Myoepithelial tumor

Summary

Myoepithelial tumor (MONDO:0002380) is a cancer with 75 cohort genes (4 CIViC-evidence somatic drivers; 95 ClinVar predisposition records) and 5 clinical trials. Top therapeutic interventions include ifosfamide, selinexor, and seclidemstat.

At a glance

• Classification: Cancer
• Cohort genes: 75
• ClinVar variants: 95
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoepithelial tumor
Mondo ID	MONDO:0002380
MeSH	D009208
DOID	DOID:2661
NCIT	C40392
UMLS	C0027070
MedGen	10235
Is cancer (heuristic)	yes

Also known as: benign myoepithelioma · myoepithelial neoplasm · myoepithelial tumor · myoepithelioma

Data availability: 95 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (23): ovarian epithelial tumor, endometrioid tumor, squamous cell neoplasm, pancreatic delta cell neuroendocrine tumor, thyroid hyalinizing trabecular adenoma, Wolffian adnexal tumor, adenoma, carcinoma, cystic, mucinous, and serous neoplasm, thymic epithelial neoplasm, epithelial tumor of anal canal, growth hormone-producing pituitary gland neoplasm, basal cell neoplasm, sympathetic paraganglioma, papillary epithelial neoplasm, epithelial skin neoplasm, glandular cell neoplasm, intraepithelial neoplasia, epithelial neoplasm of rectum, epithelial tumor of colon, mesonephric neoplasm, benign epithelial neoplasm, transitional cell neoplasm

Subtypes (4): carcinoma ex pleomorphic adenoma, breast myoepithelial tumor, malignant myoepithelioma, parachordoma

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

ClinVar germline variants

95 retrieved; paginated sample, class counts are floors:

82 uncertain significance, 6 pathogenic, 3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1801782	NM_004454.3(ETV5):c.536A>C (p.His179Pro)	ETV5	Pathogenic	no assertion criteria provided
1801795	NM_004690.4(LATS1):c.375A>T (p.Lys125Asn)	LATS1	Pathogenic	no assertion criteria provided
1801783	NM_006185.4(NUMA1):c.3716G>C (p.Arg1239Pro)	NUMA1	Pathogenic	no assertion criteria provided
1801750	NM_006231.4(POLE):c.2489A>G (p.Glu830Gly)	POLE	Pathogenic	no assertion criteria provided
1801743	NM_015001.3(SPEN):c.5197G>A (p.Ala1733Thr)	SPEN	Pathogenic	no assertion criteria provided
1801744	NM_001048166.1(STIL):c.1639C>A (p.Gln547Lys)	STIL	Pathogenic	no assertion criteria provided
44816	NM_004333.6(BRAF):c.1798G>T (p.Val600Leu)	BRAF	Likely pathogenic	criteria provided, single submitter
1801767	NM_015155.3(LARP4B):c.1345G>T (p.Val449Phe)	LARP4B	Likely pathogenic	no assertion criteria provided
1801728	NM_001243439.2(SPECC1):c.1747A>G (p.Met583Val)	SPECC1	Likely pathogenic	no assertion criteria provided
11877	NM_002769.5(PRSS1):c.86A>T (p.Asn29Ile)	PRSS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
186303	NM_005732.4(RAD50):c.282A>G (p.Ile94Met)	RAD50	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1801732	NM_001025389.2(AMPD3):c.2101G>A (p.Val701Met)	AMPD3	Uncertain significance	no assertion criteria provided
1801796	NM_001162383.2(ARHGEF2):c.2072G>T (p.Ser691Ile)	ARHGEF2	Uncertain significance	no assertion criteria provided
1801797	NM_018071.5(ARHGEF40):c.1760_1771del (p.Gly587_Leu591delinsVal)	ARHGEF40	Uncertain significance	no assertion criteria provided
1801738	NM_006321.4(ARIH2):c.847G>A (p.Asp283Asn)	ARIH2	Uncertain significance	no assertion criteria provided
1801731	NM_004192.4(ASMTL):c.599C>T (p.Pro200Leu)	ASMTL	Uncertain significance	no assertion criteria provided
1801751	NM_015439.3(CCDC28A):c.61G>A (p.Val21Ile)	CCDC28A	Uncertain significance	no assertion criteria provided
1801768	NM_152562.4(CDCA2):c.696C>G (p.Asp232Glu)	CDCA2	Uncertain significance	no assertion criteria provided
1801811	NM_022842.5(CDCP1):c.2170A>T (p.Lys724Ter)	CDCP1	Uncertain significance	no assertion criteria provided
1801784	NM_020180.4(CELF4):c.658-152G>A	CELF4	Uncertain significance	no assertion criteria provided
1801737	NM_053277.3(CLIC6):c.787G>A (p.Gly263Arg)	CLIC6	Uncertain significance	no assertion criteria provided
1801733	NM_022111.4(CLSPN):c.3585A>T (p.Glu1195Asp)	CLSPN	Uncertain significance	no assertion criteria provided
1801798	NM_001846.4(COL4A2):c.1197G>C (p.Arg399Ser)	COL4A2	Uncertain significance	no assertion criteria provided
1801799	NM_052820.4(CORO2A):c.398G>A (p.Arg133His)	CORO2A	Uncertain significance	criteria provided, single submitter
1801770	NM_004938.4(DAPK1):c.415G>C (p.Asp139His)	DAPK1	Uncertain significance	no assertion criteria provided
1801800	NM_003737.4(DCHS1):c.8890C>T (p.Arg2964Cys)	DCHS1	Uncertain significance	criteria provided, single submitter
1801745	NM_004714.3(DYRK1B):c.586A>C (p.Asn196His)	DYRK1B	Uncertain significance	no assertion criteria provided
1801771	NM_001142616.3(EHBP1):c.1699A>T (p.Ser567Cys)	EHBP1	Uncertain significance	no assertion criteria provided
1801752	NM_021814.5(ELOVL5):c.58+1262G>A	ELOVL5	Uncertain significance	no assertion criteria provided
1801753	NM_004445.6(EPHB6):c.197G>C (p.Arg66Pro)	EPHB6	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 65 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
TGFBR1	LoF	ESCA
SPEN	LoF	AML,BRCA,CCRCC,CESC,CLLSLL,DLBCLNOS,LUAD,MLYM,NPC,PRAD,SACA	CIViC #9216
ETV5	Act	AML	CIViC #1768

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SACS	Orphanet:98	Autosomal recessive spastic ataxia of Charlevoix-Saguenay
SCNN1G	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1G	Orphanet:526	Liddle syndrome
SCNN1G	Orphanet:60033	Idiopathic bronchiectasis
STIL	Orphanet:220386	Semilobar holoprosencephaly
STIL	Orphanet:2512	Autosomal recessive primary microcephaly
STIL	Orphanet:280195	Septopreoptic holoprosencephaly
STIL	Orphanet:93924	Lobar holoprosencephaly
STIL	Orphanet:93925	Alobar holoprosencephaly
STIL	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
STIL	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
TEX15	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
TGFBR1	Orphanet:284973	Marfan syndrome type 2
TGFBR1	Orphanet:60030	Loeys-Dietz syndrome
TGFBR1	Orphanet:65748	Multiple self-healing squamous epithelioma
TGFBR1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
DCHS1	Orphanet:314679	Cerebrofacioarticular syndrome
DCHS1	Orphanet:741	Familial mitral valve prolapse
SPEN	Orphanet:1606	1p36 deletion syndrome
SPEN	Orphanet:662234	Neurodevelopmental delay-congenital heart defects-intellectual disability syndrome
TRPM4	Orphanet:130	Brugada syndrome
TRPM4	Orphanet:316	Progressive symmetric erythrokeratodermia
TRPM4	Orphanet:871	Hereditary progressive cardiac conduction defect
TRPV4	Orphanet:1216	Autosomal dominant congenital benign spinal muscular atrophy
TRPV4	Orphanet:263482	Spondyloepimetaphyseal dysplasia, Maroteaux type
TRPV4	Orphanet:2635	Metatropic dysplasia
TRPV4	Orphanet:431255	Scapuloperoneal spinal muscular atrophy
TRPV4	Orphanet:85169	Familial digital arthropathy-brachydactyly
TRPV4	Orphanet:86820	Familial avascular necrosis of femoral head
TRPV4	Orphanet:93304	Autosomal dominant brachyolmia
TRPV4	Orphanet:93314	Spondylometaphyseal dysplasia, Kozlowski type
TRPV4	Orphanet:99937	Autosomal dominant Charcot-Marie-Tooth disease type 2C
TDP1	Orphanet:94124	Spinocerebellar ataxia with axonal neuropathy type 1
FRAS1	Orphanet:2052	Fraser syndrome
FRAS1	Orphanet:93100	Renal agenesis, unilateral
ELOVL5	Orphanet:423296	Spinocerebellar ataxia type 38
COL4A2	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A2	Orphanet:99810	Familial porencephaly
VAC14	Orphanet:3472	Yunis-Varon syndrome

Cohort genes → proteins

75 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SACS	HGNC:10519	ENSG00000151835	Q9NZJ4	Sacsin	clinvar
SCNN1G	HGNC:10602	ENSG00000166828	P51170	Epithelial sodium channel subunit gamma	clinvar
STIL	HGNC:10879	ENSG00000123473	Q15468	SCL-interrupting locus protein	clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
SLC27A5	HGNC:10999	ENSG00000083807	Q9Y2P5	Long-chain fatty acid transport protein 5	clinvar
SLC7A2	HGNC:11060	ENSG00000003989	P52569	Cationic amino acid transporter 2	clinvar
SMC1B	HGNC:11112	ENSG00000077935	Q8NDV3	Structural maintenance of chromosomes protein 1B	clinvar
SYT7	HGNC:11514	ENSG00000011347	O43581	Synaptotagmin-7	clinvar
TEX15	HGNC:11738	ENSG00000133863	Q9BXT5	Testis-expressed protein 15	clinvar
TGFBR1	HGNC:11772	ENSG00000106799	P36897	TGF-beta receptor type-1	clinvar
VIPR2	HGNC:12695	ENSG00000106018	P41587	Vasoactive intestinal polypeptide receptor 2	clinvar
MLXIPL	HGNC:12744	ENSG00000009950	Q9NP71	Carbohydrate-responsive element-binding protein	clinvar
NAPSA	HGNC:13395	ENSG00000131400	O96009	Napsin-A	clinvar
RPL36	HGNC:13631	ENSG00000130255	C0HME6	RPL36 alternative reading frame protein	clinvar
DCHS1	HGNC:13681	ENSG00000166341	Q96JQ0	Protocadherin-16	clinvar
CELF4	HGNC:14015	ENSG00000101489	Q9BZC1	CUGBP Elav-like family member 4	clinvar
MMP26	HGNC:14249	ENSG00000167346	Q9NRE1	Matrix metalloproteinase-26	clinvar
LRP10	HGNC:14553	ENSG00000197324	Q7Z4F1	Low-density lipoprotein receptor-related protein 10	clinvar
CDCA2	HGNC:14623	ENSG00000184661	Q69YH5	Cell division cycle-associated protein 2	clinvar
TLN2	HGNC:15447	ENSG00000171914	Q9Y4G6	Talin-2	clinvar
EPPK1	HGNC:15577	ENSG00000261150	P58107	Epiplakin	clinvar
LENG9	HGNC:16306	ENSG00000275183	Q96B70	Leukocyte receptor cluster member 9	clinvar
GRIN3A	HGNC:16767	ENSG00000198785	Q8TCU5	Glutamate receptor ionotropic, NMDA 3A	clinvar
MFHAS1	HGNC:16982	ENSG00000147324	Q9Y4C4	Malignant fibrous histiocytoma-amplified sequence 1	clinvar
STON1	HGNC:17003	ENSG00000243244	Q9Y6Q2	Stonin-1	clinvar
SPEN	HGNC:17575	ENSG00000065526	Q96T58	Msx2-interacting protein	clinvar
YLPM1	HGNC:17798	ENSG00000119596	P49750	YLP motif-containing protein 1	clinvar
SENP3	HGNC:17862	ENSG00000161956	Q9H4L4	Sentrin-specific protease 3	clinvar
TRPM4	HGNC:17993	ENSG00000130529	Q8TD43	Transient receptor potential cation channel subfamily M member 4	clinvar
TRPV4	HGNC:18083	ENSG00000111199	Q9HBA0	Transient receptor potential cation channel subfamily V member 4	clinvar
TDP1	HGNC:18884	ENSG00000042088	Q9NUW8	Tyrosyl-DNA phosphodiesterase 1	clinvar
CNOT12	HGNC:19081	ENSG00000149115	Q9C0C2	182 kDa tankyrase-1-binding protein	clinvar
FRAS1	HGNC:19185	ENSG00000138759	Q86XX4	Extracellular matrix organizing protein FRAS1	clinvar
CLSPN	HGNC:19715	ENSG00000092853	Q9HAW4	Claspin	clinvar
TMEM121	HGNC:20511	ENSG00000184986	Q9BTD3	Transmembrane protein 121	clinvar
KRTAP10-11	HGNC:20528	ENSG00000243489	P60412	Keratin-associated protein 10-11	clinvar
CLIC6	HGNC:2065	ENSG00000159212	Q96NY7	Chloride intracellular channel protein 6	clinvar
QTMAN	HGNC:20887	ENSG00000121964	Q4AE62	tRNA-queuosine alpha-mannosyltransferase	clinvar
CCDC28A	HGNC:21098	ENSG00000024862	Q8IWP9	Coiled-coil domain-containing protein 28A	clinvar
LINGO3	HGNC:21206	ENSG00000220008	P0C6S8	Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 3	clinvar
ELOVL5	HGNC:21308	ENSG00000012660	Q9NYP7	Very long chain fatty acid elongase 5	clinvar
COL4A2	HGNC:2203	ENSG00000134871	P08572	Collagen alpha-2(IV) chain	clinvar
CORO2A	HGNC:2255	ENSG00000106789	Q92828	Coronin-2A	clinvar
CDCP1	HGNC:24357	ENSG00000163814	Q9H5V8	CUB domain-containing protein 1	clinvar
VAC14	HGNC:25507	ENSG00000103043	Q08AM6	Protein VAC14 homolog	clinvar
ARHGEF40	HGNC:25516	ENSG00000165801	Q8TER5	Rho guanine nucleotide exchange factor 40	clinvar
TANGO6	HGNC:25749	ENSG00000103047	Q9C0B7	Transport and Golgi organization protein 6 homolog	clinvar
ZNF668	HGNC:25821	ENSG00000167394	Q96K58	Zinc finger protein 668	clinvar
INTS3	HGNC:26153	ENSG00000143624	Q68E01	Integrator complex subunit 3	clinvar
DAPK1	HGNC:2674	ENSG00000196730	P53355	Death-associated protein kinase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SACS	Sacsin	Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins.
SCNN1G	Epithelial sodium channel subunit gamma	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
STIL	SCL-interrupting locus protein	Immediate-early gene.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
SLC27A5	Long-chain fatty acid transport protein 5	May mediate the import of long-chain fatty acids (LCFA) by facilitating their transport across cell membranes.
SLC7A2	Cationic amino acid transporter 2	Functions as a permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine); the affinity for its substrates differs between isoforms created by alternative splicing.
SMC1B	Structural maintenance of chromosomes protein 1B	Meiosis-specific component of cohesin complex.
SYT7	Synaptotagmin-7	Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain.
TEX15	Testis-expressed protein 15	Required during spermatogenesis for normal chromosome synapsis and meiotic recombination in germ cells.
TGFBR1	TGF-beta receptor type-1	Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
VIPR2	Vasoactive intestinal polypeptide receptor 2	G protein-coupled receptor activated by the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP).
MLXIPL	Carbohydrate-responsive element-binding protein	Glucose-responsive transcription activator that regulates fatty acid synthesis and glycolysis.
NAPSA	Napsin-A	May be involved in processing of pneumocyte surfactant precursors.
RPL36	RPL36 alternative reading frame protein	Inhibits C2CD2L/TMEM24-dependent transport of phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane.
DCHS1	Protocadherin-16	Calcium-dependent cell-adhesion protein.
CELF4	CUGBP Elav-like family member 4	RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing.
MMP26	Matrix metalloproteinase-26	May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor.
LRP10	Low-density lipoprotein receptor-related protein 10	Probable receptor, which is involved in the internalization of lipophilic molecules and/or signal transduction.
CDCA2	Cell division cycle-associated protein 2	Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase.
TLN2	Talin-2	As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion.
EPPK1	Epiplakin	Cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to stress.
GRIN3A	Glutamate receptor ionotropic, NMDA 3A	Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with low calcium permeability and low voltage-dependent block by Mg(2+).
MFHAS1	Malignant fibrous histiocytoma-amplified sequence 1	Probable GTP-binding protein.
STON1	Stonin-1	May be involved in the endocytic machinery.
SPEN	Msx2-interacting protein	May serve as a nuclear matrix platform that organizes and integrates transcriptional responses.
YLPM1	YLP motif-containing protein 1	Plays a role in the reduction of telomerase activity during differentiation of embryonic stem cells by binding to the core promoter of TERT and controlling its down-regulation.
SENP3	Sentrin-specific protease 3	Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates.
TRPM4	Transient receptor potential cation channel subfamily M member 4	Calcium-activated selective cation channel that mediates membrane depolarization.
TRPV4	Transient receptor potential cation channel subfamily V member 4	Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity.
TDP1	Tyrosyl-DNA phosphodiesterase 1	DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3’-phosphodiester bond, giving rise to DNA with a free 3’ phosphate.
FRAS1	Extracellular matrix organizing protein FRAS1	Involved in extracellular matrix organization.
CLSPN	Claspin	Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation.
TMEM121	Transmembrane protein 121	May play a role in MAPK signaling.
KRTAP10-11	Keratin-associated protein 10-11	In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through t…
CLIC6	Chloride intracellular channel protein 6	In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.
QTMAN	tRNA-queuosine alpha-mannosyltransferase	Glycosyltransferase that specifically catalyzes mannosylation of cytoplasmic tRNA(Asp) modified with queuosine at position 34 (queuosine(34)).
ELOVL5	Very long chain fatty acid elongase 5	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.
COL4A2	Collagen alpha-2(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
CDCP1	CUB domain-containing protein 1	May be involved in cell adhesion and cell matrix association.
VAC14	Protein VAC14 homolog	Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
ARHGEF40	Rho guanine nucleotide exchange factor 40	Acts as a guanine nucleotide exchange factor (GEF) for RHOA and RHOC.
ZNF668	Zinc finger protein 668	May be involved in transcriptional regulation.
INTS3	Integrator complex subunit 3	Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes.
DAPK1	Death-associated protein kinase 1	Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy.
FAM168B	Myelin-associated neurite-outgrowth inhibitor	Inhibitor of neuronal axonal outgrowth.
LARP4B	La-related protein 4B	Stimulates mRNA translation.
IFT140	Intraflagellar transport protein 140 homolog	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
EHBP1	EH domain-binding protein 1	May play a role in actin reorganization.
TENM3	Teneurin-3	Involved in neural development by regulating the establishment of proper connectivity within the nervous system.
PARS2	Probable proline–tRNA ligase, mitochondrial	Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the proline amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis.

Protein-family classification

Druggable: 19 · Difficult: 8 · Unknown: 48 · Druggable fraction: 0.25

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
Ion channel	2	3.0×	0.437
Kinase	5	1.9×	0.437
Other/Unknown	48	1.1×	0.437
Protease	3	1.5×	0.757
Antibody/Immunoglobulin	3	1.2×	0.858
Scaffold/PPI	4	0.9×	0.956
Enzyme (other)	4	0.6×	0.985
GPCR	2	0.6×	0.985
Transcription factor	4	0.4×	0.985

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SACS	Other/Unknown	no		Ubiquitin-like_dom, DnaJ_domain, HEPN_dom
SCNN1G	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
STIL	Other/Unknown	no		STIL, STIL_CC, STIL_N
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
SLC27A5	Other/Unknown	no		AMP-dep_synth/lig_dom, AMP-binding_CS, AMP-bd_C
SLC7A2	Other/Unknown	no		AA/rel_permease1, Cat_AA_permease, CAT_C
SMC1B	Other/Unknown	no		RecF/RecN/SMC_N, SMC_hinge, SMC
SYT7	Other/Unknown	no		C2_dom, Synaptotagmin, C2_domain_sf
TEX15	Other/Unknown	no		TEX15, TEX15_dom
TGFBR1	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
VIPR2	GPCR	yes		GPCR_2_secretin-like, GPCR_2_VIP_rcpt, GPCR_2_extracellular_dom
MLXIPL	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, Max-like/E-box_TFs
NAPSA	Protease	yes	3.4.23.B1	Aspartic_peptidase_A1, Aspartic_peptidase_AS, Peptidase_aspartic_dom_sf
RPL36	Other/Unknown	no		Ribosomal_eL36, Ribosomal_eL36_sf
DCHS1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CELF4	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, CELF3/4/5/6_RRM1
MMP26	Protease	yes	3.4.24.B7	Pept_M10_metallopeptidase, Peptidase_Metallo, Pept_M10A
LRP10	Other/Unknown	no		CUB_dom, LDrepeatLR_classA_rpt, LDLR_class-A_CS
CDCA2	Other/Unknown	no		PP1-bd
TLN2	Other/Unknown	no		FERM_domain, IRS_PTB, ILWEQ_dom
EPPK1	Other/Unknown	no		Plectin_repeat, Plakin_repeat_sf, Plakin
LENG9	Transcription factor	no		Znf_CCCH, Cyclic_Pdiesterase, AKAP7-like_phosphoesterase
GRIN3A	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
MFHAS1	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, ROC
STON1	Other/Unknown	no		SHD_dom, Stonin, MHD
SPEN	Other/Unknown	no		RRM_dom, SPOC_met, Nucleotide-bd_a/b_plait_sf
YLPM1	Other/Unknown	no		YLP_motif_con_p1, P-loop_NTPase, Spectrin_YLPM1-like
SENP3	Protease	yes	3.4.22.B72	Peptidase_C48_C, Papain-like_cys_pep_sf, SENP3_5_cons_dom
TRPM4	Ion channel	yes		Ion_trans_dom, TRPM_SLOG, TRPM
TRPV4	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4
TDP1	Enzyme (other)	yes	3.1.4.1	Tdp1
CNOT12	Other/Unknown	no		Tankyrase-bd_C, TNKS1BP1-like
FRAS1	Other/Unknown	no		EGF, VWF_dom, Calx_beta
CLSPN	Other/Unknown	no		Claspin
TMEM121	Other/Unknown	no		CECR6/TMEM121, TMEM121
KRTAP10-11	Other/Unknown	no		KAP
CLIC6	Other/Unknown	no		CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_sf
QTMAN	Other/Unknown	no		Glyco_trans_1, QTMAN_N, GT-like_domain_containing_1
CCDC28A	Other/Unknown	no		CCDC28
LINGO3	Antibody/Immunoglobulin	yes		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
ELOVL5	Other/Unknown	no		ELO_fam, ELOVL5
COL4A2	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
CORO2A	Scaffold/PPI	no		WD40_rpt, DUF1899, Coronin
CDCP1	Other/Unknown	no		Sperma_CUB_dom_sf, CDCP1, CDCP1_CUB_3rd_6th
VAC14	Other/Unknown	no		ARM-like, ARM-type_fold, VAC14_Fig4p-bd
ARHGEF40	Scaffold/PPI	no		DH_dom, PH_domain, PH-like_dom_sf
TANGO6	Other/Unknown	no		ARM-like, ARM-type_fold, Rtp1_C2
ZNF668	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
INTS3	Other/Unknown	no		INTS3_N, INTS3, HEAT_Ints3_C
DAPK1	Kinase	yes	2.7.11.1	Death_dom, Prot_kinase_dom, Ankyrin_rpt

Expression context

Cohort genes with no expression data: 0.

64 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)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	9
secondary oocyte	8
male germ line stem cell (sensu Vertebrata) in testis	7
cortical plate	7
oocyte	5
ganglionic eminence	5
stromal cell of endometrium	5
sural nerve	5
buccal mucosa cell	4
calcaneal tendon	4
right testis	4
mucosa of transverse colon	4
adrenal tissue	4
Brodmann (1909) area 23	3
renal medulla	3
right lobe of liver	3
right frontal lobe	3
saphenous vein	3
apex of heart	3
right adrenal gland	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SACS	286	ubiquitous	marker	Brodmann (1909) area 23, middle frontal gyrus, frontal pole
SCNN1G	133	broad	marker	renal medulla, kidney epithelium, bronchial epithelial cell
STIL	221	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
SLC27A5	197	ubiquitous	marker	right lobe of liver, liver, nucleus accumbens
SLC7A2	236	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii
SMC1B	31	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
SYT7	170	broad	marker	islet of Langerhans, right hemisphere of cerebellum, right frontal lobe
TEX15	76	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, sperm, male germ cell
TGFBR1	269	ubiquitous	marker	saphenous vein, tibia, visceral pleura
VIPR2	169	broad	marker	mucosa of stomach, apex of heart, heart left ventricle
MLXIPL	203	broad	marker	right lobe of liver, right adrenal gland, left adrenal gland cortex
NAPSA	167	tissue_specific	marker	lower lobe of lung, upper lobe of lung, upper lobe of left lung
RPL36	288	ubiquitous	marker	ganglionic eminence, cortical plate, left ovary
DCHS1	259	broad	marker	tendon of biceps brachii, ganglionic eminence, cortical plate
CELF4	183	broad	marker	cerebellar cortex, cerebellar hemisphere, Brodmann (1909) area 9
MMP26	38	tissue_specific	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, endometrium
LRP10	284	ubiquitous	marker	stromal cell of endometrium, decidua, right coronary artery
CDCA2	166	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
TLN2	257	ubiquitous	marker	sural nerve, middle temporal gyrus, frontal pole
EPPK1	190	broad	marker	skin of hip, upper leg skin, gingival epithelium
LENG9	131	ubiquitous	yes	body of pancreas, mucosa of transverse colon, primordial germ cell in gonad
GRIN3A	149	tissue_specific	marker	Brodmann (1909) area 46, middle temporal gyrus, male germ line stem cell (sensu Vertebrata) in testis
MFHAS1	266	ubiquitous	marker	saphenous vein, secondary oocyte, renal medulla
STON1	244	ubiquitous	marker	decidua, cauda epididymis, myometrium
SPEN	293	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
YLPM1	290	ubiquitous	marker	ganglionic eminence, cortical plate, tendon of biceps brachii
SENP3	185	ubiquitous	yes	right hemisphere of cerebellum, right frontal lobe, cerebellar hemisphere
TRPM4	201	ubiquitous	marker	mucosa of transverse colon, rectum, apex of heart
TRPV4	171	ubiquitous	marker	cartilage tissue, lower esophagus mucosa, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRAF	7,394
TGFBR1	4,828
IGF2R	3,464
DAPK1	3,133
SMC1B	2,962
HAS1	2,826
SENP3	2,798
COL4A2	2,746
CNOT12	2,591
FRAS1	2,552

Intra-cohort edges

A	B	Sources
ARHGEF40	DYRK1B	biogrid_interaction
DAPK1	MFHAS1	string_interaction
ETV5	MFHAS1	intact
HIVEP1	SPEN	string_interaction
IGF2R	NAPSA	biogrid_interaction
LINGO3	SCNN1G	string_interaction
RBM12B	TSKS	string_interaction
RBM12B	YLPM1	string_interaction
TDP1	VAC14	intact
TRPM4	TRPV4	string_interaction

Structural data

PDB: 35 · AlphaFold-only: 38 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL36	C0HME6	194
BRAF	P15056	131
GABRB3	P28472	95
DAPK1	P53355	79
TDP1	Q9NUW8	48
TGFBR1	P36897	44
ITGAL	P20701	41
TRPM4	Q8TD43	29
IGF2R	P11717	24
TRPV4	Q9HBA0	19
SACS	Q9NZJ4	7
MLXIPL	Q9NP71	7
INTS3	Q68E01	7
HRH2	P25021	6
SCNN1G	P51170	5
STIL	Q15468	5
CLSPN	Q9HAW4	5
CDCA2	Q69YH5	4
SPEN	Q96T58	4
COL4A2	P08572	4
IFT140	Q96RY7	4
EHBP1	Q8NDI1	4
VIPR2	P41587	3
GRIN3A	Q8TCU5	3
HIVEP1	P15822	3
DCHS1	Q96JQ0	2
CELF4	Q9BZC1	2
ETV5	P41161	2
SYT7	O43581	1
TLN2	Q9Y4G6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FTCD	O95954	95.30
HAS1	Q92839	88.79
PARS2	Q7L3T8	88.30
SLC27A5	Q9Y2P5	86.32
LINGO3	P0C6S8	86.16
AMPD3	Q01432	85.74
CORO2A	Q92828	85.12
MFHAS1	Q9Y4C4	84.62
SMC1B	Q8NDV3	83.44
QTMAN	Q4AE62	83.04
ELOVL5	Q9NYP7	82.53
NAPSA	O96009	82.49
IGSF3	O75054	81.81
SLC7A2	P52569	81.15
MMP26	Q9NRE1	79.33
TANGO6	Q9C0B7	79.25
CDCP1	Q9H5V8	78.13
TENM3	Q9P273	77.76
TMEM121	Q9BTD3	73.01
ZNF668	Q96K58	72.87
TMCC3	Q9ULS5	70.84
SPECC1	Q5M775	68.05
LRP10	Q7Z4F1	67.84
LENG9	Q96B70	66.33
TSKS	Q9UJT2	66.05
STON1	Q9Y6Q2	65.75
ARHGEF40	Q8TER5	64.28
EYA4	O95677	63.79
CCDC28A	Q8IWP9	62.27
CLIC6	Q96NY7	60.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 282. Enrichment computed across 95 evidence-associated genes (58 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 58 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Potassium transport channels	1	65.6×	0.280	KCNJ10
Loss of Function of TGFBR2 in Cancer	1	65.6×	0.280	TGFBR1
TGFBR2 Kinase Domain Mutants in Cancer	1	65.6×	0.280	TGFBR1
TGFBR1 LBD Mutants in Cancer	1	49.2×	0.280	TGFBR1
Histamine receptors	1	49.2×	0.280	HRH2
Lysosomal oligosaccharide catabolism	1	49.2×	0.280	MAN2B1
Signaling by MRAS-complex mutants	1	49.2×	0.280	BRAF
PKA-mediated phosphorylation of key metabolic factors	1	39.4×	0.280	MLXIPL
Signalling to p38 via RIT and RIN	1	39.4×	0.280	BRAF
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	39.4×	0.280	LRRFIP1
Loss of Function of TGFBR1 in Cancer	1	39.4×	0.280	TGFBR1
Loss of Function of SMAD2/3 in Cancer	1	32.8×	0.280	TGFBR1
Signaling by TGF-beta Receptor Complex in Cancer	1	32.8×	0.280	TGFBR1
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	32.8×	0.280	TGFBR1
TGFBR1 KD Mutants in Cancer	1	32.8×	0.280	TGFBR1
Negative feedback regulation of MAPK pathway	1	32.8×	0.280	BRAF
Sensing of DNA Double Strand Breaks	1	32.8×	0.280	RAD50
RUNX3 Regulates Immune Response and Cell Migration	1	32.8×	0.280	ITGAL
Sensory perception of salty taste	1	32.8×	0.280	SCNN1G
PP2A-mediated dephosphorylation of key metabolic factors	1	28.1×	0.280	MLXIPL
ARMS-mediated activation	1	28.1×	0.280	BRAF
AMPK inhibits chREBP transcriptional activation activity	1	24.6×	0.280	MLXIPL
Prolonged ERK activation events	1	24.6×	0.280	BRAF
DNA replication initiation	1	24.6×	0.280	POLE
SHOC2 M1731 mutant abolishes MRAS complex function	1	24.6×	0.280	BRAF
Gain-of-function MRAS complexes activate RAF signaling	1	24.6×	0.280	BRAF
TGFBR3 regulates TGF-beta signaling	1	24.6×	0.280	TGFBR1
ChREBP activates metabolic gene expression	1	21.9×	0.280	MLXIPL
Prostanoid ligand receptors	1	21.9×	0.280	PTGFR
G protein gated Potassium channels	1	19.7×	0.280	KCNJ10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 83 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA repair	9	6.9×	0.004	TEX15, TDP1, CLSPN, ZNF668, INTS3, DYRK1B, EYA4, RAD50 (+1 more)
regulation of response to tumor cell	1	203.0×	0.129	DAPK1
reproductive behavior	1	203.0×	0.129	GABRB3
hyperosmotic salinity response	1	203.0×	0.129	TRPV4
circadian sleep/wake cycle, REM sleep	1	203.0×	0.129	GABRB3
extracellular structure organization	1	203.0×	0.129	TGFBR1
anastral spindle assembly	1	203.0×	0.129	NUMA1
blood vessel endothelial cell delamination	1	203.0×	0.129	TRPV4
positive regulation of protein localization to spindle pole body	1	203.0×	0.129	NUMA1
positive regulation of mitotic spindle elongation	1	203.0×	0.129	NUMA1
regulation of retina development in camera-type eye	1	203.0×	0.129	CELF4
positive regulation of atrial cardiac muscle cell action potential	1	203.0×	0.129	TRPM4
positive regulation of autophagic cell death	1	203.0×	0.129	DAPK1
positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization	1	203.0×	0.129	TRPM4
regulation of epithelium regeneration	1	203.0×	0.129	EPPK1
mitotic DNA-templated DNA replication	1	203.0×	0.129	RECQL5
regulation of mitotic recombination	1	101.5×	0.129	RAD50
prolyl-tRNA aminoacylation	1	101.5×	0.129	PARS2
L-amino acid transport	1	101.5×	0.129	SLC7A2
vasopressin secretion	1	101.5×	0.129	TRPV4
memory T cell extravasation	1	101.5×	0.129	ITGAL
positive regulation of striated muscle contraction	1	101.5×	0.129	TRPV4
regulation of response to osmotic stress	1	101.5×	0.129	TRPV4
developmental cell growth	1	101.5×	0.129	ARIH2
glutamate reuptake	1	101.5×	0.129	KCNJ10
calcium ion import into cytosol	1	101.5×	0.129	TRPV4
regulation of homophilic cell adhesion	1	101.5×	0.129	TENM3
epicardium morphogenesis	1	101.5×	0.129	TGFBR1
sister chromatid segregation	1	67.7×	0.129	LATS1
inner cell mass cell fate commitment	1	67.7×	0.129	LATS1

Therapeutics

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 13 · Phased (≥1): 16 · Undrugged: 59

Druggability breadth: 43 of 95 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
BRAF	VEMURAFENIB
TGFBR1	MOMELOTINIB
GRIN3A	DEXTROMETHORPHAN
TDP1	LEVODOPA
DAPK1	FEDRATINIB
DYRK1B	NIRAPARIB
EPHB6	AFATINIB
GABRB3	LINDANE
HRH2	CETIRIZINE
ITGAL	LOVASTATIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TDP1	313	4
HRH2	115	4
EPHB6	50	4
BRAF	48	4
DYRK1B	35	4
GABRB3	32	4
TGFBR1	28	4
GRIN3A	22	4
DAPK1	17	4
TRPV4	6	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF, DAPK1, DYRK1B, EPHB6
SORAFENIB	4	BRAF, EPHB6
DASATINIB ANHYDROUS	4	BRAF, EPHB6
RUXOLITINIB	4	BRAF, DAPK1, EPHB6
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, EPHB6, TGFBR1
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, EPHB6
ABEMACICLIB	4	BRAF, DYRK1B
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF, EPHB6
PAZOPANIB	4	BRAF, EPHB6
DASATINIB	4	BRAF, EPHB6, TGFBR1
ERLOTINIB	4	BRAF, EPHB6
GEFITINIB	4	BRAF, EPHB6
IMATINIB	4	BRAF, HRH2
MOMELOTINIB	4	TGFBR1
NINTEDANIB	4	DYRK1B, EPHB6, TGFBR1
CRIZOTINIB	4	EPHB6, HRH2, TGFBR1
DEXTROMETHORPHAN	4	GRIN3A
LEVORPHANOL	4	GRIN3A
AMANTADINE	4	GRIN3A
CHLORPROMAZINE	4	GRIN3A, HRH2, TDP1
KETAMINE	4	GRIN3A
MEMANTINE	4	GRIN3A
PROCYCLIDINE	4	GRIN3A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
GABRB3	887	Binding:722, Functional:156, ADMET:6, Toxicity:3
TGFBR1	541	Binding:516, Functional:13, ADMET:12
HRH2	508	Binding:430, Functional:73, ADMET:5
DYRK1B	422	Binding:412, Functional:5, ADMET:5
DAPK1	332	Binding:330, ADMET:2
GRIN3A	195	Binding:183, Functional:7, ADMET:4, Toxicity:1
ITGAL	146	Binding:109, Functional:37
TDP1	109	Binding:105, Functional:4
TRPV4	99	Binding:94, Functional:5
EPHB6	87	Binding:87
VIPR2	27	Functional:14, Binding:13
HIVEP1	26	Binding:26
TRPM4	14	Binding:13, Functional:1
MMP26	8	Binding:8
CDCA2	6	Binding:6
SPEN	6	Binding:6
SCNN1G	5	Binding:3, ADMET:1, Functional:1
CNOT12	5	Binding:5
ELOVL5	5	Binding:5
IGF2R	5	Binding:4, Functional:1
AMPD3	4	Binding:4
SLC27A5	1	Binding:1
SENP3	1	Binding:1
CLSPN	1	Binding:1
VAC14	1	Binding:1
RBM12B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
TGFBR1	2.7.10.2, 2.7.11.30	non-specific protein-tyrosine kinase, receptor protein serine/threonine kinase
NAPSA	3.4.23.B1
MMP26	3.4.24.B7
SENP3	3.4.22.B72
TDP1	3.1.4.1	phosphodiesterase I
DAPK1	2.7.11.1	non-specific serine/threonine protein kinase
DYRK1B	2.7.12.1	dual-specificity kinase
FTCD	2.1.2.5, 4.3.1.4	glutamate formimidoyltransferase, formimidoyltetrahydrofolate cyclodeaminase
AMPD3	3.5.4.6	AMP deaminase
HAS1	2.4.1.212	hyaluronan synthase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
TGFBR1	541
GRIN3A	195
TDP1	109
DAPK1	332
DYRK1B	422
GABRB3	887
HRH2	508
ITGAL	146

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; 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)
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF, DAPK1, DYRK1B, EPHB6
SORAFENIB	4	BRAF, EPHB6
DASATINIB ANHYDROUS	4	BRAF, EPHB6
RUXOLITINIB	4	BRAF, DAPK1, EPHB6
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, EPHB6, TGFBR1
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, EPHB6
ABEMACICLIB	4	BRAF, DYRK1B
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF, EPHB6
PAZOPANIB	4	BRAF, EPHB6
DASATINIB	4	BRAF, EPHB6, TGFBR1
ERLOTINIB	4	BRAF, EPHB6
GEFITINIB	4	BRAF, EPHB6
IMATINIB	4	BRAF, HRH2
MOMELOTINIB	4	TGFBR1
NINTEDANIB	4	DYRK1B, EPHB6, TGFBR1
CRIZOTINIB	4	EPHB6, HRH2, TGFBR1
DEXTROMETHORPHAN	4	GRIN3A
LEVORPHANOL	4	GRIN3A
AMANTADINE	4	GRIN3A
CHLORPROMAZINE	4	GRIN3A, HRH2, TDP1
KETAMINE	4	GRIN3A
MEMANTINE	4	GRIN3A
PROCYCLIDINE	4	GRIN3A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	BRAF, TGFBR1, GRIN3A, TDP1, DAPK1, DYRK1B, EPHB6, GABRB3, HRH2, ITGAL
B	Phased (≥1) drug, not yet approved	6	VIPR2, MMP26, CDCA2, SPEN, TRPV4, AMPD3
C	Druggable family + PDB, no drug	2	SENP3, TRPM4
D	Druggable family + AlphaFold only, no drug	5	NAPSA, LINGO3, FTCD, HAS1, IGSF3
E	Difficult family or no structure, no drug	52	SACS, SCNN1G, STIL, SLC27A5, SLC7A2, SMC1B, SYT7, TEX15, MLXIPL, RPL36 (+42 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MFHAS1	0	DAPK1
SACS	0	—
SCNN1G	5	—
STIL	0	—
SLC27A5	1	—
SLC7A2	0	—
SMC1B	0	—
SYT7	0	—
TEX15	0	—
MLXIPL	0	—
NAPSA	0	—
RPL36	0	—
DCHS1	0	—
CELF4	0	—
LRP10	0	—
TLN2	0	—
EPPK1	0	—
LENG9	0	—
STON1	0	—
YLPM1	0	—
SENP3	1	—
TRPM4	14	—
CNOT12	5	—
FRAS1	0	—
CLSPN	1	—
TMEM121	0	—
KRTAP10-11	0	—
CLIC6	0	—
QTMAN	0	—
CCDC28A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	3
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IFOSFAMIDE	4	1
SELINEXOR	4	1
SECLIDEMSTAT	2	2