	0.28	intron_variant	UCK2	2e-08	Tier 4: intronic/intergenic
rs3805663	5	135030510	A>G	0.37	intron_variant	PITX1	2e-08	Tier 4: intronic/intergenic
rs2072499	1	156199819	A>C,G,T	0.35	splice_polypyrimidine_tract_variant	SLC25A44	3e-08	Tier 2: splice/UTR
rs7659556	4	103244962	T>A,G	0.05	intergenic_variant	CENPE - LINC02428	4e-08	Tier 4: intronic/intergenic
rs7010162	8	70064270	C>A,G,T	0.39	intron_variant	PRDM14	5e-08	Tier 4: intronic/intergenic
rs111581773	1	17770950	G>C	0.03	intron_variant	ACTL8	1e-07	Tier 4: intronic/intergenic
rs4699052	4	103216633	C>T	0.39	intron_variant	CENPE - LINC02428	2e-07	Tier 4: intronic/intergenic

ClinVar germline variants

29 retrieved; paginated sample, class counts are floors:

13 conflicting classifications of pathogenicity, 8 uncertain significance, 6 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30361	NM_003921.5(BCL10):c.488C>T (p.Thr163Met)	BCL10	Pathogenic	no assertion criteria provided
16327	NM_000142.5(FGFR3):c.1138G>A (p.Gly380Arg)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16332	NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16338	NM_000142.5(FGFR3):c.1620C>G (p.Asn540Lys)	FGFR3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16339	NM_000142.5(FGFR3):c.746C>G (p.Ser249Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
65855	NM_000142.5(FGFR3):c.1949A>C (p.Lys650Thr)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
7448	NM_000455.5(STK11):c.488G>A (p.Gly163Asp)	STK11	Pathogenic	criteria provided, single submitter
182902	NM_000455.5(STK11):c.719C>G (p.Ser240Trp)	STK11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
521225	NM_000142.5(FGFR3):c.2153A>G (p.Asn718Ser)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
546226	NM_000142.5(FGFR3):c.200G>A (p.Gly67Asp)	FGFR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
237252	NM_000222.3(KIT):c.200C>G (p.Thr67Ser)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409779	NM_000222.3(KIT):c.2104C>G (p.Leu702Val)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409788	NM_000222.3(KIT):c.101C>T (p.Pro34Leu)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
458940	NM_000222.3(KIT):c.302A>G (p.His101Arg)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
576610	NM_000222.3(KIT):c.2836C>T (p.Arg946Ter)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
142198	NM_000455.5(STK11):c.1012G>A (p.Val338Met)	LOC130062899	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141128	NM_000455.5(STK11):c.566C>T (p.Thr189Ile)	STK11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141354	NM_000455.5(STK11):c.464+5G>A	STK11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
182910	NM_000455.5(STK11):c.632G>A (p.Arg211Gln)	STK11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
220264	NM_000455.5(STK11):c.1243C>G (p.Arg415Gly)	STK11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
403791	NM_000455.5(STK11):c.1195C>A (p.Gln399Lys)	STK11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
465350	NM_000142.5(FGFR3):c.1993G>T (p.Ala665Ser)	FGFR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
237245	NM_000222.3(KIT):c.1553C>T (p.Pro518Leu)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts
237271	NM_000222.3(KIT):c.2881G>A (p.Gly961Ser)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts
409730	NM_000222.3(KIT):c.2294A>G (p.Asp765Gly)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts
409774	NM_000222.3(KIT):c.2887A>G (p.Thr963Ala)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts
409783	NM_000222.3(KIT):c.2863G>T (p.Val955Leu)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts
458902	NM_000222.3(KIT):c.2057G>A (p.Arg686His)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts
458936	NM_000222.3(KIT):c.2900C>G (p.Ser967Cys)	KIT	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 67 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
TERT	Act	PRCC	CIViC #79
ATF7IP	LoF	LUAD,UCEC
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29
RAD51C			CIViC #4762
BCL10	LoF	DLBCLNOS,MLYM	CIViC #7074

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STK11	Orphanet:2869	Peutz-Jeghers syndrome
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
TEX14	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
SPRY4	Orphanet:363494	Non-seminomatous germ cell tumor of testis
SPRY4	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
SPRY4	Orphanet:478	Kallmann syndrome
SMARCAD1	Orphanet:1658	Absence of fingerprints-congenital milia syndrome
SMARCAD1	Orphanet:289465	Isolated congenital adermatoglyphia
SMARCAD1	Orphanet:384	Huriez syndrome
CENPE	Orphanet:2512	Autosomal recessive primary microcephaly
CENPE	Orphanet:808	Seckel syndrome
RFWD3	Orphanet:84	Fanconi anemia
HEATR3	Orphanet:124	Diamond-Blackfan anemia
DMRT1	Orphanet:242	46,XY complete gonadal dysgenesis
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans

Cohort genes → proteins

33 cohort genes, 33 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	29
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TEX14	HGNC:11737	ENSG00000121101	Q8IWB6	Inactive serine/threonine-protein kinase TEX14	gwas
UCK2	HGNC:12562	ENSG00000143179	Q9BZX2	Uridine-cytidine kinase 2	gwas
PRDM14	HGNC:14001	ENSG00000147596	Q9GZV8	PR domain zinc finger protein 14	gwas
SPRY4	HGNC:15533	ENSG00000187678	Q9C004	Protein sprouty homolog 4	gwas
HPGDS	HGNC:17890	ENSG00000163106	O60760	Hematopoietic prostaglandin D synthase	gwas
SMARCAD1	HGNC:18398	ENSG00000163104	Q9H4L7	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1	gwas
CENPE	HGNC:1856	ENSG00000138778	Q02224	Centromere-associated protein E	gwas
PPM1E	HGNC:19322	ENSG00000175175	Q8WY54	Protein phosphatase 1E	gwas
ATF7IP	HGNC:20092	ENSG00000171681	Q6VMQ6	Activating transcription factor 7-interacting protein 1	gwas
CATSPER3	HGNC:20819	ENSG00000152705	Q86XQ3	Cation channel sperm-associated protein 3	gwas
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	gwas
RFWD3	HGNC:25539	ENSG00000168411	Q6PCD5	E3 ubiquitin-protein ligase RFWD3	gwas
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gwas
MLKL	HGNC:26617	ENSG00000168404	Q8NB16	Mixed lineage kinase domain-like protein	gwas
DAZL	HGNC:2685	ENSG00000092345	Q92904	Deleted in azoospermia-like	gwas
SKA2	HGNC:28006	ENSG00000182628	Q8WVK7	Spindle and kinetochore-associated protein 2	gwas
SLC25A44	HGNC:29036	ENSG00000160785	Q96H78	Solute carrier family 25 member 44	gwas
DMRT1	HGNC:2934	ENSG00000137090	Q9Y5R6	Doublesex- and mab-3-related transcription factor 1	gwas
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar
GLG1	HGNC:4316	ENSG00000090863	Q92896	Golgi apparatus protein 1	gwas
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	clinvar
KITLG	HGNC:6343	ENSG00000049130	P21583	Kit ligand	gwas
LIPG	HGNC:6623	ENSG00000101670	Q9Y5X9	Endothelial lipase	gwas
MAD1L1	HGNC:6762	ENSG00000002822	Q9Y6D9	Mitotic spindle assembly checkpoint protein MAD1	gwas
MCM3AP	HGNC:6946	ENSG00000160294	O60318	Germinal-center associated nuclear protein	gwas
TRIM37	HGNC:7523	ENSG00000108395	O94972	E3 ubiquitin-protein ligase TRIM37	gwas
PITX1	HGNC:9004	ENSG00000069011	P78337	Pituitary homeobox 1	gwas
SEPTIN4	HGNC:9165	ENSG00000108387	O43236	Septin-4	gwas
BAK1	HGNC:949	ENSG00000030110	Q16611	Bcl-2 homologous antagonist/killer	gwas
RAD51C	HGNC:9820	ENSG00000108384	O43502	DNA repair protein RAD51 homolog 3	gwas
BCL10	HGNC:989	ENSG00000142867	O95999	B-cell lymphoma/leukemia 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TEX14	Inactive serine/threonine-protein kinase TEX14	Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis.
UCK2	Uridine-cytidine kinase 2	Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate.
PRDM14	PR domain zinc finger protein 14	Transcription factor that has both positive and negative roles on transcription.
SPRY4	Protein sprouty homolog 4	Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras.
HPGDS	Hematopoietic prostaglandin D synthase	Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range…
SMARCAD1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1	Protein that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization.
CENPE	Centromere-associated protein E	Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation.
PPM1E	Protein phosphatase 1E	Protein phosphatase that inactivates multifunctional CaM kinases such as CAMK4 and CAMK2.
ATF7IP	Activating transcription factor 7-interacting protein 1	Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation.
CATSPER3	Cation channel sperm-associated protein 3	Pore-forming subunit of the CatSper complex, a sperm-specific voltage-gated calcium channel that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acros…
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…
RFWD3	E3 ubiquitin-protein ligase RFWD3	E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage.
HEATR3	HEAT repeat-containing protein 3	Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5).
MLKL	Mixed lineage kinase domain-like protein	Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process.
DAZL	Deleted in azoospermia-like	RNA-binding protein, which is essential for gametogenesis in both males and females.
SKA2	Spindle and kinetochore-associated protein 2	Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation.
SLC25A44	Solute carrier family 25 member 44	Mitochondrial solute transporter which transports branched-chain amino acid (BCAA; valine, leucine and isoleucine) into mitochondria in brown adipose tissue (BAT).
DMRT1	Doublesex- and mab-3-related transcription factor 1	Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
GLG1	Golgi apparatus protein 1	Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils).
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
KITLG	Kit ligand	Ligand for the receptor-type protein-tyrosine kinase KIT.
LIPG	Endothelial lipase	Exerts both phospholipase and triglyceride lipase activities.
MAD1L1	Mitotic spindle assembly checkpoint protein MAD1	Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate.
MCM3AP	Germinal-center associated nuclear protein	As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.
TRIM37	E3 ubiquitin-protein ligase TRIM37	E3 ubiquitin-protein ligase required to prevent centriole reduplication.
PITX1	Pituitary homeobox 1	Sequence-specific transcription factor that binds gene promoters and activates their transcription.
SEPTIN4	Septin-4	Filament-forming cytoskeletal GTPase.
BAK1	Bcl-2 homologous antagonist/killer	Plays a role in the mitochondrial apoptotic process.
RAD51C	DNA repair protein RAD51 homolog 3	Essential for the homologous recombination (HR) pathway of DNA repair.
BCL10	B-cell lymphoma/leukemia 10	Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation.

Protein-family classification

Druggable: 10 · Difficult: 4 · Unknown: 19 · Druggable fraction: 0.3

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	6	5.0×	0.007
Ion channel	1	3.4×	0.763
Phosphatase	1	2.5×	0.763
Other/Unknown	19	1.0×	0.798
Transcription factor	4	1.0×	0.798
Antibody/Immunoglobulin	1	0.9×	0.798
Enzyme (other)	1	0.4×	0.944

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TEX14	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ankyrin_rpt
UCK2	Kinase	yes	2.7.1.48	Uridine_kinase-like, PRK/URK, P-loop_NTPase
PRDM14	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
SPRY4	Other/Unknown	no		Sprouty, Sprouty_domain
HPGDS	Enzyme (other)	yes	2.5.1.18	Glutathione_S-Trfase_N, GST_C, Glutathione-S-Trfase_C-like
SMARCAD1	Other/Unknown	no		SNF2_N, Helicase_C-like, CUE
CENPE	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
PPM1E	Phosphatase	yes		PP2C_BS, PPM-type_phosphatase-like_dom, PP2C
ATF7IP	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, ATF7-int
CATSPER3	Ion channel	yes		Ion_trans_dom, Volt_channel_dom_sf
CLPTM1L	Other/Unknown	no		CLPTM1
RFWD3	Transcription factor	no		WD40_rpt, Znf_RING, Znf_RING/FYVE/PHD
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like
MLKL	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Kinase-like_dom_sf
DAZL	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
SKA2	Other/Unknown	no		Ska2, Ska2_N
SLC25A44	Other/Unknown	no		MCP, MCP_transmembrane, MCP_dom_sf
DMRT1	Other/Unknown	no		DM_DNA-bd, DMRT1-like, DMRT
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
GLG1	Other/Unknown	no		Cys-rich_GLG1_repeat, Cys-rich_GLG1_repeat_euk, GLG1
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
KITLG	Other/Unknown	no		SCF, 4_helix_cytokine-like_core
LIPG	Other/Unknown	no		TAG_lipase, PLAT/LH2_dom, Lipo_Lipase
MAD1L1	Other/Unknown	no		Mad1
MCM3AP	Other/Unknown	no		PCI_dom, SAC3/GANP/THP3_conserved, MCM3AP_GANP
TRIM37	Transcription factor	no		Znf_B-box, Znf_RING, MATH/TRAF_dom
PITX1	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
SEPTIN4	Other/Unknown	no		Septin, P-loop_NTPase, G_SEPTIN_dom
BAK1	Other/Unknown	no		Bcl2-like, Bcl2_BH1_motif_CS, Bcl2_BH2_motif_CS
RAD51C	Other/Unknown	no		Rad51_C, DNA_recomb/repair_RecA-like, RecA_ATP-bd
BCL10	Other/Unknown	no		CARD, DEATH-like_dom_sf, BCL10/E10

Expression context

Cohort genes with no expression data: 0.

31 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)	32
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right testis	5
male germ line stem cell (sensu Vertebrata) in testis	5
left testis	4
ventricular zone	4
primordial germ cell in gonad	4
oocyte	4
secondary oocyte	4
ganglionic eminence	3
buccal mucosa cell	3
endothelial cell	3
stromal cell of endometrium	2
mucosa of transverse colon	2
cardia of stomach	2
nipple	2
right lobe of thyroid gland	2
leukocyte	2
monocyte	2
granulocyte	2
tendon of biceps brachii	2
lower esophagus mucosa	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TEX14	162	broad	marker	right testis, left testis, testis
UCK2	238	ubiquitous	marker	mucosa of transverse colon, ventricular zone, ganglionic eminence
PRDM14	15	tissue_specific	marker	buccal mucosa cell, primordial germ cell in gonad, triceps brachii
SPRY4	219	ubiquitous	marker	left coronary artery, right lung, ascending aorta
HPGDS	220	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, placenta, calcaneal tendon
SMARCAD1	245	ubiquitous	marker	adrenal tissue, ganglionic eminence, tibia
CENPE	176	ubiquitous	marker	oocyte, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis
PPM1E	172	broad	marker	endothelial cell, cortical plate, Brodmann (1909) area 23
ATF7IP	285	ubiquitous	marker	buccal mucosa cell, cardia of stomach, nipple
CATSPER3	162	tissue_specific	yes	sperm, right testis, left testis
CLPTM1L	255	ubiquitous	marker	ileal mucosa, kidney epithelium, right lobe of thyroid gland
RFWD3	216	ubiquitous	marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
HEATR3	248	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
MLKL	234	ubiquitous	marker	granulocyte, monocyte, leukocyte
DAZL	59	tissue_specific	marker	oocyte, secondary oocyte, primordial germ cell in gonad
SKA2	256	ubiquitous	marker	ventricular zone, ganglionic eminence, endothelial cell
SLC25A44	253	ubiquitous	marker	prefrontal cortex, blood, tendon of biceps brachii
DMRT1	23	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
GLG1	299	ubiquitous	marker	stromal cell of endometrium, renal medulla, nipple
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
KITLG	262	ubiquitous	marker	visceral pleura, cardia of stomach, lower lobe of lung
LIPG	195	ubiquitous	marker	ventricular zone, right lobe of thyroid gland, left lobe of thyroid gland
MAD1L1	137	ubiquitous	marker	sural nerve, right testis, left testis
MCM3AP	287	ubiquitous	marker	tendon of biceps brachii, tibial nerve, right uterine tube
TRIM37	294	ubiquitous	marker	endothelial cell, endometrium epithelium, secondary oocyte
PITX1	180	broad	marker	lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa
SEPTIN4	225	broad	marker	C1 segment of cervical spinal cord, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 19.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIT	6,087
TERT	5,717
STK11	5,146
FGFR3	4,510
RAD51C	3,396
KITLG	3,075
TRIM37	3,035
MAD1L1	2,947
SMARCAD1	2,862
DAZL	2,661

Intra-cohort edges

A	B	Sources
ATF7IP	CLPTM1L	string_interaction
ATF7IP	DMRT1	string_interaction
ATF7IP	SPRY4	string_interaction
ATF7IP	TERT	string_interaction
CENPE	MAD1L1	intact
CLPTM1L	DMRT1	string_interaction
CLPTM1L	TERT	string_interaction
DAZL	PRDM14	string_interaction
DAZL	TEX14	string_interaction
DMRT1	KITLG	string_interaction
DMRT1	TEX14	string_interaction
GLG1	MLKL	biogrid_interaction, intact
GLG1	RFWD3	biogrid_interaction, intact
KIT	KITLG	biogrid_interaction, intact, string_interaction
MAD1L1	PPM1E	string_interaction
MAD1L1	RFWD3	string_interaction
PPM1E	RFWD3	string_interaction
PPM1E	TEX14	string_interaction
RAD51C	RFWD3	string_interaction

Structural data

PDB: 23 · AlphaFold-only: 10 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BAK1	Q16611	55
KIT	P10721	52
HPGDS	O60760	30
TERT	O14746	23
MLKL	Q8NB16	22
RAD51C	O43502	17
FGFR3	P22607	15
UCK2	Q9BZX2	11
MCM3AP	O60318	7
CENPE	Q02224	6
KITLG	P21583	6
MAD1L1	Q9Y6D9	5
BCL10	O95999	5
STK11	Q15831	4
SMARCAD1	Q9H4L7	4
TEX14	Q8IWB6	2
SPRY4	Q9C004	1
ATF7IP	Q6VMQ6	1
RFWD3	Q6PCD5	1
SKA2	Q8WVK7	1
DMRT1	Q9Y5R6	1
TRIM37	O94972	1
SEPTIN4	O43236	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HEATR3	Q7Z4Q2	83.07
LIPG	Q9Y5X9	82.76
SLC25A44	Q96H78	80.66
CATSPER3	Q86XQ3	80.01
CLPTM1L	Q96KA5	78.54
GLG1	Q92896	78.35
PPM1E	Q8WY54	64.66
PITX1	P78337	62.81
PRDM14	Q9GZV8	60.83
DAZL	Q92904	57.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 162. Enrichment computed across 33 evidence-associated genes (24 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 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
t(4;14) translocations of FGFR3	1	475.8×	0.014	FGFR3
Signaling by FGFR3 fusions in cancer	1	475.8×	0.014	FGFR3
Dasatinib-resistant KIT mutants	1	475.8×	0.014	KIT
Imatinib-resistant KIT mutants	1	475.8×	0.014	KIT
KIT mutants bind TKIs	1	475.8×	0.014	KIT
Masitinib-resistant KIT mutants	1	475.8×	0.014	KIT
Nilotinib-resistant KIT mutants	1	475.8×	0.014	KIT
Regorafenib-resistant KIT mutants	1	475.8×	0.014	KIT
Signaling by kinase domain mutants of KIT	1	475.8×	0.014	KIT
Sunitinib-resistant KIT mutants	1	475.8×	0.014	KIT
Signaling by juxtamembrane domain KIT mutants	1	475.8×	0.014	KIT
Sorafenib-resistant KIT mutants	1	475.8×	0.014	KIT
Drug resistance of KIT mutants	1	475.8×	0.014	KIT
Signaling by extracellular domain mutants of KIT	1	475.8×	0.014	KIT
Release of apoptotic factors from the mitochondria	2	135.9×	0.014	SEPTIN4, BAK1
Regulated Necrosis	2	59.5×	0.014	MLKL, BAK1
Regulation of KIT signaling	2	50.1×	0.014	KIT, KITLG
Amplification of signal from the kinetochores	3	24.6×	0.014	CENPE, SKA2, MAD1L1
Mitotic Spindle Checkpoint	3	19.8×	0.014	CENPE, SKA2, MAD1L1
Constitutive Signaling by Aberrant PI3K in Cancer	3	15.9×	0.014	FGFR3, KIT, KITLG
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	3	14.6×	0.014	CENPE, SKA2, MAD1L1
Mitotic Metaphase and Anaphase	3	12.1×	0.014	CENPE, SKA2, MAD1L1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	3	12.1×	0.014	FGFR3, KIT, KITLG
Mitotic Anaphase	3	12.1×	0.014	CENPE, SKA2, MAD1L1
EML4 and NUDC in mitotic spindle formation	3	11.6×	0.014	CENPE, SKA2, MAD1L1
Cell Cycle Checkpoints	3	11.1×	0.015	CENPE, SKA2, MAD1L1
Resolution of Sister Chromatid Cohesion	3	10.8×	0.015	CENPE, SKA2, MAD1L1
RHO GTPases Activate Formins	3	9.7×	0.020	CENPE, SKA2, MAD1L1
Activation and oligomerization of BAK protein	1	237.9×	0.022	BAK1
Signaling by SCF-KIT	2	20.7×	0.022	KIT, KITLG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 33 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
attachment of mitotic spindle microtubules to kinetochore	3	95.8×	0.002	CENPE, SKA2, MAD1L1
melanocyte migration	2	340.4×	0.002	KIT, KITLG
positive regulation of mast cell cytokine production	2	204.3×	0.003	KIT, BCL10
mast cell proliferation	2	204.3×	0.003	KIT, KITLG
positive regulation of mast cell proliferation	2	204.3×	0.003	KIT, KITLG
primordial germ cell migration	2	113.5×	0.009	DMRT1, KIT
telomere maintenance via recombination	2	92.8×	0.012	TERT, RAD51C
B cell apoptotic process	2	85.1×	0.012	BAK1, BCL10
negative regulation of fibroblast growth factor receptor signaling pathway	2	63.8×	0.020	PRDM14, SPRY4
embryonic hemopoiesis	2	60.1×	0.020	KIT, KITLG
ectopic germ cell programmed cell death	2	51.1×	0.026	KIT, KITLG
meiotic DNA recombinase assembly	1	510.7×	0.027	RAD51C
RNA-templated transcription	1	510.7×	0.027	TERT
female meiosis sister chromatid cohesion	1	510.7×	0.027	RAD51C
branched-chain amino acid transport	1	510.7×	0.027	SLC25A44
DNA strand elongation	1	510.7×	0.027	TERT
intercellular bridge organization	1	510.7×	0.027	TEX14
negative regulation of developmental growth	1	510.7×	0.027	FGFR3
melanocyte adhesion	1	510.7×	0.027	KIT
microtubule plus-end directed mitotic chromosome migration	1	510.7×	0.027	CENPE
lateral attachment of mitotic spindle microtubules to kinetochore	1	510.7×	0.027	CENPE
positive regulation of pyloric antrum smooth muscle contraction	1	510.7×	0.027	KIT
siRNA transcription	1	510.7×	0.027	TERT
positive regulation of vesicle transport along microtubule	1	510.7×	0.027	STK11
positive regulation of transdifferentiation	1	510.7×	0.027	TERT
positive regulation of colon smooth muscle contraction	1	510.7×	0.027	KIT
positive regulation of tyrosine phosphorylation of STAT protein	2	44.4×	0.027	FGFR3, KIT
response to cadmium ion	2	44.4×	0.027	TERT, KIT
bone morphogenesis	2	36.5×	0.027	FGFR3, GLG1
mitotic spindle assembly checkpoint signaling	2	34.0×	0.027	TEX14, MAD1L1

Therapeutics

Drugs indicated for this disease

1 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ifosfamide	Approved (phase 4)
Bleomycin	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Olanzapine	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Vinblastine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cabazitaxel, Dactinomycin, Epirubicin, Gemcitabine, Melphalan, Methotrexate, Milademetan, Pegfilgrastim, Sorafenib, Testosterone, Veliparib.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 9 · Undrugged: 24

Druggability breadth: 14 of 33 evidence-associated genes (42%) 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
STK11	FEDRATINIB
TERT	BERBERINE
MLKL	CRIZOTINIB
FGFR3	PONATINIB
KIT	PONATINIB
LIPG	ORLISTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIT	99	4
FGFR3	64	4
STK11	17	4
TERT	10	4
HPGDS	1	3
CENPE	1	1
MLKL	1	4
LIPG	1	4
BAK1	1	1
TEX14	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	FGFR3, KIT, STK11
PACRITINIB	4	STK11
NINTEDANIB	4	FGFR3, KIT, STK11
SUNITINIB	4	FGFR3, KIT, STK11
MIDOSTAURIN	4	FGFR3, KIT, STK11
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
CRIZOTINIB	4	FGFR3, KIT, MLKL
PONATINIB	4	FGFR3, KIT
PEMIGATINIB	4	FGFR3
LENVATINIB	4	FGFR3, KIT
AXITINIB	4	FGFR3, KIT
SORAFENIB	4	FGFR3, KIT
INFIGRATINIB PHOSPHATE	4	FGFR3, KIT
INFIGRATINIB	4	FGFR3, KIT
ENTRECTINIB	4	FGFR3, KIT
CERITINIB	4	FGFR3, KIT
VANDETANIB	4	FGFR3, KIT
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3, KIT
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3, KIT
DASATINIB	4	FGFR3, KIT
TIVOZANIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
REGORAFENIB	4	KIT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
FGFR3	975	Binding:948, Functional:18, ADMET:9
TERT	391	Binding:389, Functional:2
CENPE	346	Functional:241, Binding:105
STK11	244	Binding:244
MLKL	112	Binding:112
HPGDS	90	Binding:89, ADMET:1
LIPG	51	Binding:51
BAK1	28	Binding:27, Functional:1
UCK2	25	Binding:25
PRDM14	1	Binding:1
CLPTM1L	1	Binding:1
GLG1	1	Binding:1
KITLG	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STK11	2.7.11.1	non-specific serine/threonine protein kinase
UCK2	2.7.1.48	uridine/cytidine kinase
HPGDS	2.5.1.18, 5.3.99.2	glutathione transferase, Prostaglandin-D synthase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
KIT	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
STK11	244
TERT	391
CENPE	346
MLKL	112
FGFR3	975
KIT	2,305

Pharmacogenomics

Cohort genes with a PharmGKB record: 33; 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)
FEDRATINIB	4	FGFR3, KIT, STK11
PACRITINIB	4	STK11
NINTEDANIB	4	FGFR3, KIT, STK11
SUNITINIB	4	FGFR3, KIT, STK11
MIDOSTAURIN	4	FGFR3, KIT, STK11
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
CRIZOTINIB	4	FGFR3, KIT, MLKL
PONATINIB	4	FGFR3, KIT
PEMIGATINIB	4	FGFR3
LENVATINIB	4	FGFR3, KIT
AXITINIB	4	FGFR3, KIT
SORAFENIB	4	FGFR3, KIT
INFIGRATINIB PHOSPHATE	4	FGFR3, KIT
INFIGRATINIB	4	FGFR3, KIT
ENTRECTINIB	4	FGFR3, KIT
CERITINIB	4	FGFR3, KIT
VANDETANIB	4	FGFR3, KIT
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3, KIT
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3, KIT
DASATINIB	4	FGFR3, KIT
TIVOZANIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
REGORAFENIB	4	KIT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	STK11, TERT, MLKL, FGFR3, KIT, LIPG
B	Phased (≥1) drug, not yet approved	3	HPGDS, CENPE, BAK1
C	Druggable family + PDB, no drug	3	TEX14, UCK2, ATF7IP
D	Druggable family + AlphaFold only, no drug	2	PPM1E, CATSPER3
E	Difficult family or no structure, no drug	19	PRDM14, SPRY4, SMARCAD1, CLPTM1L, RFWD3, HEATR3, DAZL, SKA2, SLC25A44, DMRT1 (+9 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLPTM1L	1	TERT
KITLG	1	KIT
TEX14	0	—
UCK2	25	—
PRDM14	1	—
SPRY4	0	—
SMARCAD1	0	—
PPM1E	0	—
ATF7IP	0	—
CATSPER3	0	—
RFWD3	0	—
HEATR3	0	—
DAZL	0	—
SKA2	0	—
SLC25A44	0	—
DMRT1	0	—
GLG1	1	—
MAD1L1	0	—
MCM3AP	0	—
TRIM37	0	—
PITX1	0	—
SEPTIN4	0	—
RAD51C	0	—
BCL10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 105.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	69
PHASE2	19
PHASE1	11
PHASE1/PHASE2	3
PHASE4	1
PHASE2/PHASE3	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01641172	PHASE4	COMPLETED	Taste, Smell and Chemotherapy (TASTY)
NCT06593665	PHASE3	RECRUITING	Intrathecal Morphine Versus Intravenous Methadone for Postoperative Analgesia Following Retroperitoneal Lymph Node Dissection.
NCT02991209	PHASE2/PHASE3	COMPLETED	Study of Testosterone vs Placebo in Testicular Cancer Survivors
NCT03937843	PHASE2	ACTIVE_NOT_RECRUITING	Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma
NCT05969860	PHASE2	RECRUITING	At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
NCT06684327	PHASE2	RECRUITING	Multi-cohort, Single-arm Phase II Study of Albumin-paclitaxel, Ifosfamide, and Cisplatin in the Treatment of Rare Advanced Tumors
NCT06814496	PHASE1/PHASE2	RECRUITING	Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors
NCT06866964	PHASE2	RECRUITING	A Single-arm, Phase II Clinical Trial of ASPIRin to prEvent Venous Thromboembolism in Patients With Advanced Germ Cell Tumors Receiving Chemotherapy
NCT06932458	PHASE2	RECRUITING	A Clinical Trial of Primary Retroperitoneal Lymph Node Dissection in Patients With Testicular Seminoma With Limited Retroperitoneal Metastases
NCT07407582	PHASE1/PHASE2	RECRUITING	Ph. I/II Sodium Thiosulfate for OtoProtection During Cisplatin (STOP-CIS)
NCT00183820	PHASE2	COMPLETED	Study of Gemcitabine, Oxaliplatin, and Paclitaxel in Patients With Refractory Germ Cell Carcinoma
NCT00531687	PHASE2	TERMINATED	Trial of Paclitaxel, Gemcitabine and Cisplatin in Patients With Relapsing Germ Cell Cancer
NCT00587964	PHASE2	COMPLETED	Phase II Trial of Stereotactic Radiosurgery Boost Following Surgical Resection for Brain Metastases
NCT00772694	PHASE2	UNKNOWN	Sorafenib Monotherapy in Inoperable/Recurrent Germ Cell Carcinoma Refractory to Chemotherapy
NCT00936936	PHASE2	COMPLETED	High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors
NCT00957905	PHASE2	COMPLETED	Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors
NCT01242631	PHASE2	COMPLETED	Everolimus for Patients With Relapsed/Refractory Germ Cell Cancer
NCT01684098	PHASE2	COMPLETED	Safety and Efficacy of FalateScan (Technetium Tc 99m EC20) in Patients With Known Suspected Recurrent or Metastatic Cancer From a Solid Tumor
NCT02478502	PHASE2	TERMINATED	Testis CAB: Cabazitaxel as Salvage Treatment for Cisplatin-resistant Germ Cell Cancer
NCT02643303	PHASE1/PHASE2	COMPLETED	A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers
NCT02689219	PHASE2	TERMINATED	Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
NCT02860819	PHASE2	COMPLETED	Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer
NCT03339635	PHASE2	COMPLETED	Short-term Testosterone Replacement in Testicular Cancer Survivors
NCT04150848	PHASE2	UNKNOWN	A Biobehavioral Intervention for Young Men With Testicular Cancer
NCT07568444	PHASE2	COMPLETED	Enhancing Readability of Lay Abstracts and Summaries for Medical Knowledge Using Generative Artificial Intelligence (BRIDGE AI 3)
NCT01366144	PHASE1	ACTIVE_NOT_RECRUITING	Veliparib, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction
NCT04459273	PHASE1	ACTIVE_NOT_RECRUITING	Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
NCT06515613	PHASE1	RECRUITING	A Phase 1 Study of CTIM-76 in Patients With Recurring Ovarian Cancer and Other Advanced Solid Tumors
NCT06673329	PHASE1	RECRUITING	Brodalumab in the Treatment of Immune-Related Adverse Events
NCT07106827	PHASE1	RECRUITING	A Study of GV20-0251 in Advanced or Refractory Solid Tumors
NCT07118176	PHASE1	RECRUITING	Determining the Biodistribution of an Imaging Tracer (68Ga-FAPi-46) in Patients With Solid Tumors or Hematologic Cancers
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00423254	PHASE1	COMPLETED	Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-PP) for Patients With Advanced Cancer.
NCT01242072	PHASE1	UNKNOWN	Intravenous Palifosfamide-tris in Combination With Etoposide and Carboplatin in Patients With Malignancies
NCT02429466	PHASE1	COMPLETED	Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors
NCT06681870	PHASE1	WITHDRAWN	A Study of ASP1893 in Adults With Advanced CLDN6-positive Solid Tumors
NCT01783145	Not specified	ACTIVE_NOT_RECRUITING	Shared Care Follow-up After Chemotherapy for Testicular Cancer
NCT02012699	Not specified	RECRUITING	Integrated Cancer Repository for Cancer Research
NCT02099734	Not specified	RECRUITING	Germ Cell Tumor and Testicular Tumor DNA Registry
NCT02276430	Not specified	ACTIVE_NOT_RECRUITING	TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
2-MERCAPTOETHANESULFONIC ACID	4	2
BRENTUXIMAB VEDOTIN	4	1
BRODALUMAB	4	1
CABAZITAXEL	4	1
METHADONE	4	1
SODIUM THIOSULFATE	4	1
TARLATAMAB	4	1
TESTOSTERONE	4	1
TREMELIMUMAB	4	1
VELIPARIB	3	4
GUADECITABINE	3	1
FAPI-46 GA-68	2	2
ALVOCIDIB HYDROCHLORIDE	2	1
HILTONOL	2	1
CHEMBL4746472	0	1
PALIFOSFAMIDE TROMETHAMINE	-1	1