Alopecia

Summary

Alopecia (MONDO:0004907) is a disease (an umbrella term covering 26 Mondo subtypes) with 75 cohort genes (359 GWAS associations across 20 studies) and 338 clinical trials. Top therapeutic interventions include tofacitinib, ritlecitinib, and minoxidil.

At a glance

• Umbrella term: 26 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 359
• ClinVar variants: 2
• Clinical trials: 338

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	alopecia
Mondo ID	MONDO:0004907
MeSH	D000505
Orphanet	79364
DOID	DOID:987
ICD-11	1313926062
NCIT	C50575
SNOMED CT	56317004
UMLS	C0002170
MedGen	7982
Is cancer (heuristic)	no

Also known as: alopecia · alopecia areata · hair loss · loss Of hair

Data availability: 2 ClinVar variants · 359 GWAS associations (20 studies) · 10 cell lines.

Disease family

An umbrella term covering 26 Mondo subtypes.

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

Related subtypes (7): ringed hair disease, trichodysplasia-xeroderma syndrome, uncombable hair syndrome, isolated familial wooly hair disorder, pili torti, pili bifurcati, pili gemini

Subtypes (26): alopecia, isolated, telogen effluvium, alopecia areata, chemotherapy-induced alopecia, alopecia mucinosa, atrichia with papular lesions, loose anagen syndrome, Satoyoshi syndrome, alopecia-intellectual disability-hypergonadotropic hypogonadism syndrome, hereditary hypotrichosis with recurrent skin vesicles, alopecia antibody deficiency, pseudopelade of Brocq, frontal fibrosing alopecia, Quinquaud’s folliculitis decalvans, Graham Little-Piccardi-Lassueur syndrome, lichen planopilaris, hypotrichosis simplex, alopecia totalis, hypotrichosis simplex of the scalp, endocrine alopecia, alopecia universalis onychodystrophy vitiligo, central centrifugal cicatricial alopecia, ectodermal dysplasia alopecia preaxial polydactyly, Slti-Salem syndrome, microcephaly sparse hair intellectual disability seizures, alopecia universalis

Genetics & variants

GWAS landscape

359 GWAS associations across 20 studies. Top hits map to 14 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6625163	1e-300	RNU6-394P - AR	G	0.53
rs2497938	1e-300	RNU6-394P - AR	C	0.53
rs73221556	5e-178	RNU6-394P - AR	A	0.53
rs12558842	5e-178	RNU6-394P - AR	C	0.54
rs5919427	5e-178	AR - BMI1P1	C	0.35
rs201593	1e-103	RPL41P1 - LINC01432	A	0.13
rs6047844	1e-103	LINC01432	C	0.13
rs201563	3e-102	RPL41P1 - LINC01432	T	0.13
rs1160312	3e-98	LINC01432	G	0.13
rs6113491	2e-95	LINC01432 - LINC01427	C	0.13
rs201571	7e-88	RPL41P1 - LINC01432	T	0.13
rs6035986	1e-87	RPL41P1 - LINC01432	T	0.12
rs1998076	5e-87	RPL41P1 - LINC01432	G	0.12
rs2180439	7e-87	RPL41P1 - LINC01432	T	0.12
rs71530654	5e-70	HDAC9	G	0.11
rs7801037	8e-68	HDAC9	A	0.11
rs7362397	3e-65	LINC01432 - LINC01427	T	0.11
rs7362398	3e-65	LINC01432 - LINC01427	T	0.11
rs140488081	5e-61	OPHN1	T	0.4
rs147154263	4e-58	CCNYL5 - RBMXP5	T	0.43
rs7542354	6e-55	CIROZ	A	0.12
rs756853	6e-55	HDAC9	A	0.1
rs12565727	8e-53	CIROZ	G	0.11
rs2095921	9e-53	CIROZ	G	0.11
rs2073963	1e-51	HDAC9	G	0.1
rs12203592	3e-49	IRF4	T	0.11
rs939963	4e-48	RNA5SP231 - RNU6-832P	C	0.09
rs34991987	4e-47	RNU6-832P - MTCO2P25	C	0.09
rs1422798	3e-46	EBF1	G	0.09
rs62385385	1e-45	EBF1	A	0.09

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90727045	Kim HI	2026	3,340	40,686	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90473958	UK Biobank Whole-Genome Sequencing Consortium	2025	2,920	455,520	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667892	UK Biobank Whole-Genome Sequencing Consortium	2025	2,920	455,520	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478821	Verma A	2024	2,261	117,826	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480821	Verma A	2024	2,261	117,826	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478822	Verma A	2024	2,139	445,650	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651797	Liu TY	2025	880	231,046	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90478820	Verma A	2024	848	58,211	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080358	Backman JD	2021	834	384,476	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084344	Backman JD	2021	834	384,476	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	48

MAF distribution

Bucket	Variants
common (>=0.05)	49
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	24
intergenic_variant	23
regulatory_region_variant	1
missense_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6625163	X	67291142	G>A,C	0.05	intergenic_variant	RNU6-394P - AR	1e-300	Tier 4: intronic/intergenic
rs2497938	X	67343176	T>C	0.05	intergenic_variant	RNU6-394P - AR	1e-300	Tier 4: intronic/intergenic
rs73221556	X	66713443	C>A,T	0.05	intergenic_variant	RNU6-394P - AR	5e-178	Tier 4: intronic/intergenic
rs12558842	X	67261958	C>A,G,T	0.05	intergenic_variant	RNU6-394P - AR	5e-178	Tier 4: intronic/intergenic
rs5919427	X	67783742	C>A,T	0.05	intergenic_variant	AR - BMI1P1	5e-178	Tier 4: intronic/intergenic
rs201593	20	22053181	G>A	0.05	intergenic_variant	RPL41P1 - LINC01432	1e-103	Tier 4: intronic/intergenic
rs6047844	20	22056937	T>C	0.05	intron_variant	LINC01432	1e-103	Tier 4: intronic/intergenic
rs201563	20	22019643	C>T	0.05	intergenic_variant	RPL41P1 - LINC01432	3e-102	Tier 4: intronic/intergenic
rs1160312	20	22069865	A>C,G,T	0.05	intron_variant	LINC01432	3e-98	Tier 4: intronic/intergenic
rs6113491	20	22076777	A>C,G,T	0.05	intergenic_variant	LINC01432 - LINC01427	2e-95	Tier 4: intronic/intergenic
rs201571	20	22032876	C>A,T	0.05	intergenic_variant	RPL41P1 - LINC01432	7e-88	Tier 4: intronic/intergenic
rs6035986	20	21914126	G>C,T	0.05	intron_variant	RPL41P1 - LINC01432	1e-87	Tier 4: intronic/intergenic
rs1998076	20	21899407	A>C,G,T	0.05	intron_variant	RPL41P1 - LINC01432	5e-87	Tier 4: intronic/intergenic
rs2180439	20	21872462	C>T	0.05	intergenic_variant	RPL41P1 - LINC01432	7e-87	Tier 4: intronic/intergenic
rs71530654	7	18857365	A>C,G,T	0.05	intron_variant	HDAC9	5e-70	Tier 4: intronic/intergenic
rs7801037	7	18857888	C>A,G,T	0.05	intron_variant	HDAC9	8e-68	Tier 4: intronic/intergenic
rs7362397	20	22119432	C>G,T	0.05	intergenic_variant	LINC01432 - LINC01427	3e-65	Tier 4: intronic/intergenic
rs7362398	20	22119434	C>G,T	0.05	intergenic_variant	LINC01432 - LINC01427	3e-65	Tier 4: intronic/intergenic
rs140488081	X	68276160	C>T	0.05	intron_variant	OPHN1	5e-61	Tier 4: intronic/intergenic
rs147154263	X	65863405	G>T	0.05	intergenic_variant	CCNYL5 - RBMXP5	4e-58	Tier 4: intronic/intergenic
rs7542354	1	10980328	G>A	0.05	intron_variant	CIROZ	6e-55	Tier 4: intronic/intergenic
rs756853	7	18850377	G>A,C	0.05	intron_variant	HDAC9	6e-55	Tier 4: intronic/intergenic
rs12565727	1	10973025	A>G	0.05	intron_variant	CIROZ	8e-53	Tier 4: intronic/intergenic
rs2095921	1	10973265	C>G,T	0.05	intron_variant	CIROZ	9e-53	Tier 4: intronic/intergenic
rs2073963	7	18838251	T>G	0.05	intron_variant	HDAC9	1e-51	Tier 4: intronic/intergenic
rs12203592	6	396321	C>G,T	0.05	intron_variant	IRF4	3e-49	Tier 4: intronic/intergenic
rs939963	7	69122810	G>A,C,T	0.05	intergenic_variant	RNA5SP231 - RNU6-832P	4e-48	Tier 4: intronic/intergenic
rs34991987	7	69130240	CA>C,CAA	0.05	intergenic_variant	RNU6-832P - MTCO2P25	4e-47	Tier 4: intronic/intergenic
rs1422798	5	158893869	C>G,T	0.05	intron_variant	EBF1	3e-46	Tier 4: intronic/intergenic
rs62385385	5	158940241	T>A,G	0.05	intron_variant	EBF1	1e-45	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
156162	NM_015278.5(SASH1):c.1849G>A (p.Glu617Lys)	SASH1	Pathogenic/Likely pathogenic	no assertion criteria provided
523239	GRCh37/hg19 18p11.32-11.31(chr18:1345040-3479168)	SMCHD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 55 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCS1L	Orphanet:123	Björnstad syndrome
BCS1L	Orphanet:1460	Isolated complex III deficiency
BCS1L	Orphanet:254902	Renal tubulopathy-encephalopathy-liver failure syndrome
BCS1L	Orphanet:53693	GRACILE syndrome
RORA	Orphanet:528084	Non-specific syndromic intellectual disability
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
FOXL2	Orphanet:572333	Blepharophimosis-ptosis-epicanthus inversus syndrome plus
FOXL2	Orphanet:572354	Blepharophimosis-ptosis-epicanthus inversus syndrome type 1
FOXL2	Orphanet:572361	Blepharophimosis-ptosis-epicanthus inversus syndrome type 2
FOXL2	Orphanet:99915	Malignant granulosa cell tumor of the ovary
SNRPE	Orphanet:55654	Hypotrichosis simplex
SORD	Orphanet:700508	Distal muscle weakness-foot deformity-elevated sorbitol level-hereditary motor neuropathy
SPAST	Orphanet:100985	Autosomal dominant spastic paraplegia type 4
SRD5A2	Orphanet:1331	Familial prostate cancer
SRD5A2	Orphanet:753	46,XY difference of sex development due to 5-alpha-reductase 2 deficiency
SUCLA2	Orphanet:1933	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
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
TCF12	Orphanet:209916	Extraskeletal myxoid chondrosarcoma
TCF12	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
TCF4	Orphanet:171	Primary sclerosing cholangitis
TCF4	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
TCF4	Orphanet:2896	Pitt-Hopkins syndrome
TCF4	Orphanet:98974	Fuchs endothelial corneal dystrophy
TIA1	Orphanet:603	Distal myopathy, Welander type
MYRF	Orphanet:647811	Cardiac-urogenital syndrome
TRPS1	Orphanet:502	Trichorhinophalangeal syndrome type 2
TRPS1	Orphanet:77258	Trichorhinophalangeal syndrome type 1
TSPEAR	Orphanet:685067	Hypodontia-scalp hypotrichosis-facial dysmorphism syndrome
WARS2	Orphanet:238455	Infantile dystonia-parkinsonism
WARS2	Orphanet:572798	WARS2-related combined oxidative phosphorylation defect
WNT3	Orphanet:3301	Tetraamelia-multiple malformations syndrome
ZNF142	Orphanet:528084	Non-specific syndromic intellectual disability
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
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)
ARHGEF9	Orphanet:163985	Hyperekplexia-epilepsy syndrome
SETBP1	Orphanet:436151	Intellectual disability-expressive aphasia-facial dysmorphism syndrome
SETBP1	Orphanet:798	Schinzel-Giedion syndrome
NLRC4	Orphanet:436166	Periodic fever-infantile enterocolitis-autoinflammatory syndrome
NLRC4	Orphanet:576349	NLRC4-related familial cold autoinflammatory syndrome

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	74
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF11	HGNC:10056	ENSG00000123091	Q9Y3C5	RING finger protein 11	gwas
BCS1L	HGNC:1020	ENSG00000074582	Q9Y276	Mitochondrial chaperone BCS1	gwas
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas
CNOT9	HGNC:10445	ENSG00000144580	Q92600	CCR4-NOT transcription complex subunit 9	gwas
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	gwas
RUNX3	HGNC:10473	ENSG00000020633	Q13761	Runt-related transcription factor 3	gwas
S100A11	HGNC:10488	ENSG00000163191	P31949	Protein S100-A11	gwas
SLC14A2	HGNC:10919	ENSG00000132874	Q15849	Urea transporter 2	gwas
FOXL2	HGNC:1092	ENSG00000183770	P58012	Forkhead box protein L2	gwas
SNRPE	HGNC:11161	ENSG00000182004	P62304	Small nuclear ribonucleoprotein E	gwas
SNRPG	HGNC:11163	ENSG00000143977	P62308	Small nuclear ribonucleoprotein G	gwas
SORD	HGNC:11184	ENSG00000140263	Q00796	Sorbitol dehydrogenase	gwas
SPAST	HGNC:11233	ENSG00000021574	Q9UBP0	Spastin	gwas
SRD5A2	HGNC:11285	ENSG00000277893	P31213	3-oxo-5-alpha-steroid 4-dehydrogenase 2	gwas
SSPN	HGNC:11322	ENSG00000123096	Q14714	Sarcospan	gwas
SUCLA2	HGNC:11448	ENSG00000136143	Q9P2R7	Succinate–CoA ligase [ADP-forming] subunit beta, mitochondrial	gwas
TARDBP	HGNC:11571	ENSG00000120948	Q13148	TAR DNA-binding protein 43	gwas
TBX15	HGNC:11594	ENSG00000092607	Q96SF7	T-box transcription factor TBX15	gwas
TCF12	HGNC:11623	ENSG00000140262	Q99081	Transcription factor 12	gwas
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	gwas
TMEM258	HGNC:1164	ENSG00000134825	P61165	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit TMEM258	gwas
TCHH	HGNC:11791	ENSG00000159450	Q07283	Trichohyalin	gwas
TIA1	HGNC:11802	ENSG00000116001	P31483	Cytotoxic granule associated RNA binding protein TIA1	gwas
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	gwas
TOP1	HGNC:11986	ENSG00000198900	P11387	DNA topoisomerase 1	gwas
FMNL1	HGNC:1212	ENSG00000184922	O95466	Formin-like protein 1	gwas
TRPS1	HGNC:12340	ENSG00000104447	Q9UHF7	Zinc finger transcription factor Trps1	gwas
TSPEAR	HGNC:1268	ENSG00000175894	Q8WU66	Thrombospondin-type laminin G domain and EAR repeat-containing protein	gwas
VIL1	HGNC:12690	ENSG00000127831	P09327	Villin-1	gwas
WARS2	HGNC:12730	ENSG00000116874	Q9UGM6	Tryptophan–tRNA ligase, mitochondrial	gwas
WNT3	HGNC:12782	ENSG00000108379	P56703	Proto-oncogene Wnt-3	gwas
WNT6	HGNC:12785	ENSG00000115596	Q9Y6F9	Protein Wnt-6	gwas
ZNF142	HGNC:12927	ENSG00000115568	P52746	Zinc finger protein 142	gwas
ZXDA	HGNC:13198	ENSG00000198205	P98168	Zinc finger X-linked protein ZXDA	gwas
LGR4	HGNC:13299	ENSG00000205213	Q9BXB1	Leucine-rich repeat-containing G-protein coupled receptor 4	gwas
TNFRSF21	HGNC:13469	ENSG00000146072	O75509	Tumor necrosis factor receptor superfamily member 21	gwas
BIRC6	HGNC:13516	ENSG00000115760	Q9NR09	Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6	gwas
CLIC4	HGNC:13518	ENSG00000169504	Q9Y696	Chloride intracellular channel protein 4	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
MEMO1	HGNC:14014	ENSG00000162959	Q9Y316	Protein MEMO1	gwas
HDAC9	HGNC:14065	ENSG00000048052	Q9UKV0	Histone deacetylase 9	gwas
AUTS2	HGNC:14262	ENSG00000158321	Q8WXX7	Autism susceptibility gene 2 protein	gwas
BBX	HGNC:14422	ENSG00000114439	Q8WY36	HMG box transcription factor BBX	gwas
LPIN3	HGNC:14451	ENSG00000132793	Q9BQK8	Phosphatidate phosphatase LPIN3	gwas
KLF15	HGNC:14536	ENSG00000163884	Q9UIH9	Krueppel-like factor 15	gwas
ARHGEF9	HGNC:14561	ENSG00000131089	O43307	Rho guanine nucleotide exchange factor 9	gwas
RNF25	HGNC:14662	ENSG00000163481	Q96BH1	E3 ubiquitin-protein ligase RNF25	gwas
SETBP1	HGNC:15573	ENSG00000152217	Q9Y6X0	SET-binding protein	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF11	RING finger protein 11	Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways.
BCS1L	Mitochondrial chaperone BCS1	Chaperone necessary for the incorporation of Rieske iron-sulfur protein UQCRFS1 into the mitochondrial respiratory chain complex III.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
CNOT9	CCR4-NOT transcription complex subunit 9	Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational in…
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.
S100A11	Protein S100-A11	Facilitates the differentiation and the cornification of keratinocytes.
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.
FOXL2	Forkhead box protein L2	Transcriptional regulator.
SNRPE	Small nuclear ribonucleoprotein E	Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
SNRPG	Small nuclear ribonucleoprotein G	Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
SORD	Sorbitol dehydrogenase	Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols.
SPAST	Spastin	ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated.
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.
SUCLA2	Succinate–CoA ligase [ADP-forming] subunit beta, mitochondrial	ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA.
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.
TCF12	Transcription factor 12	Transcriptional regulator.
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
TMEM258	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit TMEM258	Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Se…
TCHH	Trichohyalin	Intermediate filament-associated protein that associates in regular arrays with keratin intermediate filaments (KIF) of the inner root sheath cells of the hair follicle and the granular layer of the epidermis.
TIA1	Cytotoxic granule associated RNA binding protein TIA1	RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences.
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.
TOP1	DNA topoisomerase 1	Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex.
FMNL1	Formin-like protein 1	May play a role in the control of cell motility and survival of macrophages.
TRPS1	Zinc finger transcription factor Trps1	Transcriptional repressor.
TSPEAR	Thrombospondin-type laminin G domain and EAR repeat-containing protein	Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.
VIL1	Villin-1	Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments.
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.
WNT6	Protein Wnt-6	Ligand for members of the frizzled family of seven transmembrane receptors.
ZNF142	Zinc finger protein 142	May be involved in transcriptional regulation.
ZXDA	Zinc finger X-linked protein ZXDA	Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.
LGR4	Leucine-rich repeat-containing G-protein coupled receptor 4	Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs.
TNFRSF21	Tumor necrosis factor receptor superfamily member 21	Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B.
BIRC6	Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6	Anti-apoptotic protein known as inhibitor of apoptosis (IAP) which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase.
CLIC4	Chloride intracellular channel protein 4	In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.
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.
MEMO1	Protein MEMO1	May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton.
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.
BBX	HMG box transcription factor BBX	Transcription factor that is necessary for cell cycle progression from G1 to S phase.
LPIN3	Phosphatidate phosphatase LPIN3	Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis therefore regulates fatty acid me…
KLF15	Krueppel-like factor 15	Transcriptional regulator that binds to the GA element of the CLCNKA promoter.
ARHGEF9	Rho guanine nucleotide exchange factor 9	Acts as a guanine nucleotide exchange factor (GEF) for CDC42.
RNF25	E3 ubiquitin-protein ligase RNF25	E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of trans…
ZHX3	Zinc fingers and homeoboxes protein 3	Acts as a transcriptional repressor.

Protein-family classification

Druggable: 17 · Difficult: 20 · Unknown: 38 · Druggable fraction: 0.23

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
Transcription factor	18	2.0×	0.034
Nuclear receptor	1	5.2×	0.937
Enzyme (other)	8	1.3×	0.937
Phosphatase	1	1.1×	0.937
Transporter	1	1.0×	0.937
GPCR	3	1.0×	0.937
Other/Unknown	38	0.9×	0.937
Protease	1	0.5×	0.937
Scaffold/PPI	2	0.5×	0.937
Antibody/Immunoglobulin	1	0.4×	0.937
Kinase	1	0.4×	0.937

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF11	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, RNF11_RING-H2
BCS1L	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
CNOT9	Other/Unknown	no		CNOT9, ARM-like, ARM-type_fold
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
S100A11	Other/Unknown	no		S100/CaBP7/8-like_CS, EF_hand_dom, EF-hand-dom_pair
SLC14A2	Transporter	yes		Urea_transporter, Ammonium/urea_transptr
FOXL2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
SNRPE	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, snRNP-E
SNRPG	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Sm_G
SORD	Enzyme (other)	yes	1.1.1.14	ADH_Zn_CS, GroES-like_sf, ADH-like_C
SPAST	Enzyme (other)	yes	5.6.1.1	AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
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
SUCLA2	Enzyme (other)	yes	6.2.1.5	Succ_CoA_ligase-like_bsu, SUCC_ACL_C, ATP-grasp
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
TCF12	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TMEM258	Enzyme (other)	yes	2.4.99.18	TMEM258/Ost5
TCHH	Other/Unknown	no		S100/CaBP7/8-like_CS, EF_hand_dom, EF-hand-dom_pair
TIA1	Other/Unknown	no		RRM_dom, RRM_euk-type, Nucleotide-bd_a/b_plait_sf
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
TOP1	Enzyme (other)	yes	5.6.2.1	TopoI, TopoI_DNA-bd_euk, DNA_brk_join_enz
FMNL1	Other/Unknown	no		FH3_dom, GTPase-bd, ARM-like
TRPS1	Transcription factor	no		Znf_GATA, Znf_C2H2_type, Znf_NHR/GATA
TSPEAR	Other/Unknown	no		EPTP, EAR, ConA-like_dom_sf
VIL1	Other/Unknown	no		Villin_headpiece, Villin/Gelsolin, Gelsolin-like_dom
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
WNT6	Other/Unknown	no		Wnt, Wnt6, Wnt_CS
ZNF142	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Znf-C2H2_CTCF
ZXDA	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf,
LGR4	GPCR	yes		GPCR_Rhodpsn, LRRNT, Leu-rich_rpt
TNFRSF21	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
BIRC6	Other/Unknown	no		UBC, BIR_rpt, UBQ-conjugating_enzyme/RWD
CLIC4	Other/Unknown	no		CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_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
MEMO1	Other/Unknown	no		MEMO1_fam
HDAC9	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
AUTS2	Other/Unknown	no		AUTS2
BBX	Transcription factor	no		HMG_box_dom, TF_HMG_box_BBX_DUF2028, HMG_box_dom_sf
LPIN3	Other/Unknown	no		Lipin_N, LNS2, LIPIN
KLF15	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
ARHGEF9	Scaffold/PPI	no		DH_dom, SH3_domain, PH_domain
RNF25	Transcription factor	no	2.3.2.27	Znf_RING, RWD_dom, Znf_RING/FYVE/PHD
SETBP1	Other/Unknown	no		AT_hook_DNA-bd_motif

Expression context

Cohort genes with no expression data: 0.

65 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)	0
broad (>20)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	8
primordial germ cell in gonad	7
ganglionic eminence	7
secondary oocyte	6
calcaneal tendon	6
endothelial cell	5
cortical plate	5
skin of hip	4
buccal mucosa cell	4
corpus epididymis	4
right uterine tube	4
monocyte	4
lateral nuclear group of thalamus	3
prefrontal cortex	3
body of pancreas	3
adrenal tissue	3
gingival epithelium	3
granulocyte	3
lower esophagus mucosa	3
right lobe of thyroid gland	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF11	303	ubiquitous	marker	lateral nuclear group of thalamus, endothelial cell, prefrontal cortex
BCS1L	279	ubiquitous	marker	body of pancreas, metanephros cortex, apex of heart
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
CNOT9	286	ubiquitous	marker	adrenal tissue, gingival epithelium, epithelium of nasopharynx
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
S100A11	292	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, olfactory segment of nasal mucosa
SLC14A2	100	tissue_specific	marker	primordial germ cell in gonad, hair follicle, right adrenal gland
FOXL2	84	broad	marker	left ovary, stromal cell of endometrium, ovary
SNRPE	175	ubiquitous	marker	ganglionic eminence, ventricular zone, cortical plate
SNRPG	140	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
SORD	199	ubiquitous	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
SPAST	284	ubiquitous	marker	cortical plate, oocyte, secondary oocyte
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
SUCLA2	294	ubiquitous	marker	jejunal mucosa, pons, lateral nuclear group of thalamus
TARDBP	301	ubiquitous	marker	secondary oocyte, ventricular zone, ganglionic eminence
TBX15	172	broad	marker	gastrocnemius, muscle of leg, skeletal muscle tissue of rectus abdominis
TCF12	295	ubiquitous	marker	periodontal ligament, ventricular zone, ganglionic eminence
TCF4	292	ubiquitous	marker	endothelial cell, skin of hip, pericardium
TMEM258	288	ubiquitous	marker	type B pancreatic cell, corpus epididymis, parotid gland
TCHH	101	tissue_specific	yes	upper arm skin, tongue squamous epithelium, skin of hip
TIA1	297	ubiquitous	marker	right uterine tube, right ovary, ganglionic eminence
MYRF	223	ubiquitous	marker	middle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion
TOP1	278	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
FMNL1	236	ubiquitous	marker	granulocyte, monocyte, leukocyte
TRPS1	284	ubiquitous	marker	mammary duct, epithelium of mammary gland, calcaneal tendon
TSPEAR	88	tissue_specific	yes	primordial germ cell in gonad, adenohypophysis, pituitary gland
VIL1	152	tissue_specific	marker	jejunal mucosa, ileal mucosa, ileum
WARS2	226	ubiquitous	marker	primordial germ cell in gonad, bronchial epithelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 22.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TARDBP	7,245
BIRC6	5,905
ATG7	5,169
RUNX1	4,994
TOP1	4,535
SORD	3,915
BCS1L	3,789
SNRPG	3,577
TIA1	3,482
SPAST	3,393

Intra-cohort edges

A	B	Sources
CDKN2C	TCF12	biogrid_interaction, intact
CDKN2C	TCF4	biogrid_interaction, intact
CHD6	FEV	intact
CHD6	TCF4	string_interaction
LPIN3	ZHX3	string_interaction
MED4	SNRPG	intact
MED4	SRRM1	intact
MEMO1	SLC30A6	string_interaction
MEMO1	TCF4	intact
RNF11	RNF25	string_interaction
RUNX1	RUNX3	string_interaction
RUNX1	SETBP1	string_interaction
RUNX1	TCF12	string_interaction
RUNX3	TRPS1	string_interaction
SNRPE	SNRPG	biogrid_interaction, intact
SNRPE	STARD8	biogrid_interaction
STH	WNT3	string_interaction
STK36	ZNF142	string_interaction
TARDBP	TIA1	string_interaction
TBX15	WARS2	string_interaction
TIA1	TMEM258	intact
TOP1	ZHX3	string_interaction

Structural data

PDB: 47 · AlphaFold-only: 28 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SNRPE	P62304	84
SNRPG	P62308	84
TARDBP	Q13148	44
LGR4	Q9BXB1	23
BIRC6	Q9NR09	22
TOP1	P11387	15
CNOT9	Q92600	14
VSIG4	Q9Y279	12
MED4	Q9NPJ6	11
TIA1	P31483	10
ADGRF1	Q5T601	10
SLC14A2	Q15849	9
SRRM1	Q8IYB3	9
DUSP22	Q9NRW4	8
SPAST	Q9UBP0	7
TNFRSF21	O75509	7
TMEM258	P61165	6
NLRC4	Q9NPP4	6
CDKN2C	P42773	6
RUNX1	Q01196	5
TCF4	P15884	5
MEMO1	Q9Y316	5
RNF25	Q96BH1	5
RORA	P35398	3
S100A11	P31949	3
SORD	Q00796	3
CLIC4	Q9Y696	3
FOXL2	P58012	2
SUCLA2	Q9P2R7	2
TCF12	Q99081	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AADAC	P22760	95.64
ATG7	O95352	88.06
TSPEAR	Q8WU66	87.47
BCS1L	Q9Y276	87.10
HINT3	Q9NQE9	86.44
WNT6	Q9Y6F9	83.62
WNT10A	Q9GZT5	82.36
STK36	Q9NRP7	81.22
RNF11	Q9Y3C5	78.98
ADGRF5	Q8IZF2	74.74
SSPN	Q14714	74.41
SLC30A6	Q6NXT4	71.44
CDK5R2	Q13319	70.01
EDA2R	Q9HAV5	69.14
TCHH	Q07283	67.96
MMRN2	Q9H8L6	66.64
STARD8	Q92502	63.19
LPIN3	Q9BQK8	61.59
ZNF142	P52746	61.51
TBX15	Q96SF7	61.41
STH	Q8IWL8	57.88
DMRTA2	Q96SC8	57.64
PRDM8	Q9NQV8	55.64
ZXDA	P98168	55.14
BBX	Q8WY36	50.79
TRPS1	Q9UHF7	49.12
SETBP1	Q9Y6X0	43.30
AUTS2	Q8WXX7	41.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 548. Enrichment computed across 211 evidence-associated genes (126 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 126 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates RUNX1-mediated transcription	2	60.4×	0.093	RUNX1, RUNX3
NFE2L2 regulating tumorigenic genes	3	22.7×	0.093	AREG, PDGFA, BCL2
Class B/2 (Secretin family receptors)	5	7.5×	0.093	WNT3, WNT6, WNT10A, CRHR1, PTHLH
Phospholipase C-mediated cascade: FGFR1	3	16.0×	0.109	FGF5, FGFR1, PLCG1
Signaling by ALK fusions and activated point mutants	5	6.0×	0.164	BIRC6, IRF4, MSN, PIK3CB, PLCG1
SLBP independent Processing of Histone Pre-mRNAs	2	18.1×	0.176	SNRPE, SNRPG
Linoleic acid (LA) metabolism	2	18.1×	0.176	FADS1, FADS2
EGFR interacts with phospholipase C-gamma	2	18.1×	0.176	AREG, PLCG1
RUNX3 regulates p14-ARF	2	18.1×	0.176	RUNX1, RUNX3
TGFBR3 expression	3	10.9×	0.176	TCF12, TCF4, HELLS
Synthesis of IP3 and IP4 in the cytosol	3	10.1×	0.176	PLCD3, PLCD4, PLCG1
WNT ligand biogenesis and trafficking	3	10.1×	0.176	WNT3, WNT6, WNT10A
Downstream signal transduction	3	9.1×	0.176	PDGFA, PIK3CB, PLCG1
Constitutive Signaling by Aberrant PI3K in Cancer	5	5.0×	0.176	FGF5, FGFR1, AREG, PDGFA, PIK3CB
TCF dependent signaling in response to WNT	5	4.7×	0.176	RUNX3, WNT3, LGR4, RSPO2, DKK2
RAF/MAP kinase cascade	7	3.4×	0.176	FGF5, FGFR1, ANGPT1, IQGAP1, AREG, PDGFA, PIK3CB
Processing of Capped Intronless Pre-mRNA	2	16.5×	0.189	SNRPE, SNRPG
SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs	2	16.5×	0.189	SNRPE, SNRPG
Signaling by activated point mutants of FGFR1	2	15.1×	0.214	FGF5, FGFR1
Phospholipase C-mediated cascade; FGFR3	2	13.9×	0.214	FGF5, PLCG1
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	2	13.9×	0.214	RUNX1, RUNX3
Signaling by FGFR1 in disease	3	7.0×	0.214	FGF5, FGFR1, PLCG1
CDC42 GTPase cycle	6	3.4×	0.214	FMNL1, ARHGEF9, STARD8, ARHGAP27, IQGAP1, OPHN1
Defective CYP27A1 causes CTX	1	90.6×	0.218	CYP27A1
FGFR1c ligand binding and activation	2	12.1×	0.218	FGF5, FGFR1
SLC-mediated transport of organic cations	2	12.1×	0.218	RUNX1, SLC14A2
PI3K Cascade	3	6.5×	0.218	FGF5, FGFR1, PIK3CB
Signaling by ALK in cancer	3	6.5×	0.218	BIRC6, IRF4, MSN
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	3.8×	0.218	FGF5, FGFR1, AREG, PDGFA, PIK3CB
Activation of anterior HOX genes in hindbrain development during early embryogenesis	5	3.6×	0.226	CNOT9, DPY30, HOXD1, HOXD3, HOXD4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 191 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peripheral nervous system neuron development	4	32.1×	0.006	RUNX1, RUNX3, HOXD10, HOXD9
regulation of transcription by RNA polymerase II	35	2.1×	0.008	RORA, RUNX1, RUNX3, FOXL2, TBX15, TCF12, TCF4, TRPS1 (+27 more)
gamete generation	4	18.6×	0.020	WNT3, SPIN2A, SPIN3, SPIN2B
embryonic skeletal system morphogenesis	5	10.3×	0.034	GSC, HOXD10, HOXD3, HOXD4, HOXD9
negative regulation of CD4-positive, alpha-beta T cell differentiation	2	44.1×	0.170	RUNX1, RUNX3
positive regulation of CD8-positive, alpha-beta T cell differentiation	2	35.3×	0.176	RUNX1, RUNX3
male genitalia development	3	13.9×	0.176	SRD5A2, LGR4, HOXD13
regulation of cell differentiation	4	9.1×	0.176	RUNX1, RUNX3, FADS1, FGFR1
arachidonate metabolite production involved in inflammatory response	1	88.2×	0.182	FADS2
melanin metabolic process	1	88.2×	0.182	BCL2
succinyl-CoA pathway	1	88.2×	0.182	SUCLA2
axis specification	1	88.2×	0.182	WNT6
peptidyl-glutamic acid modification	1	88.2×	0.182	TTLL4
phthalate metabolic process	1	88.2×	0.182	SRD5A2
female somatic sex determination	1	88.2×	0.182	FOXL2
obsolete negative regulation of cellular pH reduction	1	88.2×	0.182	BCL2
peroxisome transport along microtubule	1	88.2×	0.182	PEX14
pigment granule organization	1	88.2×	0.182	BCL2
regulation of striated muscle cell differentiation	1	88.2×	0.182	HDAC9
granulosa cell differentiation	1	88.2×	0.182	FOXL2
Spemann organizer formation at the anterior end of the primitive streak	1	88.2×	0.182	WNT3
branch elongation of an epithelium	1	88.2×	0.182	HOXD13
regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling	1	88.2×	0.182	PDGFA
mitochondrial tryptophanyl-tRNA aminoacylation	1	88.2×	0.182	WARS2
regulation of neuron projection regeneration	1	88.2×	0.182	PRRX1
regulation of zinc ion transport	1	88.2×	0.182	SLC30A6
nuclear inner membrane organization	1	88.2×	0.182	TARDBP
plus-end-directed organelle transport along microtubule	1	88.2×	0.182	MAPT
intestinal iron absorption	1	88.2×	0.182	HEPH
regulation of protein K63-linked ubiquitination	1	88.2×	0.182	SASH1

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)
Dutasteride	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Alcohol, Bimatoprost, Brepocitinib, Efalizumab, Ritlecitinib, Setipiprant.

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 11 · Phased (≥1): 12 · Undrugged: 63

Druggability breadth: 76 of 211 evidence-associated genes (36%) 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
RORA	TRETINOIN
RUNX1	APOMORPHINE HYDROCHLORIDE
SORD	EPALRESTAT
SRD5A2	FINASTERIDE
TARDBP	MITOXANTRONE
TOP1	TOPOTECAN HYDROCHLORIDE
HDAC9	CELECOXIB
AADAC	FLUTAMIDE
STK36	FEDRATINIB
ADGRF1	SALMETEROL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HDAC9	28	4
STK36	19	4
TOP1	12	4
SRD5A2	5	4
RORA	2	4
RUNX1	2	4
SORD	2	4
ADGRF1	2	4
SUCLA2	1	3
TARDBP	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRETINOIN	4	RORA
APOMORPHINE HYDROCHLORIDE	4	RUNX1
EPALRESTAT	4	SORD
FINASTERIDE	4	SRD5A2
MITOXANTRONE	4	TARDBP
TOPOTECAN HYDROCHLORIDE	4	TOP1
RIBAVIRIN	4	TOP1
AMSACRINE	4	TOP1
DOXORUBICIN	4	TOP1
TOPOTECAN	4	TOP1
CELECOXIB	4	HDAC9
PHENYLBUTANOIC ACID	4	HDAC9
SODIUM PHENYLBUTYRATE	4	HDAC9
ROMIDEPSIN	4	HDAC9
BELINOSTAT	4	HDAC9
PANOBINOSTAT	4	HDAC9
VORINOSTAT	4	HDAC9
GIVINOSTAT	4	HDAC9
FLUTAMIDE	4	AADAC
FEDRATINIB	4	STK36
SORAFENIB	4	STK36
NERATINIB	4	STK36
BOSUTINIB	4	STK36
PAZOPANIB	4	STK36
DASATINIB	4	STK36
ERLOTINIB	4	STK36
GEFITINIB	4	STK36
SALMETEROL	4	ADGRF1
LOPERAMIDE HYDROCHLORIDE	4	ADGRF1
QUERCETIN	3	SORD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
HDAC9	1,625	Binding:1612, ADMET:8, Functional:4, Toxicity:1
TOP1	1,200	Binding:1161, Functional:38, ADMET:1
SRD5A2	119	Binding:115, Functional:4
RORA	115	Binding:111, Functional:3, Unclassified:1
STK36	77	Binding:77
TCF4	31	Binding:31
RUNX1	20	Binding:17, Functional:3
AADAC	20	ADMET:19, Binding:1
DUSP22	19	Binding:19
SORD	17	Binding:16, Functional:1
NLRC4	13	Binding:13
ATG7	12	Binding:12
TARDBP	8	Binding:7, Functional:1
SNRPE	7	Binding:7
FMNL1	7	Binding:7
ADGRF1	7	Functional:5, Binding:2
SRRM1	6	Binding:6
WNT3	5	Functional:3, Binding:2
CNOT9	2	Binding:2
SUCLA2	2	Binding:2
LGR4	2	Binding:2
ADGRF5	2	Binding:2
S100A11	1	Binding:1
SPAST	1	Binding:1
TCF12	1	Binding:1
TIA1	1	Binding:1
VIL1	1	Binding:1
CLIC4	1	Binding:1
PRDM8	1	Binding:1
SLC30A6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SORD	1.1.1.14	L-iditol 2-dehydrogenase
SPAST	5.6.1.1	microtubule-severing ATPase
SRD5A2	1.3.1.22, 1.3.99.5	3-oxo-5alpha-steroid 4-dehydrogenase (NADP+), 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor)
SUCLA2	6.2.1.5	succinate-CoA ligase (ADP-forming)
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
TMEM258	2.4.99.18	dolichyl-diphosphooligosaccharide-protein glycotransferase
TOP1	5.6.2.1, 5.99.1.2	DNA topoisomerase, DNA topoisomerase
WARS2	6.1.1.2	tryptophan-tRNA ligase
HDAC9	3.5.1.98	histone deacetylase
RNF25	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RORA	115
SRD5A2	119
TOP1	1,200
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)
TRETINOIN	4	RORA
APOMORPHINE HYDROCHLORIDE	4	RUNX1
EPALRESTAT	4	SORD
MITOXANTRONE	4	TARDBP
TOPOTECAN HYDROCHLORIDE	4	TOP1
RIBAVIRIN	4	TOP1
AMSACRINE	4	TOP1
DOXORUBICIN	4	TOP1
TOPOTECAN	4	TOP1
CELECOXIB	4	HDAC9
PHENYLBUTANOIC ACID	4	HDAC9
SODIUM PHENYLBUTYRATE	4	HDAC9
ROMIDEPSIN	4	HDAC9
BELINOSTAT	4	HDAC9
PANOBINOSTAT	4	HDAC9
VORINOSTAT	4	HDAC9
GIVINOSTAT	4	HDAC9
FLUTAMIDE	4	AADAC
FEDRATINIB	4	STK36
SORAFENIB	4	STK36
NERATINIB	4	STK36
BOSUTINIB	4	STK36
PAZOPANIB	4	STK36
DASATINIB	4	STK36
ERLOTINIB	4	STK36
GEFITINIB	4	STK36
SALMETEROL	4	ADGRF1
LOPERAMIDE HYDROCHLORIDE	4	ADGRF1
QUERCETIN	3	SORD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	RORA, RUNX1, SORD, SRD5A2, TARDBP, TOP1, HDAC9, AADAC, STK36, ADGRF1
B	Phased (≥1) drug, not yet approved	2	SUCLA2, TCF4
C	Druggable family + PDB, no drug	8	SLC14A2, SPAST, TMEM258, WARS2, LGR4, DUSP22, VSIG4, USP37
D	Druggable family + AlphaFold only, no drug	1	ADGRF5
E	Difficult family or no structure, no drug	54	RNF11, BCS1L, CNOT9, RUNX3, S100A11, FOXL2, SNRPE, SNRPG, SSPN, TBX15 (+44 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CHD6	0	TCF4
RNF11	0	—
BCS1L	0	—
CNOT9	2	—
RUNX3	0	—
S100A11	1	—
SLC14A2	0	—
FOXL2	0	—
SNRPE	7	—
SNRPG	0	—
SPAST	1	—
SSPN	0	—
TBX15	0	—
TCF12	1	—
TMEM258	0	—
TCHH	0	—
TIA1	1	—
MYRF	0	—
FMNL1	7	—
TRPS1	0	—
TSPEAR	0	—
VIL1	1	—
WARS2	0	—
WNT3	5	—
WNT6	0	—
ZNF142	0	—
ZXDA	0	—
LGR4	2	—
TNFRSF21	0	—
BIRC6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 338.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	163
PHASE2	71
PHASE3	30
PHASE4	25
PHASE1	21
PHASE1/PHASE2	13
EARLY_PHASE1	10
PHASE2/PHASE3	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06399783	PHASE4	NOT_YET_RECRUITING	Topical Simvastatin Versus Topical Steroid in Treatment of Alopecia Areata
NCT07381556	PHASE4	RECRUITING	Cyclosporine Or Methotrexate for Pediatric Alopecia Areata: Routine Clinical Care Effectiveness Study
NCT07406204	PHASE4	NOT_YET_RECRUITING	Tofacitinib vs Methotrexate for Severe Alopecia Areata (TOFA-MTX-AA)
NCT07453238	PHASE4	NOT_YET_RECRUITING	Comparison of Topical Calcipotriol and Intralesional Steroids in Alopecia Areata
NCT07459933	PHASE4	NOT_YET_RECRUITING	Topical Methotrexate vs Minoxidil for Localized Alopecia Areata
NCT00176943	PHASE4	COMPLETED	Characteristics of T Cells From Alopecia Areata Scalp Skin Before and After Treatment With Aldara 5%
NCT00176969	PHASE4	COMPLETED	Response of Topical Capsaicin in Alopecia Areata
NCT00176982	PHASE4	COMPLETED	Plaquenil for Alopecia Areata, Alopecia Totalis
NCT00177021	PHASE4	COMPLETED	Aldara for the Treatment of Extensive Alopecia Areata
NCT01023841	PHASE4	COMPLETED	Safety and Efficacy of Bimatoprost Solution in Treating Eyelash Loss or Hypotrichosis in Children
NCT01111981	PHASE4	UNKNOWN	Safety and Efficacy of Clobetasol Propionate 0.05% E Foam in Alopecia
NCT01898806	PHASE4	TERMINATED	Intralesional Steroids in the Treatment of Alopecia Areata
NCT02350023	PHASE4	COMPLETED	Comparison of Topical Latanoprost vs Topical Corticosteroid in Treatment of Localized Alopecia Areata
NCT03473600	PHASE4	UNKNOWN	Cryotherapy Versus Steroids In Alopecia Areata:Trichoscopic Evaluation
NCT03535233	PHASE4	COMPLETED	Topical 5% Minoxidil and Potent Topical Corticosteroid Versus Intralesional Corticosteroid in the Treatment of Alopecia Areata
NCT03630198	PHASE4	COMPLETED	Pain Outcomes Following Intralesional Corticosteroid Injections
NCT03800979	PHASE4	COMPLETED	Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata
NCT04003376	PHASE4	UNKNOWN	Efficacy of Fractional CO2 Laser as a Mono- or Adjuvant Therapy for Alopecia Areata
NCT04228029	PHASE4	UNKNOWN	Comparative Study for Treatment of Alopecia Areata Using Carboxytherapy and Intralesional Steroids
NCT04412148	PHASE4	UNKNOWN	Modified SALT Score for Alopecia Areata
NCT04793945	PHASE4	UNKNOWN	Excimer Light and Topical Steroid in Treatment of Alopecia Areata
NCT05278858	PHASE4	TERMINATED	Needle-free Delivery of Intralesional Triamcinolone for Pediatric Alopecia Areata
NCT05926882	PHASE4	COMPLETED	Efficacy of Oral Apremilast in the Treatment of Alopecia Areata at the Tertiary Care Hospital, Karachi.
NCT06355856	PHASE4	UNKNOWN	Efficacy/ Safety of DNN.22.17.036 in Male Patients With Pattern Hair Loss
NCT07174011	PHASE4	COMPLETED	Evaluation of the Efficacy and Safety of Oral Roflumilast Versus Intralesional Corticosteroids Injection (ILCs) in the Treatment of Alopecia Areata
NCT03898479	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Extension Study to Evaluate Safety and Efficacy of CTP-543 in Adults With Alopecia Areata
NCT05723198	PHASE3	RECRUITING	A Study of Baricitinib (LY3009104) in Children From 6 Years to Less Than 18 Years of Age With Alopecia Areata
NCT06012240	PHASE3	RECRUITING	A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants With Severe Alopecia Areata
NCT06873945	PHASE3	ACTIVE_NOT_RECRUITING	A Study of 2 Doses of Ritlecitinib in People 12 Years of Age and Older With Alopecia Areata
NCT07023302	PHASE3	RECRUITING	A Study to Evaluate the Safety and Effectiveness of Upadacitinib Tablets in Adult and Adolescent Participants in Japan With Alopecia Areata
NCT07029711	PHASE3	RECRUITING	A Study to Learn About Medicine Called Ritlecitinib in Children Aged Between 6 to 12 Years With Severe Alopecia Areata
NCT07029828	PHASE3	RECRUITING	A Long-Term Study to Learn About The Study Medicine Called Ritlecitinib in Children With Severe Alopecia Areata.
NCT07133308	PHASE3	RECRUITING	Study to Evaluate the Efficacy and Safety of Deuruxolitinib in Adolescents With Severe Alopecia Areata
NCT07146022	PHASE3	RECRUITING	Safety and Efficacy of VDPHL01 in Females With Androgenetic Alopecia (AGA)
NCT00063076	PHASE2/PHASE3	COMPLETED	Phase II Randomized Bilateral Comparison of Topical Targretin Gel 1% in Alopecia Areata
NCT00441116	PHASE3	COMPLETED	A Study To Assess The Efficacy And Safety Of Dutasteride 0.5mg Once Daily For 6 Months In The Treatment Of Male Subjects With Androgenetic Alopecia
NCT01145625	PHASE3	COMPLETED	Clinical Trial in Females With Female Pattern Hair Loss
NCT01453686	PHASE3	COMPLETED	A Trial of Clobetasol Propionate Versus Hydrocortisone in Children With Alopecia Areata
NCT01590238	PHASE3	COMPLETED	Enhancing Hair Density With Platelet Rich Fibrin Matrix (PRFM)
NCT01831791	PHASE3	COMPLETED	A Long-term Study to Determine Safety and Efficacy of Dutasteride in Male Subjects With Androgenetic Alopecia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TOFACITINIB	4	13
RITLECITINIB	4	12
MINOXIDIL	4	8
BIMATOPROST	4	4
TRIAMCINOLONE ACETONIDE	4	4
BARICITINIB	4	3
CALCIPOTRIENE	4	3
CLOBETASOL PROPIONATE	4	3
CRAVACITINIB	4	3
DUPILUMAB	4	3
DUTASTERIDE	4	3
UPADACITINIB	4	3
ABROCITINIB	4	2
BETAMETHASONE VALERATE	4	2
ABATACEPT	4	1
ALEFACEPT	4	1
APREMILAST	4	1
AZATHIOPRINE	4	1
CAPSAICIN	4	1
CETIRIZINE	4	1
CRISABOROLE	4	1
ETRASIMOD	4	1
FINASTERIDE	4	1
HYDROCORTISONE	4	1
HYDROXYCHLOROQUINE	4	1
LACTIC ACID	4	1
LATANOPROST	4	1
MOMETASONE FUROATE	4	1
ROFLUMILAST	4	1
SIMVASTATIN	4	1