Squamous cell carcinoma

Summary

Squamous cell carcinoma (MONDO:0005096) is a cancer (an umbrella term covering 39 Mondo subtypes) with 75 cohort genes (143 GWAS associations across 17 studies; 23 CIViC-evidence somatic drivers; 39 ClinVar predisposition records) and 302 clinical trials. The dominant Reactome pathway is Melanin biosynthesis (3 cohort genes). Molecularly, PIK3CA Q75E confers sensitivity to Alpelisib in Squamous Cell Carcinoma (CIViC Level C); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include cisplatin, panitumumab, and cemiplimab.

At a glance

• Classification: Cancer
• Umbrella term: 39 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 143
• ClinVar variants: 39
• Clinical trials: 302
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	squamous cell carcinoma
Mondo ID	MONDO:0005096
EFO	EFO:0000707
MeSH	D002294
DOID	DOID:1749
NCIT	C2929
SNOMED CT	402815007
UMLS	C0007137
MedGen	2874
Is cancer (heuristic)	yes

Also known as: carcinoma, squamous cell, malignant · epidermoid carcinoma · epidermoid cell cancer · malignant epidermoid cell neoplasm · malignant epidermoid cell tumor · malignant epidermoid cell tumour · malignant squamous cell neoplasm · malignant squamous cell tumor · malignant squamous cell tumour · squamous carcinoma · squamous cell cancer · squamous cell carcinoma · squamous cell carcinoma (morphologic abnormality) · squamous cell carcinoma NOS (morphologic abnormality) · squamous cell epithelioma

Data availability: 39 ClinVar variants · 143 GWAS associations (17 studies) · 3 cell lines.

Disease family

An umbrella term covering 39 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › squamous cell neoplasm › squamous cell carcinoma

Related subtypes (6): vaginal squamous tumor, vulvar squamous neoplasm, ovarian squamous cell neoplasm, craniopharyngioma, squamous cell intraepithelial neoplasia, ocular surface squamous neoplasia

Subtypes (39): bone squamous cell carcinoma, prostate squamous cell carcinoma, trachea squamous cell carcinoma, scrotum squamous cell carcinoma, skin squamous cell carcinoma, bladder squamous cell carcinoma, urethra squamous cell carcinoma, papillary squamous carcinoma, basaloid squamous cell carcinoma, pseudoglandular squamous cell carcinoma, thymus squamous cell carcinoma, ovarian squamous cell carcinoma, renal pelvis squamous cell carcinoma, ureter squamous cell carcinoma, fallopian tube squamous cell carcinoma, squamous carcinoma in situ, keratinizing squamous cell carcinoma, squamous cell lung carcinoma, esophageal squamous cell carcinoma, squamous cell breast carcinoma, adenosquamous carcinoma, cervical squamous cell carcinoma, colorectal squamous cell carcinoma, endometrial squamous cell carcinoma, gallbladder squamous cell carcinoma, gastric squamous cell carcinoma, thyroid gland squamous cell carcinoma, vaginal squamous cell carcinoma, head and neck squamous cell carcinoma, squamous cell carcinoma of the corpus uteri, squamous cell carcinoma of penis, squamous cell carcinoma of the small intestine, squamous cell carcinoma of pancreas, squamous cell carcinoma of liver and intrahepatic biliary tract, human papillomavirus-related squamous cell carcinoma, sarcomatoid squamous cell carcinoma, vulvar squamous cell carcinoma, metastatic squamous cell carcinoma, pure squamous carcinoma of the urothelial tract

Genetics & variants

GWAS landscape

143 GWAS associations across 17 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12203592	3e-238	IRF4	C	0.47
rs1805007	1e-146	MC1R	C	0.43
rs11018564	1e-129	TYR - NOX4	C
rs2153271	3e-123	BNC2	T
rs7498985	6e-84	GAS8	A
rs62211989	5e-57	TPM3P2 - PIGPP3	G	0.29
rs117132860	4e-56	AHR	A
rs16891982	2e-52	SLC45A2	C	0.57
rs7713279	5e-50	ADAMTS12 - RXFP3	G
rs1126809	5e-49	TYR	G	0.17
rs2737205	4e-48	TRPS1	C
rs2797305	3e-45	DUSP22 - IRF4	T
rs4268748	2e-44	DEF8	C	1.33
rs3213737	6e-38	HAL	A
rs7534124	8e-36	CTSS - CTSK	T
rs1830298	1e-33	CASP8, FLACC1	T
rs72928038	2e-33	BACH2	A
rs62209647	9e-30	TPM3P2 - PIGPP3	C	1.32
rs12350739	3e-26	BNC2 - RN7SL720P	G	0.11
rs35563099	5e-26	LINC02674 - RAB11FIP2	T
rs607860	1e-24	KRT5	T
rs3742233	3e-23	ATP11A	A
rs4822983	2e-22	CHEK2	T	1.27
rs6689641	2e-22	SLC6A17	G
rs12913832	5e-22	HERC2	A	0.12
rs1800440	1e-21	CYP1B1	C
rs6059655	9e-21	RALY	A	1.32
rs35063026	1e-20	SPATA33	T	1.33
rs6790260	1e-20	LPP	C	0.11
rs4785204	2e-20	HEATR3	T	1.24

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475583	Verma A	2024	19,217	419,674	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST008872	Liyanage UE	2019	9,674	625,657	Combined analysis of keratinocyte cancers identifies novel genome-wide loci.
GCST90137412	Seviiri M	2022	7,402	286,892	A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma.
GCST003327	Asgari MM	2016	6,891	54,566	Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma.
GCST002466	Wang Y	2014	3,442	15,861	Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
GCST001718	Jin G	2012	2,331	4,006	Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.
GCST004134	Pardo LM	2017	2,106	0	Genome-Wide Association Studies of Multiple Keratinocyte Cancers.
GCST001674	Wu C	2012	2,031	2,044	Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
GCST90503208	Mo M	2024	1,928	7,712	Shared genetic factors and the interactions with fresh fruit intake contributes to four types squamous cell carcinomas.
GCST002010	Wu C	2013	1,331	0	Genome-wide association study identifies common variants in SLC39A6 associated with length of survival in esophageal squamous-cell carcinoma.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	6
Tier 2: splice/UTR	4
Tier 3: regulatory	3
Tier 4: intronic/intergenic	37

MAF distribution

Bucket	Variants
common (>=0.05)	44
low_freq (0.01-0.05)	2
rare (<0.01)	3
unknown	1

Functional consequences

Consequence	Count
intron_variant	24
intergenic_variant	9
missense_variant	5
3_prime_UTR_variant	3
non_coding_transcript_exon_variant	2
unknown	2
regulatory_region_variant	2
TF_binding_site_variant	1
stop_gained	1
splice_polypyrimidine_tract_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12203592	6	396321	C>G,T	0.16	intron_variant	IRF4	3e-238	Tier 4: intronic/intergenic
rs1805007	16	89919709	C>A,G,T	0.082	missense_variant	MC1R	1e-146	Tier 1: coding
rs11018564	11	89301966	T>A,C,G	0.05	intergenic_variant	TYR - NOX4	1e-129	Tier 4: intronic/intergenic
rs2153271	9	16864523	C>A,G,T	0.05	intron_variant	BNC2	3e-123	Tier 4: intronic/intergenic
rs7498985	16	90036709	G>A	0.05	intron_variant	GAS8	6e-84	Tier 4: intronic/intergenic
rs62211989	20	33950585	G>C	0.076	intergenic_variant	TPM3P2 - PIGPP3	5e-57	Tier 4: intronic/intergenic
rs117132860	7	17095084	G>A,C,T		intron_variant	AHR	4e-56	Tier 4: intronic/intergenic
rs16891982	5	33951588	C>A,G	0.038	missense_variant	SLC45A2	2e-52	Tier 1: coding
rs7713279	5	33928797	T>A,G	0.05	intergenic_variant	ADAMTS12 - RXFP3	5e-50	Tier 4: intronic/intergenic
rs1126809	11	89284793	G>A	0.283	missense_variant	TYR	5e-49	Tier 1: coding
rs2737205	8	115597953	T>C	0.05	intron_variant	TRPS1	4e-48	Tier 4: intronic/intergenic
rs2797305	6	390658	C>T	0.05	intron_variant	DUSP22 - IRF4	3e-45	Tier 4: intronic/intergenic
rs4268748	16	89960104	T>C	0.26	intron_variant	DEF8	2e-44	Tier 4: intronic/intergenic
rs3213737	12	95986028	G>A,C,T	0.05	intron_variant	HAL	6e-38	Tier 4: intronic/intergenic
rs7534124	1	150766597	C>T	0.05	intergenic_variant	CTSS - CTSK	8e-36	Tier 4: intronic/intergenic
rs1830298	2	201316524	C>G,T	0.05	intron_variant	CASP8, FLACC1	1e-33	Tier 4: intronic/intergenic
rs72928038	6	90267049	G>A	0.05	intron_variant	BACH2	2e-33	Tier 4: intronic/intergenic
rs62209647	20	33917852	G>C	0.059	intron_variant	TPM3P2 - PIGPP3	9e-30	Tier 4: intronic/intergenic
rs12350739	9	16885019	G>A,C,T	0.435	TF_binding_site_variant	BNC2 - RN7SL720P	3e-26	Tier 3: regulatory
rs35563099	10	117812892	C>T	0.05	intron_variant	LINC02674 - RAB11FIP2	5e-26	Tier 4: intronic/intergenic
rs607860	12	52519245	C>A,T	0.05	non_coding_transcript_exon_variant	KRT5	1e-24	Tier 4: intronic/intergenic
rs3742233	13	112883134	G>A,C	0.05	3_prime_UTR_variant	ATP11A	3e-23	Tier 2: splice/UTR
rs4822983	22	28719078	C>T	0.2	intron_variant	CHEK2	2e-22	Tier 4: intronic/intergenic
rs6689641	1	110177778	A>C,G	0.05	non_coding_transcript_exon_variant	SLC6A17	2e-22	Tier 4: intronic/intergenic
rs12913832	15	28120472	A>C,G	0.241	intron_variant	HERC2	5e-22	Tier 4: intronic/intergenic
rs1800440	2	38070996	T>A,C,G	0.05	missense_variant	CYP1B1	1e-21	Tier 1: coding
rs6059655	20	34077942	A>G	0.08	intron_variant	RALY	9e-21	Tier 4: intronic/intergenic
rs35063026	16	89669749	C>G,T	0.05	3_prime_UTR_variant	SPATA33	1e-20	Tier 2: splice/UTR
rs6790260	3	188399291	C>G,T	0.454	intron_variant	LPP	1e-20	Tier 4: intronic/intergenic
rs4785204	16	50069823	C>T	0.26	intron_variant	HEATR3	2e-20	Tier 4: intronic/intergenic

ClinVar germline variants

39 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 4 benign, 2 pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2431072	NM_000321.3(RB1):c.1172C>G (p.Ser391Ter)	RB1	Pathogenic	criteria provided, single submitter
12353	NM_000546.6(TP53):c.469G>T (p.Val157Phe)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
186451	NM_000546.6(TP53):c.527G>A (p.Cys176Tyr)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
2394713	NM_014883.4(FAM13A):c.2465C>T (p.Pro822Leu)	FAM13A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301439	NM_000314.8(PTEN):c.*667A>T	PTEN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2431106	NM_033274.5(ADAM19):c.252-190C>A	ADAM19	Uncertain significance	criteria provided, single submitter
2431107	NM_033274.5(ADAM19):c.252-193T>G	ADAM19	Uncertain significance	criteria provided, single submitter
2431108	NM_207517.3(ADAMTSL3):c.2490+210C>G	ADAMTSL3	Uncertain significance	criteria provided, single submitter
2431109	NM_207517.3(ADAMTSL3):c.2490+207A>C	ADAMTSL3	Uncertain significance	criteria provided, single submitter
2431115	NM_207517.3(ADAMTSL3):c.1700+350A>T	ADAMTSL3	Uncertain significance	criteria provided, single submitter
2431120	NM_001382430.1(AKT1):c.633+300T>C	AKT1	Uncertain significance	criteria provided, single submitter
2431149	NM_000038.6(APC):c.1743+254T>C	APC	Uncertain significance	criteria provided, single submitter
2431126	NM_203416.4(CD163):c.1100-317C>A	CD163	Uncertain significance	criteria provided, single submitter
2431112	NM_000743.5(CHRNA3):c.267+14C>T	CHRNA3	Uncertain significance	criteria provided, single submitter
2431164	NM_000745.4(CHRNA5):c.*747T>C	CHRNA3	Uncertain significance	criteria provided, single submitter
2431083	NM_005228.5(EGFR):c.3114+101A>G	EGFR	Uncertain significance	criteria provided, single submitter
2431104	NM_005228.5(EGFR):c.2701+77T>G	EGFR	Uncertain significance	criteria provided, single submitter
2431156	NM_005228.5(EGFR):c.*2368G>T	EGFR	Uncertain significance	criteria provided, single submitter
2431168	NM_001964.3(EGR1):c.-205G>A	EGR1	Uncertain significance	criteria provided, single submitter
2431148	NM_002019.4(FLT1):c.64+22G>T	FLT1	Uncertain significance	criteria provided, single submitter
2431186	NM_002019.4(FLT1):c.513+216C>T	FLT1	Uncertain significance	criteria provided, single submitter
2431159	NM_014491.4(FOXP2):c.2003+2748G>A	FOXP2	Uncertain significance	criteria provided, single submitter
2431071	NM_000455.5(STK11):c.464+140dup	LOC110006318	Uncertain significance	criteria provided, single submitter
2431065	NM_000249.4(MLH1):c.116+1017T>A	MLH1	Uncertain significance	criteria provided, single submitter
2431151	NM_001304359.2(MUC5AC):c.10898C>T (p.Ala3633Val)	MUC5AC	Uncertain significance	criteria provided, single submitter
2431157	NM_001304359.2(MUC5AC):c.6811G>T (p.Ala2271Ser)	MUC5AC	Uncertain significance	criteria provided, single submitter
2431165	NM_001304359.2(MUC5AC):c.7411G>C (p.Ala2471Pro)	MUC5AC	Uncertain significance	criteria provided, single submitter
2431155	NM_001079668.3(NKX2-1):c.*726G>C	NKX2-1	Uncertain significance	criteria provided, single submitter
2431110	NM_001243133.2(NLRP3):c.398-24C>G	NLRP3	Uncertain significance	criteria provided, single submitter
2431166	NM_024832.5(RIN3):c.-7C>A	RIN3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 164 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
BRCA2	BRCA2	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
NFE2L2	Act	BLCA,CESC,ESCA,HCC,HNSC,LUSC,NSCLC,PRCC,UCEC	CIViC #3878
ROS1	LoF	HCC,HNSC,OVT,PRAD,STAD	CIViC #4941
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
NKX2-1	LoF	LGGNOS	CIViC #80
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
TYR			CIViC #5972
BACH2			CIViC #14160
TP63	LoF	BLCA,CESC,HNSC,MEL,NBL
CHEK2	Act	BRCA	CIViC #8950
TUBB3			CIViC #8262
TET2	LoF	AML,MDS,MLYM,NHL,PCM,RCC,SOFT_TISSUE	CIViC #55
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
FOXP1	LoF	BRCA,PRAD	CIViC #56
AKT1	Act	ALL,BRCA,CESC,COADREAD,PRAD,PROSTATE,SARCNOS,UCEC,WDTC	CIViC #2
HLA-DQA1	Act	PLMESO
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66
IRF4	Act	CLLSLL,DLBCLNOS,MLYM,NHL,PCM	CIViC #3043
MLH1			CIViC #3532
PRKN			CIViC #4103
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
RB1	LoF	ACC,BLADDER,BLCA,BRCA,CESC,ESCA,GB,GBM,GIST,HCC,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MEL,MT,NSCLC,OS,OVT,PANCREAS,PCM,PRAD,PROSTATE,RBL,SCLC,SKCM,SOFT_TISSUE,STAD,STOMACH,UCEC,UCS	CIViC #4795

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
NFE2L2	Orphanet:619979	Developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome
ROS1	Orphanet:251579	Giant cell glioblastoma
ROS1	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
SRC	Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis
STK11	Orphanet:2869	Peutz-Jeghers syndrome
NKX2-1	Orphanet:1429	Benign hereditary chorea
NKX2-1	Orphanet:146	Differentiated thyroid carcinoma
NKX2-1	Orphanet:209905	Brain-lung-thyroid syndrome
NKX2-1	Orphanet:95713	Athyreosis
TLR4	Orphanet:117	Behçet 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

Cohort genes → proteins

75 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	48
civic_only	2
multi_evidence	25

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
NFE2L2	HGNC:7782	ENSG00000116044	Q16236	Nuclear factor erythroid 2-related factor 2	civic_evidence
ROS1	HGNC:10261	ENSG00000047936	P08922	Proto-oncogene tyrosine-protein kinase ROS	clinvar
ST6GAL1	HGNC:10860	ENSG00000073849	P15907	Beta-galactoside alpha-2,6-sialyltransferase 1	gwas
ST3GAL1	HGNC:10862	ENSG00000008513	Q11201	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 1	gwas
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas
SP4	HGNC:11209	ENSG00000105866	Q02446	Transcription factor Sp4	gwas
SRC	HGNC:11283	ENSG00000197122	P12931	Proto-oncogene tyrosine-protein kinase Src	gwas
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
NKX2-1	HGNC:11825	ENSG00000136352	P43699	Homeobox protein Nkx-2.1	clinvar
TLR4	HGNC:11850	ENSG00000136869	O00206	Toll-like receptor 4	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
TRPS1	HGNC:12340	ENSG00000104447	Q9UHF7	Zinc finger transcription factor Trps1	gwas
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	gwas
XBP1	HGNC:12801	ENSG00000100219	P17861	X-box-binding protein 1	gwas
FOXP2	HGNC:13875	ENSG00000128573	O15409	Forkhead box protein P2	clinvar
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	gwas
FLACC1	HGNC:14439	ENSG00000155749	Q96Q35	Flagellum-associated coiled-coil domain-containing protein 1	gwas
ADAMTSL3	HGNC:14633	ENSG00000156218	P82987	ADAMTS-like protein 3	clinvar
ERBIN	HGNC:15842	ENSG00000112851	Q96RT1	Erbin	gwas
RALY	HGNC:15921	ENSG00000125970	Q9UKM9	RNA-binding protein Raly	gwas
TP63	HGNC:15979	ENSG00000073282	Q9H3D4	Tumor protein 63	gwas
CD163	HGNC:1631	ENSG00000177575	Q86VB7	Scavenger receptor cysteine-rich type 1 protein M130	clinvar
NLRP3	HGNC:16400	ENSG00000162711	Q96P20	NACHT, LRR and PYD domains-containing protein 3	clinvar
SLC45A2	HGNC:16472	ENSG00000164175	Q9UMX9	Membrane-associated transporter protein	gwas
TPM3P2	HGNC:16556	ENSG00000214200		tropomyosin 3 pseudogene 2	gwas
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	gwas
DTNBP1	HGNC:17328	ENSG00000047579	Q96EV8	Dysbindin	gwas
SMG6	HGNC:17809	ENSG00000070366	Q86US8	Telomerase-binding protein EST1A	gwas
SLC39A6	HGNC:18607	ENSG00000141424	Q13433	Zinc transporter ZIP6	gwas
RIN3	HGNC:18751	ENSG00000100599	Q8TB24	Ras and Rab interactor 3	clinvar
FAM13A	HGNC:19367	ENSG00000138640	O94988	Protein FAM13A	clinvar
CHRNA3	HGNC:1957	ENSG00000080644	P32297	Neuronal acetylcholine receptor subunit alpha-3	clinvar
ADAM19	HGNC:197	ENSG00000135074	Q9H013	Disintegrin and metalloproteinase domain-containing protein 19	clinvar
FRY	HGNC:20367	ENSG00000073910	Q5TBA9	Protein furry homolog	gwas
TUBB3	HGNC:20772	ENSG00000258947	Q13509	Tubulin beta-3 chain	gwas
LRFN2	HGNC:21226	ENSG00000156564	Q9ULH4	Leucine-rich repeat and fibronectin type-III domain-containing protein 2	gwas
HAPLN3	HGNC:21446	ENSG00000140511	Q96S86	Hyaluronan and proteoglycan link protein 3	gwas
CNTLN	HGNC:23432	ENSG00000044459	Q9NXG0	Centlein	gwas
TPRG1	HGNC:24759	ENSG00000188001	Q6ZUI0	Tumor protein p63-regulated gene 1 protein	gwas
TET2	HGNC:25941	ENSG00000168769	Q6N021	Methylcytosine dioxygenase TET2	clinvar
DEF8	HGNC:25969	ENSG00000140995	Q6ZN54	Differentially expressed in FDCP 8 homolog	gwas
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gwas
SPATA33	HGNC:26463	ENSG00000167523	Q96N06	Spermatogenesis-associated protein 33	gwas
SEC16A	HGNC:29006	ENSG00000148396	O15027	Protein transport protein Sec16A	gwas
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	gwas
BNC2	HGNC:30988	ENSG00000173068	Q6ZN30	Zinc finger protein basonuclin-2	gwas
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	clinvar
EGR1	HGNC:3238	ENSG00000120738	P18146	Early growth response protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
NFE2L2	Nuclear factor erythroid 2-related factor 2	Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes the…
ROS1	Proto-oncogene tyrosine-protein kinase ROS	Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium.
ST6GAL1	Beta-galactoside alpha-2,6-sialyltransferase 1	Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.
ST3GAL1	CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 1	A beta-galactoside alpha2->3 sialyltransferase involved in terminal sialylation of glycoproteins and glycolipids.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SP4	Transcription factor Sp4	Binds to GT and GC boxes promoters elements.
SRC	Proto-oncogene tyrosine-protein kinase Src	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G…
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…
NKX2-1	Homeobox protein Nkx-2.1	Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor.
TLR4	Toll-like receptor 4	Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TRPS1	Zinc finger transcription factor Trps1	Transcriptional repressor.
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
XBP1	X-box-binding protein 1	Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR).
FOXP2	Forkhead box protein P2	Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
ERBIN	Erbin	Acts as an adapter for the receptor ERBB2, in epithelia.
RALY	RNA-binding protein Raly	RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver.
TP63	Tumor protein 63	Acts as a sequence specific DNA binding transcriptional activator or repressor.
CD163	Scavenger receptor cysteine-rich type 1 protein M130	Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage.
NLRP3	NACHT, LRR and PYD domains-containing protein 3	Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis.
SLC45A2	Membrane-associated transporter protein	Proton-associated glucose and sucrose transporter.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
DTNBP1	Dysbindin	Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes.
SMG6	Telomerase-binding protein EST1A	Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
SLC39A6	Zinc transporter ZIP6	Zinc-influx transporter which plays a role in zinc homeostasis and in the induction of epithelial-to-mesenchymal transition (EMT).
RIN3	Ras and Rab interactor 3	Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP.
CHRNA3	Neuronal acetylcholine receptor subunit alpha-3	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
ADAM19	Disintegrin and metalloproteinase domain-containing protein 19	Participates in the proteolytic processing of beta-type neuregulin isoforms which are involved in neurogenesis and synaptogenesis, suggesting a regulatory role in glial cell.
FRY	Protein furry homolog	Plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity by promoting PLK1 activity at the spindle poles in early mitosis.
TUBB3	Tubulin beta-3 chain	Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers.
LRFN2	Leucine-rich repeat and fibronectin type-III domain-containing protein 2	Promotes neurite outgrowth in hippocampal neurons.
HAPLN3	Hyaluronan and proteoglycan link protein 3	May function in hyaluronic acid binding.
CNTLN	Centlein	Required for centrosome cohesion and recruitment of CEP68 to centrosomes.
TET2	Methylcytosine dioxygenase TET2	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
DEF8	Differentially expressed in FDCP 8 homolog	Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts.
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).
SPATA33	Spermatogenesis-associated protein 33	Plays an important role in sperm motility and male fertility.
SEC16A	Protein transport protein Sec16A	Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER).
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.
BNC2	Zinc finger protein basonuclin-2	Probable transcription factor specific for skin keratinocytes.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
EGR1	Early growth response protein 1	Transcriptional regulator.
FLT1	Vascular endothelial growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage funct…
FOXP1	Forkhead box protein P1	Transcriptional repressor.
AKT1	RAC-alpha serine/threonine-protein kinase	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
HERC2	E3 ubiquitin-protein ligase HERC2	E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes.
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.

Protein-family classification

Druggable: 27 · Difficult: 18 · Unknown: 30 · Druggable fraction: 0.36

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	8	3.0×	0.066
Phosphatase	4	4.5×	0.074
Complement	2	7.2×	0.101
Transcription factor	15	1.6×	0.101
Transporter	2	2.1×	0.511
Antibody/Immunoglobulin	4	1.6×	0.511
Ion channel	1	1.5×	0.843
Other/Unknown	30	0.7×	0.998
Scaffold/PPI	3	0.7×	0.998
GPCR	2	0.6×	0.998
Protease	1	0.5×	0.998
Enzyme (other)	3	0.5×	0.998

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
NFE2L2	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
ROS1	Kinase	yes	2.7.10.1	LDLR_classB_rpt, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ST6GAL1	Enzyme (other)	yes	2.4.99.1	Glyco_trans_29, Sialyl_trans, GT29-like_sf
ST3GAL1	Enzyme (other)	yes	2.4.99.2	Glyco_trans_29, Sialyl_trans, GT29-like_sf
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SP4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sp4-like
SRC	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
NKX2-1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
TLR4	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TRPS1	Transcription factor	no		Znf_GATA, Znf_C2H2_type, Znf_NHR/GATA
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
XBP1	Transcription factor	no		bZIP, bZIP_sf, ER_Stress-Reg_TF
FOXP2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
FLACC1	Other/Unknown	no		FLACC1
ADAMTSL3	Antibody/Immunoglobulin	yes		TSP1_rpt, Ig_sub2, Ig_sub
ERBIN	Scaffold/PPI	no		PDZ, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
RALY	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, hnRNP_C
TP63	Transcription factor	no		SAM, p53_tumour_suppressor, p53-like_TF_DNA-bd_sf
CD163	Other/Unknown	no		SRCR, SRCR-like_dom_sf
NLRP3	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase
SLC45A2	Transporter	yes		MFS, MFS_trans_sf
TPM3P2	Other/Unknown	no
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
DTNBP1	Other/Unknown	no		Dysbindin
SMG6	Other/Unknown	no		PIN_dom, TPR-like_helical_dom_sf, DNA/RNA-bd_Est1-type
SLC39A6	Transporter	yes		ZIP, ZIP_Transporter
RIN3	Scaffold/PPI	no		RA_dom, SH2, VPS9
FAM13A	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, FAM13
CHRNA3	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
ADAM19	Protease	yes		EGF, Peptidase_M12B, Disintegrin_dom
FRY	Other/Unknown	no		Cell_Morphogen_C, Cell_morpho_N, MOR2-PAG1_mid
TUBB3	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
LRFN2	Antibody/Immunoglobulin	yes		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
HAPLN3	Antibody/Immunoglobulin	yes		Link_dom, Ig_sub, Ig-like_dom
CNTLN	Other/Unknown	no		CNTLN
TPRG1	Phosphatase	yes		Inositol_phosphatase, hSac2, TPRG1-like
TET2	Other/Unknown	no		2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase
DEF8	Other/Unknown	no		PKC_DAG/PE, RH_dom, C1-like_sf
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like
SPATA33	Other/Unknown	no		DUF4609
SEC16A	Other/Unknown	no		Sec16_Sec23-bd, Sec16_CCD
DNAH11	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
BNC2	Transcription factor	no		Znf_C2H2_type, Disconnected-like
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
EGR1	Transcription factor	no		Znf_C2H2_type, EGR1_C, EGR_N

Expression context

Cohort genes with no expression data: 0.

71 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)	3
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	7
ventricular zone	6
monocyte	6
ganglionic eminence	5
calcaneal tendon	5
pigmented layer of retina	5
granulocyte	5
epithelium of nasopharynx	4
secondary oocyte	4
leukocyte	4
cortical plate	4
sural nerve	4
primordial germ cell in gonad	4
stromal cell of endometrium	4
blood	4
upper leg skin	3
gall bladder	3
hindlimb stylopod muscle	3
left testis	3
right testis	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
NFE2L2	295	ubiquitous	marker	epithelium of nasopharynx, pharyngeal mucosa, oral cavity
ROS1	79	tissue_specific	marker	upper lobe of left lung, upper lobe of lung, corpus epididymis
ST6GAL1	294	ubiquitous	marker	liver, right lobe of liver, renal medulla
ST3GAL1	253	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SP4	265	ubiquitous	marker	cerebellar vermis, germinal epithelium of ovary, superficial temporal artery
SRC	236	ubiquitous	marker	body of stomach, gall bladder, rectum
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
NKX2-1	101	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TLR4	233	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TRPS1	284	ubiquitous	marker	mammary duct, epithelium of mammary gland, calcaneal tendon
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
XBP1	167	broad	marker	body of pancreas, trachea, pancreas
FOXP2	237	broad	marker	buccal mucosa cell, tibialis anterior, mucosa of paranasal sinus
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
BACH2	237	ubiquitous	marker	cortical plate, sural nerve, epithelium of nasopharynx
FLACC1	168	tissue_specific	marker	right uterine tube, bronchial epithelial cell, bronchus
ADAMTSL3	218	broad	marker	calcaneal tendon, descending thoracic aorta, thoracic aorta
ERBIN	296	ubiquitous	marker	corpus callosum, lateral globus pallidus, cranial nerve II
RALY	294	ubiquitous	marker	ganglionic eminence, granulocyte, ventricular zone
TP63	207	broad	marker	upper leg skin, skin of hip, upper arm skin
CD163	243	broad	marker	right lung, mucosa of stomach, lower lobe of lung
NLRP3	172	broad	marker	monocyte, mononuclear cell, leukocyte
SLC45A2	100	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, primordial germ cell in gonad
TPM3P2	6		marker	male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius, muscle of leg
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
DTNBP1	249	ubiquitous	marker	tendon of biceps brachii, nucleus accumbens, putamen
SMG6	201	ubiquitous	marker	stromal cell of endometrium, left ovary, right testis

Protein interactions among cohort

Intra-cohort edges: 66.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
AKT1	16,601
PTEN	11,626
SRC	11,608
PRKN	10,281
TLR4	6,974
TUBB3	6,797
EGR1	5,209
STK11	5,146

Intra-cohort edges

A	B	Sources
ADAM19	FAM13A	string_interaction
ADAM19	SRC	intact
AKT1	EGR1	string_interaction
AKT1	NKX2-1	intact
AKT1	PTEN	string_interaction
AKT1	ROS1	intact
APEX1	NFE2L2	intact
APEX1	TP53	string_interaction
BACH2	IRF4	string_interaction
BACH2	PTPN2	string_interaction
BACH2	XBP1	string_interaction
BNC2	DEF8	string_interaction
BNC2	MC1R	string_interaction
BNC2	OCA2	string_interaction
BNC2	SLC45A2	string_interaction
BNC2	TYR	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	MLH1	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
CHEK2	TP53	intact, string_interaction
CHEK2	TP63	biogrid_interaction, intact
CHRNA3	FAM13A	string_interaction
DEF8	MC1R	string_interaction
DEF8	RALY	string_interaction
DEF8	SERPINA1	intact
DEF8	SLC45A2	string_interaction
DEF8	SPATA33	string_interaction
DEF8	TUBB3	biogrid_interaction
DTNBP1	SP4	string_interaction
EGFR	ERBIN	string_interaction
EGFR	HEATR3	intact
EGFR	KRT5	string_interaction
EGFR	PTEN	string_interaction
EGFR	SRC	intact
EGR1	TP53	intact, string_interaction
FAM13A	RIN3	string_interaction
FAM13A	SERPINA1	string_interaction
FGFR3	TET2	intact
FLACC1	SRC	intact
FOXP1	FOXP2	biogrid_interaction, intact
FOXP1	TP53	biogrid_interaction
FOXP2	NKX2-1	string_interaction
FOXP2	SP4	biogrid_interaction, intact
HEATR3	ST6GAL1	biogrid_interaction
HERC2	OCA2	string_interaction
HERC2	STK11	string_interaction
IRF4	SLC45A2	string_interaction
KRT5	NKX2-1	string_interaction
KRT5	TP63	string_interaction

Structural data

PDB: 46 · AlphaFold-only: 25 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EGFR	P00533	388
TP53	P04637	313
SRC	P12931	79
APEX1	P27695	67
SERPINA1	P01009	46
AKT1	P31749	43
CHEK2	O96017	38
APC	P25054	31
TUBB3	Q13509	28
HLA-DQA1	P01909	28
TP63	Q9H3D4	26
NLRP3	Q96P20	24
NFE2L2	Q16236	23
PRKN	O60260	21
IRF4	Q15306	19
RB1	P06400	19
FGFR3	P22607	15
TLR4	O00206	15
HERC2	O95714	15
BRCA2	P51587	14
CD163	Q86VB7	14
MUC5AC	P98088	14
PTPN2	P17706	14
FLT1	P17948	12
PTEN	P60484	12
ERBIN	Q96RT1	11
MLH1	P40692	7
TET2	Q6N021	6
ROS1	P08922	5
XBP1	P17861	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRF1	P14222	91.01
ST3GAL1	Q11201	89.97
PPP2R2C	Q9Y2T4	89.53
HAPLN3	Q96S86	87.85
HEATR3	Q7Z4Q2	83.07
SLC45A2	Q9UMX9	77.96
DEF8	Q6ZN54	76.04
FLACC1	Q96Q35	75.95
DTNBP1	Q96EV8	75.92
TPRG1	Q6ZUI0	73.90
OCA2	Q04671	73.79
CNTLN	Q9NXG0	71.14
LRFN2	Q9ULH4	70.36
ADAM19	Q9H013	69.93
SPATA33	Q96N06	66.26
ADAMTSL3	P82987	65.99
FAM13A	O94988	61.00
LPP	Q93052	60.99
SLC39A6	Q13433	60.04
BNC2	Q6ZN30	54.10
TRPS1	Q9UHF7	49.12
SEC16A	O15027	41.07
SP4	Q02446	39.58
FRY	Q5TBA9
DNAH11	Q96DT5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 596. Enrichment computed across 75 evidence-associated genes (52 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 52 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	3	131.8×	5e-04	TYR, SLC45A2, OCA2
Signaling by ERBB2	4	26.6×	0.004	SRC, ERBIN, EGFR, AKT1
Regulation of TP53 Activity through Association with Co-factors	3	47.1×	0.006	TP53, TP63, AKT1
Developmental Lineage of Mammary Gland Myoepithelial Cells	3	31.4×	0.013	TP63, EGFR, KRT5
Disease	13	3.3×	0.013	ST6GAL1, ST3GAL1, BRCA2, SRC, ADAMTSL3, CD163, TUBB3, AKT1 (+5 more)
Termination of O-glycan biosynthesis	3	28.6×	0.015	ST6GAL1, ST3GAL1, MUC5AC
Downregulation of ERBB2 signaling	3	22.0×	0.028	ERBIN, EGFR, AKT1
Maturation of protein 3a	2	48.8×	0.033	ST6GAL1, ST3GAL1
Nuclear events stimulated by ALK signaling in cancer	3	18.8×	0.033	IRF4, PRF1, RB1
Regulation of TP53 Degradation	3	16.9×	0.033	TP53, CHEK2, AKT1
O-linked glycosylation	4	11.1×	0.033	ST6GAL1, ST3GAL1, ADAMTSL3, MUC5AC
TP53 Regulates Metabolic Genes	4	10.0×	0.033	TP53, TP63, AKT1, PTEN
Activation of PUMA and translocation to mitochondria	2	43.9×	0.033	TP53, TP63
Negative regulation of the PI3K/AKT network	3	16.1×	0.033	SRC, AKT1, PTEN
Ovarian tumor domain proteases	3	16.1×	0.033	TP53, APC, PTEN
TP53 Regulates Transcription of Caspase Activators and Caspases	2	36.6×	0.039	TP53, TP63
TP53 Regulates Transcription of Death Receptors and Ligands	2	36.6×	0.039	TP53, TP63
Positive Regulation of CDH1 Gene Transcription	2	36.6×	0.039	FOXP2, RB1
Post-translational protein modification	9	3.3×	0.039	ST6GAL1, ST3GAL1, ADAMTSL3, TUBB3, SEC16A, APC, MUC5AC, NFE2L2 (+1 more)
Translation of Structural Proteins	2	33.8×	0.043	ST6GAL1, ST3GAL1
Transport to the Golgi and subsequent modification	4	7.9×	0.043	ST6GAL1, TUBB3, SEC16A, SERPINA1
Asparagine N-linked glycosylation	5	5.8×	0.043	ST6GAL1, ST3GAL1, TUBB3, SEC16A, SERPINA1
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	2	29.3×	0.045	TP53, TP63
Stabilization of p53	2	29.3×	0.045	TP53, CHEK2
Developmental Lineage of Mammary Stem Cells	2	29.3×	0.045	TP63, KRT5
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	4	7.4×	0.045	SRC, EGFR, FGFR3, AKT1
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	2	25.8×	0.053	TP53, RB1
Signaling by ERBB2 ECD mutants	2	25.8×	0.053	ERBIN, EGFR
Reproduction	3	11.0×	0.053	BRCA2, TET2, MLH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 67 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
melanin biosynthetic process from tyrosine	3	188.6×	3e-04	TYR, SLC45A2, OCA2
positive regulation of transcription by RNA polymerase II	17	3.8×	8e-04	NKX2-1, TLR4, TP53, XBP1, TP63, NLRP3, TET2, EGFR (+9 more)
melanin biosynthetic process	3	58.0×	0.003	TYR, MC1R, OCA2
cellular response to fluid shear stress	3	58.0×	0.003	SRC, XBP1, NFE2L2
positive regulation of gene expression via chromosomal CpG island demethylation	3	53.9×	0.003	TET2, EGR1, APEX1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4	29.6×	0.003	BRCA2, TP53, TP63, CHEK2
gene expression	7	8.3×	0.003	NKX2-1, TLR4, FOXP2, CSMD1, EGFR, AKT1, NFE2L2
positive regulation of gene expression	9	5.2×	0.008	NKX2-1, TLR4, TP53, DTNBP1, ADAM19, EGR1, AKT1, NFE2L2 (+1 more)
response to UV-A	2	125.8×	0.012	EGFR, AKT1
N-acetylneuraminate metabolic process	2	100.6×	0.015	ST6GAL1, ST3GAL1
lysosomal lumen pH elevation	2	100.6×	0.015	SLC45A2, OCA2
epidermal growth factor receptor signaling pathway	4	14.8×	0.015	SRC, ERBIN, EGFR, AKT1
cellular response to gamma radiation	3	26.9×	0.015	TP53, CHEK2, EGR1
cellular response to xenobiotic stimulus	4	14.4×	0.015	TP53, CHEK2, NFE2L2, RB1
response to insulin-like growth factor stimulus	2	83.8×	0.016	XBP1, AKT1
cellular response to vascular endothelial growth factor stimulus	3	25.1×	0.016	XBP1, FLT1, AKT1
DNA damage response	7	5.6×	0.016	STK11, TP53, TP63, CHEK2, FOXP1, HERC2, APC
phosphatidylinositol 3-kinase/protein kinase B signal transduction	4	12.6×	0.018	XBP1, EGFR, AKT1, PTEN
negative regulation of cell cycle G1/S phase transition	2	71.9×	0.019	APC, PTEN
negative regulation of transcription by RNA polymerase II	12	3.2×	0.019	SRC, NKX2-1, TP53, TRPS1, XBP1, BACH2, RALY, TP63 (+4 more)
vascular endothelial growth factor receptor signaling pathway	3	21.6×	0.019	SRC, XBP1, FLT1
osteoclast development	2	62.9×	0.021	SRC, FOXP1
cellular response to laminar fluid shear stress	2	62.9×	0.021	XBP1, NFE2L2
protein stabilization	6	6.0×	0.023	TP53, CHEK2, SEC16A, HERC2, PRKN, PTEN
sialylation	2	55.9×	0.025	ST6GAL1, ST3GAL1
endochondral bone growth	2	50.3×	0.026	BNC2, FGFR3
negative regulation of glial cell proliferation	2	50.3×	0.026	TP53, RB1
positive regulation of protein localization to nucleus	3	17.6×	0.026	SRC, STK11, AKT1
T cell differentiation	3	17.1×	0.026	EGR1, NFE2L2, PTPN2
regulation of signal transduction by p53 class mediator	3	17.1×	0.026	STK11, CHEK2, AKT1

Therapeutics

Drugs indicated for this disease

8 approved, 33 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cemiplimab	Approved (phase 4)
Cetuximab	Approved (phase 4)
Hydroxyurea	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Podofilox	Approved (phase 4)
Retifanlimab	Approved (phase 4)
TECHNETIUM TC 99M TILMANOCEPT	Approved (phase 4)
Temoporfin	Approved (phase 4)
Afatinib	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Ficlatuzumab	Phase 3 (in late-stage trials)
Figitumumab	Phase 3 (in late-stage trials)
Finotonlimab	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gefitinib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Monalizumab	Phase 3 (in late-stage trials)
Nedaplatin	Phase 3 (in late-stage trials)
Nimorazole	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Palbociclib	Phase 3 (in late-stage trials)
Palifermin	Phase 3 (in late-stage trials)
Panitumumab	Phase 3 (in late-stage trials)
Pelareorep	Phase 3 (in late-stage trials)
Raltitrexed	Phase 3 (in late-stage trials)
Tirapazamine	Phase 3 (in late-stage trials)
Tretinoin	Phase 3 (in late-stage trials)
Zalutumumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Adebrelimab, Alpelisib, Aumolertinib, Bavituximab, Bevacizumab, Capivasertib, Catequentinib, Ceralasertib, Crizotinib, Dacomitinib Anhydrous, Dasatinib Anhydrous, Demplatin Pegraglumer, Futuximab, Ingenol Mebutate, Irinotecan, Lapatinib, Lenalidomide, Metenkefalin, Metformin, Necitumumab, Niacinamide, Niraparib, Nogapendekin Alfa, Olaparib, Osimertinib, PEGINTERFERON ALFA-2B, Pioglitazone, Quercetin, Relatlimab, Rivoceranib, Selinexor, Selumetinib, Sintilimab, Sitravatinib, Temsirolimus, Tislelizumab, Toripalimab, Ubidecarenone.

Drug target analysis

Approved (phase 4): 20 · Phase ≥3: 20 · Phased (≥1): 22 · Undrugged: 53

Druggability breadth: 34 of 75 evidence-associated genes (45%) 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
FGFR3	PONATINIB
NFE2L2	DIMETHYL FUMARATE
ROS1	LORLATINIB
SRC	PONATINIB
STK11	FEDRATINIB
TLR4	METHOTREXATE
TP53	NITROFURANTOIN
TYR	ASCORBIC ACID
XBP1	TERFENADINE
NLRP3	CLOMIPHENE
CHEK2	NERATINIB
CHRNA3	VARENICLINE
TUBB3	COLCHICINE
TET2	VADADUSTAT
EGFR	LEVODOPA
FLT1	PONATINIB
AKT1	CAPIVASERTIB
HTR4	PRUCALOPRIDE
APEX1	CEFOTAXIME SODIUM
MC1R	BREMELANOTIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
SRC	103	4
FLT1	77	4
FGFR3	64	4
APEX1	53	4
ROS1	41	4
CHEK2	30	4
AKT1	30	4
CHRNA3	21	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	EGFR, FGFR3, FLT1, SRC
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3, FLT1, ROS1, SRC, STK11
FEDRATINIB	4	EGFR, FGFR3, FLT1, ROS1, SRC, STK11
LENVATINIB	4	FGFR3, FLT1
AXITINIB	4	EGFR, FGFR3, FLT1, ROS1
SORAFENIB	4	EGFR, FGFR3, FLT1, SRC
INFIGRATINIB PHOSPHATE	4	FGFR3, FLT1, ROS1, SRC
INFIGRATINIB	4	FGFR3, FLT1, ROS1, SRC
ENTRECTINIB	4	FGFR3, FLT1, ROS1, SRC
CERITINIB	4	EGFR, FGFR3, ROS1, SRC
VANDETANIB	4	EGFR, FGFR3, FLT1, SRC
NINTEDANIB ESYLATE	4	FGFR3, FLT1
BRIGATINIB	4	CHEK2, EGFR, FGFR3, ROS1, SRC
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3, FLT1, ROS1, SRC
SUNITINIB	4	CHEK2, EGFR, FGFR3, FLT1, SRC, STK11
DASATINIB	4	EGFR, FGFR3, FLT1, SRC
CRIZOTINIB	4	EGFR, FGFR3, FLT1, ROS1, SRC
MIDOSTAURIN	4	AKT1, EGFR, FGFR3, FLT1, ROS1, SRC
DIMETHYL FUMARATE	4	NFE2L2
DUTASTERIDE	4	NFE2L2
KETOCONAZOLE	4	NFE2L2
TOPOTECAN HYDROCHLORIDE	4	NFE2L2
DOXORUBICIN HYDROCHLORIDE	4	NFE2L2
ZAFIRLUKAST	4	EGFR, NFE2L2
DIPYRIDAMOLE	4	APEX1, NFE2L2
LORLATINIB	4	EGFR, ROS1
REPOTRECTINIB	4	ROS1, SRC

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 15.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
SRC	1,917	Binding:1858, Functional:43, ADMET:16
TUBB3	1,781	Binding:1741, Functional:34, ADMET:6
FGFR3	975	Binding:948, Functional:18, ADMET:9
FLT1	896	Binding:852, Functional:38, ADMET:6
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
NFE2L2	861	Binding:812, Functional:49
CHEK2	690	Binding:687, Functional:2, ADMET:1
NLRP3	534	Binding:527, Functional:6, ADMET:1
ROS1	461	Binding:459, Functional:2
CHRNA3	436	Binding:343, Functional:91, ADMET:2
HTR4	349	Binding:233, Functional:113, ADMET:2, Unclassified:1
MC1R	319	Functional:164, Binding:155
TLR4	267	Binding:254, Functional:10, ADMET:3
PTPN2	250	Binding:246, ADMET:4
STK11	244	Binding:244
TYR	211	Binding:209, ADMET:2
RB1	59	Binding:59
APEX1	49	Binding:45, Functional:4
EGR1	35	Binding:35
PRF1	34	Binding:34
ST6GAL1	27	Binding:27
TET2	24	Binding:24
APC	24	Binding:24
PTEN	8	Binding:8
XBP1	7	Binding:6, Functional:1
ST3GAL1	4	Binding:4
BACH2	3	Binding:3
SEC16A	3	Binding:3
IRF4	3	Binding:3
HLA-DQA1	2	Binding:2
ERBIN	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
ROS1	2.7.10.1	receptor protein-tyrosine kinase
ST6GAL1	2.4.99.1	beta-galactoside alpha-(2,6)-sialyltransferase
ST3GAL1	2.4.99.2, 2.4.99.4	beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminide alpha-2,3-sialyltransferase, beta-galactoside alpha-2,3-sialyltransferase
SRC	2.7.10.2	non-specific protein-tyrosine kinase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
TYR	1.14.18.1	tyrosinase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
FLT1	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
APEX1	4.2.99.18	DNA-(apurinic or apyrimidinic site) lyase
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
PTPN2	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR3	975
NFE2L2	861
ROS1	461
SRC	1,917
STK11	244
TLR4	267
TP53	869
TYR	211
NLRP3	534
CHEK2	690
CHRNA3	436
TUBB3	1,781
EGFR	6,531
FLT1	896
AKT1	1,942
HTR4	349
MC1R	319
PTPN2	250

Pharmacogenomics

Cohort genes with a PharmGKB record: 72; 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)
PONATINIB	4	EGFR, FGFR3, FLT1, SRC
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3, FLT1, ROS1, SRC, STK11
FEDRATINIB	4	EGFR, FGFR3, FLT1, ROS1, SRC, STK11
LENVATINIB	4	FGFR3, FLT1
AXITINIB	4	EGFR, FGFR3, FLT1, ROS1
SORAFENIB	4	EGFR, FGFR3, FLT1, SRC
INFIGRATINIB PHOSPHATE	4	FGFR3, FLT1, ROS1, SRC
INFIGRATINIB	4	FGFR3, FLT1, ROS1, SRC
ENTRECTINIB	4	FGFR3, FLT1, ROS1, SRC
CERITINIB	4	EGFR, FGFR3, ROS1, SRC
VANDETANIB	4	EGFR, FGFR3, FLT1, SRC
NINTEDANIB ESYLATE	4	FGFR3, FLT1
BRIGATINIB	4	CHEK2, EGFR, FGFR3, ROS1, SRC
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3, FLT1, ROS1, SRC
SUNITINIB	4	CHEK2, EGFR, FGFR3, FLT1, SRC, STK11
DASATINIB	4	EGFR, FGFR3, FLT1, SRC
CRIZOTINIB	4	EGFR, FGFR3, FLT1, ROS1, SRC
MIDOSTAURIN	4	AKT1, EGFR, FGFR3, FLT1, ROS1, SRC
DIMETHYL FUMARATE	4	NFE2L2
DUTASTERIDE	4	NFE2L2
KETOCONAZOLE	4	NFE2L2
TOPOTECAN HYDROCHLORIDE	4	NFE2L2
DOXORUBICIN HYDROCHLORIDE	4	NFE2L2
ZAFIRLUKAST	4	EGFR, NFE2L2
DIPYRIDAMOLE	4	APEX1, NFE2L2
LORLATINIB	4	EGFR, ROS1
REPOTRECTINIB	4	ROS1, SRC

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	20	FGFR3, NFE2L2, ROS1, SRC, STK11, TLR4, TP53, TYR, XBP1, NLRP3 (+10 more)
B	Phased (≥1) drug, not yet approved	2	PTPN2, RB1
C	Druggable family + PDB, no drug	4	ST6GAL1, CSMD1, HLA-DQA1, PTEN
D	Druggable family + AlphaFold only, no drug	10	ST3GAL1, ADAMTSL3, SLC45A2, SLC39A6, ADAM19, LRFN2, HAPLN3, TPRG1, OCA2, PRF1
E	Difficult family or no structure, no drug	39	BRCA2, SP4, NKX2-1, TRPS1, FOXP2, BACH2, FLACC1, ERBIN, RALY, TP63 (+29 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RALY	0	MC1R
SLC45A2	0	TYR, MC1R
FAM13A	0	CHRNA3
KRT5	0	EGFR
OCA2	0	TYR
PTEN	8	STK11, TP53, AKT1
ST6GAL1	27	—
ST3GAL1	4	—
BRCA2	0	—
SP4	0	—
NKX2-1	0	—
TRPS1	0	—
FOXP2	0	—
CSMD1	0	—
BACH2	3	—
FLACC1	0	—
ADAMTSL3	0	—
ERBIN	1	—
TP63	0	—
CD163	0	—
TPM3P2	0	—
DTNBP1	0	—
SMG6	0	—
SLC39A6	0	—
RIN3	0	—
ADAM19	0	—
FRY	0	—
LRFN2	0	—
HAPLN3	0	—
CNTLN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 302.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	129
PHASE2	78
PHASE1	36
PHASE1/PHASE2	32
PHASE3	12
EARLY_PHASE1	6
PHASE2/PHASE3	5
PHASE4	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00868088	PHASE4	COMPLETED	Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip
NCT02088515	PHASE4	COMPLETED	Nedaplatin (Jiebaishu®) Combined With Docetaxel for Advanced Lung Squamous Cell Carcinoma
NCT02151149	PHASE4	COMPLETED	Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT03388931	PHASE4	WITHDRAWN	Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
NCT01706939	PHASE3	ACTIVE_NOT_RECRUITING	The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
NCT03952585	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer
NCT00101582	PHASE3	COMPLETED	Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
NCT00201279	PHASE3	COMPLETED	Chemoprevention Study of Oral Cavity Squamous Cell Carcinoma
NCT00201383	PHASE3	COMPLETED	Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
NCT00363441	PHASE2/PHASE3	WITHDRAWN	A Study of Conventional 3D Radiation vs. Intensity-Modulated Radiation in Squamous Cell Cancer of the Head and Neck
NCT00382031	PHASE3	COMPLETED	Zalutumumab in Patients With Non-curable Head and Neck Cancer
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00559351	PHASE3	TERMINATED	RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
NCT00770393	PHASE2/PHASE3	COMPLETED	Laryngeal Preservation in Pyriform Sinus Carcinoma
NCT01161498	PHASE3	TERMINATED	Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
NCT01211938	PHASE2/PHASE3	COMPLETED	Trial Comparing Two Protocols of re Irradiation in an Irradiated Area for Carcinoma of the Upper Aerodigestive Tract
NCT01363466	PHASE3	TERMINATED	Evaluation of Hysterectomy After Chemoradiation Therapy for Stage IB2/II Cervical Cancer
NCT01532453	PHASE3	TERMINATED	Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients
NCT01631357	PHASE2/PHASE3	COMPLETED	Study of Chemotherapy Combination With Autologous Cytokine-Induced Killer Cell Immunotherapy to Treat Lung Cancer
NCT03115476	PHASE3	TERMINATED	A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp
NCT03257267	PHASE3	COMPLETED	Study of Cemiplimab in Adults With Cervical Cancer
NCT02128906	PHASE2	RECRUITING	Radiotherapy With Cisplatin vs. Docetaxel-cetuximab in HNSCC: ERCC1 Biomarker Enrichment and Interaction Design
NCT02133196	PHASE2	RECRUITING	T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer
NCT02817958	PHASE2	ACTIVE_NOT_RECRUITING	Evaluation of Lymphadenectomy and Chemotherapy TIP on Inguinal Lymph Nodes in Squamous Cell Carcinoma of the Penis
NCT03708224	PHASE2	RECRUITING	Preoperative Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck
NCT03854032	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck
NCT03935893	PHASE2	RECRUITING	Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers
NCT04150900	PHASE2	ACTIVE_NOT_RECRUITING	1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck
NCT04370587	PHASE1/PHASE2	RECRUITING	A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
NCT04808999	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Study of PD-1 Inhibitor Pembrolizumab in PD-1 Naive Cutaneous Squamous Cell Carcinoma (cSCC)
NCT04889742	PHASE2	NOT_YET_RECRUITING	Hyperthermia Enhanced Re-irradiation of Loco-regional Recurrent Tumors
NCT05027633	PHASE2	RECRUITING	Immunotherapy With Chemotherapy and Chemoradiation for Advanced Squamous Cancer of Nasal Cavity / Paranasal Sinuses (I-NAPA)
NCT05070403	PHASE2	RECRUITING	Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma
NCT05202860	PHASE2	ACTIVE_NOT_RECRUITING	Impact of Human Papillomavirus (HPV) Vaccination on Burden of Disease in Patients with Actinic Keratosis
NCT05574101	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer
NCT05681039	PHASE2	RECRUITING	Phase 2 Trial of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab in Patients With Newly Diagnosed PD-L1 CPS Positive Resectable Stage 3-4 Oral Cavity Squamous Cell Carcinoma (OCSCC).
NCT05858229	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Neo-adjuvant Treatment for Squamous Cell Carcinoma Using Direct Tumor Injection With RP1.
NCT05910827	PHASE1/PHASE2	RECRUITING	A Phase Ib/II Study of an Anti-HER3 Antibody, HMBD-001, With Cetuximab +/- Docetaxel in Advanced Squamous Cell Cancers
NCT06041802	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Pembrolizumab (+) Berahyaluronidase Alfa (MK-3475A) (Pembrolizumab Formulated With Berahyaluronidase Alfa (MK-5180)) in Japanese Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC) or Locally Advanced (LA) Unresectable cSCC (MK-3475A-E39)
NCT06047379	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	34
PANITUMUMAB	4	4
CEMIPLIMAB	4	3
DOCETAXEL ANHYDROUS	4	3
TEMSIROLIMUS	4	2
ALPELISIB	4	1
CARBOPLATIN	4	1
CIPROFLOXACIN	4	1
FLUDEOXYGLUCOSE F 18	4	1
HYDROXYUREA	4	1
NIRAPARIB	4	1
NIVOLUMAB	4	1
PALIFERMIN	4	1
SELINEXOR	4	1
TALIMOGENE LAHERPAREPVEC	4	1
ZALUTUMUMAB	3	4
NEDAPLATIN	3	1
NIMOTUZUMAB	3	1
UBIDECARENONE	3	1
AXL-1717	2	1
GLYCOLIC ACID	2	1
CHEMBL1510899	0	1
FOLINIC ACID	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items; also 2 oncogenic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
PIK3CA Q75E	Alpelisib	Sensitivity/Response	CIViC C	EID12159
PIK3CA N345K OR PIK3CA M1043V OR PIK3CA Q75E	Alpelisib	Sensitivity/Response	CIViC D	EID12160