Breast ductal adenocarcinoma

Summary

Breast ductal adenocarcinoma (MONDO:0005590) is a disease with 75 cohort genes and 11 clinical trials. The dominant Reactome pathway is CDC42 GTPase cycle (11 cohort genes). Molecularly, BRAF G469E confers sensitivity to Trametinib in Breast Ductal Carcinoma (CIViC Level C). Top therapeutic interventions include indocyanine green acid form and talimogene laherparepvec.

At a glance

• Cohort genes: 75
• ClinVar variants: 258
• Clinical trials: 11
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast ductal adenocarcinoma
Mondo ID	MONDO:0005590
EFO	EFO:0006318
MeSH	D018270
DOID	DOID:3007
NCIT	C4017
UMLS	C1527349
MedGen	315942
Anatomy (UBERON)	UBERON:0001765
Is cancer (heuristic)	no

Also known as: breast ductal carcinoma · duct adenocarcinoma · duct carcinoma · ductal adenocarcinoma · ductal breast adenocarcinoma · ductal breast carcinoma · ductal carcinoma · ductal carcinoma of breast · ductal carcinoma of the breast · mammary duct adenocarcinoma

Data availability: 258 ClinVar variants · 63 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system cancer › breast adenocarcinoma › breast ductal adenocarcinoma

Related subtypes (12): breast lobular carcinoma, mammary Paget disease, signet ring cell breast carcinoma, breast mucinous cystadenocarcinoma, mucoepidermoid breast carcinoma, adenoid cystic breast carcinoma, sebaceous breast carcinoma, oncocytic breast carcinoma, breast malignant eccrine spiradenoma, lobular breast carcinoma in situ, mixed lobular and ductal breast carcinoma, inflammatory breast carcinoma

Subtypes (4): breast papillary carcinoma, breast apocrine carcinoma, invasive ductal breast carcinoma, ductal breast carcinoma in situ

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

258 retrieved; paginated sample, class counts are floors:

252 uncertain significance, 4 benign, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6193	NM_003579.4(RAD54L):c.973G>A (p.Gly325Arg)	RAD54L	Pathogenic	no assertion criteria provided
221328	NM_021098.3(CACNA1H):c.1624G>A (p.Glu542Lys)	CACNA1H	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
221372	GRCh38/hg38 1p36.21(chr1:13272807-13275727)x1		Uncertain significance	no assertion criteria provided
221375	GRCh38/hg38 1p36.11(chr1:26519016-26520363)x0		Uncertain significance	no assertion criteria provided
221345	Single allele	AARS1	Uncertain significance	no assertion criteria provided
221391	GRCh37/hg19 16p13.3-11.2(chr16:1279324-31926800)x3	ABAT	Uncertain significance	no assertion criteria provided
221428	GRCh37/hg19 2q34-35(chr2:211515125-215797412)x3	ABCA12	Uncertain significance	no assertion criteria provided
221521	GRCh38/hg38 16q12.1(chr16:47497444-48230506)x1	ABCC11	Uncertain significance	no assertion criteria provided
221326	NM_020297.4(ABCC9):c.2663G>T (p.Gly888Val)	ABCC9	Uncertain significance	no assertion criteria provided
221461	GRCh37/hg19 7q11.23(chr7:73122969-73256410)x3	ABHD11	Uncertain significance	no assertion criteria provided
221546	GRCh37/hg19 20p11.21(chr20:25284225-25371245)x3	ABHD12	Uncertain significance	no assertion criteria provided
221452	GRCh37/hg19 6p22.2-22.1(chr6:26545571-27115102)x3	ABT1	Uncertain significance	no assertion criteria provided
221528	GRCh37/hg19 17p13.1(chr17:7121580-7186623)x3	ACADVL	Uncertain significance	no assertion criteria provided
221513	GRCh37/hg19 16p12.3-11.2(chr16:19590412-29814175)x3	ACSM1	Uncertain significance	no assertion criteria provided
221491	GRCh37/hg19 12q21.31(chr12:80927874-81503412)x3	ACSS3	Uncertain significance	no assertion criteria provided
221359	chr1:17555508-24706269 complex variant	ACTL8	Uncertain significance	no assertion criteria provided
221397	GRCh37/hg19 19p13.2(chr19:8661944-10104083)x1	ACTL9	Uncertain significance	no assertion criteria provided
221466	GRCh37/hg19 8p11.22(chr8:39645687-39694694)x4	ADAM2	Uncertain significance	no assertion criteria provided
221543	GRCh38/hg38 20p13(chr20:3672810-3673617)x1	ADAM33	Uncertain significance	no assertion criteria provided
221418	GRCh37/hg19 1q21.3(chr1:150531540-150679158)x3	ADAMTSL4	Uncertain significance	no assertion criteria provided
221396	GRCh38/hg38 19p13.3(chr19:1508507-1510399)x0	ADAMTSL5	Uncertain significance	no assertion criteria provided
221356	chr21:45970718..47545826 complex variant	ADARB1	Uncertain significance	no assertion criteria provided
221522	GRCh38/hg38 16q12.1-12.2(chr16:48543083-53879916)x1	ADCY7	Uncertain significance	no assertion criteria provided
221346	Single allele	ADORA2B	Uncertain significance	no assertion criteria provided
221406	GRCh37/hg19 20q13.33(chr20:60882468-62045494)x1	ADRM1	Uncertain significance	no assertion criteria provided
221519	GRCh37/hg19 16p11.2(chr16:31154186-31926800)x3	AHSP	Uncertain significance	no assertion criteria provided
221331	NM_003488.4(AKAP1):c.946GGCTTGGATAGAAATGAGGAG[1] (p.316GLDRNEE[1])	AKAP1	Uncertain significance	criteria provided, single submitter
221462	GRCh37/hg19 7q21.12-21.2(chr7:87840219-91707100)x3	AKAP9	Uncertain significance	no assertion criteria provided
221515	GRCh37/hg19 16p11.2(chr16:29841933-30381027)x3	ALDOA	Uncertain significance	no assertion criteria provided
221481	GRCh37/hg19 11q23.1(chr11:111735939-111784393)x3	ALG9	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 73 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
SLC12A2	Orphanet:633021	SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome
SLC12A2	Orphanet:633024	SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
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
SREBF1	Orphanet:388	Hirschsprung disease
BRSK2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
BTNL2	Orphanet:797	Sarcoidosis
TBX3	Orphanet:3138	Ulnar-mammary syndrome
FERRY3	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
ALOXE3	Orphanet:281122	Self-improving collodion baby
ALOXE3	Orphanet:313	Lamellar ichthyosis
ALOXE3	Orphanet:79394	Congenital ichthyosiform erythroderma
CACNA1C	Orphanet:101016	Romano-Ward syndrome
CACNA1C	Orphanet:130	Brugada syndrome
CACNA1C	Orphanet:528084	Non-specific syndromic intellectual disability
CACNA1C	Orphanet:595098	Timothy syndrome type 1
CACNA1C	Orphanet:595105	Timothy syndrome type 2
CACNA1C	Orphanet:595109	Atypical Timothy syndrome
CACNA1H	Orphanet:642671	Familial hyperaldosteronism type IV
CACNA1H	Orphanet:64280	Childhood absence epilepsy

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1
multi_evidence	74

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
CNNM1	HGNC:102	ENSG00000119946	Q9NRU3	Metal transporter CNNM1	clinvar
BMI1	HGNC:1066	ENSG00000168283	P35226	Polycomb complex protein BMI-1	clinvar
SCAF11	HGNC:10784	ENSG00000139218	Q99590	Protein SCAF11	clinvar
SLC12A2	HGNC:10911	ENSG00000064651	P55011	Solute carrier family 12 member 2	clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
SREBF1	HGNC:11289	ENSG00000072310	P36956	Sterol regulatory element-binding protein 1	clinvar
ITPRID2	HGNC:11319	ENSG00000138434	P28290	Protein ITPRID2	clinvar
BTN3A2	HGNC:1139	ENSG00000186470	P78410	Butyrophilin subfamily 3 member A2	clinvar
AURKB	HGNC:11390	ENSG00000178999	Q96GD4	Aurora kinase B	clinvar
BRSK2	HGNC:11405	ENSG00000174672	Q8IWQ3	Serine/threonine-protein kinase BRSK2	clinvar
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	clinvar
TBX3	HGNC:11602	ENSG00000135111	O15119	T-box transcription factor TBX3	clinvar
FERRY3	HGNC:1184	ENSG00000047621	Q9NQ89	Ferry endosomal RAB5 effector complex subunit 3	clinvar
TSPAN8	HGNC:11855	ENSG00000127324	P19075	Tetraspanin-8	clinvar
VAV3	HGNC:12659	ENSG00000134215	Q9UKW4	Guanine nucleotide exchange factor VAV3	clinvar
POLR1H	HGNC:13182	ENSG00000066379	Q9P1U0	DNA-directed RNA polymerase I subunit RPA12	clinvar
ANP32A	HGNC:13233	ENSG00000140350	P39687	Acidic leucine-rich nuclear phosphoprotein 32 family member A	clinvar
CDIP1	HGNC:13234	ENSG00000089486	Q9H305	Cell death-inducing p53-target protein 1	clinvar
ALOXE3	HGNC:13743	ENSG00000179148	Q9BYJ1	Hydroperoxide isomerase ALOXE3	clinvar
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	clinvar
CCHCR1	HGNC:13930	ENSG00000204536	Q8TD31	Coiled-coil alpha-helical rod protein 1	clinvar
CACNA1H	HGNC:1395	ENSG00000196557	O95180	Voltage-dependent T-type calcium channel subunit alpha-1H	clinvar
ANTKMT	HGNC:14152	ENSG00000103254	Q9BQD7	Adenine nucleotide translocase lysine N-methyltransferase	clinvar
FAM234A	HGNC:14163	ENSG00000167930	Q9H0X4	Protein FAM234A	clinvar
ARHGEF12	HGNC:14193	ENSG00000196914	Q9NZN5	Rho guanine nucleotide exchange factor 12	clinvar
AUTS2	HGNC:14262	ENSG00000158321	Q8WXX7	Autism susceptibility gene 2 protein	clinvar
HTRA2	HGNC:14348	ENSG00000115317	O43464	Serine protease HTRA2, mitochondrial	clinvar
ELOVL2	HGNC:14416	ENSG00000197977	Q9NXB9	Very long chain fatty acid elongase 2	clinvar
ABCA12	HGNC:14637	ENSG00000144452	Q86UK0	Glucosylceramide transporter ABCA12	clinvar
ABCC11	HGNC:14639	ENSG00000121270	Q96J66	ATP-binding cassette sub-family C member 11	clinvar
COL5A3	HGNC:14864	ENSG00000080573	P25940	Collagen alpha-3(V) chain	clinvar
ASPN	HGNC:14872	ENSG00000106819	Q9BXN1	Asporin	clinvar
CAPZA1	HGNC:1488	ENSG00000116489	P52907	F-actin-capping protein subunit alpha-1	clinvar
OR2T4	HGNC:15016	ENSG00000196944	Q8NH00	Olfactory receptor 2T4	clinvar
ADAM33	HGNC:15478	ENSG00000149451	Q9BZ11	Disintegrin and metalloproteinase domain-containing protein 33	clinvar
BTBD2	HGNC:15504	ENSG00000133243	Q9BX70	BTB/POZ domain-containing protein 2	clinvar
ALG9	HGNC:15672	ENSG00000086848	Q9H6U8	Alpha-1,2-mannosyltransferase ALG9	clinvar
ADRM1	HGNC:15759	ENSG00000130706	Q16186	Proteasomal ubiquitin receptor ADRM1	clinvar
ARFGAP1	HGNC:15852	ENSG00000101199	Q8N6T3	ADP-ribosylation factor GTPase-activating protein 1	clinvar
ABHD12	HGNC:15868	ENSG00000100997	Q8N2K0	Lysophosphatidylserine lipase ABHD12	clinvar
DBNDD2	HGNC:15881	ENSG00000244274	Q9BQY9	Dysbindin domain-containing protein 2	clinvar
ESF1	HGNC:15898	ENSG00000089048	Q9H501	ESF1 homolog	clinvar
CDH26	HGNC:15902	ENSG00000124215	Q8IXH8	Cadherin-like protein 26	clinvar
NAA20	HGNC:15908	ENSG00000173418	P61599	N-alpha-acetyltransferase 20	clinvar
CCNH	HGNC:1594	ENSG00000134480	P51946	Cyclin-H	clinvar
ASB3	HGNC:16013	ENSG00000115239	Q9Y575	Ankyrin repeat and SOCS box protein 3	clinvar
CASD1	HGNC:16014	ENSG00000127995	Q96PB1	N-acetylneuraminate (7)9-O-acetyltransferase	clinvar
OSBPL8	HGNC:16396	ENSG00000091039	Q9BZF1	Oxysterol-binding protein-related protein 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
CNNM1	Metal transporter CNNM1	Probable metal transporter.
BMI1	Polycomb complex protein BMI-1	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
SCAF11	Protein SCAF11	Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly.
SLC12A2	Solute carrier family 12 member 2	Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane.
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SREBF1	Sterol regulatory element-binding protein 1	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane.
BTN3A2	Butyrophilin subfamily 3 member A2	Plays a role in T-cell responses in the adaptive immune response.
AURKB	Aurora kinase B	Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis.
BRSK2	Serine/threonine-protein kinase BRSK2	Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
TBX3	T-box transcription factor TBX3	Transcriptional repressor involved in developmental processes.
FERRY3	Ferry endosomal RAB5 effector complex subunit 3	Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary).
TSPAN8	Tetraspanin-8	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.
VAV3	Guanine nucleotide exchange factor VAV3	Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1.
POLR1H	DNA-directed RNA polymerase I subunit RPA12	Core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates.
ANP32A	Acidic leucine-rich nuclear phosphoprotein 32 family member A	Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription.
CDIP1	Cell death-inducing p53-target protein 1	Acts as an important p53/TP53-apoptotic effector.
ALOXE3	Hydroperoxide isomerase ALOXE3	Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced lipoxygenases activity.
CACNA1C	Voltage-dependent L-type calcium channel subunit alpha-1C	Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CCHCR1	Coiled-coil alpha-helical rod protein 1	May be a regulator of keratinocyte proliferation or differentiation.
CACNA1H	Voltage-dependent T-type calcium channel subunit alpha-1H	Voltage-sensitive calcium channel that gives rise to T-type calcium currents.
ANTKMT	Adenine nucleotide translocase lysine N-methyltransferase	Mitochondrial protein-lysine N-methyltransferase that trimethylates adenine nucleotide translocases ANT2/SLC25A5 and ANT3/SLC25A6, thereby regulating mitochondrial respiration.
ARHGEF12	Rho guanine nucleotide exchange factor 12	Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.
AUTS2	Autism susceptibility gene 2 protein	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
HTRA2	Serine protease HTRA2, mitochondrial	Serine protease that shows proteolytic activity against a non-specific substrate beta-casein.
ELOVL2	Very long chain fatty acid elongase 2	Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle.
ABCA12	Glucosylceramide transporter ABCA12	Transports lipids such as glucosylceramides from the outer to the inner leaflet of lamellar granules (LGs) membrane, whereby the lipids are finally transported to the keratinocyte periphery via the trans-Golgi network and LGs and released…
ABCC11	ATP-binding cassette sub-family C member 11	ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells.
COL5A3	Collagen alpha-3(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
ASPN	Asporin	Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system.
CAPZA1	F-actin-capping protein subunit alpha-1	F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends.
OR2T4	Olfactory receptor 2T4	Odorant receptor.
ALG9	Alpha-1,2-mannosyltransferase ALG9	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
ADRM1	Proteasomal ubiquitin receptor ADRM1	Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
ARFGAP1	ADP-ribosylation factor GTPase-activating protein 1	GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1).
ABHD12	Lysophosphatidylserine lipase ABHD12	Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes.
DBNDD2	Dysbindin domain-containing protein 2	May modulate the activity of casein kinase-1.
ESF1	ESF1 homolog	May constitute a novel regulatory system for basal transcription.
CDH26	Cadherin-like protein 26	Cadherins are calcium-dependent cell adhesion proteins.
NAA20	N-alpha-acetyltransferase 20	Catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln.
CCNH	Cyclin-H	Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex.
ASB3	Ankyrin repeat and SOCS box protein 3	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CASD1	N-acetylneuraminate (7)9-O-acetyltransferase	Key enzyme in the biosynthesis of O-acetylated (O-Ac) sialoglycans such as gangliosides O-AcGD3 and O-AcGD2, which affect various processes such as cell-cell interactions, host-pathogen recognition.
OSBPL8	Oxysterol-binding protein-related protein 8	Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the pl…
ABHD11	sn-1-specific diacylglycerol lipase ABHD11	Catalyzes the hydrolysis of diacylglycerol in vitro and may function as a key regulator in lipid metabolism, namely by regulating the intracellular levels of diacylglycerol. 1,2-diacyl-sn-glycerols are the preferred substrate over 1,3-diac…
CD22	B-cell receptor CD22	Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and trafficking to bone marrow.
BCKDK	Branched-chain alpha-ketoacid dehydrogenase kinase	Serine/threonine-protein kinase component of macronutrients metabolism.
CIB1	Calcium and integrin-binding protein 1	Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis.

Protein-family classification

Druggable: 20 · Difficult: 13 · Unknown: 42 · Druggable fraction: 0.27

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	3	4.5×	0.299
Transporter	2	2.1×	0.714
Kinase	4	1.5×	0.714
Scaffold/PPI	6	1.4×	0.714
Antibody/Immunoglobulin	3	1.2×	0.873
Other/Unknown	42	1.0×	0.873
Protease	2	1.0×	0.873
Enzyme (other)	5	0.8×	0.910
Transcription factor	7	0.8×	0.910
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
CNNM1	Other/Unknown	no		CBS_dom, CNNM, Ion_transp-like_CBS
BMI1	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
SCAF11	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
SLC12A2	Other/Unknown	no		SLC12A1/SLC12A2, NKCC1, AA-permease/SLC12A_dom
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SREBF1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
ITPRID2	Other/Unknown	no		ITPR-bd, SSFA2_C, TESPA1-like
BTN3A2	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
AURKB	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BRSK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
TBX3	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
FERRY3	Other/Unknown	no		Fy-3
TSPAN8	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
VAV3	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
POLR1H	Transcription factor	no		Znf_TFIIS, Rpa12/Rpb9/Rpc10/TFS, DNA-dir_RNA_pol-M_15_CS
ANP32A	Other/Unknown	no		Leu-rich_rpt, U2A’_phosphoprotein32A_C, LRR_dom_sf
CDIP1	Other/Unknown	no		LITAF, LITAF_fam
ALOXE3	Enzyme (other)	yes	4.2.1.152	LipOase, PLAT/LH2_dom, LipOase_mml
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
CCHCR1	Other/Unknown	no		HCR
CACNA1H	Ion channel	yes		VDCC_T_a1, Ion_trans_dom, Volt_channel_dom_sf
ANTKMT	Other/Unknown	no		FAM173A/B, SAM-dependent_MTases_sf
FAM234A	Other/Unknown	no		Quinoprotein_ADH-like_sf, FAM234, Beta-prop_FAM234A_B
ARHGEF12	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, PDZ
AUTS2	Other/Unknown	no		AUTS2
HTRA2	Protease	yes	3.4.21.108	PDZ, Peptidase_S1C, Peptidase_S1_PA
ELOVL2	Other/Unknown	no		ELO_fam, ELO_CS, ELOVL2
ABCA12	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
ABCC11	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
COL5A3	Other/Unknown	no		Fib_collagen_C, Collagen, ConA-like_dom_sf
ASPN	Other/Unknown	no		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
CAPZA1	Other/Unknown	no		CapZ_alpha, F-actin_cap_asu_CS, CapZ_alpha/beta
OR2T4	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
ADAM33	Protease	yes		EGF, Peptidase_M12B, Disintegrin_dom
BTBD2	Other/Unknown	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, BACK
ALG9	Enzyme (other)	yes	2.4.1.259	GPI_mannosylTrfase
ADRM1	Other/Unknown	no		Rpn13/ADRM1, RPN13_DEUBAD, RPN13_DEUBAD_sf
ARFGAP1	Other/Unknown	no		ArfGAP_dom, ARFGAP/RecO, ArfGAP_dom_sf
ABHD12	Other/Unknown	no		AB_hydrolase_1, AB_hydrolase_fold
DBNDD2	Other/Unknown	no		Dysbindin
ESF1	Other/Unknown	no		NUC153, Nucleotide-bd_a/b_plait_sf, Esf1
CDH26	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
NAA20	Enzyme (other)	yes	2.3.1.254	GNAT_dom, Acyl_CoA_acyltransferase, NatB_acetyltransferase_subunit
CCNH	Other/Unknown	no		Cyclin_N, Cyclin-like_dom, CyclinH/Ccl1
ASB3	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
CASD1	Enzyme (other)	yes	2.3.1.45	Cas1_AcylTrans_dom, Cyclin-like_sf, NXPE4_C
OSBPL8	Scaffold/PPI	no		Oxysterol-bd, PH_domain, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

68 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
ventricular zone	9
ganglionic eminence	8
male germ line stem cell (sensu Vertebrata) in testis	6
secondary oocyte	6
cortical plate	6
buccal mucosa cell	5
calcaneal tendon	5
tendon of biceps brachii	5
mucosa of transverse colon	5
primordial germ cell in gonad	4
cerebellar hemisphere	4
apex of heart	4
left testis	4
right testis	4
lower esophagus mucosa	4
prefrontal cortex	3
right adrenal gland	3
granulocyte	3
oocyte	3
cerebellar cortex	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
CNNM1	176	broad	marker	postcentral gyrus, prefrontal cortex, parietal lobe
BMI1	293	ubiquitous	marker	germinal epithelium of ovary, choroid plexus epithelium, endothelial cell
SCAF11	295	ubiquitous	marker	buccal mucosa cell, colonic epithelium, tendon of biceps brachii
SLC12A2	277	ubiquitous	marker	palpebral conjunctiva, parotid gland, inferior vagus X ganglion
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SREBF1	172	ubiquitous	marker	left adrenal gland, right adrenal gland, left adrenal gland cortex
ITPRID2	294	ubiquitous	marker	body of pancreas, tibial nerve, stromal cell of endometrium
BTN3A2	266	ubiquitous	marker	granulocyte, leukocyte, monocyte
AURKB	187	ubiquitous	marker	ventricular zone, ganglionic eminence, oocyte
BRSK2	176	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
TBX3	243	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, adrenal cortex
FERRY3	280	ubiquitous	marker	tendon of biceps brachii, buccal mucosa cell, Brodmann (1909) area 23
TSPAN8	262	broad	marker	colonic mucosa, mucosa of sigmoid colon, jejunal mucosa
VAV3	258	ubiquitous	marker	tongue squamous epithelium, renal medulla, esophagus squamous epithelium
POLR1H	133	ubiquitous	marker	granulocyte, mucosa of transverse colon, primordial germ cell in gonad
ANP32A	295	ubiquitous	marker	ganglionic eminence, cortical plate, embryo
CDIP1	134	ubiquitous	yes	prefrontal cortex, right frontal lobe, frontal cortex
ALOXE3	141	tissue_specific	yes	skin of leg, skin of abdomen, zone of skin
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
CCHCR1	134	ubiquitous	marker	left testis, right testis, testis
CACNA1H	166	broad	marker	lower esophagus muscularis layer, muscle layer of sigmoid colon, lower esophagus
ANTKMT	243	ubiquitous	marker	anterior cingulate cortex, cingulate cortex, mucosa of transverse colon
FAM234A	241	ubiquitous	marker	apex of heart, mucosa of transverse colon, gastrocnemius
ARHGEF12	288	ubiquitous	marker	upper leg skin, visceral pleura, heart right ventricle
AUTS2	292	ubiquitous	marker	cortical plate, tibia, ganglionic eminence
HTRA2	280	ubiquitous	marker	cortical plate, right coronary artery, trabecular bone tissue
ELOVL2	195	broad	yes	ventricular zone, ganglionic eminence, pigmented layer of retina

Protein interactions among cohort

Intra-cohort edges: 13.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
BRAF	7,394
AURKB	6,131
BMI1	5,761
CDC27	5,006
BRCA2	4,839
SREBF1	4,089
HTRA2	4,023
BCKDK	3,756
CACNA1C	3,145

Intra-cohort edges

A	B	Sources
ABCA12	ALOXE3	string_interaction
ABCA12	BMI1	intact
ABT1	ESF1	intact, string_interaction
ABT1	SCAF11	intact
ARHGEF12	KCNT1	intact
AURKB	CDH11	intact
AURKB	CENPE	string_interaction
BMI1	ZNF638	biogrid_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	TBX3	intact
BRCA1	BRCA2	string_interaction
BRCA1	SYT6	biogrid_interaction
ELOVL2	FAM234A	biogrid_interaction

Structural data

PDB: 40 · AlphaFold-only: 35 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRAF	P15056	131
CCNH	P51946	47
BRCA1	P38398	33
CACNA1C	Q13936	33
CDC27	P30260	25
ADRM1	Q16186	21
BTN3A2	P78410	18
SLC12A2	P55011	14
BRCA2	P51587	14
BMI1	P35226	13
HTRA2	O43464	13
CAPZA1	P52907	10
ANP32A	P39687	9
CIB1	Q99828	9
AHSP	Q9NZD4	8
POLR1H	Q9P1U0	7
CD22	P20273	7
CENPE	Q02224	6
KCNT1	Q5JUK3	6
CACNA1H	O95180	5
BCKDK	O14874	5
ARHGEF12	Q9NZN5	4
OSBPL8	Q9BZF1	4
SPEN	Q96T58	4
ELP2	Q6IA86	4
RRP1	P56182	4
NAA20	P61599	3
ADAM33	Q9BZ11	2
ALG9	Q9H6U8	2
ARFGAP1	Q8N6T3	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASB3	Q9Y575	90.62
ACSM1	Q08AH1	88.80
ABHD11	Q8NFV4	88.41
CASD1	Q96PB1	87.87
TSPAN8	P19075	87.75
ELOVL2	Q9NXB9	87.30
BTNL2	Q9UIR0	85.97
ASPN	Q9BXN1	85.71
ABHD12	Q8N2K0	85.60
FERRY3	Q9NQ89	84.04
OR2T4	Q8NH00	83.85
ANTKMT	Q9BQD7	82.01
FAM234A	Q9H0X4	81.12
CCHCR1	Q8TD31	79.52
ABCC11	Q96J66	79.30
LZIC	Q8WZA0	78.77
CDH7	Q9ULB5	78.22
CDH19	Q9H159	78.14
ABT1	Q9ULW3	78.08
CDH11	P55287	77.65
SYT6	Q5T7P8	73.96
CDH26	Q8IXH8	72.84
GJC2	Q5T442	68.50
BRSK2	Q8IWQ3	68.46
ABCA12	Q86UK0	68.32
CNNM1	Q9NRU3	67.07
CDC42EP5	Q6NZY7	65.09
ESF1	Q9H501	64.81
CNTRL	Q7Z7A1	60.85
DBNDD2	Q9BQY9	60.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 857. Enrichment computed across 244 evidence-associated genes (159 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 159 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
CDC42 GTPase cycle	11	5.0×	0.011	VAV3, ARHGEF12, CDC42EP5, KCTD3, ARHGAP33, DLC1, ECT2, ARHGAP35 (+3 more)
Disease	28	2.3×	0.011	BRAF, BRCA1, BRCA2, ABCA12, ALG9, ADRM1, CCNH, BCKDK (+20 more)
Golgi-to-ER retrograde transport	7	5.8×	0.054	CAPZA1, ARFGAP1, CENPE, TUBA3E, KIFC1, KIF22, ARFGAP3
Apoptosis induced DNA fragmentation	3	15.4×	0.065	H1-2, H1-5, HMGB2
Diseases of DNA Double-Strand Break Repair	3	15.4×	0.065	BRCA1, BRCA2, ATRIP
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	15.4×	0.065	BRCA1, BRCA2, ATRIP
NCAM1 interactions	5	7.8×	0.065	CACNA1C, CACNA1H, COL5A3, COL6A1, COL6A3
Intra-Golgi and retrograde Golgi-to-ER traffic	7	4.6×	0.065	CAPZA1, ARFGAP1, CENPE, TUBA3E, KIFC1, KIF22, ARFGAP3
Cell Cycle Checkpoints	8	4.5×	0.065	BRCA1, AURKB, ADRM1, CDC27, CENPE, CENPK, CENPN, ATRIP
M Phase	9	3.7×	0.065	AURKB, ADRM1, CEP43, CDC27, CENPE, TUBA3E, CENPK, CENPN (+1 more)
Cell Cycle	13	3.0×	0.065	BRCA1, BRCA2, AURKB, ADRM1, CCNH, CEP43, CDC27, CENPE (+5 more)
Adaptive Immune System	14	2.6×	0.065	BTN3A2, BTNL2, CAPZA1, ADRM1, ASB3, CD22, CDC27, CENPE (+6 more)
Assembly of collagen fibrils and other multimeric structures	5	6.3×	0.074	COL5A3, COL6A1, COL6A3, COL7A1, LOX
Mitotic Metaphase and Anaphase	7	4.3×	0.074	AURKB, ADRM1, CDC27, CENPE, TUBA3E, CENPK, CENPN
Mitotic Anaphase	7	4.3×	0.074	AURKB, ADRM1, CDC27, CENPE, TUBA3E, CENPK, CENPN
Regulation of Homotypic Cell-Cell Adhesion	3	12.7×	0.079	ADAM33, CDH11, CDH19
Regulation of Expression and Function of Type II Classical Cadherins	3	12.7×	0.079	ADAM33, CDH11, CDH19
Cell Cycle, Mitotic	10	3.0×	0.079	AURKB, ADRM1, CCNH, CEP43, CDC27, CENPE, TUBA3E, CENPK (+2 more)
Cellular responses to stimuli	13	2.6×	0.079	BMI1, BRCA1, CACNA1H, CAPZA1, ADRM1, ARFGAP1, CDC27, TUBA3E (+5 more)
MHC class II antigen presentation	7	3.9×	0.088	CAPZA1, CENPE, TUBA3E, HLA-DQA1, AP1G1, AP2A2, KIF22
Diseases of DNA repair	3	10.8×	0.099	BRCA1, BRCA2, ATRIP
Signaling by Rho GTPases	12	2.6×	0.099	AURKB, ARHGEF12, CDC42EP5, SPEN, CENPE, TUBA3E, KCTD3, ANKRD26 (+4 more)
Collagen chain trimerization	4	6.5×	0.103	COL5A3, COL6A1, COL6A3, COL7A1
Mitotic Spindle Checkpoint	5	5.0×	0.103	AURKB, CDC27, CENPE, CENPK, CENPN
COPI-dependent Golgi-to-ER retrograde traffic	6	4.2×	0.103	ARFGAP1, CENPE, TUBA3E, KIFC1, KIF22, ARFGAP3
Factors involved in megakaryocyte development and platelet production	8	3.3×	0.103	CAPZA1, CENPE, TUBA3E, AKAP1, IFNA10, KIFC1, KIF22, PRKACB
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	12	2.5×	0.103	AURKB, ARHGEF12, CDC42EP5, SPEN, CENPE, TUBA3E, KCTD3, ANKRD26 (+4 more)
Adherens junctions interactions	4	6.2×	0.107	ADAM33, CDH11, CDH19, CDH7
Cell-cell junction organization	4	6.2×	0.107	ADAM33, CDH11, CDH19, CDH7
RHOB GTPase cycle	5	4.8×	0.107	ARHGEF12, DLC1, ECT2, ARHGAP35, ARHGDIG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 223 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
energy derivation by oxidation of organic compounds	2	75.6×	0.083	ACSM1, ACADVL
positive regulation of aspartate secretion	2	75.6×	0.083	SLC12A2, ABAT
mitotic sister chromatid biorientation	2	75.6×	0.083	AURKB, BOD1
establishment of organelle localization	2	50.4×	0.113	NLRP5, CROCC
branching involved in mammary gland duct morphogenesis	3	18.9×	0.113	TBX3, DDR1, PML
forebrain development	5	7.9×	0.113	HTRA2, DLC1, ARHGAP35, LRP2, NOTCH3
cell morphogenesis	7	4.9×	0.113	CDH26, CDH11, CDH19, CDH7, COL6A1, ECT2, NFIA
cell communication by electrical coupling	2	37.8×	0.125	GJC2, KCNA1
prostate gland stromal morphogenesis	2	37.8×	0.125	CRIP1, FOXA1
cellular response to potassium ion	3	14.2×	0.125	SLC12A2, CACNA1H, ABCC9
adherens junction organization	4	9.2×	0.125	CDH26, CDH11, CDH19, CDH7
calcium-dependent cell-cell adhesion	4	8.6×	0.125	CDH26, CDH11, CDH19, CDH7
chromatin remodeling	10	3.3×	0.125	BMI1, BRCA1, CHD3, DPF1, YEATS2, NIPBL, KDM4E, HMGB2 (+2 more)
ciliary basal body organization	2	30.2×	0.152	CROCC, CCP110
negative regulation of vascular wound healing	2	30.2×	0.152	SLC12A2, ALOX5
cell-cell junction assembly	4	8.0×	0.152	CDH26, CDH11, CDH19, CDH7
response to ionizing radiation	4	7.4×	0.164	BRCA1, LZIC, INTS3, RAD54L
cell-cell adhesion mediated by cadherin	4	7.4×	0.164	CDH26, CDH11, CDH19, CDH7
L-isoleucine catabolic process	2	25.2×	0.167	BCKDK, BCAT2
protection from natural killer cell mediated cytotoxicity	2	25.2×	0.167	HLA-A, HLA-B
regulation of cell size	3	10.3×	0.167	VAV3, COL6A1, ARHGAP35
positive regulation of cilium assembly	3	10.3×	0.167	CROCC, CCP110, ARHGAP35
regulation of cell division	3	10.3×	0.167	CIB1, NLRP5, YEATS2
mitotic metaphase chromosome alignment	4	6.9×	0.167	CENPE, BOD1, KIFC1, KIF22
vesicle-mediated transport	8	3.5×	0.167	ARFGAP1, SYT6, ARL5B, NECAP2, AP1G1, AP2A2, AP3B2, ARFGAP3
response to UV	4	6.6×	0.174	COL6A1, COL6A3, ERCC8, PML
response to auditory stimulus	3	9.9×	0.177	ABHD12, ERCC8, ATP1A2
muscle tissue morphogenesis	2	21.6×	0.179	ADARB1, MYL11
antigen processing and presentation of polysaccharide antigen via MHC class II	1	75.6×	0.184	ARL8B
antigen processing and presentation following phagocytosis	1	75.6×	0.184	ARL8B

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Lapatinib, Paclitaxel, Trastuzumab.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 14 · Undrugged: 61

Druggability breadth: 96 of 244 evidence-associated genes (39%) 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
SLC12A2	BUMETANIDE
BRCA1	RIBOFLAVIN
SREBF1	CALCIFEDIOL ANHYDROUS
AURKB	SORAFENIB TOSYLATE
BRSK2	BRIGATINIB
CACNA1C	REMIFENTANIL
CACNA1H	PIMOZIDE
ADRM1	BORTEZOMIB
ABHD12	ORLISTAT
CCNH	ABEMACICLIB
KCNT1	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1C	85	4
AURKB	82	4
BRAF	48	4
CCNH	28	4
BRCA1	12	4
BRSK2	10	4
CACNA1H	10	4
ADRM1	2	4
ABHD12	2	4
KCNT1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	AURKB, BRAF
SORAFENIB	4	AURKB, BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, CACNA1C
ABEMACICLIB	4	BRAF, CCNH
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	AURKB, BRAF
DASATINIB	4	AURKB, BRAF, CACNA1C
ERLOTINIB	4	AURKB, BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
BUMETANIDE	4	SLC12A2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CALCIFEDIOL ANHYDROUS	4	SREBF1
SORAFENIB TOSYLATE	4	AURKB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
AURKB	1,227	Binding:1199, ADMET:22, Functional:6
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
CCNH	348	Binding:346, Functional:2
CENPE	346	Functional:241, Binding:105
BRSK2	230	Binding:230
CACNA1H	124	Binding:102, Functional:17, ADMET:4, Toxicity:1
ADRM1	60	Binding:60
ABHD12	35	Binding:31, Toxicity:3, ADMET:1
BMI1	25	Binding:25
KCNT1	24	Binding:24
BCKDK	18	Binding:18
SREBF1	17	Binding:17
CD22	16	Binding:15, Functional:1
ABCC11	15	Functional:15
SLC12A2	13	Binding:9, Functional:4
BRCA1	13	Binding:9, Functional:4
CIB1	12	Binding:12
ARHGEF12	11	Binding:11
HTRA2	11	Binding:11
CAPZA1	8	Binding:8
SPEN	6	Binding:6
LZIC	5	Binding:5
ELOVL2	4	Binding:4
ABHD11	4	Binding:2, Functional:2
ANP32A	3	Binding:3
ADAM33	2	Binding:2
ARFGAP1	2	Binding:2
CEP43	2	Binding:2
OSBPL8	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
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
ALOXE3	4.2.1.152	hydroperoxy icosatetraenoate dehydratase
HTRA2	3.4.21.108	HtrA2 peptidase
ALG9	2.4.1.259, 2.4.1.261	dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase, dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase
NAA20	2.3.1.254	N-terminal methionine Nalpha-acetyltransferase NatB
CASD1	2.3.1.45	N-acetylneuraminate 9-O-acetyltransferase
CSAD	4.1.1.29	sulfinoalanine decarboxylase

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
AURKB	1,227
BRSK2	230
CACNA1C	575
CACNA1H	124
CCNH	348
CENPE	346

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	AURKB, BRAF
SORAFENIB	4	AURKB, BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, CACNA1C
ABEMACICLIB	4	BRAF, CCNH
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	AURKB, BRAF
DASATINIB	4	AURKB, BRAF, CACNA1C
ERLOTINIB	4	AURKB, BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
BUMETANIDE	4	SLC12A2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CALCIFEDIOL ANHYDROUS	4	SREBF1
SORAFENIB TOSYLATE	4	AURKB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	BRAF, SLC12A2, BRCA1, SREBF1, AURKB, BRSK2, CACNA1C, CACNA1H, ADRM1, ABHD12 (+2 more)
B	Phased (≥1) drug, not yet approved	2	SPEN, CENPE
C	Druggable family + PDB, no drug	9	BTN3A2, ALOXE3, HTRA2, ADAM33, ALG9, NAA20, CD22, BCKDK, CSAD
D	Druggable family + AlphaFold only, no drug	5	BTNL2, ABCA12, ABCC11, OR2T4, CASD1
E	Difficult family or no structure, no drug	47	CNNM1, BMI1, SCAF11, BRCA2, ITPRID2, TBX3, FERRY3, TSPAN8, VAV3, POLR1H (+37 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
CNNM1	0	—
BMI1	25	—
SCAF11	0	—
ITPRID2	0	—
BTN3A2	0	—
BTNL2	0	—
TBX3	0	—
FERRY3	0	—
TSPAN8	0	—
VAV3	0	—
POLR1H	0	—
ANP32A	3	—
CDIP1	0	—
ALOXE3	0	—
CCHCR1	0	—
ANTKMT	0	—
FAM234A	0	—
ARHGEF12	11	—
AUTS2	0	—
HTRA2	11	—
ELOVL2	4	—
ABCA12	0	—
ABCC11	15	—
COL5A3	0	—
ASPN	0	—
CAPZA1	8	—
OR2T4	0	—
ADAM33	2	—
BTBD2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2	2
PHASE1/PHASE2	2
EARLY_PHASE1	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INDOCYANINE GREEN ACID FORM	4	2
TALIMOGENE LAHERPAREPVEC	4	1
CHEMBL1510899	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
BRAF G469E	Trametinib	Sensitivity/Response	CIViC C	EID7861