Androgenetic alopecia

Summary

Androgenetic alopecia (MONDO:0005339) is a disease with 75 cohort genes (132 GWAS associations across 12 studies) and 170 clinical trials. The dominant Reactome pathway is RUNX3 regulates p14-ARF (3 cohort genes). Top therapeutic interventions include minoxidil, finasteride, and bimatoprost.

At a glance

• Cohort genes: 75
• GWAS associations: 132
• Clinical trials: 170

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	androgenetic alopecia
Mondo ID	MONDO:0005339
EFO	EFO:0004191
DOID	DOID:0050801
SNOMED CT	87872006
UMLS	C0162311
MedGen	56404
Is cancer (heuristic)	no

Also known as: male pattern baldness

Data availability: 132 GWAS associations (12 studies).

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hair anomaly › alopecia › endocrine alopecia › androgenetic alopecia

Subtypes (4): alopecia, androgenetic, 1, alopecia, androgenetic, 2, alopecia, androgenetic, 3, baldness, male pattern

Genetics & variants

GWAS landscape

132 GWAS associations across 12 studies. Top hits map to 25 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs200644307	1e-247	RNU6-394P - AR	?	2.28
rs11087368	1e-105	LINC01432	G	0.31
rs2497938	2e-91	RNU6-394P - AR	T	2.2
rs201563	3e-81	RPL41P1 - LINC01432	?	1.55
rs71530654	7e-63	HDAC9	A	0.24
rs552649178	6e-59	RPL41P1 - LINC01432	G	0.27
rs12203592	2e-52	IRF4	C	0.26
rs7542354	6e-49	CIROZ	G	0.25
rs77410716	5e-45	RPL41P1 - LINC01432	C	0.28
rs1422798	2e-44	EBF1	C	0.2
rs939963	2e-41	RNA5SP231 - RNU6-832P	G	0.19
rs11684254	1e-39	LINC01937 - TWIST2	C	0.19
rs6047844	2e-39	LINC01432	T	1.6
rs7801037	1e-36	HDAC9	?	1.33
rs7061504	3e-35	OPHN1	A	0.4
rs34624408	9e-29	HULC - OFCC1	T	0.16
rs2095921	3e-27	CIROZ	?	1.34
rs4718886	8e-27	RNU6-229P - Y_RNA	A	0.17
rs919462	1e-26	MAPT	C	0.17
rs34991987	2e-26	RNU6-832P - MTCO2P25	?	1.27
rs13021718	2e-26	DPY30, MEMO1	G	0.21
rs7680591	5e-25	FGF5	T	0.15
rs8085664	8e-25	SLC14A2	C	0.16
chr17:43947866	1e-24		GTGTGTGTGTGTGGGTGT	0.24
rs11593840	9e-24	LRMDA	A	0.14
rs17833789	9e-23	AKAP1 - MSI2	C	0.14
rs79593277	2e-22	EMC2	G	0.62
rs62385385	7e-22	EBF1	?	1.25
rs7642536	2e-21	MRPS22	T	0.2
rs2064251	1e-20	IFITM3P7 - SYF2	G	0.15

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90043616	Jiang L	2021	66,172	140,864	A generalized linear mixed model association tool for biobank-scale data.
GCST90043618	Jiang L	2021	55,137	151,899	A generalized linear mixed model association tool for biobank-scale data.
GCST90043617	Jiang L	2021	47,867	159,169	A generalized linear mixed model association tool for biobank-scale data.
GCST90043619	Jiang L	2021	37,860	169,176	A generalized linear mixed model association tool for biobank-scale data.
GCST005116	Pirastu N	2017	25,662	17,928	GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.
GCST003983	Pickrell JK	2016	9,009	8,491	Detection and interpretation of shared genetic influences on 42 human traits.
GCST001548	Li R	2012	3,891	8,915	Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.
GCST001297	Brockschmidt FF	2011	581	0	Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness.
GCST000250	Richards JB	2008	578	0	Male-pattern baldness susceptibility locus at 20p11.
GCST000251	Hillmer AM	2008	296	0	Susceptibility variants for male-pattern baldness on chromosome 20p11.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	49

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	5

Functional consequences

Consequence	Count
intron_variant	38
intergenic_variant	10
regulatory_region_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs200644307	X	67081073	T>TATATGTGTATATATACATAA,TATATGTGTATATATACATAAATATGTGTATATATGTGTATATATACATAA	0.05	intergenic_variant	RNU6-394P - AR	1e-247	Tier 4: intronic/intergenic
rs11087368	20	22057342	GT>G,GTT,GTTT,GTTTT	0.05	intron_variant	LINC01432	1e-105	Tier 4: intronic/intergenic
rs2497938	X	67343176	T>C	0.15	intergenic_variant	RNU6-394P - AR	2e-91	Tier 4: intronic/intergenic
rs201563	20	22019643	C>T	0.05	intergenic_variant	RPL41P1 - LINC01432	3e-81	Tier 4: intronic/intergenic
rs71530654	7	18857365	A>C,G,T	0.05	intron_variant	HDAC9	7e-63	Tier 4: intronic/intergenic
rs552649178	20	21961007	GTTT>G,GT,GTT,GTTTT,GTTTTTTTTTTTTTTTTTGTGGTAGGCTGGTTTTTGATTTGTGGTCTTTTTTTTGTTTTT,GTTTTT,GTTTTTT,GTTTTTTTTTTTTTTTTTTTGTTAGGCTGGTTTTTTTTTTTTGTTTT,GTTTTTTTTTTTTTTTTTTTTGGTTGGTTGGTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTGGTTTTTGTGTTTTTTTTTTGTTTT,GTTTTTTTT	0.05	intron_variant	RPL41P1 - LINC01432	6e-59	Tier 4: intronic/intergenic
rs12203592	6	396321	C>G,T	0.05	intron_variant	IRF4	2e-52	Tier 4: intronic/intergenic
rs7542354	1	10980328	G>A	0.05	intron_variant	CIROZ	6e-49	Tier 4: intronic/intergenic
rs77410716	20	21912814	C>T	0.05	intron_variant	RPL41P1 - LINC01432	5e-45	Tier 4: intronic/intergenic
rs1422798	5	158893869	C>G,T	0.05	intron_variant	EBF1	2e-44	Tier 4: intronic/intergenic
rs939963	7	69122810	G>A,C,T	0.05	intergenic_variant	RNA5SP231 - RNU6-832P	2e-41	Tier 4: intronic/intergenic
rs11684254	2	238787252	C>G,T	0.05	regulatory_region_variant	LINC01937 - TWIST2	1e-39	Tier 3: regulatory
rs6047844	20	22056937	T>C	0.46	intron_variant	LINC01432	2e-39	Tier 4: intronic/intergenic
rs7801037	7	18857888	C>A,G,T	0.05	intron_variant	HDAC9	1e-36	Tier 4: intronic/intergenic
rs7061504	X	68143959	A>G	0.05	intron_variant	OPHN1	3e-35	Tier 4: intronic/intergenic
rs34624408	6	9333352	TA>T,TAA,TAAA	0.05	intergenic_variant	HULC - OFCC1	9e-29	Tier 4: intronic/intergenic
rs2095921	1	10973265	C>G,T	0.05	intron_variant	CIROZ	3e-27	Tier 4: intronic/intergenic
rs4718886	7	69433703	A>G	0.05	intergenic_variant	RNU6-229P - Y_RNA	8e-27	Tier 4: intronic/intergenic
rs919462	17	45988374	C>T	0.05	intron_variant	MAPT	1e-26	Tier 4: intronic/intergenic
rs34991987	7	69130240	CA>C,CAA	0.05	intergenic_variant	RNU6-832P - MTCO2P25	2e-26	Tier 4: intronic/intergenic
rs13021718	2	31956355	G>A	0.05	intron_variant	DPY30, MEMO1	2e-26	Tier 4: intronic/intergenic
rs7680591	4	80276795	T>A,G	0.05	intron_variant	FGF5	5e-25	Tier 4: intronic/intergenic
rs8085664	18	45234191	C>A,T	0.05	intron_variant	SLC14A2	8e-25	Tier 4: intronic/intergenic
chr17:43947866							1e-24	Tier 4: intronic/intergenic
rs11593840	10	76436854	A>G	0.05	intron_variant	LRMDA	9e-24	Tier 4: intronic/intergenic
rs17833789	17	57153267	C>A	0.05	intron_variant	AKAP1 - MSI2	9e-23	Tier 4: intronic/intergenic
rs79593277	8	108483382	G>C		intron_variant	EMC2	2e-22	Tier 4: intronic/intergenic
rs62385385	5	158940241	T>A,G	0.05	intron_variant	EBF1	7e-22	Tier 4: intronic/intergenic
rs7642536	3	139313491	T>C	0.05	intron_variant	MRPS22	2e-21	Tier 4: intronic/intergenic
rs2064251	1	25143422	G>A,T	0.05	intron_variant	IFITM3P7 - SYF2	1e-20	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 47 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
SRD5A2	Orphanet:1331	Familial prostate cancer
SRD5A2	Orphanet:753	46,XY difference of sex development due to 5-alpha-reductase 2 deficiency
TARDBP	Orphanet:275872	Frontotemporal dementia with motor neuron disease
TARDBP	Orphanet:700154	TARDBP-related predominantly upper-limb distal myopathy
TARDBP	Orphanet:803	Amyotrophic lateral sclerosis
TBX15	Orphanet:93333	Pelviscapular dysplasia
TWIST1	Orphanet:35093	Non-syndromic sagittal craniosynostosis
TWIST1	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
TWIST1	Orphanet:794	Saethre-Chotzen syndrome
WARS2	Orphanet:238455	Infantile dystonia-parkinsonism
WARS2	Orphanet:572798	WARS2-related combined oxidative phosphorylation defect
WNT3	Orphanet:3301	Tetraamelia-multiple malformations syndrome
ESPN	Orphanet:231169	Usher syndrome type 1
ESPN	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
WNT10A	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
WNT10A	Orphanet:2721	Odonto-onycho-dermal dysplasia
WNT10A	Orphanet:50944	Schöpf-Schulz-Passarge syndrome
WNT10A	Orphanet:99798	Oligodontia
PRDM8	Orphanet:324290	PRDM8-related progressive myoclonus epilepsy
HDAC4	Orphanet:1001	2q37 microdeletion syndrome
AUTS2	Orphanet:352490	Autism spectrum disorder due to AUTS2 deficiency
AUTS2	Orphanet:641372	B-lymphoblastic leukemia/lymphoma with t(7;9)(q11.2;p13.2)
MRPS22	Orphanet:137908	Hypotonia with lactic acidemia and hyperammonemia
MRPS22	Orphanet:243	46,XX gonadal dysgenesis
CDCA7	Orphanet:2268	ICF syndrome
SETBP1	Orphanet:436151	Intellectual disability-expressive aphasia-facial dysmorphism syndrome
SETBP1	Orphanet:798	Schinzel-Giedion syndrome
EDA2R	Orphanet:181	X-linked hypohidrotic ectodermal dysplasia
TWIST2	Orphanet:1231	Barber-Say syndrome
TWIST2	Orphanet:1807	Focal facial dermal dysplasia type III
TWIST2	Orphanet:920	Ablepharon macrostomia syndrome
COPB2	Orphanet:2512	Autosomal recessive primary microcephaly
LRMDA	Orphanet:352745	Oculocutaneous albinism type 7
KANSL1	Orphanet:363958	17q21.31 microdeletion syndrome
KANSL1	Orphanet:363965	Koolen-De Vries syndrome due to a point mutation
GORAB	Orphanet:2078	Geroderma osteodysplastica
SPAG17	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
SPAG17	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
RSPO2	Orphanet:3301	Tetraamelia-multiple malformations syndrome
EDAR	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
EDAR	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
PLEKHM1	Orphanet:210110	Intermediate osteopetrosis
FGF5	Orphanet:411788	Familial isolated trichomegaly

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPLP1	HGNC:10372	ENSG00000137818	P05386	Large ribosomal subunit protein P1	gwas
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	gwas
RUNX3	HGNC:10473	ENSG00000020633	Q13761	Runt-related transcription factor 3	gwas
SLC14A2	HGNC:10919	ENSG00000132874	Q15849	Urea transporter 2	gwas
SP3	HGNC:11208	ENSG00000172845	Q02447	Transcription factor Sp3	gwas
SRD5A2	HGNC:11285	ENSG00000277893	P31213	3-oxo-5-alpha-steroid 4-dehydrogenase 2	gwas
SSPN	HGNC:11322	ENSG00000123096	Q14714	Sarcospan	gwas
SUPT3H	HGNC:11466	ENSG00000196284	O75486	Transcription initiation protein SPT3 homolog	gwas
TARDBP	HGNC:11571	ENSG00000120948	Q13148	TAR DNA-binding protein 43	gwas
TBX15	HGNC:11594	ENSG00000092607	Q96SF7	T-box transcription factor TBX15	gwas
TLE3	HGNC:11839	ENSG00000140332	Q04726	Transducin-like enhancer protein 3	gwas
TWIST1	HGNC:12428	ENSG00000122691	Q15672	Twist-related protein 1	gwas
UBL3	HGNC:12504	ENSG00000122042	O95164	Ubiquitin-like protein 3	gwas
WARS2	HGNC:12730	ENSG00000116874	Q9UGM6	Tryptophan–tRNA ligase, mitochondrial	gwas
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gwas
ZXDA	HGNC:13198	ENSG00000198205	P98168	Zinc finger X-linked protein ZXDA	gwas
ESPN	HGNC:13281	ENSG00000187017	B1AK53	Espin	gwas
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	gwas
DMRTA2	HGNC:13908	ENSG00000142700	Q96SC8	Doublesex- and mab-3-related transcription factor A2	gwas
PRDM8	HGNC:13993	ENSG00000152784	Q9NQV8	PR domain zinc finger protein 8	gwas
HDAC4	HGNC:14063	ENSG00000068024	P56524	Histone deacetylase 4	gwas
HDAC9	HGNC:14065	ENSG00000048052	Q9UKV0	Histone deacetylase 9	gwas
AUTS2	HGNC:14262	ENSG00000158321	Q8WXX7	Autism susceptibility gene 2 protein	gwas
MRPS22	HGNC:14508	ENSG00000175110	P82650	Small ribosomal subunit protein mS22	gwas
CDCA7	HGNC:14628	ENSG00000144354	Q9BWT1	Cell division cycle-associated protein 7	gwas
SETBP1	HGNC:15573	ENSG00000152217	Q9Y6X0	SET-binding protein	gwas
ASB1	HGNC:16011	ENSG00000065802	Q9Y576	Ankyrin repeat and SOCS box protein 1	gwas
AADAC	HGNC:17	ENSG00000114771	P22760	Arylacetamide deacetylase	gwas
CDC5L	HGNC:1743	ENSG00000096401	Q99459	Cell division cycle 5-like protein	gwas
EDA2R	HGNC:17756	ENSG00000131080	Q9HAV5	Tumor necrosis factor receptor superfamily member 27	gwas
EPS15P1	HGNC:18166	ENSG00000242948		epidermal growth factor receptor pathway substrate 15 pseudogene 1	gwas
FAM9A	HGNC:18403	ENSG00000183304	Q8IZU1	Protein FAM9A	gwas
FAM9B	HGNC:18404	ENSG00000177138	Q8IZU0	Protein FAM9B	gwas
MSI2	HGNC:18585	ENSG00000153944	Q96DH6	RNA-binding protein Musashi homolog 2	gwas
THADA	HGNC:19217	ENSG00000115970	Q6YHU6	tRNA (32-2’-O)-methyltransferase regulator THADA	gwas
SYF2	HGNC:19824	ENSG00000117614	O95926	Pre-mRNA-splicing factor SYF2	gwas
RRAGB	HGNC:19901	ENSG00000083750	Q5VZM2	Ras-related GTP-binding protein B	gwas
TWIST2	HGNC:20670	ENSG00000233608	Q8WVJ9	Twist-related protein 2	gwas
RSPO3	HGNC:20866	ENSG00000146374	Q9BXY4	R-spondin-3	gwas
OFCC1	HGNC:21017	ENSG00000181355	Q8IZS5	Orofacial cleft 1 candidate gene 1 protein	gwas
CENPW	HGNC:21488	ENSG00000203760	Q5EE01	Centromere protein W	gwas
SLC35B3	HGNC:21601	ENSG00000124786	Q9H1N7	Adenosine 3’-phospho 5’-phosphosulfate transporter 2	gwas
TNS3	HGNC:21616	ENSG00000136205	Q68CZ2	Tensin-3	gwas
COPB2	HGNC:2232	ENSG00000184432	P35606	Coatomer subunit beta'	gwas
LRMDA	HGNC:23405	ENSG00000148655	Q9H2I8	Leucine-rich melanocyte differentiation-associated protein	gwas
KANSL1	HGNC:24565	ENSG00000120071	Q7Z3B3	KAT8 regulatory NSL complex subunit 1	gwas
ETAA1	HGNC:24648	ENSG00000143971	Q9NY74	Ewing’s tumor-associated antigen 1	gwas
HNRNPA3	HGNC:24941	ENSG00000170144	P51991	Heterogeneous nuclear ribonucleoprotein A3	gwas
VCF2	HGNC:25085	ENSG00000182518	Q5XKR9	Protein VCF2	gwas
FAR2	HGNC:25531	ENSG00000064763	Q96K12	Fatty acyl-CoA reductase 2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPLP1	Large ribosomal subunit protein P1	Plays an important role in the elongation step of protein synthesis.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
RUNX3	Runt-related transcription factor 3	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
SLC14A2	Urea transporter 2	Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism.
SP3	Transcription factor Sp3	Transcriptional factor that can act as an activator or repressor depending on isoform and/or post-translational modifications.
SRD5A2	3-oxo-5-alpha-steroid 4-dehydrogenase 2	Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids.
SSPN	Sarcospan	Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix.
SUPT3H	Transcription initiation protein SPT3 homolog	Probable transcriptional activator.
TARDBP	TAR DNA-binding protein 43	RNA-binding protein that is involved in various steps of RNA biogenesis and processing.
TBX15	T-box transcription factor TBX15	Probable transcriptional regulator involved in the development of the skeleton of the limb, vertebral column and head.
TLE3	Transducin-like enhancer protein 3	Transcriptional coregulator that binds to a number of transcription factors.
TWIST1	Twist-related protein 1	Acts as a transcriptional regulator.
WARS2	Tryptophan–tRNA ligase, mitochondrial	Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of tRNA(Trp).
WNT3	Proto-oncogene Wnt-3	Ligand for members of the frizzled family of seven transmembrane receptors.
ZXDA	Zinc finger X-linked protein ZXDA	Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.
ESPN	Espin	Multifunctional actin-bundling protein.
WNT10A	Protein Wnt-10a	Ligand for members of the frizzled family of seven transmembrane receptors.
DMRTA2	Doublesex- and mab-3-related transcription factor A2	May be involved in sexual development.
PRDM8	PR domain zinc finger protein 8	Probable histone methyltransferase, preferentially acting on ‘Lys-9’ of histone H3.
HDAC4	Histone deacetylase 4	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
HDAC9	Histone deacetylase 9	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
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.
CDCA7	Cell division cycle-associated protein 7	Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells.
ASB1	Ankyrin repeat and SOCS box protein 1	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
AADAC	Arylacetamide deacetylase	Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly.
CDC5L	Cell division cycle 5-like protein	DNA-binding protein involved in cell cycle control.
EDA2R	Tumor necrosis factor receptor superfamily member 27	Receptor for EDA isoform A2, but not for EDA isoform A1.
FAM9B	Protein FAM9B	May play a role in meiosis.
MSI2	RNA-binding protein Musashi homolog 2	RNA binding protein that regulates the expression of target mRNAs at the translation level.
THADA	tRNA (32-2’-O)-methyltransferase regulator THADA	Together with methyltransferase FTSJ1, methylates the 2’-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs.
SYF2	Pre-mRNA-splicing factor SYF2	Involved in pre-mRNA splicing as component of the spliceosome.
RRAGB	Ras-related GTP-binding protein B	Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.
TWIST2	Twist-related protein 2	Binds to the E-box consensus sequence 5’-CANNTG-3’ as a heterodimer and inhibits transcriptional activation by MYOD1, MYOG, MEF2A and MEF2C.
RSPO3	R-spondin-3	Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis.
CENPW	Centromere protein W	Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation.
SLC35B3	Adenosine 3’-phospho 5’-phosphosulfate transporter 2	Probably functions as a 3’-phosphoadenylyl sulfate:adenosine 3’,5’-bisphosphate antiporter at the Golgi membranes.
TNS3	Tensin-3	May act as a protein phosphatase and/or a lipid phosphatase.
COPB2	Coatomer subunit beta’	The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Go…
LRMDA	Leucine-rich melanocyte differentiation-associated protein	Required for melanocyte differentiation.
KANSL1	KAT8 regulatory NSL complex subunit 1	Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at ‘Lys-5’- and ‘Lys-8’ (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiatio…
ETAA1	Ewing’s tumor-associated antigen 1	Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity.
HNRNPA3	Heterogeneous nuclear ribonucleoprotein A3	Plays a role in cytoplasmic trafficking of RNA.
FAR2	Fatty acyl-CoA reductase 2	Catalyzes the reduction of saturated but not unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols (FAls).
TMEM74	Transmembrane protein 74	Plays an essential role in autophagy.
SPAG17	Sperm-associated antigen 17	Component of the central pair apparatus of ciliary axonemes.
CIROZ	Ciliated left-right organizer ZP-N domains-containing protein	Plays a role in left-right patterning process.
DFFA	DNA fragmentation factor subunit alpha	Inhibitor of the caspase-activated DNase (DFF40).
UBLCP1	Ubiquitin-like domain-containing CTD phosphatase 1	Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity.
KATNAL1	Katanin p60 ATPase-containing subunit A-like 1	Regulates microtubule dynamics in Sertoli cells, a process that is essential for spermiogenesis and male fertility.
RSPO2	R-spondin-2	Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors.

Protein-family classification

Druggable: 8 · Difficult: 17 · Unknown: 50 · Druggable fraction: 0.11

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
Other/Unknown	50	1.2×	0.219
Transcription factor	12	1.3×	0.576
Scaffold/PPI	5	1.1×	0.622
Phosphatase	1	1.1×	0.622
Transporter	1	1.0×	0.622
Enzyme (other)	6	1.0×	0.622

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPLP1	Other/Unknown	no		Ribosomal_P1/P2, P1/P2_N_sf
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
RUNX3	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
SLC14A2	Transporter	yes		Urea_transporter, Ammonium/urea_transptr
SP3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
SRD5A2	Enzyme (other)	yes	1.3.1.22	3-oxo-5_a-steroid_4-DH_C, 3-oxo-5-alpha-steroid_4-DH, SRD5A/TECR
SSPN	Other/Unknown	no		CD20-like_TM, Sarcospan
SUPT3H	Other/Unknown	no		TFIID_TAF13, Histone-fold
TARDBP	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
TBX15	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TLE3	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
TWIST1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, TWIST1_bHLH
UBL3	Other/Unknown	no		Ubiquitin-like_dom, MUB, Ubiquitin-like_domsf
WARS2	Enzyme (other)	yes	6.1.1.2	aa-tRNA-synth_I_CS, aa-tRNA-synth_Ic, Trp-tRNA-ligase
WNT3	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
ZXDA	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,
ESPN	Scaffold/PPI	no		Ankyrin_rpt, WH2_dom, Ankyrin_rpt-contain_sf
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS
DMRTA2	Other/Unknown	no		DM_DNA-bd, DMA, UBA-like_sf
PRDM8	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
HDAC4	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
HDAC9	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
AUTS2	Other/Unknown	no		AUTS2
MRPS22	Other/Unknown	no		Ribosomal_mS22
CDCA7	Transcription factor	no		Znf-4CXXC_R1, CDCA7/CDA7L
SETBP1	Other/Unknown	no		AT_hook_DNA-bd_motif
ASB1	Scaffold/PPI	no		SOCS_box, Ankyrin_rpt, SOCS_box-like_dom_sf
AADAC	Other/Unknown	no		AB_hydrolase_3, Arylacetamide_deacetylase, AB_hydrolase_fold
CDC5L	Transcription factor	no		SANT/Myb, Homeodomain-like_sf, Myb_dom
EDA2R	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_27, TNFRSF27_N
EPS15P1	Other/Unknown	no
FAM9A	Other/Unknown	no		XLR/SYCP3
FAM9B	Other/Unknown	no		XLR/SYCP3/FAM9_dom, XLR/SYCP3
MSI2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, MSI_RRM2
THADA	Other/Unknown	no		ARM-type_fold, THADA/TRM732_DUF2428, tRNA_methyltransferase_THADA
SYF2	Other/Unknown	no		mRNA_splic_SYF2
RRAGB	Other/Unknown	no		Gtr1_RagA, P-loop_NTPase, RagA/B
TWIST2	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, Twist2_bHLH
RSPO3	Other/Unknown	no		TSP1_rpt, Furin_repeat, Growth_fac_rcpt_cys_sf
OFCC1	Other/Unknown	no		OFCC1
CENPW	Other/Unknown	no		Histone-fold, CENP-W, CENP-W/WIP1
SLC35B3	Other/Unknown	no		HUT1
TNS3	Phosphatase	yes		Tyr_Pase_dom, SH2, Tyr_Pase_cat
COPB2	Scaffold/PPI	no		WD40_rpt, Beta-prop_COPA/B_2nd, WD40/YVTN_repeat-like_dom_sf
LRMDA	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, LRMDA
KANSL1	Other/Unknown	no		NSL1, PEHE_dom
ETAA1	Other/Unknown	no		ETAA1
HNRNPA3	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, hnRNPA1/3_RRM2
VCF2	Other/Unknown	no		VCF1/2-like
FAR2	Other/Unknown	no		FAR_NAD-bd, FAR, FAR_C

Expression context

Cohort genes with no expression data: 0.

66 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	2
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	10
calcaneal tendon	10
buccal mucosa cell	9
primordial germ cell in gonad	9
secondary oocyte	8
oocyte	8
ganglionic eminence	7
ventricular zone	7
right testis	6
cortical plate	5
sperm	4
endothelial cell	4
right uterine tube	4
mucosa of stomach	4
stromal cell of endometrium	4
epithelium of bronchus	3
mucosa of paranasal sinus	3
right adrenal gland	3
bronchial epithelial cell	3
left testis	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPLP1	156	ubiquitous	marker	epithelium of bronchus, thymus, trachea
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
RUNX3	220	broad	marker	granulocyte, buccal mucosa cell, lymph node
SLC14A2	100	tissue_specific	marker	primordial germ cell in gonad, hair follicle, right adrenal gland
SP3	299	ubiquitous	marker	hair follicle, germinal epithelium of ovary, sural nerve
SRD5A2	66	tissue_specific	marker	corpus epididymis, bronchial epithelial cell, epithelium of bronchus
SSPN	285	ubiquitous	marker	synovial joint, skeletal muscle tissue of rectus abdominis, body of tongue
SUPT3H	206	ubiquitous	yes	primordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
TARDBP	301	ubiquitous	marker	secondary oocyte, ventricular zone, ganglionic eminence
TBX15	172	broad	marker	gastrocnemius, muscle of leg, skeletal muscle tissue of rectus abdominis
TLE3	248	ubiquitous	marker	blood, cortical plate, ganglionic eminence
TWIST1	233	ubiquitous	marker	periodontal ligament, mucosa of paranasal sinus, oocyte
UBL3	295	ubiquitous	marker	inferior olivary complex, amniotic fluid, dorsal motor nucleus of vagus nerve
WARS2	226	ubiquitous	marker	primordial germ cell in gonad, bronchial epithelial cell, calcaneal tendon
WNT3	129	broad	yes	skin of abdomen, zone of skin, hypothalamus
ZXDA	208	tissue_specific	yes	endothelial cell, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis
ESPN	184	broad	marker	right testis, left testis, right uterine tube
WNT10A	151	broad	marker	primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell
DMRTA2	54	tissue_specific	yes	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell
PRDM8	159	ubiquitous	marker	cortical plate, ganglionic eminence, mucosa of stomach
HDAC4	277	ubiquitous	marker	sural nerve, gluteal muscle, gastrocnemius
HDAC9	277	ubiquitous	marker	oocyte, monocyte, secondary oocyte
AUTS2	292	ubiquitous	marker	cortical plate, tibia, ganglionic eminence
MRPS22	289	ubiquitous	marker	adrenal tissue, right adrenal gland, right adrenal gland cortex
CDCA7	215	ubiquitous	marker	ileal mucosa, ventricular zone, embryo
SETBP1	280	ubiquitous	marker	ventricular zone, buccal mucosa cell, caput epididymis
ASB1	270	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, nucleus accumbens
AADAC	164	tissue_specific	marker	jejunal mucosa, right adrenal gland, right adrenal gland cortex
CDC5L	290	ubiquitous	marker	buccal mucosa cell, sperm, male germ cell
EDA2R	157	ubiquitous	marker	olfactory bulb, type B pancreatic cell, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TARDBP	7,245
CDC5L	5,930
RUNX1	4,994
HDAC4	4,771
HNRNPA3	3,962
FGF5	3,791
TWIST1	3,507
RPLP1	3,497
RUNX3	3,293
DIP2B	3,108

Intra-cohort edges

A	B	Sources
AUTS2	TLE3	biogrid_interaction, intact
C1D	SPAG17	string_interaction
CDC5L	SYF2	string_interaction
CDCA7	SP3	string_interaction
COPB2	MRPS22	string_interaction
EDAR	UBL3	biogrid_interaction, intact
EDAR	WNT10A	string_interaction
FAM9A	FAM9B	intact
FAM9A	PAGE2B	string_interaction
FAR2	TMEM74	biogrid_interaction
FGF5	RSPO2	string_interaction
HDAC4	HDAC9	biogrid_interaction
HDAC4	RUNX3	intact
HNRNPA3	TARDBP	string_interaction
KANSL1	WNT3	string_interaction
PAGE2B	VCF2	string_interaction
RUNX1	RUNX3	string_interaction
RUNX1	SETBP1	string_interaction
RUNX3	TLE3	string_interaction
TBX15	TLE3	string_interaction
TBX15	WARS2	string_interaction

Structural data

PDB: 33 · AlphaFold-only: 41 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRPS22	P82650	77
TARDBP	Q13148	44
CDC5L	Q99459	37
HDAC4	P56524	19
SYF2	O95926	17
EMC2	Q15006	11
SLC14A2	Q15849	9
CENPW	Q5EE01	9
RSPO2	Q6UXX9	8
RUNX1	Q01196	5
PLEKHM1	Q9Y4G2	5
SUPT3H	O75486	4
NTMT2	Q5VVY1	4
RPLP1	P05386	3
MSI2	Q96DH6	3
DFFA	O00273	3
UBLCP1	Q8WVY7	3
TWIST1	Q15672	2
HDAC9	Q9UKV0	2
CDCA7	Q9BWT1	2
THADA	Q6YHU6	2
COPB2	P35606	2
KANSL1	Q7Z3B3	2
EBF1	Q9UH73	2
RUNX3	Q13761	1
SRD5A2	P31213	1
UBL3	O95164	1
WARS2	Q9UGM6	1
WNT3	P56703	1
TNS3	Q68CZ2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AADAC	P22760	95.64
FAR2	Q96K12	94.15
EEF1AKMT2	Q5JPI9	91.22
C1D	Q13901	88.37
RRAGB	Q5VZM2	82.50
WNT10A	Q9GZT5	82.36
ASB1	Q9Y576	80.61
FAM9B	Q8IZU0	79.88
DIP2B	Q9P265	78.83
LRMDA	Q9H2I8	78.40
RSPO3	Q9BXY4	78.27
SLC35B3	Q9H1N7	77.40
FGF5	P12034	76.62
SSPN	Q14714	74.41
TWIST2	Q8WVJ9	73.94
GORAB	Q5T7V8	71.86
DKK2	Q9UBU2	70.82
TMEM132D	Q14C87	70.52
EDA2R	Q9HAV5	69.14
HNRNPA3	P51991	69.10
ESPN	B1AK53	68.76
TLE3	Q04726	68.65
FAM9A	Q8IZU1	66.59
SPAG17	Q6Q759	64.20
PAGE2B	Q5JRK9	62.21
TBX15	Q96SF7	61.41
VCF2	Q5XKR9	61.07
OFCC1	Q8IZS5	60.75
PRR23C	Q6ZRP0	58.54
DMRTA2	Q96SC8	57.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 346. Enrichment computed across 94 evidence-associated genes (57 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 57 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates p14-ARF	3	60.1×	0.005	RUNX1, RUNX3, HDAC4
RUNX3 regulates RUNX1-mediated transcription	2	133.6×	0.013	RUNX1, RUNX3
TCF dependent signaling in response to WNT	5	10.3×	0.014	RUNX3, WNT3, RSPO3, RSPO2, DKK2
RUNX1 regulates transcription of genes involved in WNT signaling	2	66.8×	0.031	RUNX1, RSPO3
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	2	30.8×	0.080	RUNX1, RUNX3
Transcriptional regulation by RUNX2	3	13.4×	0.080	RUNX1, TWIST1, TWIST2
NOTCH1 Intracellular Domain Regulates Transcription	3	12.5×	0.080	TLE3, HDAC4, HDAC9
Signaling by WNT	4	7.9×	0.080	RUNX3, RSPO3, RSPO2, ITPR2
SLC-mediated transport of organic cations	2	26.7×	0.095	RUNX1, SLC14A2
Class B/2 (Secretin family receptors)	3	10.0×	0.114	WNT3, WNT10A, FZD10
Regulation of FZD by ubiquitination	2	18.2×	0.167	RSPO3, RSPO2
Transcriptional regulation by RUNX1	3	7.7×	0.183	RUNX1, AUTS2, RSPO3
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	3	7.7×	0.183	HDAC4, HDAC9, IRF4
WNT ligand biogenesis and trafficking	2	14.8×	0.196	WNT3, WNT10A
Notch-HLH transcription pathway	2	14.3×	0.196	HDAC4, HDAC9
TNFs bind their physiological receptors	2	13.8×	0.197	EDA2R, EDAR
Metabolism of RNA	5	3.7×	0.236	CDC5L, THADA, SYF2, HNRNPA3, C1D
Nuclear events stimulated by ALK signaling in cancer	2	11.4×	0.252	TWIST1, IRF4
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	2	10.5×	0.265	RUNX1, AUTS2
mRNA Splicing	3	5.8×	0.265	CDC5L, SYF2, HNRNPA3
Signaling by Overexpressed Wild-Type EGFR in Cancer	1	50.1×	0.267	AREG
Wax biosynthesis	1	50.1×	0.267	FAR2
MET interacts with TNS proteins	1	40.1×	0.267	TNS3
RUNX1 regulates expression of components of tight junctions	1	40.1×	0.267	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	40.1×	0.267	RUNX1
RUNX2 regulates chondrocyte maturation	1	40.1×	0.267	HDAC4
RUNX2 regulates genes involved in differentiation of myeloid cells	1	40.1×	0.267	RUNX1
RUNX3 regulates BCL2L11 (BIM) transcription	1	40.1×	0.267	RUNX3
Transcriptional regulation by RUNX3	2	9.5×	0.267	RUNX1, RUNX3
Intracellular signaling by second messengers	3	4.8×	0.267	RRAGB, ITPR2, AREG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 85 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic hindlimb morphogenesis	4	27.4×	0.004	TWIST1, WNT3, RSPO2, ALX4
embryonic forelimb morphogenesis	4	23.3×	0.004	TWIST1, WNT3, RSPO2, ALX4
regulation of transcription by RNA polymerase II	20	2.7×	0.004	RUNX1, RUNX3, SP3, SUPT3H, TBX15, TWIST1, ZXDA, DMRTA2 (+12 more)
negative regulation of CD4-positive, alpha-beta T cell differentiation	2	99.1×	0.019	RUNX1, RUNX3
positive regulation of CD8-positive, alpha-beta T cell differentiation	2	79.3×	0.021	RUNX1, RUNX3
canonical Wnt signaling pathway	5	9.0×	0.021	WNT3, WNT10A, RSPO3, RSPO2, FZD10
dopaminergic neuron differentiation	3	22.0×	0.024	DMRTA2, RSPO2, FOXA2
embryonic cranial skeleton morphogenesis	3	20.5×	0.026	TBX15, TWIST1, PRRX1
ossification	4	10.7×	0.030	RUNX1, RUNX3, SP3, TWIST1
positive regulation of DNA-templated transcription	10	3.3×	0.046	RUNX1, RUNX3, SP3, SUPT3H, TBX15, ZXDA, HDAC4, KANSL1 (+2 more)
peripheral nervous system neuron development	2	36.0×	0.055	RUNX1, RUNX3
hair follicle development	3	13.5×	0.055	WNT10A, EDAR, ALX4
positive regulation of Wnt signaling pathway	3	13.5×	0.055	WNT3, RSPO3, RSPO2
neuron differentiation	5	5.9×	0.058	RUNX1, RUNX3, WNT3, WNT10A, FZD10
positive regulation of canonical Wnt signaling pathway	4	7.3×	0.076	RSPO3, RSPO2, DKK2, FAM53B
N-terminal protein amino acid methylation	1	198.3×	0.080	NTMT2
phthalate metabolic process	1	198.3×	0.080	SRD5A2
microvillar actin bundle assembly	1	198.3×	0.080	ESPN
positive regulation of striated muscle tissue development	1	198.3×	0.080	MRTFB
regulation of striated muscle cell differentiation	1	198.3×	0.080	HDAC9
Spemann organizer formation at the anterior end of the primitive streak	1	198.3×	0.080	WNT3
mitochondrial tryptophanyl-tRNA aminoacylation	1	198.3×	0.080	WARS2
regulation of neuron projection regeneration	1	198.3×	0.080	PRRX1
nuclear inner membrane organization	1	198.3×	0.080	TARDBP
plus-end-directed organelle transport along microtubule	1	198.3×	0.080	MAPT
regulation of proteasome assembly	1	198.3×	0.080	UBLCP1
regulation of connective tissue replacement	1	198.3×	0.080	RUNX1
cell proliferation involved in heart valve development	1	198.3×	0.080	TWIST1
positive regulation of endocardial cushion to mesenchymal transition involved in heart valve formation	1	198.3×	0.080	TWIST1
male genitalia development	2	20.9×	0.080	SRD5A2, ASB1

Therapeutics

Drugs indicated for this disease

2 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Finasteride	Approved (phase 4)
Minoxidil	Approved (phase 4)
Clascoterone	Phase 3 (in late-stage trials)
Dutasteride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bimatoprost, Cetirizine, Incobotulinumtoxina, Onabotulinumtoxina, Valproic Acid.

Drug target analysis

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

Druggability breadth: 32 of 94 evidence-associated genes (34%) 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
RPLP1	GENTAMICIN SULFATE
RUNX1	APOMORPHINE HYDROCHLORIDE
SRD5A2	FINASTERIDE
TARDBP	MITOXANTRONE
HDAC4	CELECOXIB
HDAC9	CELECOXIB
AADAC	FLUTAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HDAC4	31	4
HDAC9	28	4
SRD5A2	5	4
RUNX1	2	4
RPLP1	1	4
TARDBP	1	4
AADAC	1	4
RUNX3	0	0
SLC14A2	0	0
SP3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPLP1
APOMORPHINE HYDROCHLORIDE	4	RUNX1
FINASTERIDE	4	SRD5A2
MITOXANTRONE	4	TARDBP
CELECOXIB	4	HDAC4, HDAC9
PHENYLBUTANOIC ACID	4	HDAC4, HDAC9
SODIUM PHENYLBUTYRATE	4	HDAC4, HDAC9
ROMIDEPSIN	4	HDAC4, HDAC9
BELINOSTAT	4	HDAC4, HDAC9
PANOBINOSTAT	4	HDAC4, HDAC9
VORINOSTAT	4	HDAC4, HDAC9
GIVINOSTAT	4	HDAC4, HDAC9
BENDAMUSTINE	4	HDAC4
FLUTAMIDE	4	AADAC
GAMOLENIC ACID	3	SRD5A2
CURCUMIN	3	HDAC4, HDAC9
CAFFEIC ACID	3	HDAC4, HDAC9
PRACINOSTAT	3	HDAC4, HDAC9
TACEDINALINE	3	HDAC4, HDAC9
ENTINOSTAT	3	HDAC4, HDAC9
TUCIDINOSTAT	3	HDAC4, HDAC9
ABEXINOSTAT	3	HDAC4, HDAC9
TASQUINIMOD	3	HDAC4
EBSELEN	3	HDAC9
MOLIBRESIB	2	RUNX1
EPRISTERIDE	2	SRD5A2
TUROSTERIDE	2	SRD5A2
BEXLOSTERIDE	2	SRD5A2
NANATINOSTAT	2	HDAC4, HDAC9
AR-42	2	HDAC4, HDAC9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
HDAC9	1,625	Binding:1612, ADMET:8, Functional:4, Toxicity:1
SRD5A2	119	Binding:115, Functional:4
RPLP1	90	Binding:90
RUNX1	20	Binding:17, Functional:3
AADAC	20	ADMET:19, Binding:1
TARDBP	8	Binding:7, Functional:1
WNT3	5	Functional:3, Binding:2
UBLCP1	5	Binding:5
NTMT2	5	Binding:5
MSI2	3	Binding:3
PRDM8	1	Binding:1
MRPS22	1	Binding:1
CDC5L	1	Binding:1
TNS3	1	Binding:1
COPB2	1	Binding:1
HNRNPA3	1	Binding:1
EDAR	1	Binding:1
EMC2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SRD5A2	1.3.1.22, 1.3.99.5	3-oxo-5alpha-steroid 4-dehydrogenase (NADP+), 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor)
WARS2	6.1.1.2	tryptophan-tRNA ligase
HDAC4	3.5.1.98	histone deacetylase
HDAC9	3.5.1.98	histone deacetylase
KATNAL1	5.6.1.1	microtubule-severing ATPase
NTMT2	2.1.1.299	protein N-terminal monomethyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SRD5A2	119
HDAC4	1,941
HDAC9	1,625

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

29 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)
GENTAMICIN SULFATE	4	RPLP1
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MITOXANTRONE	4	TARDBP
CELECOXIB	4	HDAC4, HDAC9
PHENYLBUTANOIC ACID	4	HDAC4, HDAC9
SODIUM PHENYLBUTYRATE	4	HDAC4, HDAC9
ROMIDEPSIN	4	HDAC4, HDAC9
BELINOSTAT	4	HDAC4, HDAC9
PANOBINOSTAT	4	HDAC4, HDAC9
VORINOSTAT	4	HDAC4, HDAC9
GIVINOSTAT	4	HDAC4, HDAC9
BENDAMUSTINE	4	HDAC4
FLUTAMIDE	4	AADAC
GAMOLENIC ACID	3	SRD5A2
CURCUMIN	3	HDAC4, HDAC9
CAFFEIC ACID	3	HDAC4, HDAC9
PRACINOSTAT	3	HDAC4, HDAC9
TACEDINALINE	3	HDAC4, HDAC9
ENTINOSTAT	3	HDAC4, HDAC9
TUCIDINOSTAT	3	HDAC4, HDAC9
ABEXINOSTAT	3	HDAC4, HDAC9
TASQUINIMOD	3	HDAC4
EBSELEN	3	HDAC9
MOLIBRESIB	2	RUNX1
EPRISTERIDE	2	SRD5A2
TUROSTERIDE	2	SRD5A2
BEXLOSTERIDE	2	SRD5A2
NANATINOSTAT	2	HDAC4, HDAC9
AR-42	2	HDAC4, HDAC9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	RPLP1, RUNX1, SRD5A2, TARDBP, HDAC4, HDAC9, AADAC
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	5	SLC14A2, WARS2, TNS3, KATNAL1, NTMT2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	63	RUNX3, SP3, SSPN, SUPT3H, TBX15, TLE3, TWIST1, UBL3, WNT3, ZXDA (+53 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)
RUNX3	0	—
SLC14A2	0	—
SP3	0	—
SSPN	0	—
SUPT3H	0	—
TBX15	0	—
TLE3	0	—
TWIST1	0	—
UBL3	0	—
WARS2	0	—
WNT3	5	—
ZXDA	0	—
ESPN	0	—
WNT10A	0	—
DMRTA2	0	—
PRDM8	1	—
AUTS2	0	—
MRPS22	1	—
CDCA7	0	—
SETBP1	0	—
ASB1	0	—
CDC5L	1	—
EDA2R	0	—
EPS15P1	0	—
FAM9A	0	—
FAM9B	0	—
MSI2	3	—
THADA	0	—
SYF2	0	—
RRAGB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 170.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	66
PHASE2	39
PHASE3	21
PHASE1/PHASE2	15
PHASE1	14
PHASE4	6
PHASE2/PHASE3	6
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07518342	PHASE4	NOT_YET_RECRUITING	The Effect of Nanofat Injection on Androgenetic Alopecia
NCT02999737	PHASE4	UNKNOWN	Comparing Different Platelet Rich Plasma (PRP) Treatment Regimens for Management of Androgenic Alopecia
NCT03388840	PHASE4	UNKNOWN	Adipose Derived Stem Cells Versus Platelet Rich Plasma on Follicular Unit Extraction
NCT04209803	PHASE4	COMPLETED	N-Acetyl-Cysteine for Treatment of AGA in Men
NCT04293822	PHASE4	UNKNOWN	Topical Cetirizine 1% vs Minoxidil 5% Gel in Treatment of Androgenetic Alopecia
NCT06043349	PHASE4	UNKNOWN	Effectiveness and Safety of Platelet-rich Plasma and Topical 5% Minoxidil Combination in Male Androgenetic Alopecia
NCT04594018	PHASE3	RECRUITING	Efficacy and Safety of Finlândia Hair Lotion Association on Androgenetic Alopecia
NCT05888922	PHASE3	RECRUITING	Evaluation of Efficacy and Safety of Oral Minoxidil 1 mg in Female Androgenetic Alopecia
NCT06501924	PHASE3	NOT_YET_RECRUITING	Clinical Study of DA-002 and DA-005 As a Treatment for Hair Loss
NCT06622824	PHASE2/PHASE3	NOT_YET_RECRUITING	To Evaluate Efficacy and Safety of TopicalKX-826 Solution in Chinese Male Patients With Androgenetic Alopecia
NCT06648850	PHASE2/PHASE3	NOT_YET_RECRUITING	Clinical Study of DA-001 as a Treatment for Hair Shedding Reduction and Hair Re-Growth
NCT06724614	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of VDPHL01 in Males With AGA
NCT06916793	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of CKD-843 in Male Patients With Androgenetic Alopecia
NCT06972264	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy of VDPHL01 in Males With AGA
NCT07080931	PHASE3	RECRUITING	Efficacy and Safety of 5% Minoxidil Foam in Female Androgenetic Alopecia
NCT07146022	PHASE3	RECRUITING	Safety and Efficacy of VDPHL01 in Females With Androgenetic Alopecia (AGA)
NCT07529977	PHASE3	NOT_YET_RECRUITING	Phase 3 Study to Evaluate the Efficacy and Safety of Oral Minoxidil (N1087) in Men With Androgenetic Alopecia.
NCT00151515	PHASE3	COMPLETED	A Study to Evaluate the Effectiveness and Safety of 5 Percent Minoxidil Foam in the Treatment of Male Pattern Hair Loss
NCT00396175	PHASE3	COMPLETED	Effects of Finasteride on Serum Prostate-Specific Antigen (0906-111)
NCT00958750	PHASE3	COMPLETED	Efficacy and Safety Study to Compare Two Minoxidil Formulations on Women With Androgenetic Alopecia
NCT01226459	PHASE3	COMPLETED	Clinical Trial in Females for Female Pattern Hair Loss
NCT01231607	PHASE3	COMPLETED	Dutasteride Versus Placebo and Finasteride in Men With Androgenetic Alopecia
NCT01391156	PHASE3	COMPLETED	Efficacy Study of Minoxidil Lotion Versus Combined Minoxidil and Finasteride Lotion to Treat Male Pattern Hair Loss
NCT03742518	PHASE2/PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of SM04554 Topical Solution in Male Subjects With Androgenetic Alopecia
NCT03753113	PHASE3	COMPLETED	Evaluating the Topical Herbal Solution on the Treatment of Male Pattern Hair Loss and Comparison With Minoxidil 5%
NCT04481412	PHASE2/PHASE3	COMPLETED	Topical Cetirizine in Androgenetic Alopecia in Females
NCT04825561	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AD-208
NCT05989165	PHASE3	COMPLETED	Effectiveness of Combination Therapy of Microneedling and Minoxidil in Androgenetic Alopecia of Indonesian Men
NCT05990400	PHASE2/PHASE3	UNKNOWN	Effectiveness and Safety of Topical Finasteride and Minoxidil Combination Compared to Topical Minoxidil for The Treatment of Male Androgenetic Alopecia
NCT06126965	PHASE3	UNKNOWN	Phase III Study of KX-826 With Adult Male Patients With AGA
NCT06484881	PHASE3	WITHDRAWN	Clinical Study of Probiotic Treatment for Androgenetic Alopecia
NCT06539273	PHASE3	COMPLETED	Exosome Treatment in Androgenetic Alopecia
NCT06924632	PHASE3	COMPLETED	Efficacy & Safety of Minoxidil SL Tablets in Men With AGA
NCT05456087	PHASE2	ACTIVE_NOT_RECRUITING	Use of Botulinum Toxin in the Treatment of Androgenic Alopecia
NCT06527365	PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of VDPHL01 in Males and Females With AGA
NCT06764329	PHASE1/PHASE2	ENROLLING_BY_INVITATION	The Effectiveness of Allogenic Mesenchymal Stem Cells Therapy on Hair Regrowth in Androgenetic Alopecia.
NCT06826001	PHASE2	NOT_YET_RECRUITING	Various Procedural Treatment Options for Androgenetic Alopecia
NCT07011485	PHASE2	ACTIVE_NOT_RECRUITING	A Safety and Efficacy Study of PDFE-2304 Topical Solution for the Treatment of Androgenic Alopecia.
NCT07112586	PHASE1/PHASE2	NOT_YET_RECRUITING	Evaluation of Exosomes Injection in Treatment of Male Androgenetic Alopecia: Clinical and Immunohistochemical Study
NCT07317544	PHASE1/PHASE2	RECRUITING	Study of ABS-201 Evaluating Single and Multiple Ascending Doses in Healthy Adults With and Without Androgenetic Alopecia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MINOXIDIL	4	29
FINASTERIDE	4	8
BIMATOPROST	4	2
CETIRIZINE	4	2
DUTASTERIDE	4	2
ARTENIMOL	4	1
CLASCOTERONE	4	1
PHENYLEPHRINE	4	1
VALPROIC ACID	4	1
DOCONEXENT	3	1
PRUXELUTAMIDE	3	1
DALOSIRVAT	2	3
IFIDANCITINIB	2	1
CHEMBL609587	0	29
CHEMBL4777013	0	8
VEHICLE	0	5
CHEMBL4303730	0	2