Brain aneurysm

Summary

Brain aneurysm (MONDO:0005291) is a disease caused by ANGPTL6 (GenCC Strong), with 75 cohort genes (157 GWAS associations across 30 studies) and 27 clinical trials. The dominant Reactome pathway is SLC-mediated transport of organic cations (3 cohort genes).

At a glance

• Causal gene: ANGPTL6 (GenCC Strong)
• Cohort genes: 75
• GWAS associations: 157
• ClinVar variants: 1
• Clinical trials: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain aneurysm
Mondo ID	MONDO:0005291
EFO	EFO:0003870
MeSH	D002532
DOID	DOID:10941
UMLS	C0751003
MedGen	196706
Anatomy (UBERON)	UBERON:0003499
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 157 GWAS associations (30 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › intracranial arterial disease › cerebral arterial disease › brain aneurysm

Related subtypes (3): middle cerebral artery infarction, posterior cerebral artery infarction, Moyamoya disease

Subtypes (1): intracranial berry aneurysm

Genetics & variants

GWAS landscape

157 GWAS associations across 30 studies. Top hits map to 29 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1537373	3e-29	CDKN2B-AS1	T	0.18
rs371331393	9e-27	ARHGAP32	A	43.57
rs6841581	3e-26	PRMT5P1 - EDNRA	A	0.22
rs138525217	6e-23	CD163L1	T	75.98
rs1333040	2e-22	CDKN2B-AS1	T	1.32
rs75822236	1e-19	GBA1	T	161.4
rs79134766	2e-19	OLFML2A	G	7.14
rs55965782	9e-18	RPL31P26 - PRMT5P1	T	0.26
rs11661542	3e-17	RBBP8-AS1	A	0.14
rs112859779	3e-16	TCF24	C	5.26
rs78458145	3e-15	LINC01237	G	4.17
rs116969723	4e-15	LRRC3	G	4.17
rs3742321	5e-15	STARD13	T	0.14
rs7184525	6e-15	CFDP1	A	0.14
rs118107419	1e-14	SLC2A14	C	4
rs6997005	1e-14	RP1	A	0.15
rs2280543	1e-14	BET1L	T	0.24
rs4977574	1e-14	CDKN2B-AS1	G	0.18
rs79780963	2e-14	NT5C2	T	0.19
rs62516550	3e-14	RP1	T	0.16
rs6741819	4e-14	RNF144A	C	4
rs727333	4e-14	DSCAM	C	3.85
rs7137731	5e-14	FGD6	T	0.12
rs59626274	6e-14	LINC02991	C	3.85
rs7866503	2e-13	CDKN2B-AS1	T	1.26
rs74487487	2e-13	LINC00992 - LINC02147	G	2.89
rs549990459	2e-13	NHLRC2 - ADRB1	C	3.22
rs55800589	3e-13	NAPA-AS1	G	2.63
rs573922818	3e-13	GNLY - RNU1-38P	C	3.69
rs61775135	4e-13	PRDM2	C	3.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011020	Bakker MK	2020	7,495	71,934	Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
GCST011021	Bakker MK	2020	7,495	71,934	Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
GCST90018595	Sakaue S	2021	3,132	152,022	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90013685	Ishigaki K	2020	2,820	192,383	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST000646	Yasuno K	2010	2,780	12,515	Genome-wide association study of intracranial aneurysm identifies three new risk loci.
GCST002633	Foroud T	2014	2,617	2,548	Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.
GCST90013762	Ishigaki K	2020	1,818	94,928	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST90477997	Verma A	2024	1,609	449,069	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST000262	Bilguvar K	2008	1,580	6,276	Susceptibility loci for intracranial aneurysm in European and Japanese populations.
GCST003683	van ’t Hof FN	2016	1,516	9,507	Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	5
Tier 2: splice/UTR	3
Tier 3: regulatory	2
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	4
rare (<0.01)	8
unknown	0

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	10
missense_variant	4
regulatory_region_variant	2
synonymous_variant	2
3_prime_UTR_variant	2
non_coding_transcript_exon_variant	2
stop_gained	1
splice_acceptor_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1537373	9	22103342	T>A,G	0.462	intron_variant	CDKN2B-AS1	3e-29	Tier 4: intronic/intergenic
rs371331393	11	128969377	G>A	0.02	stop_gained	ARHGAP32	9e-27	Tier 1: coding
rs6841581	4	147480038	G>A,C,T	0.222	regulatory_region_variant	PRMT5P1 - EDNRA	3e-26	Tier 3: regulatory
rs138525217	12	7375596	C>T	0.01	splice_acceptor_variant	CD163L1	6e-23	Tier 2: splice/UTR
rs1333040	9	22083405	C>G,T	0.44	intron_variant	CDKN2B-AS1	2e-22	Tier 4: intronic/intergenic
rs75822236	1	155235002	C>T	0.01	missense_variant	GBA1	1e-19	Tier 1: coding
rs79134766	9	124799444	G>A,T	0.37	missense_variant	OLFML2A	2e-19	Tier 1: coding
rs55965782	4	147457290	T>C	0.13	intergenic_variant	RPL31P26 - PRMT5P1	9e-18	Tier 4: intronic/intergenic
rs11661542	18	22643732	C>A	0.471	intron_variant	RBBP8-AS1	3e-17	Tier 4: intronic/intergenic
rs112859779	8	66948134	C>A,G,T	0.33	missense_variant	TCF24	3e-16	Tier 1: coding
rs78458145	2	241934884	G>A	0.4	intron_variant	LINC01237	3e-15	Tier 4: intronic/intergenic
rs116969723	21	44456833	G>A	0.35	synonymous_variant	LRRC3	4e-15	Tier 4: intronic/intergenic
rs3742321	13	33129928	T>C	0.238	missense_variant	STARD13	5e-15	Tier 1: coding
rs7184525	16	75403288	A>C,G,T	0.453	intron_variant	CFDP1	6e-15	Tier 4: intronic/intergenic
rs118107419	12	7827798	C>A	0.39	intron_variant	SLC2A14	1e-14	Tier 4: intronic/intergenic
rs6997005	8	54541946	G>A	0.414	intergenic_variant	RP1	1e-14	Tier 4: intronic/intergenic
rs2280543	11	203788	C>T	0.101	3_prime_UTR_variant	BET1L	1e-14	Tier 2: splice/UTR
rs4977574	9	22098575	A>G,T	0.05	intron_variant	CDKN2B-AS1	1e-14	Tier 4: intronic/intergenic
rs79780963	10	103192742	C>G,T	0.254	intron_variant	NT5C2	2e-14	Tier 4: intronic/intergenic
rs62516550	8	54554468	C>G,T	0.335	regulatory_region_variant	RP1	3e-14	Tier 3: regulatory
rs6741819	2	7007842	C>T	0.37	intron_variant	RNF144A	4e-14	Tier 4: intronic/intergenic
rs727333	21	40331020	C>A	0.38	intron_variant	DSCAM	4e-14	Tier 4: intronic/intergenic
rs7137731	12	95097223	T>C	0.356	intron_variant	FGD6	5e-14	Tier 4: intronic/intergenic
rs59626274	2	239578555	C>T	0.36	non_coding_transcript_exon_variant	LINC02991	6e-14	Tier 4: intronic/intergenic
rs7866503	9	22091925	G>A,C,T	0.416	intron_variant	CDKN2B-AS1	2e-13	Tier 4: intronic/intergenic
rs74487487	5	117713533	G>A,C,T	0.001	intergenic_variant	LINC00992 - LINC02147	2e-13	Tier 4: intronic/intergenic
rs549990459	10	113986576	C>T	0	intron_variant	NHLRC2 - ADRB1	2e-13	Tier 4: intronic/intergenic
rs55800589	19	47487632	G>A,C	0.4	intron_variant	NAPA-AS1	3e-13	Tier 4: intronic/intergenic
rs573922818	2	85718806	C>T	0	intergenic_variant	GNLY - RNU1-38P	3e-13	Tier 4: intronic/intergenic
rs61775135	1	13821912	C>A,G,T	0.41	intron_variant	PRDM2	4e-13	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
213286	NM_001999.4(FBN2):c.2260G>A (p.Gly754Ser)	FBN2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 45 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
FBN1	FBN1	GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ANGPTL6	Strong	Autosomal dominant	brain aneurysm	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANGPTL6	Orphanet:231160	Familial cerebral saccular aneurysm
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
SLC22A5	Orphanet:158	Systemic primary carnitine deficiency
CAMK2B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
CARD11	Orphanet:300324	Persistent polyclonal B-cell lymphocytosis
CARD11	Orphanet:357237	Combined immunodeficiency due to CARD11 deficiency
CARD11	Orphanet:464336	BENTA disease
CARD11	Orphanet:619972	CADINS disease
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
SOX17	Orphanet:275777	Heritable pulmonary arterial hypertension
SOX17	Orphanet:289365	Familial vesicoureteral reflux
RSPH9	Orphanet:244	Primary ciliary dyskinesia
EDNRA	Orphanet:443995	Mandibulofacial dysostosis with alopecia
EDNRA	Orphanet:586	Cystic fibrosis
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia
FBN2	Orphanet:115	Congenital contractural arachnodactyly
FHIT	Orphanet:422526	Hereditary clear cell renal cell carcinoma
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
GBA1	Orphanet:2072	Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
GBA1	Orphanet:411602	Hereditary late-onset Parkinson disease
GBA1	Orphanet:77259	Gaucher disease type 1
GBA1	Orphanet:77260	Gaucher disease type 2
GBA1	Orphanet:77261	Gaucher disease type 3
GBA1	Orphanet:85212	Fetal Gaucher disease
HLCS	Orphanet:79242	Holocarboxylase synthetase deficiency

Cohort genes → proteins

75 cohort genes, 66 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	73
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ANGPTL6	HGNC:23140	ENSG00000130812	Q8NI99	Angiopoietin-related protein 6	gencc
RGS6	HGNC:10002	ENSG00000182732	P49758	Regulator of G-protein signaling 6	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
SLC22A4	HGNC:10968	ENSG00000197208	Q9H015	Solute carrier family 22 member 4	gwas
SLC22A5	HGNC:10969	ENSG00000197375	O76082	Organic cation/carnitine transporter 2	gwas
SYN3	HGNC:11496	ENSG00000185666	O14994	Synapsin-3	gwas
TMOD1	HGNC:11871	ENSG00000136842	P28289	Tropomodulin-1	gwas
RBMS3	HGNC:13427	ENSG00000144642	Q6XE24	RNA-binding motif, single-stranded-interacting protein 3	gwas
BOLL	HGNC:14273	ENSG00000152430	Q8N9W6	Protein boule-like	gwas
PARD3B	HGNC:14446	ENSG00000116117	Q8TEW8	Partitioning defective 3 homolog B	gwas
CAMK2B	HGNC:1461	ENSG00000058404	Q13554	Calcium/calmodulin-dependent protein kinase type II subunit beta	gwas
DNAJA4	HGNC:14885	ENSG00000140403	Q8WW22	DnaJ homolog subfamily A member 4	gwas
LRRC3	HGNC:14965	ENSG00000160233	Q9BY71	Leucine-rich repeat-containing protein 3	gwas
SIRPG	HGNC:15757	ENSG00000089012	Q9P1W8	Signal-regulatory protein gamma	gwas
CARD11	HGNC:16393	ENSG00000198286	Q9BXL7	Caspase recruitment domain-containing protein 11	gwas
SCARF1	HGNC:16820	ENSG00000074660	Q14162	Scavenger receptor class F member 1	gwas
CARHSP1	HGNC:17150	ENSG00000153048	Q9Y2V2	Calcium-regulated heat-stable protein 1	gwas
ARHGAP32	HGNC:17399	ENSG00000134909	A7KAX9	Rho GTPase-activating protein 32	gwas
MINK1	HGNC:17565	ENSG00000141503	Q8N4C8	Misshapen-like kinase 1	gwas
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
POLR1F	HGNC:18027	ENSG00000105849	Q3B726	DNA-directed RNA polymerase I subunit RPA43	gwas
SOX17	HGNC:18122	ENSG00000164736	Q9H6I2	Transcription factor SOX-17	gwas
SOX7	HGNC:18196	ENSG00000171056	Q9BT81	Transcription factor SOX-7	gwas
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	gwas
SLC2A14	HGNC:18301	ENSG00000173262	Q8TDB8	Solute carrier family 2, facilitated glucose transporter member 14	gwas
PDZD2	HGNC:18486	ENSG00000133401	O15018	PDZ domain-containing protein 2	gwas
LINC03041	HGNC:19054	ENSG00000205549	A6NGG3	Putative uncharacterized protein encoded by LINC03041	gwas
STARD13	HGNC:19164	ENSG00000133121	Q9Y3M8	StAR-related lipid transfer protein 13	gwas
BET1L	HGNC:19348	ENSG00000177951	Q9NYM9	BET1-like protein	gwas
RNF144A	HGNC:20457	ENSG00000151692	P50876	E3 ubiquitin-protein ligase RNF144A	gwas
RSPH9	HGNC:21057	ENSG00000172426	Q9H1X1	Radial spoke head protein 9 homolog	gwas
LINGO2	HGNC:21207	ENSG00000174482	Q7L985	Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2	gwas
FGD6	HGNC:21740	ENSG00000180263	Q6ZV73	FYVE, RhoGEF and PH domain-containing protein 6	gwas
TMEM196	HGNC:22431	ENSG00000173452	Q5HYL7	Transmembrane protein 196	gwas
CPNE4	HGNC:2317	ENSG00000196353	Q96A23	Copine-4	gwas
LINC00474	HGNC:23367	ENSG00000204148	Q9P2X8	Putative uncharacterized protein encoded by LINC00474	gwas
SLC35F3	HGNC:23616	ENSG00000183780	Q8IY50	Solute carrier family 35 member F3	gwas
ANKRD44	HGNC:25259	ENSG00000065413	Q8N8A2	Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B	gwas
SUSD1	HGNC:25413	ENSG00000106868	Q6UWL2	Sushi domain-containing protein 1	gwas
CUL4A	HGNC:2554	ENSG00000139842	Q13619	Cullin-4A	gwas
SLC47A1	HGNC:25588	ENSG00000142494	Q96FL8	Multidrug and toxin extrusion protein 1	gwas
DRAM1	HGNC:25645	ENSG00000136048	Q8N682	DNA damage-regulated autophagy modulator protein 1	gwas
SPCS3	HGNC:26212	ENSG00000129128	P61009	Signal peptidase complex subunit 3	gwas
OLFML2A	HGNC:27270	ENSG00000185585	Q68BL7	Olfactomedin-like protein 2A	gwas
XKR6	HGNC:27806	ENSG00000171044	Q5GH73	XK-related protein 6	gwas
PLB1	HGNC:30041	ENSG00000163803	Q6P1J6	Phospholipase B1, membrane-associated	gwas
CD163L1	HGNC:30375	ENSG00000177675	Q9NR16	Scavenger receptor cysteine-rich type 1 protein M160	gwas
DSCAM	HGNC:3039	ENSG00000171587	O60469	Cell adhesion molecule DSCAM	gwas
DTNB	HGNC:3058	ENSG00000138101	O60941	Dystrobrevin beta	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANGPTL6	Angiopoietin-related protein 6	May play a role in the wound healing process.
RGS6	Regulator of G-protein signaling 6	Regulates G protein-coupled receptor signaling cascades.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
SLC22A4	Solute carrier family 22 member 4	Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations.
SLC22A5	Organic cation/carnitine transporter 2	Sodium-ion dependent, high affinity carnitine transporter.
SYN3	Synapsin-3	May be involved in the regulation of neurotransmitter release and synaptogenesis.
TMOD1	Tropomodulin-1	Blocks the elongation and depolymerization of the actin filaments at the pointed end.
RBMS3	RNA-binding motif, single-stranded-interacting protein 3	Binds poly(A) and poly(U) oligoribonucleotides.
BOLL	Protein boule-like	Probable RNA-binding protein, which may be required during spermatogenesis.
PARD3B	Partitioning defective 3 homolog B	Putative adapter protein involved in asymmetrical cell division and cell polarization processes.
CAMK2B	Calcium/calmodulin-dependent protein kinase type II subunit beta	Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic r…
SIRPG	Signal-regulatory protein gamma	Probable immunoglobulin-like cell surface receptor.
CARD11	Caspase recruitment domain-containing protein 11	Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement.
SCARF1	Scavenger receptor class F member 1	Mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL).
CARHSP1	Calcium-regulated heat-stable protein 1	Binds mRNA and regulates the stability of target mRNA.
ARHGAP32	Rho GTPase-activating protein 32	GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases.
MINK1	Misshapen-like kinase 1	Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
POLR1F	DNA-directed RNA polymerase I subunit RPA43	Component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates.
SOX17	Transcription factor SOX-17	Acts as a transcription regulator that binds target promoter DNA.
SOX7	Transcription factor SOX-7	Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
SLC2A14	Solute carrier family 2, facilitated glucose transporter member 14	Hexose transporter that can mediate the transport of glucose and dehydroascorbate across the cell membrane.
STARD13	StAR-related lipid transfer protein 13	GTPase-activating protein for RhoA, and perhaps for Cdc42.
BET1L	BET1-like protein	Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex.
RNF144A	E3 ubiquitin-protein ligase RNF144A	E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
RSPH9	Radial spoke head protein 9 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
FGD6	FYVE, RhoGEF and PH domain-containing protein 6	May activate CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP.
TMEM196	Transmembrane protein 196	Acts as a tumor suppressor in lung cancer.
CPNE4	Copine-4	Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.
SLC35F3	Solute carrier family 35 member F3	Mediates thiamine transport.
ANKRD44	Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B	Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates.
CUL4A	Cullin-4A	Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins.
SLC47A1	Multidrug and toxin extrusion protein 1	Multidrug efflux pump that functions as a H(+)/organic cation antiporter.
DRAM1	DNA damage-regulated autophagy modulator protein 1	Lysosomal modulator of autophagy that plays a central role in p53/TP53-mediated apoptosis.
SPCS3	Signal peptidase complex subunit 3	Essential component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum.
PLB1	Phospholipase B1, membrane-associated	Calcium-independent membrane-associated phospholipase that catalyzes complete diacylation of phospholipids by hydrolyzing both sn-1 and sn-2 fatty acyl chains attached to the glycerol backbone (phospholipase B activity).
DSCAM	Cell adhesion molecule DSCAM	Cell adhesion molecule that plays a role in neuronal self-avoidance.
DTNB	Dystrobrevin beta	Scaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids.
CCDC80	Coiled-coil domain-containing protein 80	Promotes cell adhesion and matrix assembly.
EDNRA	Endothelin-1 receptor	Receptor for endothelin-1.
TCF24	Transcription factor 24	Putative transcription factor.
ESRRG	Estrogen-related receptor gamma	Orphan receptor that acts as a transcription activator in the absence of bound ligand.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.
FHIT	Bis(5’-adenosyl)-triphosphatase	Possesses dinucleoside triphosphate hydrolase activity.
FMO4	Dimethylaniline monooxygenase [N-oxide-forming] 4	This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides.
ALDH2	Aldehyde dehydrogenase, mitochondrial	Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.

Protein-family classification

Druggable: 16 · Difficult: 14 · Unknown: 45 · Druggable fraction: 0.21

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
Nuclear receptor	2	10.3×	0.162
Transporter	3	3.1×	0.361
Scaffold/PPI	7	1.6×	0.474
Other/Unknown	45	1.1×	0.676
Antibody/Immunoglobulin	3	1.2×	0.953
Phosphatase	1	1.1×	0.960
Transcription factor	7	0.8×	0.960
Kinase	2	0.7×	0.960
Enzyme (other)	4	0.6×	0.960
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANGPTL6	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS
RGS6	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
SLC22A4	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC22A5	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SYN3	Other/Unknown	no		Synapsin, ATP_grasp_subdomain_1, PreATP-grasp_dom_sf
TMOD1	Other/Unknown	no		TMOD, LRR_dom_sf
RBMS3	Other/Unknown	no		RRM_dom, Hud_Sxl_RNA, Nucleotide-bd_a/b_plait_sf
BOLL	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
PARD3B	Scaffold/PPI	no		PDZ, Par3/HAL_N, PDZ_sf
CAMK2B	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
DNAJA4	Other/Unknown	no		HSP_DnaJ_Cys-rich_dom, DnaJ_domain, DnaJ_C
LRRC3	Other/Unknown	no		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
SIRPG	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
CARD11	Scaffold/PPI	no		CARD, DEATH-like_dom_sf, P-loop_NTPase
SCARF1	Other/Unknown	no		EGF, LE_dom, Growth_fac_rcpt_cys_sf
CARHSP1	Other/Unknown	no		CSP_DNA-bd, CSD, NA-bd_OB-fold
ARHGAP32	Scaffold/PPI	no		RhoGAP_dom, SH3_domain, Rho_GTPase_activation_prot
MINK1	Kinase	yes		Prot_kinase_dom, CNH_dom, Ser/Thr_kinase_AS
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
POLR1F	Other/Unknown	no		Rpb7-like_N, RNA_pol_Rpb7-like_N_sf, RPA43_OB
SOX17	Transcription factor	no		HMG_box_dom, Sox_C, Sox7/17/18_central
SOX7	Transcription factor	no		HMG_box_dom, Sox_C, Sox7/17/18_central
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
SLC2A14	Transporter	yes		Glc_transpt_3, Sugar/inositol_transpt, MFS_sugar_transport-like
PDZD2	Scaffold/PPI	no		PDZ, PDZ_sf
LINC03041	Other/Unknown	no		DUF5540
STARD13	Other/Unknown	no		RhoGAP_dom, SAM, START_lipid-bd_dom
BET1L	Other/Unknown	no		T_SNARE_dom, BET1_SNARE
RNF144A	Transcription factor	no	2.3.2.31	Znf_RING, IBR_dom, Znf_RING/FYVE/PHD
RSPH9	Other/Unknown	no		RSP9
LINGO2	Antibody/Immunoglobulin	yes		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
FGD6	Transcription factor	no		DH_dom, Znf_FYVE, PH_domain
TMEM196	Other/Unknown	no		TMEM196
CPNE4	Other/Unknown	no		C2_dom, VWF_A, Copine_C
LINC00474	Other/Unknown	no
SLC35F3	Other/Unknown	no		EamA_dom, Solute_c_fam_35_mem_F3/F4, EmrE-like
ANKRD44	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
SUSD1	Phosphatase	yes		EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, EGF
CUL4A	Other/Unknown	no		Cullin_N, Cullin_CS, Cullin_homology
SLC47A1	Other/Unknown	no		MATE_fam, MATE_euk
DRAM1	Other/Unknown	no		CWH43_N, DRAM/TMEM150_Autophagy_Mod
SPCS3	Other/Unknown	no		SPC3
OLFML2A	Other/Unknown	no		Olfac-like_dom, Olfactomedin-like_domain
XKR6	Other/Unknown	no		XK-rel, XK-related_scramblase
PLB1	Other/Unknown	no		GDSL, Lipase_GDSL_AS, Phospholipase_B
CD163L1	Other/Unknown	no		SRCR, SRCR-like_dom_sf
DSCAM	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
DTNB	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1

Expression context

Cohort genes with no expression data: 0.

62 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
male germ line stem cell (sensu Vertebrata) in testis	13
cortical plate	6
primordial germ cell in gonad	5
middle temporal gyrus	5
right lobe of liver	4
sural nerve	4
secondary oocyte	4
islet of Langerhans	4
left testis	4
right testis	4
cerebellar hemisphere	4
buccal mucosa cell	4
lower esophagus mucosa	4
endothelial cell	4
placenta	4
bone marrow cell	4
monocyte	4
right adrenal gland	3
bronchial epithelial cell	3
trigeminal ganglion	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANGPTL6	153	tissue_specific	yes	right lobe of liver, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
RGS6	185	broad	marker	cortical plate, sural nerve, middle temporal gyrus
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
SLC22A4	201	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
SLC22A5	235	ubiquitous	marker	gastrocnemius, mucosa of transverse colon, muscle of leg
SYN3	176	broad	marker	primordial germ cell in gonad, cortical plate, primary visual cortex
TMOD1	265	broad	marker	type B pancreatic cell, hindlimb stylopod muscle, islet of Langerhans
RBMS3	268	ubiquitous	marker	trigeminal ganglion, pericardium, calcaneal tendon
BOLL	75	tissue_specific	yes	left testis, adult organism, right testis
PARD3B	200	ubiquitous	marker	sural nerve, cardiac muscle of right atrium, ventricular zone
CAMK2B	233	broad	marker	cerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum
DNAJA4	265	ubiquitous	marker	bronchial epithelial cell, right testis, left testis
LRRC3	147	ubiquitous	yes	right lobe of liver, cortical plate, liver
SIRPG	149	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, lymph node
CARD11	188	broad	marker	granulocyte, lymph node, spleen
SCARF1	132	broad	marker	spleen, right lobe of thyroid gland, left lobe of thyroid gland
CARHSP1	282	ubiquitous	marker	right testis, left testis, ganglionic eminence
ARHGAP32	275	ubiquitous	marker	middle temporal gyrus, secondary oocyte, postcentral gyrus
MINK1	292	ubiquitous	marker	CA1 field of hippocampus, lower esophagus mucosa, skin of leg
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
POLR1F	263	ubiquitous	marker	decidua, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
SOX17	190	broad	marker	endothelial cell, omental fat pad, peritoneum
SOX7	131	broad	marker	lower esophagus mucosa, placenta, vagina
RBFOX1	220	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cortical plate
SLC2A14	130	tissue_specific	marker	left testis, right testis, testis
PDZD2	281	broad	marker	trigeminal ganglion, dorsal root ganglion, upper leg skin
LINC03041	102		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, ganglionic eminence
STARD13	256	ubiquitous	marker	sural nerve, tibial nerve, adrenal tissue
BET1L	241	ubiquitous	marker	body of pancreas, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 17.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDKN2A	9,311
GATA3	5,990
CUL4A	4,581
ALDH2	4,554
FBN1	3,640
CARD11	3,587
CDKN2B	3,431
DNAJA4	3,161
RBFOX1	2,990
DSCAM	2,848

Intra-cohort edges

A	B	Sources
ANGPT4	EDNRA	string_interaction
ANKRD44	BOLL	string_interaction
ANKRD44	FGD6	string_interaction
ARHGAP32	TCF24	string_interaction
BET1L	SLC35F3	biogrid_interaction, intact
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	FHIT	string_interaction
CDKN2A	TMOD1	intact
CNNM2	FBN2	string_interaction
CNNM2	STARD13	string_interaction
FBN1	FBN2	intact, string_interaction
FGD6	GBA1	biogrid_interaction
OLFML2A	TCF24	string_interaction
RNF144A	TCF24	string_interaction
SLC22A4	SLC22A5	intact
SLC22A4	SLC47A1	string_interaction
SLC22A5	SLC47A1	string_interaction

Structural data

PDB: 32 · AlphaFold-only: 34 · No structure: 9

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GBA1	P04062	58
ESRRG	P62508	43
ALDH2	P05091	29
CUL4A	Q13619	11
FBN1	P35555	11
FHIT	P49789	9
CNNM2	Q9H8M5	7
TMOD1	P28289	6
POLR1F	Q3B726	6
CDKN2A	P42771	5
EDNRA	P25101	5
CAMK2B	Q13554	4
RBFOX1	Q9NWB1	4
SLC47A1	Q96FL8	4
SLC22A5	O76082	3
STARD13	Q9Y3M8	3
GATA3	P23771	3
SIRPG	Q9P1W8	2
CARD11	Q9BXL7	2
SCARF1	Q14162	2
SOX17	Q9H6I2	2
RNF144A	P50876	2
SPCS3	P61009	2
ANGPTL6	Q8NI99	1
RGS6	P49758	1
SYN3	O14994	1
CARHSP1	Q9Y2V2	1
ARHGAP32	A7KAX9	1
RSPH9	Q9H1X1	1
FGD6	Q6ZV73	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DRAM1	Q8N682	94.73
FMO4	P31512	91.52
ANKRD44	Q8N8A2	90.57
CDKN2B	P42772	90.12
BET1L	Q9NYM9	89.02
SLC2A14	Q8TDB8	87.74
CPNE4	Q96A23	87.42
SLC22A4	Q9H015	85.07
LINGO2	Q7L985	85.02
DNAJA4	Q8WW22	84.76
LRRC3	Q9BY71	83.43
ANGPT4	Q9Y264	83.33
PLB1	Q6P1J6	82.18
TMEM114	B3SHH9	81.80
SUSD1	Q6UWL2	78.21
TMEM196	Q5HYL7	77.62
HLCS	P50747	77.33
DTNB	O60941	76.29
SLC35F3	Q8IY50	75.68
OLFML2A	Q68BL7	68.33
TCF24	Q7RTU0	68.14
NR2C1	P13056	65.48
XKR6	Q5GH73	64.85
MINK1	Q8N4C8	64.32
BOLL	Q8N9W6	64.18
RBMS3	Q6XE24	63.30
CCDC80	Q76M96	62.51
SOX7	Q9BT81	61.38
LINC00474	Q9P2X8	58.07
PARD3B	Q8TEW8	55.56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 361. Enrichment computed across 85 evidence-associated genes (45 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 45 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SLC-mediated transport of organic cations	3	50.8×	0.009	SLC22A4, SLC22A5, SLC47A1
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	253.8×	0.189	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	253.8×	0.189	CDKN2A
Metabolism of serotonin	1	126.9×	0.189	ALDH2
Defective SLC22A5 causes systemic primary carnitine deficiency (CDSP)	1	126.9×	0.189	SLC22A5
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	1	126.9×	0.189	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	1	126.9×	0.189	CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	126.9×	0.189	CDKN2A
R-HSA-549132	2	33.8×	0.189	SLC22A4, SLC22A5
G1 Phase	2	17.5×	0.189	CDKN2A, CDKN2B
Elastic fibre formation	2	14.9×	0.189	FBN1, FBN2
Oncogene Induced Senescence	2	14.9×	0.189	CDKN2A, CDKN2B
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	2	14.9×	0.189	ARHGAP32, SPCS3
R-HSA-425366	3	12.1×	0.189	SLC22A4, SLC22A5, SLC47A1
Cellular Senescence	3	9.2×	0.189	MINK1, CDKN2A, CDKN2B
Diseases of Cellular Senescence	1	84.6×	0.193	CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	84.6×	0.193	CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	84.6×	0.193	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	84.6×	0.193	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	84.6×	0.193	CDKN2A
Diseases of cellular response to stress	1	84.6×	0.193	CDKN2A
Molecules associated with elastic fibres	2	13.7×	0.193	FBN1, FBN2
Abacavir metabolism	1	63.4×	0.205	NT5C2
Serotonin clearance from the synaptic cleft	1	63.4×	0.205	ALDH2
Deactivation of the beta-catenin transactivating complex	2	10.4×	0.205	SOX17, SOX7
Cyclin D associated events in G1	2	10.4×	0.205	CDKN2A, CDKN2B
Regulation of RUNX3 expression and activity	2	10.4×	0.205	CDKN2A, PSMA4
Oxidative Stress Induced Senescence	3	6.0×	0.205	MINK1, CDKN2A, CDKN2B
Defects in biotin (Btn) metabolism	1	50.8×	0.214	HLCS
DSCAM interactions	1	50.8×	0.214	DSCAM

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
thymic T cell selection	2	167.7×	0.016	CARD11, GATA3
carnitine transport	2	125.8×	0.016	SLC22A4, SLC22A5
obsolete sequestering of TGFbeta in extracellular matrix	2	125.8×	0.016	FBN1, FBN2
quaternary ammonium group transport	2	100.6×	0.016	SLC22A4, SLC22A5
negative regulation of mammary gland epithelial cell proliferation	2	100.6×	0.016	CDKN2A, GATA3
camera-type eye photoreceptor cell differentiation	2	100.6×	0.016	DSCAM, PROM1
lymphocyte migration	2	71.9×	0.029	GATA3, GBA1
endothelin receptor signaling pathway	2	50.3×	0.054	EDNRA, BCAR1
embryonic eye morphogenesis	2	45.7×	0.057	FBN1, FBN2
endoderm formation	2	41.9×	0.057	SOX17, SOX7
podocyte differentiation	2	41.9×	0.057	EDNRA, PROM1
sulfur amino acid transport	1	251.5×	0.071	SLC22A4
type IV hypersensitivity	1	251.5×	0.071	GATA3
cardiogenic plate morphogenesis	1	251.5×	0.071	SOX17
obsolete GMP catabolic process to guanine	1	251.5×	0.071	NT5C2
diadenosine triphosphate catabolic process	1	251.5×	0.071	FHIT
nitroglycerin metabolic process	1	251.5×	0.071	ALDH2
regulation of dopamine biosynthetic process	1	251.5×	0.071	ALDH2
positive regulation of neuronal action potential	1	251.5×	0.071	GBA1
regulation of serotonin biosynthetic process	1	251.5×	0.071	ALDH2
regulation of protein localization to cell leading edge	1	251.5×	0.071	EDNRA
regulation of cardiac cell fate specification	1	251.5×	0.071	SOX17
obsolete negative regulation of cell proliferation involved in mesonephros development	1	251.5×	0.071	GATA3
regulation of cellular response to X-ray	1	251.5×	0.071	GATA3
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation	1	251.5×	0.071	GATA3
obsolete negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation	1	251.5×	0.071	GATA3
neuron remodeling	2	35.9×	0.071	SCARF1, EDNRA
xenobiotic detoxification by transmembrane export across the plasma membrane	2	33.5×	0.071	SLC22A5, SLC47A1
regulation of synaptic transmission, GABAergic	2	31.4×	0.071	SYN3, PLCL1
amino acid import across plasma membrane	2	31.4×	0.071	SLC22A4, SLC47A1

Therapeutics

Drugs indicated for this disease

0 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aspirin	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Esmolol	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Sevoflurane	Phase 3 (in late-stage trials)
Ticagrelor	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atorvastatin, Sirolimus.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 8 · Phased (≥1): 8 · Undrugged: 67

Druggability breadth: 26 of 85 evidence-associated genes (31%) 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
CAMK2B	FEDRATINIB
MINK1	FEDRATINIB
SLC47A1	TELMISARTAN
EDNRA	AMBRISENTAN
ESRRG	DIETHYLSTILBESTROL
ALDH2	DISULFIRAM
GBA1	MIGALASTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MINK1	47	4
SLC47A1	47	4
EDNRA	31	4
CAMK2B	25	4
GBA1	12	4
ALDH2	3	4
ESRRG	2	4
FHIT	1	3
ANGPTL6	0	0
RGS6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CAMK2B, MINK1
SORAFENIB	4	CAMK2B, MINK1
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B, EDNRA, MINK1
MIDOSTAURIN	4	CAMK2B, MINK1
AXITINIB	4	MINK1
NERATINIB	4	MINK1
VANDETANIB	4	MINK1
BOSUTINIB	4	MINK1
NINTEDANIB	4	MINK1
DASATINIB	4	MINK1
ERLOTINIB	4	MINK1
QUIZARTINIB	4	MINK1
CRIZOTINIB	4	MINK1
GEFITINIB	4	MINK1
TELMISARTAN	4	SLC47A1
IMIPRAMINE	4	SLC47A1
EPINASTINE	4	SLC47A1
VECURONIUM BROMIDE	4	SLC47A1
SUMATRIPTAN	4	SLC47A1
QUINIDINE	4	SLC47A1
CLONIDINE	4	SLC47A1
SPIRONOLACTONE	4	SLC47A1
PANTOPRAZOLE	4	SLC47A1
RITONAVIR	4	SLC47A1
DIHYDROERGOTAMINE	4	SLC47A1
RANITIDINE	4	SLC47A1
PRAZOSIN	4	SLC47A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
GBA1	436	Binding:403, Functional:33
EDNRA	418	Binding:342, Functional:73, Toxicity:2, ADMET:1
MINK1	338	Binding:335, Toxicity:2, Functional:1
CAMK2B	314	Binding:313, Functional:1
ESRRG	135	Binding:121, Functional:13, ADMET:1
CUL4A	107	Binding:106, ADMET:1
SLC22A5	97	Functional:79, ADMET:18
NR2C1	74	Binding:74
ALDH2	71	Binding:66, Functional:5
SLC22A4	29	Functional:26, ADMET:3
SLC47A1	21	Binding:16, ADMET:4, Toxicity:1
FHIT	21	Binding:19, ADMET:2
HLCS	8	Binding:8
CDKN2A	2	Binding:2
CARHSP1	1	Binding:1
SOX17	1	Binding:1
SLC2A14	1	ADMET:1
CPNE4	1	Binding:1
ANKRD44	1	Binding:1
SPCS3	1	Binding:1
FMO4	1	ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAMK2B	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
RNF144A	2.3.2.31	RBR-type E3 ubiquitin transferase
FHIT	3.6.1.29	bis(5’-adenosyl)-triphosphatase
FMO4	1.14.13.8	flavin-containing monooxygenase
ALDH2	1.2.1.3	aldehyde dehydrogenase (NAD+)
GBA1	3.2.1.45	glucosylceramidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CAMK2B	314
MINK1	338
CUL4A	107
EDNRA	418
ESRRG	135
GBA1	436

Pharmacogenomics

Cohort genes with a PharmGKB record: 68; 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)
FEDRATINIB	4	CAMK2B, MINK1
SORAFENIB	4	CAMK2B, MINK1
RUXOLITINIB	4	CAMK2B
PALBOCICLIB	4	CAMK2B
ABEMACICLIB	4	CAMK2B
SUNITINIB	4	CAMK2B, EDNRA, MINK1
MIDOSTAURIN	4	CAMK2B, MINK1
AXITINIB	4	MINK1
NERATINIB	4	MINK1
VANDETANIB	4	MINK1
BOSUTINIB	4	MINK1
NINTEDANIB	4	MINK1
DASATINIB	4	MINK1
ERLOTINIB	4	MINK1
QUIZARTINIB	4	MINK1
CRIZOTINIB	4	MINK1
GEFITINIB	4	MINK1
TELMISARTAN	4	SLC47A1
IMIPRAMINE	4	SLC47A1
EPINASTINE	4	SLC47A1
VECURONIUM BROMIDE	4	SLC47A1
SUMATRIPTAN	4	SLC47A1
QUINIDINE	4	SLC47A1
CLONIDINE	4	SLC47A1
SPIRONOLACTONE	4	SLC47A1
PANTOPRAZOLE	4	SLC47A1
RITONAVIR	4	SLC47A1
DIHYDROERGOTAMINE	4	SLC47A1
RANITIDINE	4	SLC47A1
PRAZOSIN	4	SLC47A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	CAMK2B, MINK1, SLC47A1, EDNRA, ESRRG, ALDH2, GBA1
B	Phased (≥1) drug, not yet approved	1	FHIT
C	Druggable family + PDB, no drug	3	SLC22A5, SIRPG, DSCAM
D	Druggable family + AlphaFold only, no drug	6	SLC22A4, SLC2A14, LINGO2, SUSD1, FMO4, NR2C1
E	Difficult family or no structure, no drug	58	ANGPTL6, RGS6, CNNM2, SYN3, TMOD1, RBMS3, BOLL, PARD3B, DNAJA4, LRRC3 (+48 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC22A4	29	SLC47A1
SLC22A5	97	SLC47A1
CUL4A	107	—
ANGPTL6	0	—
RGS6	0	—
CNNM2	0	—
SYN3	0	—
TMOD1	0	—
RBMS3	0	—
BOLL	0	—
PARD3B	0	—
DNAJA4	0	—
LRRC3	0	—
SIRPG	0	—
CARD11	0	—
SCARF1	0	—
CARHSP1	1	—
ARHGAP32	0	—
CDKN2A	2	—
CDKN2B	0	—
POLR1F	0	—
SOX17	1	—
SOX7	0	—
RBFOX1	0	—
SLC2A14	1	—
PDZD2	0	—
LINC03041	0	—
STARD13	0	—
BET1L	0	—
RNF144A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	24
PHASE4	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01444664	PHASE4	COMPLETED	Aneurysm Wall Histology Registry
NCT02037932	PHASE4	WITHDRAWN	Hydrogel Balloon Assisted Intracranial Aneurysm Coiling Registry
NCT00783523	PHASE1	COMPLETED	Influence of MMP on Brain AVM Hemorrhage
NCT03936647	Not specified	RECRUITING	The RISE Trial: A Randomized Trial on Intra-Saccular Endobridge Devices
NCT06456814	Not specified	RECRUITING	Epidemiological Insights Into the Formation, Progression, and Rupture of Intracranial Aneurysms: A Retrospective, Multi-Center Hospital-Based Study in China
NCT06541275	Not specified	ENROLLING_BY_INVITATION	Reduction in Volume and Prolonged Shrinkage of Brain Aneurysms After Combined Endovascular Interventions
NCT06689410	Not specified	RECRUITING	Multimodal Biocollection Linked to the French Register of Intracranial Aneurysms
NCT06761365	Not specified	RECRUITING	LUMENS-1 EU EFS CIP
NCT06798740	Not specified	RECRUITING	Post Market Registry Study of Intracranial Aneurysms Treated With Sugita Clipping Devices
NCT07143019	Not specified	RECRUITING	The Use of p48/64 MW HPC Flow Modulation Device in the Treatment of Wide-necked Intracranial Aneurysms
NCT07175519	Not specified	RECRUITING	Safety and Efficacy of Aneurysms Treated With Endovascular Devices
NCT07259018	Not specified	NOT_YET_RECRUITING	LUMENS-1 Canada Early Feasibility Study Clinical Investigation Plan
NCT00537134	Not specified	TERMINATED	Trial on Endovascular Aneurysm Management
NCT01557036	Not specified	TERMINATED	Aneurysm Study of Pipeline in an Observational Registry
NCT01558102	Not specified	COMPLETED	International Retrospective Study of Pipeline Embolization Device
NCT01716117	Not specified	COMPLETED	Safety and Effectiveness of an Intracranial Aneurysm Embolization System for Treating Large or Giant Wide Neck Aneurysms
NCT01975233	Not specified	COMPLETED	WEB French Observatory of the WEB Aneurysm Embolization System
NCT02345395	Not specified	UNKNOWN	Safety Study of Minimally Invasive Approaches to Unruptured Anterior Circulation Aneurysms
NCT02381522	Not specified	COMPLETED	Remote Ischemic Pre-conditioning in Subarachnoid Hemorrhage
NCT02435823	Not specified	COMPLETED	Safety Study of the PulseRider® in Patients Undergoing Treatment for Bifurcation Intracranial Aneurysms
NCT02687607	Not specified	COMPLETED	CLARYS: CLinical Assessment of WEB® Device in Ruptured aneurYSms
NCT03844334	Not specified	COMPLETED	CLinical EValuation of WEB 0.017 Device in Intracranial AneuRysms
NCT03852680	Not specified	UNKNOWN	Current Treatment Modalities for Wide Necked Intracranial Aneurysms
NCT04439760	Not specified	COMPLETED	Superior Cervical Ganglion Block, Transcranial Doppler
NCT04553549	Not specified	COMPLETED	Safety and Feasibility of the Infinity Catheter for Radial Access
NCT05317169	Not specified	UNKNOWN	Aneurysm Genetic Risk in Patients With QIB Changes
NCT05626504	Not specified	UNKNOWN	Outcome Study of the Pipeline Embolization Device With Vantage Technology in Unruptured Aneurysms