Erectile dysfunction

Summary

Erectile dysfunction (MONDO:0005362) is a disease with 75 cohort genes (60 GWAS associations across 17 studies) and 570 clinical trials. Top therapeutic interventions include sildenafil, tadalafil, and vardenafil.

At a glance

• Cohort genes: 75
• GWAS associations: 60
• Clinical trials: 570

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	erectile dysfunction
Mondo ID	MONDO:0005362
EFO	EFO:0004234
MeSH	D007172
DOID	DOID:1875
ICD-10-CM	F52.21
NCIT	C34801
SNOMED CT	397803000
UMLS	C0242350
MedGen	66879
Is cancer (heuristic)	no

Also known as: dysfunction, erectile · erectile dysfunction · erectile dysfunction (disease) · impotence · impotence, male · impotence, male sexual · male erectile Disorder · male impotence · male sexual impotence · sexual impotence (finding) · sexual impotence, Male

Data availability: 60 GWAS associations (17 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › male reproductive system disorder › penile disorder › erectile dysfunction

Related subtypes (6): balanitis, leukoplakia of penis, penile neoplasm, phimosis, posthitis, vascular disorder of penis

Subtypes (2): priapism, vasculogenic impotence

Genetics & variants

GWAS landscape

60 GWAS associations across 17 studies. Top hits map to 33 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr6:100610044	1e-118		A	0.13
rs17789218	2e-93	PRDX2P4 - SIM1	T	0.12
rs17185536	2e-37	PRDX2P4 - SIM1	T	1.25
rs8141413	3e-18	PHF21B	T	0.04
rs57989773	6e-14	PRDX2P4 - SIM1	C	1.2
rs13135092	3e-13	SLC39A8	A	0.06
rs56179563	3e-11	ZC3HC1	G	0.03
rs148440170	1e-08	RUNX1T1 - FLJ46284	?
rs2268363	5e-08	FSHR, MIR548BAHG	?	7.03
rs140186760	1e-07	CDH13	?
rs10194115	5e-07	TTC7A	?	9
rs2806864	6e-07	PTGFRN	?	6.42
rs113340062	6e-07	MATN2	?
rs7064929	7e-07	ZC3H12B	?	13.65
rs9810233	7e-07	EZRP1 - ALCAM	G
rs10861905	8e-07	CMKLR1 - LINC01498	?	33.95
rs10835054	9e-07	SLC5A12	?
rs12336160	1e-06	CHMP5 - NFX1	?	7.26
rs1527243	1e-06	LINC01823 - LINC01826	?	6.67
rs10210358	2e-06	LRP1B	?	5.34
rs2716734	2e-06	TMEM178A - THUMPD2	?	5.97
rs16861326	2e-06	ACTL8 - LINC01654	?	17.85
rs836589	2e-06	PDK1 - RAPGEF4-AS1	A
rs145373037	2e-06	NFIA	?
rs146119674	2e-06	EIF4EBP2P3 - POU3F2	?
rs117126914	2e-06	DNAJA3	?
rs5925696	3e-06	PTCHD1-AS	?	12.52
rs74057559	3e-06	FAM131C2P	?
rs115409097	3e-06	FOXF2 - RN7SL352P	?
rs117294484	3e-06	EBF3	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476161	Verma A	2024	110,823	271,686	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478643	Verma A	2024	47,384	47,483	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480419	Verma A	2024	47,384	47,483	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478641	Verma A	2024	15,116	33,922	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST007118	Jorgenson E	2018	11,864	17,995	Genetic variation in the SIM1 locus is associated with erectile dysfunction.
GCST90080636	Backman JD	2021	6,768	372,700	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080637	Backman JD	2021	6,768	372,688	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084622	Backman JD	2021	6,768	372,700	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084623	Backman JD	2021	6,768	372,688	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST006956	Bovijn J	2018	6,175	217,630	GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	4
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	34
intergenic_variant	12
3_prime_UTR_variant	2
unknown	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr6:100610044				0.247			1e-118	Tier 4: intronic/intergenic
rs17789218	6	100152221	T>A,C	0.203	intron_variant	PRDX2P4 - SIM1	2e-93	Tier 4: intronic/intergenic
rs17185536	6	100173055	C>G,T	0.05	intron_variant	PRDX2P4 - SIM1	2e-37	Tier 4: intronic/intergenic
rs8141413	22	44941513	T>C	0.417	intron_variant	PHF21B	3e-18	Tier 4: intronic/intergenic
rs57989773	6	100181202	T>C,G	0.24	intron_variant	PRDX2P4 - SIM1	6e-14	Tier 4: intronic/intergenic
rs13135092	4	102276925	A>G	0.086	intron_variant	SLC39A8	3e-13	Tier 4: intronic/intergenic
rs56179563	7	130045757	G>A	0.383	intron_variant	ZC3HC1	3e-11	Tier 4: intronic/intergenic
rs148440170	8	92457995	C>T		intergenic_variant	RUNX1T1 - FLJ46284	1e-08	Tier 4: intronic/intergenic
rs2268363	2	48974189	A>C,G,T	0.18	intron_variant	FSHR, MIR548BAHG	5e-08	Tier 4: intronic/intergenic
rs140186760	16	82961263	G>A		intron_variant	CDH13	1e-07	Tier 4: intronic/intergenic
rs10194115	2	47012873	G>T	0.07	intron_variant	TTC7A	5e-07	Tier 4: intronic/intergenic
rs2806864	1	116927159	C>G	0.15	intron_variant	PTGFRN	6e-07	Tier 4: intronic/intergenic
rs113340062	8	97891932	T>C	0.05	intron_variant	MATN2	6e-07	Tier 4: intronic/intergenic
rs7064929	X	65147139	G>A	0.17	intron_variant	ZC3H12B	7e-07	Tier 4: intronic/intergenic
rs9810233	3	105292046	A>C,G,T	0.27	intergenic_variant	EZRP1 - ALCAM	7e-07	Tier 4: intronic/intergenic
rs10861905	12	108373556	C>A	0.01	intron_variant	CMKLR1 - LINC01498	8e-07	Tier 4: intronic/intergenic
rs10835054	11	26670117	C>A,T	0.05	3_prime_UTR_variant	SLC5A12	9e-07	Tier 2: splice/UTR
rs12336160	9	33283584	G>T	0.09	intergenic_variant	CHMP5 - NFX1	1e-06	Tier 4: intronic/intergenic
rs1527243	2	122533446	C>A,G,T	0.43	intron_variant	LINC01823 - LINC01826	1e-06	Tier 4: intronic/intergenic
rs10210358	2	141038051	A>C,G	0.31	intron_variant	LRP1B	2e-06	Tier 4: intronic/intergenic
rs2716734	2	39720581	C>T	0.14	intergenic_variant	TMEM178A - THUMPD2	2e-06	Tier 4: intronic/intergenic
rs16861326	1	17967993	G>A	0.02	intergenic_variant	ACTL8 - LINC01654	2e-06	Tier 4: intronic/intergenic
rs836589	2	172628350	A>C,G	0.186	intergenic_variant	PDK1 - RAPGEF4-AS1	2e-06	Tier 4: intronic/intergenic
rs145373037	1	61155189	A>G		intron_variant	NFIA	2e-06	Tier 4: intronic/intergenic
rs146119674	6	98547965	T>C	0.05	intergenic_variant	EIF4EBP2P3 - POU3F2	2e-06	Tier 4: intronic/intergenic
rs117126914	16	4429757	G>A	0.05	intron_variant	DNAJA3	2e-06	Tier 4: intronic/intergenic
rs5925696	X	22873960	A>C,G	0.26	intron_variant	PTCHD1-AS	3e-06	Tier 4: intronic/intergenic
rs74057559	1	16036224	C>A,T	0.05	intron_variant	FAM131C2P	3e-06	Tier 4: intronic/intergenic
rs115409097	6	1397958	G>A,C	0.05	TF_binding_site_variant	FOXF2 - RN7SL352P	3e-06	Tier 3: regulatory
rs117294484	10	129945588	G>A	0.05	intron_variant	EBF3	3e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 35 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SIM1	Orphanet:171829	6q16 microdeletion syndrome
SIM1	Orphanet:369873	Obesity due to SIM1 deficiency
SIM1	Orphanet:398079	SIM1-related Prader-Willi-like syndrome
XPO1	Orphanet:98838	Primary mediastinal large B-cell lymphoma
ANO3	Orphanet:420485	Cranio-cervical dystonia with laryngeal and upper-limb involvement
XYLT1	Orphanet:1425	Desbuquois syndrome
XYLT1	Orphanet:370930	XYLT1-CDG
SPEN	Orphanet:1606	1p36 deletion syndrome
SPEN	Orphanet:662234	Neurodevelopmental delay-congenital heart defects-intellectual disability syndrome
EBF3	Orphanet:658843	Developmental delay-ataxia-hypotonia-facial dysmorphism syndrome
EBF3	Orphanet:96148	Distal deletion 10q syndrome
TTC7A	Orphanet:436252	Combined immunodeficiency-multiple intestinal atresia
USP45	Orphanet:65	Leber congenital amaurosis
ZC4H2	Orphanet:3454	Wieacker-Wolff syndrome
FAM161A	Orphanet:791	Retinitis pigmentosa
GLIS2	Orphanet:329469	Acute megakaryoblastic leukemia in children without Down syndrome
GLIS2	Orphanet:93592	Juvenile nephronophthisis
PAM16	Orphanet:401979	Autosomal recessive spondylometaphyseal dysplasia, Mégarbané type
F13B	Orphanet:331	Congenital factor XIII deficiency
FSHR	Orphanet:243	46,XX gonadal dysgenesis
FSHR	Orphanet:64739	Ovarian hyperstimulation syndrome
GLI2	Orphanet:220386	Semilobar holoprosencephaly
GLI2	Orphanet:280195	Septopreoptic holoprosencephaly
GLI2	Orphanet:280200	Microform holoprosencephaly
GLI2	Orphanet:420584	Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
GLI2	Orphanet:93924	Lobar holoprosencephaly
GLI2	Orphanet:93925	Alobar holoprosencephaly
GLI2	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
GLI2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms
APOB	Orphanet:391665	Homozygous familial hypercholesterolemia
NFIA	Orphanet:401986	1p31p32 microdeletion syndrome
PEX13	Orphanet:44	Neonatal adrenoleukodystrophy
PEX13	Orphanet:772	Infantile Refsum disease
PEX13	Orphanet:912	Zellweger syndrome
REL	Orphanet:697394	Combined immunodeficiency due to c-REL deficiency

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CNNM3	HGNC:104	ENSG00000168763	Q8NE01	Metal transporter CNNM3	gwas
SIM1	HGNC:10882	ENSG00000112246	P81133	Single-minded homolog 1	gwas
STAC	HGNC:11353	ENSG00000144681	Q99469	SH3 and cysteine-rich domain-containing protein	gwas
DNAJA3	HGNC:11808	ENSG00000103423	Q96EY1	DnaJ homolog subfamily A member 3, mitochondrial	gwas
XPO1	HGNC:12825	ENSG00000082898	O14980	Exportin-1	gwas
ZBTB17	HGNC:12936	ENSG00000116809	Q13105	Zinc finger and BTB domain-containing protein 17	gwas
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	gwas
PRDM11	HGNC:13996	ENSG00000019485	Q9NQV5	PR domain-containing protein 11	gwas
PRDM13	HGNC:13998	ENSG00000112238	Q9H4Q3	PR domain zinc finger protein 13	gwas
ANO3	HGNC:14004	ENSG00000134343	Q9BYT9	Anoctamin-3	gwas
PAPOLG	HGNC:14982	ENSG00000115421	Q9BWT3	Poly(A) polymerase gamma	gwas
XYLT1	HGNC:15516	ENSG00000103489	Q86Y38	Xylosyltransferase 1	gwas
SYTL5	HGNC:15589	ENSG00000147041	Q8TDW5	Synaptotagmin-like protein 5	gwas
CCNC	HGNC:1581	ENSG00000112237	P24863	Cyclin-C	gwas
PAK5	HGNC:15916	ENSG00000101349	Q9P286	Serine/threonine-protein kinase PAK 5	gwas
LAMP5	HGNC:16097	ENSG00000125869	Q9UJQ1	Lysosome-associated membrane glycoprotein 5	gwas
CCT4	HGNC:1617	ENSG00000115484	P50991	T-complex protein 1 subunit delta	gwas
DOK5	HGNC:16173	ENSG00000101134	Q9P104	Docking protein 5	gwas
GGTLC1	HGNC:16437	ENSG00000149435	Q9BX51	Glutathione hydrolase light chain 1	gwas
CDH13	HGNC:1753	ENSG00000140945	P55290	Cadherin-13	gwas
CDH18	HGNC:1757	ENSG00000145526	Q13634	Cadherin-18	gwas
SPEN	HGNC:17575	ENSG00000065526	Q96T58	Msx2-interacting protein	gwas
VASN	HGNC:18517	ENSG00000168140	Q6EMK4	Vasorin	gwas
EBF3	HGNC:19087	ENSG00000108001	Q9H4W6	Transcription factor COE3	gwas
AATF	HGNC:19235	ENSG00000275700	Q9NY61	Protein AATF	gwas
TTC7A	HGNC:19750	ENSG00000068724	Q9ULT0	Tetratricopeptide repeat protein 7A	gwas
USP34	HGNC:20066	ENSG00000115464	Q70CQ2	Ubiquitin carboxyl-terminal hydrolase 34	gwas
USP45	HGNC:20080	ENSG00000123552	Q70EL2	Ubiquitin carboxyl-terminal hydrolase 45	gwas
DDX53	HGNC:20083	ENSG00000184735	Q86TM3	Probable ATP-dependent RNA helicase DDX53	gwas
C14orf132	HGNC:20346	ENSG00000227051	Q9NPU4	Uncharacterized protein C14orf132	gwas
AHSA2P	HGNC:20437	ENSG00000173209	Q719I0	Putative activator of 90 kDa heat shock protein ATPase homolog 2	gwas
MCHR2	HGNC:20867	ENSG00000152034	Q969V1	Melanin-concentrating hormone receptor 2	gwas
HACD4	HGNC:20920	ENSG00000188921	Q5VWC8	Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4	gwas
PHACTR2	HGNC:20956	ENSG00000112419	O75167	Phosphatase and actin regulator 2	gwas
CMKLR1	HGNC:2121	ENSG00000174600	Q99788	Chemerin-like receptor 1	gwas
COMMD1	HGNC:23024	ENSG00000173163	Q8N668	COMM domain-containing protein 1	gwas
FOCAD	HGNC:23377	ENSG00000188352	Q5VW36	Focadhesin	gwas
CELA2A	HGNC:24609	ENSG00000142615	P08217	Chymotrypsin-like elastase family member 2A	gwas
ZC4H2	HGNC:24931	ENSG00000126970	Q9NQZ6	Zinc finger C4H2 domain-containing protein	gwas
NMRAL1	HGNC:24987	ENSG00000153406	Q9HBL8	NmrA-like family domain-containing protein 1	gwas
SLC25A36	HGNC:25554	ENSG00000114120	Q96CQ1	Solute carrier family 25 member 36	gwas
FAM161A	HGNC:25808	ENSG00000170264	Q3B820	Protein FAM161A	gwas
CORO7	HGNC:26161	ENSG00000262246	P57737	Coronin-7	gwas
PUS10	HGNC:26505	ENSG00000162927	Q3MIT2	tRNA pseudouridine synthase Pus10	gwas
RMDN2	HGNC:26567	ENSG00000115841	Q96LZ7	Regulator of microtubule dynamics protein 2	gwas
CHMP5	HGNC:26942	ENSG00000086065	Q9NZZ3	Charged multivesicular body protein 5	gwas
IGSF21	HGNC:28246	ENSG00000117154	Q96ID5	Immunoglobulin superfamily member 21	gwas
SRARP	HGNC:28339	ENSG00000183888	Q8NEQ6	Steroid receptor-associated and regulated protein	gwas
MAGEB18	HGNC:28515	ENSG00000176774	Q96M61	Melanoma-associated antigen B18	gwas
TMEM178A	HGNC:28517	ENSG00000152154	Q8NBL3	Transmembrane protein 178A	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNNM3	Metal transporter CNNM3	Probable metal transporter.
SIM1	Single-minded homolog 1	Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult.
STAC	SH3 and cysteine-rich domain-containing protein	Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity.
DNAJA3	DnaJ homolog subfamily A member 3, mitochondrial	Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix.
XPO1	Exportin-1	Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs.
ZBTB17	Zinc finger and BTB domain-containing protein 17	Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
PRDM11	PR domain-containing protein 11	May be involved in transcription regulation.
PRDM13	PR domain zinc finger protein 13	May be involved in transcriptional regulation.
ANO3	Anoctamin-3	Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide.
PAPOLG	Poly(A) polymerase gamma	Responsible for the post-transcriptional adenylation of the 3’-terminal of mRNA precursors and several small RNAs including signal recognition particle (SRP) RNA, nuclear 7SK RNA, U2 small nuclear RNA, and ribosomal 5S RNA.
XYLT1	Xylosyltransferase 1	Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.
SYTL5	Synaptotagmin-like protein 5	May act as Rab effector protein and play a role in vesicle trafficking.
CCNC	Cyclin-C	Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes.
PAK5	Serine/threonine-protein kinase PAK 5	Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival.
LAMP5	Lysosome-associated membrane glycoprotein 5	Plays a role in short-term synaptic plasticity in a subset of GABAergic neurons in the brain.
CCT4	T-complex protein 1 subunit delta	Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis.
DOK5	Docking protein 5	DOK proteins are enzymatically inert adaptor or scaffolding proteins.
CDH13	Cadherin-13	Cadherins are calcium-dependent cell adhesion proteins.
CDH18	Cadherin-18	Cadherins are calcium-dependent cell adhesion proteins.
SPEN	Msx2-interacting protein	May serve as a nuclear matrix platform that organizes and integrates transcriptional responses.
VASN	Vasorin	May act as an inhibitor of TGF-beta signaling.
EBF3	Transcription factor COE3	Transcriptional activator.
AATF	Protein AATF	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
TTC7A	Tetratricopeptide repeat protein 7A	Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.
USP34	Ubiquitin carboxyl-terminal hydrolase 34	Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway.
USP45	Ubiquitin carboxyl-terminal hydrolase 45	Catalyzes the deubiquitination of SPDL1.
AHSA2P	Putative activator of 90 kDa heat shock protein ATPase homolog 2	Co-chaperone that stimulates HSP90 ATPase activity.
MCHR2	Melanin-concentrating hormone receptor 2	Receptor for melanin-concentrating hormone, coupled to G proteins that activate phosphoinositide hydrolysis.
HACD4	Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4	Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle.
CMKLR1	Chemerin-like receptor 1	Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1.
COMMD1	COMM domain-containing protein 1	Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex.
FOCAD	Focadhesin	Required for the maintenance of SKIC2 and SKIC3 proteostatic levels in the liver.
CELA2A	Chymotrypsin-like elastase family member 2A	Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism.
ZC4H2	Zinc finger C4H2 domain-containing protein	Plays a role in interneurons differentiation.
NMRAL1	NmrA-like family domain-containing protein 1	Redox sensor protein.
SLC25A36	Solute carrier family 25 member 36	Mitochondrial transporter that imports/exports pyrimidine nucleotides into and from mitochondria.
FAM161A	Protein FAM161A	Involved in ciliogenesis.
CORO7	Coronin-7	F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via ‘Lys-33’-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network,…
PUS10	tRNA pseudouridine synthase Pus10	Protein with different functions depending on its subcellular location: involved in miRNA processing in the nucleus and acts as a tRNA pseudouridylate synthase in the cytoplasm.
CHMP5	Charged multivesicular body protein 5	Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs.
IGSF21	Immunoglobulin superfamily member 21	Involved in synaptic inhibition in the brain.
SRARP	Steroid receptor-associated and regulated protein	May regulate the transcriptional function of androgen and estrogen receptors.
MAGEB18	Melanoma-associated antigen B18	May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases.
TMEM178A	Transmembrane protein 178A	Acts as a negative regulator of osteoclast differentiation in basal and inflammatory conditions by regulating TNFSF11-induced Ca (2+) fluxes, thereby controlling the induction of NFATC1.
SLC5A12	Sodium-coupled monocarboxylate transporter 2	Acts as an electroneutral and low-affinity sodium (Na(+))-dependent sodium-coupled solute transporter.
ZNF608	Zinc finger protein 608	Transcription factor, which represses ZNF609 transcription.
SANBR	SANT and BTB domain regulator of class switch recombination	Negatively regulates class switch recombination or isotype switching in splenic B-cells.
GLIS2	Zinc finger protein GLIS2	Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context.
PAM16	Mitochondrial import inner membrane translocase subunit TIM16	Regulates ATP-dependent protein translocation into the mitochondrial matrix.

Protein-family classification

Druggable: 21 · Difficult: 19 · Unknown: 35 · Druggable fraction: 0.28

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
Protease	5	2.4×	0.291
Transcription factor	14	1.5×	0.291
Complement	1	3.6×	0.575
Antibody/Immunoglobulin	4	1.6×	0.575
Scaffold/PPI	5	1.1×	0.786
Enzyme (other)	6	1.0×	0.786
GPCR	3	1.0×	0.786
Kinase	2	0.7×	0.853
Other/Unknown	35	0.8×	0.956

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNNM3	Other/Unknown	no		CBS_dom, CNNM, Ion_transp-like_CBS
SIM1	Transcription factor	no		PAS, PAC, SIM_C
STAC	Scaffold/PPI	no		SH3_domain, PKC_DAG/PE, STAC1_SH3
DNAJA3	Other/Unknown	no		HSP_DnaJ_Cys-rich_dom, DnaJ_domain, DnaJ_C
XPO1	Other/Unknown	no		Importin-beta_N, ARM-like, Exportin-1/Importin-b-like
ZBTB17	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
PRDM11	Transcription factor	no		SET_dom, PRDM11_PR/SET, SET_dom_sf
PRDM13	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
ANO3	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
PAPOLG	Enzyme (other)	yes	2.7.7.19	PolA_pol_RNA-bd_dom, PolA_pol_cen_dom, NuclTrfase_I-like_C
XYLT1	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT
SYTL5	Transcription factor	no		C2_dom, Rab_BD, Znf_FYVE_PHD
CCNC	Other/Unknown	no		Cyclin_N, Cyclin-like_dom, Cyclin_C_2
PAK5	Kinase	yes	2.7.11.1	CRIB_dom, Prot_kinase_dom, Kinase-like_dom_sf
LAMP5	Other/Unknown	no		Lysosome-assoc_membr_glycop, Lamp2-like_luminal
CCT4	Enzyme (other)	yes	3.6.4.B10	Chaperonin_TCP-1_CS, Cpn60/GroEL/TCP-1, Chap_CCT_delta
DOK5	Scaffold/PPI	no		PH_domain, IRS_PTB, PH-like_dom_sf
GGTLC1	Protease	yes		GGT_peptidase, Ntn_hydrolases_N, GGT_ssub_C
CDH13	Other/Unknown	no		Cadherin-like_dom, Cadherin_pro_dom, Cadherin-like_sf
CDH18	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
SPEN	Other/Unknown	no		RRM_dom, SPOC_met, Nucleotide-bd_a/b_plait_sf
VASN	Antibody/Immunoglobulin	yes		LRRNT, Cys-rich_flank_reg_C, EGF
EBF3	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
AATF	Other/Unknown	no		AATF_C, AATF, AATF/Bfr2
TTC7A	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC7_N
USP34	Protease	yes		Peptidase_C19_UCH, ARM-type_fold, USP_CS
USP45	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD
DDX53	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, KH_dom
C14orf132	Other/Unknown	no
AHSA2P	Other/Unknown	no		ASHA1/2-like_C, AHSA1-like_N, START-like_dom_sf
MCHR2	GPCR	yes		GPCR_Rhodpsn, MCH_rcpt, MCHR2
HACD4	Other/Unknown	no		Tyr_Pase-like_PTPLA
PHACTR2	Other/Unknown	no		RPEL_repeat
CMKLR1	GPCR	yes		GPCR_Rhodpsn, Formyl_rcpt-rel, CML1
COMMD1	Other/Unknown	no		COMM, COMMD1_N, Murr1
FOCAD	Other/Unknown	no		ARM-type_fold, Focadhesin_C, FOCAD/RST1_DUF3730
CELA2A	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA
ZC4H2	Transcription factor	no		Znf-C4H2, ZF_C4H2
NMRAL1	Other/Unknown	no		NmrA-like, NAD(P)-bd_dom_sf, NmrA-like_oxidored
SLC25A36	Other/Unknown	no		MCP, MCP_transmembrane, MCP_dom_sf
FAM161A	Other/Unknown	no		FAM161A/B, FAM161
CORO7	Scaffold/PPI	no		WD40_rpt, DUF1899, Coronin
PUS10	Enzyme (other)	yes	5.4.99.25	PsdUridine_synth_cat_dom_sf, Pus10-like, Pus10-like_C
RMDN2	Other/Unknown	no		TPR-like_helical_dom_sf,
CHMP5	Other/Unknown	no		Snf7_fam
IGSF21	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
SRARP	Other/Unknown	no		C1ORF64
MAGEB18	Other/Unknown	no		MHD_dom, MAGE_N, MAGE
TMEM178A	Other/Unknown	no		PMP22/EMP/MP20/Claudin, T178A/B

Expression context

Cohort genes with no expression data: 0.

63 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)	4
broad (>20)	71
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	9
ventricular zone	7
ganglionic eminence	6
cortical plate	5
middle temporal gyrus	5
primordial germ cell in gonad	5
sperm	5
tibia	4
apex of heart	4
right coronary artery	4
buccal mucosa cell	4
endothelial cell	4
secondary oocyte	4
jejunal mucosa	4
cerebellar hemisphere	3
gastrocnemius	3
germinal epithelium of ovary	3
descending thoracic aorta	3
corpus epididymis	3
Brodmann (1909) area 23	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNNM3	250	ubiquitous	marker	gastrocnemius, muscle of leg, cerebellar hemisphere
SIM1	76	broad	yes	renal medulla, skeletal muscle tissue of biceps brachii, biceps brachii
STAC	191	ubiquitous	marker	dorsal root ganglion, periodontal ligament, trigeminal ganglion
DNAJA3	142	ubiquitous	marker	gastrocnemius, muscle of leg, skeletal muscle organ
XPO1	294	ubiquitous	marker	tibia, ventricular zone, germinal epithelium of ovary
ZBTB17	255	ubiquitous	yes	lower esophagus mucosa, sural nerve, tendon of biceps brachii
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta
PRDM11	214	ubiquitous	yes	epithelial cell of pancreas, descending thoracic aorta, thoracic aorta
PRDM13	7	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, hair follicle
ANO3	189	broad	marker	corpus epididymis, lateral globus pallidus, putamen
PAPOLG	274	ubiquitous	yes	endothelial cell, male germ line stem cell (sensu Vertebrata) in testis, Brodmann (1909) area 23
XYLT1	272	broad	marker	tibia, cartilage tissue, hair follicle
SYTL5	176	tissue_specific	marker	pancreatic ductal cell, ileal mucosa, palpebral conjunctiva
CCNC	294	ubiquitous	marker	parotid gland, oral cavity, corpus epididymis
PAK5	123	broad	marker	cortical plate, middle temporal gyrus, ganglionic eminence
LAMP5	191	broad	marker	nucleus accumbens, middle temporal gyrus, caudate nucleus
CCT4	294	ubiquitous	marker	primordial germ cell in gonad, ventricular zone, cortical plate
DOK5	248	broad	marker	ventricular zone, ganglionic eminence, pancreatic ductal cell
GGTLC1	40		marker	right lung, male germ line stem cell (sensu Vertebrata) in testis, upper lobe of left lung
CDH13	152	ubiquitous	marker	descending thoracic aorta, right coronary artery, thoracic aorta
CDH18	170	broad	marker	middle temporal gyrus, cerebellar vermis, paraflocculus
SPEN	293	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
VASN	140	ubiquitous	marker	stromal cell of endometrium, popliteal artery, tibial artery
EBF3	193	broad	marker	tibialis anterior, subcutaneous adipose tissue, tendon of biceps brachii
AATF	134	ubiquitous	marker	monocyte, leukocyte, granulocyte
TTC7A	236	ubiquitous	marker	sperm, right testis, left testis
USP34	292	ubiquitous	marker	renal medulla, nipple, cardia of stomach
USP45	225	ubiquitous	marker	calcaneal tendon, secondary oocyte, epithelial cell of pancreas
DDX53	12	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, sperm
C14orf132	263	ubiquitous	marker	middle temporal gyrus, endothelial cell, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 13.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XPO1	7,582
REL	5,998
CCT4	5,903
APOB	5,244
PDK1	4,014
DNAJA3	3,653
CCNC	3,374
FAM161A	3,370
AATF	3,194
GLI2	3,112

Intra-cohort edges

A	B	Sources
AOPEP	FSHR	string_interaction
CCNC	PRDM13	string_interaction
CCNC	SPEN	biogrid_interaction, intact
COMMD1	NMRAL1	string_interaction
FOCAD	HACD4	string_interaction
FOXF2	GLI2	string_interaction
HSPB7	REL	intact
MCHR2	SIM1	string_interaction
PEX13	SANBR	string_interaction
PEX13	USP34	string_interaction
POU3F2	SIM1	string_interaction
PRDM11	PRDM13	string_interaction
PUS10	SANBR	string_interaction

Structural data

PDB: 37 · AlphaFold-only: 38 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCT4	P50991	66
CCNC	P24863	36
ZBTB17	Q13105	19
XPO1	O14980	18
SND1	Q7KZF4	11
XYLT1	Q86Y38	9
APOB	P04114	8
CNNM3	Q8NE01	7
HMOX2	P30519	7
CHMP5	Q9NZZ3	6
CMKLR1	Q99788	5
NMRAL1	Q9HBL8	5
FSHR	P23945	5
NFIA	Q12857	5
PDK1	Q15118	5
DNAJA3	Q96EY1	4
SPEN	Q96T58	4
COMMD1	Q8N668	4
AATF	Q9NY61	3
PEX13	Q92968	3
STAC	Q99469	2
PAK5	Q9P286	2
EBF3	Q9H4W6	2
USP34	Q70CQ2	2
DDX53	Q86TM3	2
F13B	P05160	2
HSPB7	Q9UBY9	2
PRDM11	Q9NQV5	1
PAPOLG	Q9BWT3	1
DOK5	Q9P104	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CELA2A	P08217	93.66
GGTLC1	Q9BX51	93.42
PAM16	Q9Y3D7	89.52
HEPH	Q9BQS7	89.09
SLC25A36	Q96CQ1	87.02
LAMP5	Q9UJQ1	86.55
HACD4	Q5VWC8	85.73
SLC5A12	Q1EHB4	85.00
TTC7A	Q9ULT0	84.59
PTGFRN	Q9P2B2	84.25
AOPEP	Q8N6M6	83.36
FOCAD	Q5VW36	82.99
CDH18	Q13634	77.57
IGSF21	Q96ID5	76.60
ANO3	Q9BYT9	76.30
MATN2	O00339	75.94
MAGEB18	Q96M61	75.10
VASN	Q6EMK4	74.75
TMEM178A	Q8NBL3	74.31
RMDN2	Q96LZ7	74.19
DCAF8L1	A6NGE4	74.03
AHSA2P	Q719I0	69.62
SANBR	Q6NSI8	68.60
C14orf132	Q9NPU4	66.98
FAM161A	Q3B820	66.83
REL	Q04864	66.46
USP45	Q70EL2	66.28
SYTL5	Q8TDW5	65.97
PHACTR2	O75167	61.66
SIM1	P81133	60.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 191. Enrichment computed across 75 evidence-associated genes (38 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 38 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum)	1	150.3×	0.252	HEPH
ASS1 variants cause citrullinemia	1	150.3×	0.252	NMRAL1
Scavenging by Class H Receptors	1	75.1×	0.252	APOB
VLDL assembly	1	60.1×	0.252	APOB
RUNX2 regulates chondrocyte maturation	1	60.1×	0.252	GLI2
Chylomicron clearance	1	60.1×	0.252	APOB
Scavenging by Class F Receptors	1	50.1×	0.252	APOB
LDL remodeling	1	50.1×	0.252	APOB
VLDL clearance	1	50.1×	0.252	APOB
Iron uptake and transport	2	18.2×	0.252	HEPH, HMOX2
Adherens junctions interactions	2	13.1×	0.252	CDH13, CDH18
Cell-cell junction organization	2	13.1×	0.252	CDH13, CDH18
Heme signaling	2	11.3×	0.252	XPO1, APOB
Cell junction organization	2	9.8×	0.252	CDH13, CDH18
Transcriptional and post-translational regulation of MITF-M expression and activity	2	9.4×	0.252	XPO1, POU3F2
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	42.9×	0.272	GLI2
Organic anion transport by SLC5/17/25 transporters	1	37.6×	0.272	SLC5A12
Inorganic anion exchange by SLC26 transporters	1	33.4×	0.272	SLC5A12
HuR (ELAVL1) binds and stabilizes mRNA	1	33.4×	0.272	XPO1
Folding of actin by CCT/TriC	1	30.1×	0.272	CCT4
Chylomicron assembly	1	30.1×	0.272	APOB
Chylomicron remodeling	1	30.1×	0.272	APOB
Cell-Cell communication	2	7.2×	0.272	CDH13, CDH18
Scavenging by Class B Receptors	1	27.3×	0.281	APOB
Hormone ligand-binding receptors	1	25.0×	0.281	FSHR
Urea cycle	1	23.1×	0.281	NMRAL1
Induction of Cell-Cell Fusion	1	23.1×	0.281	ANO3
Fibrin formation	1	23.1×	0.281	F13B
Heme degradation	1	21.5×	0.281	HMOX2
Activation of RAC1	1	21.5×	0.281	PAK5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 69 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of proteasomal ubiquitin-dependent protein catabolic process	3	48.9×	0.012	XPO1, COMMD1, FOXF2
hypothalamus cell differentiation	2	97.7×	0.035	PRDM13, POU3F2
regulation of post-transcriptional gene silencing	1	244.2×	0.105	FOCAD
regulation of acetylcholine metabolic process	1	244.2×	0.105	FSHR
intestinal iron absorption	1	244.2×	0.105	HEPH
regulation of protein polyubiquitination	1	244.2×	0.105	FOXF2
positive regulation of iron export across plasma membrane	1	244.2×	0.105	HEPH
positive regulation of cholesterol import	1	244.2×	0.105	COMMD1
primary ovarian follicle growth	1	122.1×	0.105	FSHR
heme oxidation	1	122.1×	0.105	HMOX2
regulation of platelet-derived growth factor receptor signaling pathway	1	122.1×	0.105	FSHR
neurohypophysis development	1	122.1×	0.105	POU3F2
dendrite regeneration	1	122.1×	0.105	MATN2
regulation of neurotrophin TRK receptor signaling pathway	1	122.1×	0.105	DOK5
microtubule-based peroxisome localization	1	122.1×	0.105	PEX13
global genome nucleotide-excision repair	1	122.1×	0.105	USP45
negative regulation of hypoxia-inducible factor-1alpha signaling pathway	1	122.1×	0.105	COMMD1
cellular response to salt	1	122.1×	0.105	XPO1
pyrimidine nucleotide import into mitochondrion	1	122.1×	0.105	SLC25A36
ventral midline development	1	81.4×	0.105	GLI2
detection of temperature stimulus	1	81.4×	0.105	ANO3
floor plate formation	1	81.4×	0.105	GLI2
forebrain ventricular zone progenitor cell division	1	81.4×	0.105	POU3F2
forebrain astrocyte development	1	81.4×	0.105	POU3F2
spinal cord ventral commissure morphogenesis	1	81.4×	0.105	GLI2
follicle-stimulating hormone signaling pathway	1	81.4×	0.105	FSHR
localization within membrane	1	81.4×	0.105	CDH13
low-density lipoprotein particle mediated signaling	1	81.4×	0.105	CDH13
cell differentiation involved in kidney development	1	81.4×	0.105	GLIS2
calcium activated galactosylceramide scrambling	1	81.4×	0.105	ANO3

Therapeutics

Drugs indicated for this disease

9 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alprostadil	Approved (phase 4)
Apomorphine	Approved (phase 4)
Avanafil	Approved (phase 4)
Moxisylyte	Approved (phase 4)
Papaverine	Approved (phase 4)
Sildenafil	Approved (phase 4)
Tadalafil	Approved (phase 4)
Vardenafil	Approved (phase 4)
Yohimbine	Approved (phase 4)
Dapoxetine	Phase 3 (in late-stage trials)
Fluvastatin	Phase 3 (in late-stage trials)
Testosterone	Phase 3 (in late-stage trials)
Udenafil	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Clavulanic Acid, Nitroglycerin, Onabotulinumtoxina, Prasterone, Sodium Chloride.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 4 · Phased (≥1): 7 · Undrugged: 68

Druggability breadth: 24 of 75 evidence-associated genes (32%) 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
XPO1	SELINEXOR
CCNC	SORAFENIB
PAK5	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PAK5	11	4
XPO1	4	4
CCNC	4	4
PDK1	4	2
SPEN	1	2
CMKLR1	1	1
HMOX2	1	3
CNNM3	0	0
SIM1	0	0
STAC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SELINEXOR	4	XPO1
ZAFIRLUKAST	4	XPO1
SORAFENIB	4	CCNC
FEDRATINIB	4	PAK5
RUXOLITINIB	4	PAK5
NINTEDANIB	4	PAK5
SUNITINIB	4	PAK5
LESTAURTINIB	3	PAK5
TIVANTINIB	3	HMOX2
VERDINEXOR	2	XPO1
ISTISOCICLIB	2	CCNC
SU-014813	2	PAK5
R-406	2	PAK5
TOZASERTIB	2	PAK5
MOLIBRESIB	2	SPEN
LY-2090314	2	PDK1
JTT-251	2	PDK1
AT-9283	2	PDK1
SOTRASTAURIN	2	PDK1
AS-602868	1	XPO1
SENEXIN B	1	CCNC
SEL-120 FREE BASE	1	CCNC
KW-2449	1	PAK5
PF-03758309	1	PAK5
GSK-690693	1	PAK5
RESOLVIN E1	1	CMKLR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
PDK1	529	Binding:527, Functional:1, ADMET:1
CCNC	226	Binding:226
PAK5	217	Binding:217
XPO1	146	Binding:146
CMKLR1	58	Binding:37, Functional:21
FSHR	43	Functional:26, Binding:17
MCHR2	35	Binding:21, Functional:14
HMOX2	11	Binding:11
CCT4	7	Binding:7
SND1	7	Binding:7
SPEN	6	Binding:6
GLI2	6	Binding:6
ZBTB17	4	Binding:4
USP45	3	Binding:3
NMRAL1	3	Binding:3
F13B	3	Binding:3
REL	3	Binding:3
DNAJA3	1	Binding:1
AOPEP	1	ADMET:1
PRDM11	1	Binding:1
PRDM13	1	Binding:1
APOB	1	Binding:1
POU3F2	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PAPOLG	2.7.7.19	polynucleotide adenylyltransferase
XYLT1	2.4.2.26	protein xylosyltransferase
PAK5	2.7.11.1, 2.7.12.2	non-specific serine/threonine protein kinase, mitogen-activated protein kinase kinase
CCT4	3.6.4.B10
PUS10	5.4.99.25, 5.4.99.B22, 5.4.99.B25	tRNA pseudouridine55 synthase, ,
SND1	3.1.31.1	micrococcal nuclease
HMOX2	1.14.14.18	heme oxygenase (biliverdin-producing)
PDK1	2.7.11.2	[pyruvate dehydrogenase (acetyl-transferring)] kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
XPO1	146
CCNC	226
PAK5	217
PDK1	529

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).

Chemical tractability of cohort targets

26 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)
SELINEXOR	4	XPO1
ZAFIRLUKAST	4	XPO1
SORAFENIB	4	CCNC
FEDRATINIB	4	PAK5
RUXOLITINIB	4	PAK5
NINTEDANIB	4	PAK5
SUNITINIB	4	PAK5
LESTAURTINIB	3	PAK5
TIVANTINIB	3	HMOX2
VERDINEXOR	2	XPO1
ISTISOCICLIB	2	CCNC
SU-014813	2	PAK5
R-406	2	PAK5
TOZASERTIB	2	PAK5
MOLIBRESIB	2	SPEN
LY-2090314	2	PDK1
JTT-251	2	PDK1
AT-9283	2	PDK1
SOTRASTAURIN	2	PDK1
AS-602868	1	XPO1
SENEXIN B	1	CCNC
SEL-120 FREE BASE	1	CCNC
KW-2449	1	PAK5
PF-03758309	1	PAK5
GSK-690693	1	PAK5
RESOLVIN E1	1	CMKLR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	XPO1, CCNC, PAK5
B	Phased (≥1) drug, not yet approved	4	SPEN, CMKLR1, HMOX2, PDK1
C	Druggable family + PDB, no drug	10	PAPOLG, XYLT1, CCT4, USP34, MCHR2, PUS10, SND1, F13B, FSHR, ALCAM
D	Druggable family + AlphaFold only, no drug	7	AOPEP, GGTLC1, VASN, USP45, CELA2A, IGSF21, PTGFRN
E	Difficult family or no structure, no drug	51	CNNM3, SIM1, STAC, DNAJA3, ZBTB17, PRDM11, PRDM13, ANO3, SYTL5, LAMP5 (+41 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CNNM3	0	—
SIM1	0	—
STAC	0	—
DNAJA3	1	—
ZBTB17	4	—
AOPEP	1	—
PRDM11	1	—
PRDM13	1	—
ANO3	0	—
PAPOLG	0	—
XYLT1	0	—
SYTL5	0	—
LAMP5	0	—
CCT4	7	—
DOK5	0	—
GGTLC1	0	—
CDH13	0	—
CDH18	0	—
VASN	0	—
EBF3	0	—
AATF	0	—
TTC7A	0	—
USP34	0	—
USP45	3	—
DDX53	0	—
C14orf132	0	—
AHSA2P	0	—
MCHR2	35	—
HACD4	0	—
PHACTR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 570.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	247
PHASE3	96
PHASE4	95
PHASE1	59
PHASE2	52
PHASE1/PHASE2	13
PHASE2/PHASE3	6
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04601233	PHASE4	NOT_YET_RECRUITING	Testosterone Treatment for Erectile Dysfunction and Multiple Sclerosis
NCT07246642	PHASE4	NOT_YET_RECRUITING	IPP Placement & Intracavernosal Block
NCT07391579	PHASE4	RECRUITING	Daily Tadalafil 5 mg Combined With On-Demand Sildenafil 100 mg for Treatment of Erectile Dysfunction in PDE-5I Non Responder Patients
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00137072	PHASE4	COMPLETED	Mild To Moderate Erectile Dysfunction Study
NCT00143221	PHASE4	COMPLETED	Effectiveness and Safety of Viagra in Men With ED and LUTS Due to Benign Prostatic Hyperplasia (BPH)
NCT00143260	PHASE4	COMPLETED	Study Of Men With Mild To Moderate Erectile Dysfunction To Evaluate The Efficacy Of Viagra 8 Hours Post-Dose
NCT00147628	PHASE4	COMPLETED	Assessment Of Sildenafil On Erectile Function And Intercourse Satisfaction And To Validate A New Subject Questionnaire
NCT00150358	PHASE4	COMPLETED	To Yield Further Information On The Efficacy And Safety Of Viagra Among Subjects With Arterial Hypertension .
NCT00151463	PHASE4	COMPLETED	QEQ Treatment Responsiveness Evaluation Study
NCT00159809	PHASE4	COMPLETED	Efficacy Study Measuring The Impact Of Treatment With Viagra On The Depressive Symptoms Of Men With Erectile Dysfunction
NCT00159848	PHASE4	COMPLETED	Effect Of A Treatment Optimization Program To Improve Satisfaction With Viagra
NCT00159900	PHASE4	COMPLETED	Quality of Erection Study
NCT00199563	PHASE4	COMPLETED	Use of Sildenafil (Viagra) in Diabetic Men With Erectile Dysfunction: the Impact on Blood Vessels
NCT00245258	PHASE4	COMPLETED	Study to Evaluate Viagra’s Ability to Provide a Better Sexual Experience Through Quality Erections and Satisfaction
NCT00245596	PHASE4	COMPLETED	Evaluation of the Index of Sexual Life Questionnaire
NCT00249730	PHASE4	COMPLETED	Titration Study to Evaluate Efficacy and Satisfaction of Viagra in Men With Erectile Function.
NCT00301262	PHASE4	COMPLETED	Impact Of Viagra On Sexual Satisfaction Of Men With Mild Erectile Dysfunction Who Are Sexually Dissatisfied
NCT00313898	PHASE4	UNKNOWN	Effect of Sildenafil on Quality of Sexual Life in Mild to Normally Sexually Functioning Males
NCT00333281	PHASE4	COMPLETED	A Study of Visual Effects of Erectile Dysfunction Medications Dosed Daily for Six Months
NCT00343200	PHASE4	COMPLETED	A Study Of The Safety and Efficacy Of Viagra In Men With Erectile Dysfunction Who Do Not Self Identify.
NCT00379756	PHASE4	COMPLETED	A Study Evaluating Vardenafil Compared to Placebo in Subjects With Erectile Dysfunction (ED) and Dyslipidemia
NCT00382135	PHASE4	COMPLETED	A Study of Semen Characteristics After 9 Months of Daily Tadalafil 20 mg
NCT00421460	PHASE4	COMPLETED	The Therapy of Nebido as Mono or in Combination With PDE-5 Inhibitors in Hypogonadal Patients With Erectile Dysfunction
NCT00422578	PHASE4	COMPLETED	Effect of Tadalafil on the Quality of Life and Sexual Life in Erectile Dysfunction
NCT00468650	PHASE4	COMPLETED	A Multicenter, Open Label, To Evaluate The Efficacy And Satisfaction Of Patrex® In Men With Erectile Dysfunction.
NCT00498680	PHASE4	UNKNOWN	Safety and Clinical Effectiveness of 2 Lower Dose Combined PDE5i’s vs. Single Maximal Dose PDE5i
NCT00512707	PHASE4	COMPLETED	Effect of Testosterone in Men With Erectile Dysfunction
NCT00547092	PHASE4	COMPLETED	Study For Which Treatment, Tadalafil or Sildenafil, is Preferred For Problems Getting or Maintaining an Erection
NCT00547352	PHASE4	COMPLETED	Study to Determine a Preference Between Sildenafil or Tadalafil Treatment for Problems Getting an Erection
NCT00547599	PHASE4	COMPLETED	Determine If the Stress That Comes With Not Developing an Erection Affects Tadalafil Effects
NCT00555087	PHASE4	UNKNOWN	Treatment of Erectile Dysfunction in Hypogonadal Men With Testosterone Undecanoate
NCT00644631	PHASE4	COMPLETED	A Multicenter, Randomized, Parallel Group, Double-Blind, Placebo Controlled, Flexible Dose Escalation Study To Evaluate Sexual And Relationship Satisfaction In The Female Partner Of Men With Erectile Dysfunction Treated With Sildenafil Citrate
NCT00644956	PHASE4	COMPLETED	A Randomized, Open-Label, Crossover, Multicenter, Single Dose Comparator Study Evaluating Onset Of Penile Rigidity In Men With Erectile Dysfunction Who Are Treated With Sildenafil And Tadalafil
NCT00645268	PHASE4	COMPLETED	A Multicenter, Double-blind Study to Evaluate the Effect of Pretreatment With a Daily Dose of Sildenafil on the As-Needed Efficacy of Viagra in Men With Erectile Dysfunction and Type 2 Diabetes
NCT00648596	PHASE4	COMPLETED	A Study to Evaluate Self-esteem and Relationships in Males With Erectile Dysfuntion
NCT00654082	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Sildenafil in Men With Traumatic Spinal Cord Injury and Erectile Dysfunction
NCT00655590	PHASE4	COMPLETED	Assess the Effect of Daily Treatment of Vardenafil 20mg or Sildenafil 100mg and Placebo on Sperm Function
NCT00660998	PHASE4	COMPLETED	Evaluation of Efficacy and Safety of Vardenafil in Patients With Erectile Dysfunction and Type 1 Diabetes
NCT00662441	PHASE4	COMPLETED	Evaluating of the Efficacy and Safety of Vardenafil in Subjects With Erectile Dysfunction

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SILDENAFIL	4	83
TADALAFIL	4	40
VARDENAFIL	4	23
AVANAFIL	4	19
TAMSULOSIN	4	8
ALFUZOSIN	4	6
ENALAPRIL	4	6
ALPROSTADIL	4	4
TESTOSTERONE	4	4
ALCOHOL	4	2
COLLAGENASE CLOSTRIDIUM HISTOLYTICUM	4	2
MIRABEGRON	4	2
NITROGLYCERIN	4	2
PENTOXIFYLLINE	4	2
RIFAMPIN	4	2
TACROLIMUS ANHYDROUS	4	2
ALECTINIB	4	1
BICALUTAMIDE	4	1
BRIGATINIB	4	1
CHLORHEXIDINE	4	1
CLAVULANIC ACID	4	1
DESIPRAMINE	4	1
DICLOFENAC SODIUM	4	1
DOXAZOSIN	4	1
DOXAZOSIN MESYLATE	4	1
ERYTHROMYCIN	4	1
GENTAMICIN	4	1
INCOBOTULINUMTOXINA	4	1
INSULIN HUMAN	4	1
KETOCONAZOLE	4	1