Attention deficit-hyperactivity disorder

Summary

Attention deficit-hyperactivity disorder (MONDO:0007743) is a disease with 74 cohort genes (2,387 GWAS associations across 172 studies) and 1,257 clinical trials. The dominant Reactome pathway is TP53 Regulates Transcription of Death Receptors and Ligands (4 cohort genes). Top therapeutic interventions include atomoxetine, methylphenidate, and lisdexamfetamine.

At a glance

• Cohort genes: 74
• GWAS associations: 2,387
• ClinVar variants: 71
• Clinical trials: 1,257

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	attention deficit-hyperactivity disorder
Mondo ID	MONDO:0007743
EFO	EFO:0003888
NCIT	C97160
UMLS	C1263846
MedGen	220387
Is cancer (heuristic)	no

Also known as: ADHD · attention deficit hyperactivity disorder · attention deficit-hyperactivity disorder · attention deficit/hyperactivity disorder

Data availability: 71 ClinVar variants · 2,387 GWAS associations (172 studies) · 1 GenCC gene-disease record · 35 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › specific developmental disorder › attention deficit-hyperactivity disorder

Related subtypes (9): fetal alcohol spectrum disorder, oppositional defiant disorder, fetal nicotine spectrum disorder, communication disorder, stereotypic movement disorder, tic disorder, learning disability, developmental coordination disorder, conduct disorder

Subtypes (3): attention deficit hyperactivity disorder, inattentive type, hereditary attention deficit-hyperactivity disorder, attention deficit-hyperactivity disorder 8

Genetics & variants

GWAS landscape

2,387 GWAS associations across 172 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9919558	7e-59	NCAM1	T	0.02
rs266058	2e-38	TMEM182 - CRLF3P1	C	0.02
rs28606370	1e-33	BORCS7-ASMT - CNNM2	C	0.01
rs6452785	4e-32	TMEM161B-DT	C	0.01
rs12907546	1e-31	SEMA6D	G	0.02
rs1381287	8e-30	LINC01550 - LINC02295	C	0.01
rs458806	1e-29	REV3L, MFSD4B	C	0.02
rs13217619	1e-27	ZSCAN31	?
rs2336895	2e-27	TENM2	G	0.01
rs4349886	2e-26	SDK1	C	0.01
rs1476535	3e-26	FOXP2	C	0.01
rs10427255	3e-26	RPL6P5 - METAP2P1	C	0.01
rs6265	2e-24	BDNF-AS, BDNF	C	0.01
rs7675916	3e-24	PCDH7	C	0.01
rs12970816	3e-24	DCC	G	0.01
rs72678859	2e-23	RNU6-289P - RPL36AP23	C	0.02
rs6460944	2e-23	MAD1L1	C	0.01
rs4240671	5e-23	XKR6	G	0.01
rs4074442	1e-22	LINC01830	G	0.01
rs2865303	2e-22	LSAMP - IGSF11	G	0.01
rs6711254	2e-22	LINC01875 - TMEM18	G	0.01
rs72780741	3e-22	NIHCOLE - RNU6-334P	C	0.01
rs11596214	6e-21	SORCS3	G	0.01
rs2272168	3e-20	ZKSCAN5	G	0.01
rs7942417	5e-20	METTL15 - LINC02758	C	0.01
rs4298967	8e-20	CACNA1C, CACNA1C-IT3	?
rs10001365	3e-19	TTC29	G	0.01
rs10787738	3e-19	SHTN1	C	0.01
rs59724122	4e-19	GULOP	C	0.01
rs1899896	4e-19	RUNX1T1 - FLJ46284	C	0.01

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST008919	Zhu Z	2019	46,802	381,675	Shared Genetics of Asthma and Mental Health Disorders: A Large-Scale Genome-Wide Cross-Trait Analysis.
GCST007777	Schork AJ	2019	46,008	19,526	A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.
GCST008417	Demontis D	2019	35,006	16,366	Genome-wide association study implicates CHRNA2 in cannabis use disorder.
GCST008416	Demontis D	2019	32,716	16,269	Genome-wide association study implicates CHRNA2 in cannabis use disorder.
GCST007582	Klein M	2019	19,099	34,194	Genetic Markers of ADHD-Related Variations in Intracranial Volume.
GCST007583	Klein M	2019	19,099	34,194	Genetic Markers of ADHD-Related Variations in Intracranial Volume.
GCST007584	Klein M	2019	19,099	34,194	Genetic Markers of ADHD-Related Variations in Intracranial Volume.
GCST007585	Klein M	2019	19,099	34,194	Genetic Markers of ADHD-Related Variations in Intracranial Volume.
GCST007586	Klein M	2019	19,099	34,194	Genetic Markers of ADHD-Related Variations in Intracranial Volume.
GCST007587	Klein M	2019	19,099	34,194	Genetic Markers of ADHD-Related Variations in Intracranial Volume.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	3
Tier 3: regulatory	3
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	37
intergenic_variant	4
non_coding_transcript_exon_variant	2
3_prime_UTR_variant	2
regulatory_region_variant	2
missense_variant	1
5_prime_UTR_variant	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9919558	11	113006687	T>A,G	0.387	intron_variant	NCAM1	7e-59	Tier 4: intronic/intergenic
rs266058	2	103469970	C>A,G,T	0.472	intron_variant	TMEM182 - CRLF3P1	2e-38	Tier 4: intronic/intergenic
rs28606370	10	102911075	C>A	0.338	intron_variant	BORCS7-ASMT - CNNM2	1e-33	Tier 4: intronic/intergenic
rs6452785	5	88389683	C>G,T	0.468	intron_variant	TMEM161B-DT	4e-32	Tier 4: intronic/intergenic
rs12907546	15	47392083	G>A	0.204	intron_variant	SEMA6D	1e-31	Tier 4: intronic/intergenic
rs1381287	14	98131215	C>T	0.457	intron_variant	LINC01550 - LINC02295	8e-30	Tier 4: intronic/intergenic
rs458806	6	111354825	C>G,T	0.178	intron_variant	REV3L, MFSD4B	1e-29	Tier 4: intronic/intergenic
rs13217619	6	28338894	T>C	0.05	intron_variant	ZSCAN31	1e-27	Tier 4: intronic/intergenic
rs2336895	5	167563690	G>A	0.352	intron_variant	TENM2	2e-27	Tier 4: intronic/intergenic
rs4349886	7	3330406	C>A,T	0.462	intron_variant	SDK1	2e-26	Tier 4: intronic/intergenic
rs1476535	7	114430980	C>A,G,T	0.451	intron_variant	FOXP2	3e-26	Tier 4: intronic/intergenic
rs10427255	2	145367955	C>T	0.473	intergenic_variant	RPL6P5 - METAP2P1	3e-26	Tier 4: intronic/intergenic
rs6265	11	27658369	C>A,G,T	0.186	missense_variant	BDNF-AS, BDNF	2e-24	Tier 1: coding
rs7675916	4	31142196	C>T	0.287	intron_variant	PCDH7	3e-24	Tier 4: intronic/intergenic
rs12970816	18	52497489	G>A	0.402	intron_variant	DCC	3e-24	Tier 4: intronic/intergenic
rs72678859	4	111485805	C>T	0.167	intergenic_variant	RNU6-289P - RPL36AP23	2e-23	Tier 4: intronic/intergenic
rs6460944	7	1836563	C>G,T	0.408	intron_variant	MAD1L1	2e-23	Tier 4: intronic/intergenic
rs4240671	8	10910238	G>A	0.491	intron_variant	XKR6	5e-23	Tier 4: intronic/intergenic
rs4074442	2	22331242	G>A,C	0.397	intron_variant	LINC01830	1e-22	Tier 4: intronic/intergenic
rs2865303	3	118074139	G>A,C,T	0.15	intron_variant	LSAMP - IGSF11	2e-22	Tier 4: intronic/intergenic
rs6711254	2	624210	G>A,T	0.173	non_coding_transcript_exon_variant	LINC01875 - TMEM18	2e-22	Tier 4: intronic/intergenic
rs72780741	5	104592616	C>A	0.171	intron_variant	NIHCOLE - RNU6-334P	3e-22	Tier 4: intronic/intergenic
rs11596214	10	104694074	G>A,C	0.394	intron_variant	SORCS3	6e-21	Tier 4: intronic/intergenic
rs2272168	7	99505154	G>A,C,T	0.157	5_prime_UTR_variant	ZKSCAN5	3e-20	Tier 2: splice/UTR
rs7942417	11	28634687	C>A,G,T	0.346	intergenic_variant	METTL15 - LINC02758	5e-20	Tier 4: intronic/intergenic
rs4298967	12	2299028	A>C,G,T	0.05	intron_variant	CACNA1C, CACNA1C-IT3	8e-20	Tier 4: intronic/intergenic
rs10001365	4	146876062	G>A,T	0.386	intron_variant	TTC29	3e-19	Tier 4: intronic/intergenic
rs10787738	10	117017860	C>T	0.262	TF_binding_site_variant	SHTN1	3e-19	Tier 3: regulatory
rs59724122	8	27567179	C>T	0.169	intron_variant	GULOP	4e-19	Tier 4: intronic/intergenic
rs1899896	8	92188808	C>T	0.299	intergenic_variant	RUNX1T1 - FLJ46284	4e-19	Tier 4: intronic/intergenic

ClinVar germline variants

71 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 20 pathogenic, 11 likely pathogenic, 1 association, 1 benign/likely benign, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 association; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
267850	46;XY;t(8;10)(q13;p13)dn		Pathogenic	criteria provided, single submitter
267882	46;XX;inv(7)(q11.23q36.3)dn		Pathogenic	criteria provided, single submitter
267902	46;XY;t(3;5)(q24;p15.3)dn		Pathogenic	criteria provided, single submitter
267937	46;XY;t(5;15)(q11.2;q24)		Pathogenic	criteria provided, single submitter
268039	46;XY;t(3;18)(q13.31;q22.1)dn		Pathogenic	criteria provided, single submitter
1330165	GRCh37/hg19 3q23-25.32(chr3:142729607-157921084)x3	AADAC	Pathogenic	criteria provided, single submitter
1700599	NM_014921.5(ADGRL1):c.2998T>C (p.Trp1000Arg)	ADGRL1	Pathogenic	criteria provided, single submitter
1700604	NM_014921.5(ADGRL1):c.3476C>T (p.Ser1159Phe)	ADGRL1	Pathogenic	criteria provided, single submitter
1700605	NM_014921.5(ADGRL1):c.2049dup (p.Glu684fs)	ADGRL1	Pathogenic	criteria provided, single submitter
1700602	NM_014921.5(ADGRL1):c.819G>A (p.Trp273Ter)	ADGRL1-AS1	Pathogenic	criteria provided, single submitter
523274	GRCh37/hg19 22q11.21(chr22:18894835-21505417)	ARVCF	Pathogenic	criteria provided, single submitter
242885	NM_138425.4(C12orf57):c.53-2A>G	C12orf57	Pathogenic	criteria provided, multiple submitters, no conflicts
183276	NM_020374.4(FERRY3):c.639_640insACAA (p.Gln214fs)	FERRY3	Pathogenic/Likely pathogenic	no assertion criteria provided
254029	NM_016194.4(GNB5):c.368C>T (p.Ser123Leu)	GNB5	Pathogenic	criteria provided, multiple submitters, no conflicts
3238952	GRCh38/hg38 3q27.1-27.2(chr3:183020090-185760128)x1	LOC129938037	Pathogenic	criteria provided, single submitter
638688	NM_005909.5(MAP1B):c.5368C>T (p.Arg1790Ter)	MAP1B	Pathogenic	criteria provided, single submitter
189665	NM_001110792.2(MECP2):c.1200_1220delinsCTGAGCCCCAGGACTTGAGCA (p.Pro401_Ser407delinsTer)	MECP2	Pathogenic	criteria provided, single submitter
417685	NM_020843.3(SCAPER):c.2973_2976del (p.Ile991Metfs)	SCAPER	Pathogenic	criteria provided, single submitter
590780	NM_001378418.1(TCF20):c.5725C>T (p.His1909Tyr)	TCF20	Pathogenic	criteria provided, single submitter
523259	GRCh37/hg19 17p12(chr17:14215739-15422582)	TVP23C	Pathogenic	criteria provided, single submitter
56645	NM_152564.5(VPS13B):c.1219C>T (p.Gln407Ter)	VPS13B	Pathogenic	criteria provided, multiple submitters, no conflicts
267834	46;X;t(Y;16)(q11.23;p11.2);t(6;21)(p21.3;p13)dn		Likely pathogenic	criteria provided, single submitter
267875	46;XX;t(10;14)(p13;q21)dn		Likely pathogenic	criteria provided, single submitter
1700603	NM_014921.5(ADGRL1):c.26G>A (p.Trp9Ter)	ADGRL1	Likely pathogenic	criteria provided, single submitter
183350	NM_005441.3(CHAF1B):c.496A>G (p.Ile166Val)	CHAF1B	Likely pathogenic	no assertion criteria provided
242891	NM_004521.3(KIF5B):c.2252A>G (p.His751Arg)	KIF5B	Likely pathogenic	no assertion criteria provided
242888	NM_177433.3(MAGED2):c.1003del (p.Gln335fs)	MAGED2	Likely pathogenic	no assertion criteria provided
9733	NC_012920.1(MT-ND1):m.3697G>A	MT-ND1	Likely pathogenic	reviewed by expert panel
3233357	NM_001035006.5(RPL17):c.452del (p.Thr151fs)	RPL17	Likely pathogenic	criteria provided, single submitter
932939	NM_006593.4(TBR1):c.553C>T (p.Gln185Ter)	TBR1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 71 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 5

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

Gene	HGNC	Evidence routes
TCF20	TCF20	GWAS, Orphanet
CSMD2	CSMD2	GWAS
MARK2	MARK2	GWAS
MAP1B	MAP1B	GWAS, Orphanet
UPF1	UPF1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCF20	Orphanet:528084	Non-specific syndromic intellectual disability
MAP1B	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MAP1B	Orphanet:98892	Periventricular nodular heterotopia
UPF1	Orphanet:528084	Non-specific syndromic intellectual disability
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
CNNM4	Orphanet:1873	Jalili syndrome
ATXN7	Orphanet:94147	Spinocerebellar ataxia type 7
SEMA3A	Orphanet:130	Brugada syndrome
SEMA3A	Orphanet:478	Kallmann syndrome
BMPR1B	Orphanet:2098	Acromesomelic dysplasia, Grebe type
BMPR1B	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
BMPR1B	Orphanet:93384	Brachydactyly type C
BMPR1B	Orphanet:93388	Brachydactyly type A1
BMPR1B	Orphanet:93396	Brachydactyly type A2
SEM1	Orphanet:2440	Isolated split hand-split foot malformation
ST3GAL3	Orphanet:697734	ST3GAL3-CDG
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
SLC6A9	Orphanet:289860	Infantile glycine encephalopathy
SLC6A9	Orphanet:289863	Atypical glycine encephalopathy
SMARCA2	Orphanet:3051	Nicolaides-Baraitser syndrome
SMARCA2	Orphanet:637013	SMARCA2-related blepharophimosis-intellectual disability syndrome
SOX5	Orphanet:313884	12p12.1 microdeletion syndrome
SOX5	Orphanet:313892	Developmental and speech delay due to SOX5 deficiency
SOX5	Orphanet:626	Large/giant congenital melanocytic nevus
STIM1	Orphanet:2593	Tubular aggregate myopathy
STIM1	Orphanet:317430	Combined immunodeficiency due to STIM1 deficiency
STIM1	Orphanet:3204	Stormorken-Sjaastad-Langslet syndrome
TBR1	Orphanet:1617	Developmental delay-language impairment-dopa responsive dystonia-parkinsonism syndrome due to 2q24 microdeletion
TBR1	Orphanet:528084	Non-specific syndromic intellectual disability
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
TFAP2B	Orphanet:46627	Char syndrome
TFAP2B	Orphanet:466729	Familial patent arterial duct
TFEB	Orphanet:319308	MiT family translocation renal cell carcinoma
FERRY3	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
YWHAZ	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SCAPER	Orphanet:110	Bardet-Biedl syndrome
SCAPER	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

74 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	61
gwas_and_clinvar	5
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCF20	HGNC:11631	ENSG00000100207	Q9UGU0	Transcription factor 20	gwas,clinvar
CSMD2	HGNC:19290	ENSG00000121904	Q7Z408	CUB and sushi domain-containing protein 2	gwas,clinvar
MARK2	HGNC:3332	ENSG00000072518	Q7KZI7	Serine/threonine-protein kinase MARK2	gwas,clinvar
MAP1B	HGNC:6836	ENSG00000131711	P46821	Microtubule-associated protein 1B	gwas,clinvar
UPF1	HGNC:9962	ENSG00000005007	Q92900	Regulator of nonsense transcripts 1	gwas,clinvar
RGS6	HGNC:10002	ENSG00000182732	P49758	Regulator of G-protein signaling 6	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
RPL17	HGNC:10307	ENSG00000265681	P18621	Large ribosomal subunit protein uL22	clinvar
RPL23	HGNC:10316	ENSG00000125691	P62829	Large ribosomal subunit protein uL14	clinvar
RTN1	HGNC:10467	ENSG00000139970	Q16799	Reticulon-1	gwas
RXRG	HGNC:10479	ENSG00000143171	P48443	Retinoic acid receptor RXR-gamma	gwas
CNNM4	HGNC:105	ENSG00000158158	Q6P4Q7	Metal transporter CNNM4	gwas
ATXN7	HGNC:10560	ENSG00000163635	O15265	Ataxin-7	gwas
SEMA3A	HGNC:10723	ENSG00000075213	Q14563	Semaphorin-3A	gwas
BMPR1B	HGNC:1077	ENSG00000138696	O00238	Bone morphogenetic protein receptor type-1B	gwas
SEM1	HGNC:10845	ENSG00000127922	P60896	26S proteasome complex subunit SEM1	gwas
SHMT2	HGNC:10852	ENSG00000182199	P34897	Serine hydroxymethyltransferase, mitochondrial	gwas
ST3GAL3	HGNC:10866	ENSG00000126091	Q11203	CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferase	gwas
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	gwas
SLC6A9	HGNC:11056	ENSG00000196517	P48067	Sodium- and chloride-dependent glycine transporter 1	gwas
SMARCA2	HGNC:11098	ENSG00000080503	P51531	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	gwas
SOX5	HGNC:11201	ENSG00000134532	P35711	Transcription factor SOX-5	gwas
SP4	HGNC:11209	ENSG00000105866	Q02446	Transcription factor Sp4	clinvar
SRPK2	HGNC:11306	ENSG00000135250	P78362	SRSF protein kinase 2	gwas
STIM1	HGNC:11386	ENSG00000167323	Q13586	Stromal interaction molecule 1	gwas
STIP1	HGNC:11387	ENSG00000168439	P31948	Stress-induced-phosphoprotein 1	gwas
SUPT3H	HGNC:11466	ENSG00000196284	O75486	Transcription initiation protein SPT3 homolog	gwas
TBR1	HGNC:11590	ENSG00000136535	Q16650	T-box brain protein 1	clinvar
ELOC	HGNC:11617	ENSG00000154582	Q15369	Elongin-C	gwas
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	gwas
DAGLA	HGNC:1165	ENSG00000134780	Q9Y4D2	Diacylglycerol lipase-alpha	clinvar
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	gwas
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	gwas
TFEB	HGNC:11753	ENSG00000112561	P19484	Transcription factor EB	gwas
FERRY3	HGNC:1184	ENSG00000047621	Q9NQ89	Ferry endosomal RAB5 effector complex subunit 3	clinvar
TLL2	HGNC:11844	ENSG00000095587	Q9Y6L7	Tolloid-like protein 2	gwas
TNFRSF10A	HGNC:11904	ENSG00000104689	O00220	Tumor necrosis factor receptor superfamily member 10A	gwas
TNFRSF10D	HGNC:11907	ENSG00000173530	Q9UBN6	Tumor necrosis factor receptor superfamily member 10D	gwas
TNR	HGNC:11953	ENSG00000116147	Q92752	Tenascin-R	gwas
UBE2D3	HGNC:12476	ENSG00000109332	P61077	Ubiquitin-conjugating enzyme E2 D3	gwas
UGT1A9	HGNC:12541	ENSG00000241119	O60656	UDP-glucuronosyltransferase 1A9	gwas
UNC5B	HGNC:12568	ENSG00000107731	Q8IZJ1	Netrin receptor UNC5B	gwas
VAV1	HGNC:12657	ENSG00000141968	P15498	Proto-oncogene vav	clinvar
MIR99AHG	HGNC:1274	ENSG00000215386		mir-99a-let-7c cluster host gene	gwas
YWHAZ	HGNC:12855	ENSG00000164924	P63104	14-3-3 protein zeta/delta	gwas
SCAPER	HGNC:13081	ENSG00000140386	Q9BY12	S phase cyclin A-associated protein in the endoplasmic reticulum	clinvar
BCL11A	HGNC:13221	ENSG00000119866	Q9H165	BCL11 transcription factor A	gwas
BCL11B	HGNC:13222	ENSG00000127152	Q9C0K0	B-cell lymphoma/leukemia 11B	gwas
SLC30A9	HGNC:1329	ENSG00000014824	Q6PML9	Proton-coupled zinc antiporter SLC30A9, mitochondrial	gwas
FAM53C	HGNC:1336	ENSG00000120709	Q9NYF3	Protein FAM53C	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCF20	Transcription factor 20	Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression.
MARK2	Serine/threonine-protein kinase MARK2	Serine/threonine-protein kinase.
MAP1B	Microtubule-associated protein 1B	Facilitates tyrosination of alpha-tubulin in neuronal microtubules.
UPF1	Regulator of nonsense transcripts 1	RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs.
RGS6	Regulator of G-protein signaling 6	Regulates G protein-coupled receptor signaling cascades.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
RPL17	Large ribosomal subunit protein uL22	Component of the large ribosomal subunit.
RPL23	Large ribosomal subunit protein uL14	Component of the large ribosomal subunit.
RTN1	Reticulon-1	Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.
RXRG	Retinoic acid receptor RXR-gamma	Receptor for retinoic acid.
CNNM4	Metal transporter CNNM4	Probable metal transporter.
ATXN7	Ataxin-7	Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex.
SEMA3A	Semaphorin-3A	Involved in the development of the olfactory system and in neuronal control of puberty.
BMPR1B	Bone morphogenetic protein receptor type-1B	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
SEM1	26S proteasome complex subunit SEM1	Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
SHMT2	Serine hydroxymethyltransferase, mitochondrial	Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis.
ST3GAL3	CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferase	Catalyzes the formation of the NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc-, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc- and NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc- sequences found in terminal carbohydrate groups of glycoproteins and glycolipids.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
SLC6A9	Sodium- and chloride-dependent glycine transporter 1	Sodium- and chloride-dependent glycine transporter.
SMARCA2	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SOX5	Transcription factor SOX-5	Transcription factor involved in chondrocytes differentiation and cartilage formation.
SP4	Transcription factor Sp4	Binds to GT and GC boxes promoters elements.
SRPK2	SRSF protein kinase 2	Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splici…
STIM1	Stromal interaction molecule 1	Acts as a Ca(2+) sensor that gates two major inward rectifying Ca(2+) channels at the plasma membrane: Ca(2+) release-activated Ca(2+) (CRAC) channels and arachidonate-regulated Ca(2+)-selective (ARC) channels.
STIP1	Stress-induced-phosphoprotein 1	Acts as a co-chaperone for HSP90AA1.
SUPT3H	Transcription initiation protein SPT3 homolog	Probable transcriptional activator.
TBR1	T-box brain protein 1	Transcriptional repressor involved in multiple aspects of cortical development, including neuronal migration, laminar and areal identity, and axonal projection.
ELOC	Elongin-C	SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites.
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
DAGLA	Diacylglycerol lipase-alpha	Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG).
ELP4	Elongator complex protein 4	Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
TFEB	Transcription factor EB	Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response.
FERRY3	Ferry endosomal RAB5 effector complex subunit 3	Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary).
TLL2	Tolloid-like protein 2	Protease which specifically processes pro-lysyl oxidase.
TNFRSF10A	Tumor necrosis factor receptor superfamily member 10A	Receptor for the cytotoxic ligand TNFSF10/TRAIL.
TNFRSF10D	Tumor necrosis factor receptor superfamily member 10D	Receptor for the cytotoxic ligand TRAIL.
TNR	Tenascin-R	Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components.
UBE2D3	Ubiquitin-conjugating enzyme E2 D3	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
UGT1A9	UDP-glucuronosyltransferase 1A9	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UNC5B	Netrin receptor UNC5B	Receptor for netrin required for axon guidance.
VAV1	Proto-oncogene vav	Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
YWHAZ	14-3-3 protein zeta/delta	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
SCAPER	S phase cyclin A-associated protein in the endoplasmic reticulum	CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.
BCL11A	BCL11 transcription factor A	Transcription factor.
BCL11B	B-cell lymphoma/leukemia 11B	Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals.
SLC30A9	Proton-coupled zinc antiporter SLC30A9, mitochondrial	Mitochondrial proton-coupled zinc ion antiporter mediating the export of zinc from the mitochondria and involved in zinc homeostasis, zinc mobilization as well as mitochondrial morphology and health.
KDM3B	Lysine-specific demethylase 3B	Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.
PCLO	Protein piccolo	Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
FOLH1B	Putative N-acetylated-alpha-linked acidic dipeptidase	Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity.

Protein-family classification

Druggable: 25 · Difficult: 17 · Unknown: 32 · Druggable fraction: 0.34

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
Complement	2	7.2×	0.324
Transcription factor	14	1.6×	0.324
Nuclear receptor	1	5.2×	0.385
Ion channel	2	3.0×	0.385
Enzyme (other)	9	1.5×	0.385
Kinase	4	1.5×	0.509
Protease	3	1.5×	0.517
Antibody/Immunoglobulin	3	1.2×	0.643
Other/Unknown	32	0.8×	0.989
Scaffold/PPI	3	0.7×	0.989
GPCR	1	0.3×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCF20	Transcription factor	no		Znf_PHD, Znf_RING/FYVE/PHD, EPHD
CSMD2	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
MARK2	Kinase	yes		Prot_kinase_dom, KA1_dom, Ser/Thr_kinase_AS
MAP1B	Other/Unknown	no		MAP1B_neuraxin, MAP1, MAP1B/S_N
UPF1	Enzyme (other)	yes	3.6.4.13	Helicase/UvrB_N, UPF1_CH/ZBD, P-loop_NTPase
RGS6	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
RPL17	Other/Unknown	no		Ribosomal_uL22, Ribosomal_uL22_euk_arc, Ribosomal_uL22_CS
RPL23	Other/Unknown	no		Ribosomal_uL14, Ribosomal_uL14_CS, Ribosomal_uL14_sf
RTN1	Other/Unknown	no		Reticulon, RTN1-4
RXRG	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
CNNM4	Enzyme (other)	yes	7.2.2.14	cNMP-bd_dom, CBS_dom, CNNM
ATXN7	Other/Unknown	no		SCA7_dom, Ataxin-7-like_regulator
SEMA3A	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
BMPR1B	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
SEM1	Other/Unknown	no		DSS1_SEM1, DUF5543
SHMT2	Enzyme (other)	yes	2.1.2.1	Ser_HO-MeTrfase, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
ST3GAL3	Enzyme (other)	yes	2.4.99.2	Glyco_trans_29, Sialyl_trans, GT29-like_sf
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
SLC6A9	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_glycine_GLY1, SNS_sf
SMARCA2	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SOX5	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
SP4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sp4-like
SRPK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
STIM1	Other/Unknown	no		SAM, SAM/pointed_sf, SOAR_STIM1/2
STIP1	Other/Unknown	no		STI1_HS-bd, TPR-like_helical_dom_sf, TPR_2
SUPT3H	Other/Unknown	no		TFIID_TAF13, Histone-fold
TBR1	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
ELOC	Other/Unknown	no		SKP1-like, SKP1/BTB/POZ_sf, Skp1_comp_POZ
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
DAGLA	Enzyme (other)	yes	3.1.1.116	Fungal_lipase-type, AB_hydrolase_fold, DAG_Lipase-Related
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C
TFEB	Transcription factor	no		bHLH_dom, MiT/TFE_C, bHLHzip_TFEB
FERRY3	Other/Unknown	no		Fy-3
TLL2	Protease	yes		EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
TNFRSF10A	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
TNFRSF10D	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_10, TNFRSF10_N
TNR	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
UBE2D3	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
UGT1A9	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UNC5B	Antibody/Immunoglobulin	yes		Death_dom, TSP1_rpt, ZU5_dom
VAV1	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
MIR99AHG	Other/Unknown	no
YWHAZ	Other/Unknown	no		14-3-3, 14-3-3_CS, 14-3-3_domain
SCAPER	Transcription factor	no		Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type, SCAPER_N
BCL11A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF
BCL11B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF
SLC30A9	Other/Unknown	no		Cation_efflux, DNA-bd_dom_put_sf, Cation_efflux_TMD_sf
FAM53C	Other/Unknown	no		FAM53

Expression context

Cohort genes with no expression data: 0.

67 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)	0
broad (>20)	73
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	12
calcaneal tendon	9
buccal mucosa cell	7
ganglionic eminence	6
ventricular zone	6
primordial germ cell in gonad	6
Brodmann (1909) area 23	5
hindlimb stylopod muscle	5
sperm	5
middle temporal gyrus	4
sural nerve	4
oocyte	4
colonic epithelium	4
tendon of biceps brachii	4
gastrocnemius	4
primary visual cortex	4
endothelial cell	3
muscle of leg	3
mucosa of paranasal sinus	3
right lobe of liver	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCF20	134	ubiquitous	yes	cortical plate, ganglionic eminence, tonsil
CSMD2	166	broad	marker	buccal mucosa cell, ventricular zone, kidney epithelium
MARK2	188	ubiquitous	marker	lower esophagus mucosa, granulocyte, esophagus mucosa
MAP1B	299	ubiquitous	marker	lateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata
UPF1	262	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
RGS6	185	broad	marker	cortical plate, sural nerve, middle temporal gyrus
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
RPL17	134	ubiquitous	marker	left ovary, ovary, right ovary
RPL23	210	ubiquitous	marker	ganglionic eminence, left ovary, right ovary
RTN1	270	broad	marker	Brodmann (1909) area 23, endothelial cell, pons
RXRG	170	broad	marker	hindlimb stylopod muscle, adenohypophysis, muscle of leg
CNNM4	189	ubiquitous	marker	mucosa of transverse colon, rectum, ileal mucosa
ATXN7	290	ubiquitous	marker	mucosa of paranasal sinus, jejunal mucosa, superficial temporal artery
SEMA3A	194	ubiquitous	marker	stromal cell of endometrium, cortical plate, colonic epithelium
BMPR1B	239	broad	marker	calcaneal tendon, bronchial epithelial cell, cauda epididymis
SEM1	285	ubiquitous	marker	calcaneal tendon, tendon, tendon of biceps brachii
SHMT2	288	ubiquitous	marker	tendon of biceps brachii, cartilage tissue, right lobe of liver
ST3GAL3	178	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
SLC6A9	180	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, skin of leg
SMARCA2	301	ubiquitous	marker	calcaneal tendon, colonic epithelium, cortical plate
SOX5	221	ubiquitous	marker	cortical plate, calcaneal tendon, synovial joint
SP4	265	ubiquitous	marker	cerebellar vermis, germinal epithelium of ovary, superficial temporal artery
SRPK2	293	ubiquitous	marker	sperm, male germ cell, pons
STIM1	237	ubiquitous	marker	gastrocnemius, muscle of leg, hindlimb stylopod muscle
STIP1	294	ubiquitous	marker	adrenal tissue, left testis, ganglionic eminence
SUPT3H	206	ubiquitous	yes	primordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
TBR1	58	tissue_specific	marker	cortical plate, ganglionic eminence, Brodmann (1909) area 10
ELOC	293	ubiquitous	marker	oocyte, sperm, heart right ventricle
TCF4	292	ubiquitous	marker	endothelial cell, skin of hip, pericardium

Protein interactions among cohort

Intra-cohort edges: 24.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRAF	7,394
RPL17	5,372
SHMT2	5,293
STIP1	5,243
UPF1	4,936
HDAC4	4,771
SMARCA2	4,237
ELOC	4,044
SRPK2	3,839
MAP1B	3,724

Intra-cohort edges

A	B	Sources
ATXN7	SUPT3H	intact
BCL11A	BCL11B	biogrid_interaction
BCL11B	FOXP2	string_interaction
BCL11B	TBR1	string_interaction
BRAF	YWHAZ	biogrid_interaction, intact
CACNA1C	CACNA1I	string_interaction
CACNA1C	CACNB2	intact, string_interaction
CACNA1C	CSMD1	string_interaction
CACNA1C	JPH2	string_interaction
CACNA1C	STIM1	string_interaction
CACNA1I	CACNB2	string_interaction
CSMD1	PCLO	string_interaction
FAM53C	KDM3B	string_interaction
FAM53C	YWHAZ	biogrid_interaction, intact
FBXL16	MARK2	intact
FOXP2	SP4	biogrid_interaction, intact
FOXP2	TBR1	string_interaction
HDAC4	YWHAZ	intact
IMMP2L	SHMT2	biogrid_interaction
MARK2	PARD3B	biogrid_interaction
MARK2	YWHAZ	intact
SOX5	TBR1	string_interaction
TFEB	YWHAZ	biogrid_interaction, intact
TFEB	ZKSCAN3	string_interaction

Structural data

PDB: 42 · AlphaFold-only: 31 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ELOC	Q15369	225
RPL17	P18621	195
RPL23	P62829	190
BRAF	P15056	131
SEM1	P60896	129
MRPL33	O75394	86
YWHAZ	P63104	77
UBE2D3	P61077	45
KDM3B	Q7LBC6	36
CACNA1C	Q13936	33
SMARCA2	P51531	32
SHMT2	P34897	27
HDAC4	P56524	19
BCL11A	Q9H165	17
UPF1	Q92900	12
VAV1	P15498	10
SLC6A9	P48067	9
STIP1	P31948	8
CNNM2	Q9H8M5	7
STIM1	Q13586	6
MARK2	Q7KZI7	5
ATXN7	O15265	5
TCF4	P15884	5
SUPT3H	O75486	4
TFEB	P19484	4
CACNA1I	Q9P0X4	4
SRPK2	P78362	3
CACNB2	Q08289	3
RXRG	P48443	2
CNNM4	Q6P4Q7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOLH1B	Q9HBA9	96.69
UGT1A9	O60656	92.26
ST3GAL3	Q11203	90.87
VPS45	Q9NRW7	90.65
IMMP2L	Q96T52	87.66
OR14J1	Q9UGF5	87.60
FBXL16	Q8N461	84.53
SEMA3A	Q14563	84.50
FERRY3	Q9NQ89	84.04
IFT81	Q8WYA0	83.45
TLL2	Q9Y6L7	81.98
UNC5B	Q8IZJ1	77.60
ANO3	Q9BYT9	76.30
ELP4	Q96EB1	74.49
SLC4A10	Q6U841	71.37
ZSCAN31	Q96LW9	67.96
DAGLA	Q9Y4D2	63.87
TNFRSF10D	Q9UBN6	60.71
ZKSCAN3	Q9BRR0	60.16
SOX5	P35711	58.95
PMEPA1	Q969W9	57.03
TBR1	Q16650	56.17
PARD3B	Q8TEW8	55.56
DLEU1	O43261	55.08
FAM53C	Q9NYF3	52.63
BCL11B	Q9C0K0	51.76
RTN1	Q16799	48.88
MAP1B	P46821	46.18
SP4	Q02446	39.58
TCF20	Q9UGU0	39.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 665. Enrichment computed across 250 evidence-associated genes (139 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 139 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TP53 Regulates Transcription of Death Receptors and Ligands	4	27.4×	0.006	TNFRSF10A, TNFRSF10D, PPP1R13B, TMEM219
Late SARS-CoV-2 Infection Events	5	10.5×	0.034	ST3GAL3, SRPK2, ANO3, ANO4, ANO5
Induction of Cell-Cell Fusion	3	19.0×	0.102	ANO3, ANO4, ANO5
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	2	23.5×	0.389	CHRNA3, CHRNB4
TRAIL signaling	2	20.5×	0.389	TNFRSF10A, TNFRSF10D
Netrin mediated repulsion signals	2	18.3×	0.389	UNC5B, DCC
Highly calcium permeable nicotinic acetylcholine receptors	2	18.3×	0.389	CHRNA3, CHRNB4
Caspase activation via Dependence Receptors in the absence of ligand	2	16.4×	0.389	UNC5B, DCC
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	2	16.4×	0.389	TFAP2B, TFAP2D
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	2	14.9×	0.389	CHRNA3, CHRNB4
Presynaptic nicotinic acetylcholine receptors	2	13.7×	0.389	CHRNA3, CHRNB4
Activation of the TFAP2 (AP-2) family of transcription factors	2	13.7×	0.389	TFAP2B, TFAP2D
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	3	9.9×	0.389	SMARCA2, BCL11A, BCL11B
Chromatin organization	6	3.5×	0.389	ATXN7, SMARCA2, SUPT3H, KDM3B, KDM4A, KDM4D
SARS-CoV-2 Infection	6	3.5×	0.389	ST3GAL3, SRPK2, YWHAZ, ANO3, ANO4, ANO5
Transport of small molecules	12	2.2×	0.389	SEM1, SLC6A9, SLC4A10, ANO3, SLC28A3, SLC9A9, SLC39A8, SLC5A9 (+4 more)
Defective CYP24A1 causes HCAI	1	82.2×	0.397	CYP24A1
Defective SLC9A9 causes autism 16 (AUTS16)	1	82.2×	0.397	SLC9A9
Acetylcholine binding and downstream events	2	11.7×	0.397	CHRNA3, CHRNB4
Postsynaptic nicotinic acetylcholine receptors	2	11.7×	0.397	CHRNA3, CHRNB4
Regulation of mRNA stability by proteins that bind AU-rich elements	2	10.9×	0.397	SEM1, YWHAZ
Phase 2 - plateau phase	2	10.9×	0.397	CACNA1C, CACNB2
NCAM signaling for neurite out-growth	3	5.9×	0.397	CACNA1C, CACNA1I, CACNB2
Chromatin modifying enzymes	6	3.1×	0.397	ATXN7, SMARCA2, SUPT3H, KDM3B, KDM4A, KDM4D
NCAM1 interactions	3	5.4×	0.487	CACNA1C, CACNA1I, CACNB2
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	2	9.1×	0.488	TFAP2B, TFAP2D
Stimuli-sensing channels	4	3.9×	0.488	ANO3, ANO4, SLC9B1, ANO5
Modulation of host responses by IFN-stimulated genes	2	8.7×	0.504	IFI44, IFI44L
Formation of the embryonic stem cell BAF (esBAF) complex	2	8.7×	0.504	BCL11A, BCL11B
HDMs demethylate histones	3	4.9×	0.506	KDM3B, KDM4A, KDM4D

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 231 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neuron cell-cell adhesion	4	17.2×	0.085	TNR, NLGN1, ASTN2, CNTN4
calcium activated galactosylceramide scrambling	2	48.6×	0.168	ANO3, ANO4
membrane depolarization during atrial cardiac muscle cell action potential	2	48.6×	0.168	CACNA1C, CACNB2
synaptic transmission involved in micturition	2	36.5×	0.168	CHRNA3, CHRNB4
positive regulation of adenylate cyclase activity	2	29.2×	0.168	STIM1, CACNA1C
calcium activated phosphatidylcholine scrambling	2	29.2×	0.168	ANO3, ANO4
membrane depolarization during AV node cell action potential	2	29.2×	0.168	CACNA1C, CACNB2
Golgi reassembly	2	29.2×	0.168	YWHAZ, VPS13B
detection of mechanical stimulus	3	15.6×	0.168	ANO3, PKD1L2, PKD1L3
nucleus organization	4	9.7×	0.168	ATXN7, SYNE1, WDR73, CFAP43
monoatomic ion transmembrane transport	6	5.4×	0.168	ANO3, CHRNA3, CHRNB4, ANO4, SLC9B1, ANO5
neuron migration	7	4.0×	0.168	MARK2, MAP1B, SEMA3A, ASTN2, CEP85L, KIRREL3, DCC
nervous system development	13	2.6×	0.168	RXRG, SMARCA2, TCF4, TFAP2B, TNR, HDAC4, NLGN1, RBFOX1 (+5 more)
commitment of neuronal cell to specific neuron type in forebrain	2	24.3×	0.191	TBR1, BCL11B
anterior/posterior axon guidance	2	24.3×	0.191	UNC5B, DCC
brain development	9	3.1×	0.191	RTN1, TBR1, IMMP2L, ARNT2, NEGR1, GSX1, CNTN4, CXCR4 (+1 more)
visual perception	9	3.1×	0.191	CNNM4, ATXN7, SLC4A10, CACNB2, RIMS1, SPATA7, POU6F2, CRYBA1 (+1 more)
negative regulation of neuron projection development	5	5.1×	0.193	SEMA3A, TNR, BCL11A, PRAG1, DCC
synaptic vesicle exocytosis	3	9.9×	0.193	BRAF, PCLO, RIMS1
regulation of neurotransmitter secretion	3	9.9×	0.193	RIMS1, CHRNB4, MCTP2
positive regulation of muscle contraction	2	20.8×	0.201	CACNA1C, CACNB2
positive regulation of transmission of nerve impulse	2	20.8×	0.201	TNR, CHRNB4
camera-type eye development	4	6.2×	0.201	FOXP2, CACNA1C, FBN3, WDPCP
head morphogenesis	2	18.2×	0.229	BRAF, VPS13B
negative regulation of dendrite development	2	18.2×	0.229	BCL11A, DCC
postsynaptic modulation of chemical synaptic transmission	3	8.8×	0.229	BRAF, SORCS3, DCC
specification of animal organ identity	1	73.0×	0.231	TBR1
regulation of acetylcholine secretion, neurotransmission	1	73.0×	0.231	CHRNA3
pyrimidine nucleoside transport	1	73.0×	0.231	SLC28A3
developmental maturation	1	73.0×	0.231	MAP1B

Therapeutics

Drugs indicated for this disease

18 approved, 12 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetylcarnitine	Approved (phase 4)
Amphetamine	Approved (phase 4)
Armodafinil	Approved (phase 4)
Atomoxetine	Approved (phase 4)
Caffeine	Approved (phase 4)
Dexmethylphenidate	Approved (phase 4)
Dextroamphetamine	Approved (phase 4)
Fipexide	Approved (phase 4)
Idebenone	Approved (phase 4)
Lisdexamfetamine	Approved (phase 4)
Methamphetamine	Approved (phase 4)
Methylphenidate	Approved (phase 4)
Modafinil	Approved (phase 4)
Pemoline	Approved (phase 4)
Piracetam	Approved (phase 4)
Pyritinol	Approved (phase 4)
Solriamfetol	Approved (phase 4)
Vinpocetine	Approved (phase 4)
Bupropion	Phase 3 (in late-stage trials)
Centanafadine	Phase 3 (in late-stage trials)
Citicoline	Phase 3 (in late-stage trials)
Clonidine	Phase 3 (in late-stage trials)
Dasotraline	Phase 3 (in late-stage trials)
Doconexent	Phase 3 (in late-stage trials)
Maritime Pine	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Molindone	Phase 3 (in late-stage trials)
OMEGA-3 FATTY ACIDS	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Zolpidem	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Amantadine, Ampreloxetine, Aripiprazole, Buspirone, Droxidopa, Duloxetine, Edivoxetine, Guanfacine, Lactose, Anhydrous, Levomefolic Acid, Mazindol, Oxiracetam, Pyridoxine, Quetiapine, Reboxetine, St. John’S Wort, Sucrose, Theanine, Vortioxetine.

Drug target analysis

Approved (phase 4): 17 · Phase ≥3: 17 · Phased (≥1): 19 · Undrugged: 55

Druggability breadth: 66 of 250 evidence-associated genes (26%) 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
MARK2	MOMELOTINIB
RPL17	GENTAMICIN SULFATE
RPL23	GENTAMICIN SULFATE
RXRG	BEXAROTENE
BMPR1B	MOMELOTINIB
SEM1	BORTEZOMIB
SHMT2	OXAPROZIN
BRAF	VEMURAFENIB
SLC6A9	GLYCINE
SRPK2	FEDRATINIB
STIM1	TERIFLUNOMIDE
DAGLA	ORLISTAT
UGT1A9	DICLOFENAC
CACNA1C	REMIFENTANIL
CACNA1I	NIMODIPINE
CACNB2	NIMODIPINE
HDAC4	CELECOXIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1C	85	4
BRAF	48	4
MARK2	45	4
HDAC4	31	4
BMPR1B	28	4
SRPK2	11	4
SHMT2	7	4
CACNA1I	7	4
RXRG	6	4
SLC6A9	6	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	BMPR1B, MARK2
FEDRATINIB	4	BMPR1B, BRAF, MARK2, SRPK2
RUXOLITINIB	4	BMPR1B, BRAF, MARK2
BARICITINIB	4	MARK2
TOFACITINIB	4	MARK2
BRIGATINIB	4	MARK2
NINTEDANIB	4	MARK2, SRPK2
SUNITINIB	4	BMPR1B, CACNA1C, MARK2, SRPK2
MIDOSTAURIN	4	MARK2, SRPK2
GENTAMICIN SULFATE	4	RPL17, RPL23
BEXAROTENE	4	RXRG
OXAPROZIN	4	RXRG, SHMT2
TRETINOIN	4	RXRG
ALITRETINOIN	4	RXRG
AXITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B, BRAF
DASATINIB	4	BMPR1B, BRAF, CACNA1C
QUIZARTINIB	4	BMPR1B
CRIZOTINIB	4	BMPR1B
BORTEZOMIB	4	SEM1
CARFILZOMIB	4	SEM1
DULOXETINE	4	CACNA1C, SHMT2
PYRVINIUM	4	SHMT2
FLUPIRTINE	4	SHMT2
METHOTREXATE	4	SHMT2
PRIMAQUINE	4	SHMT2
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
MARK2	356	Binding:355, Functional:1
SMARCA2	311	Binding:274, Functional:25, ADMET:12
SRPK2	221	Binding:221
RXRG	193	Binding:169, Functional:24
BMPR1B	166	Binding:164, ADMET:2
UGT1A9	153	ADMET:149, Binding:4
ELOC	97	Binding:97
RPL17	90	Binding:90
RPL23	90	Binding:90
SLC6A9	88	Binding:83, Functional:5
CACNA1I	56	Binding:44, Functional:9, ADMET:3
DAGLA	48	Binding:48
STIM1	35	Binding:33, Functional:1, ADMET:1
TCF4	31	Binding:31
SEM1	26	Binding:26
YWHAZ	23	Binding:23
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
UBE2D3	18	Binding:18
STIP1	13	Binding:13
KDM3B	13	Binding:13
MAP1B	10	Binding:6, Functional:4
SHMT2	6	Binding:6
ATXN7	5	Binding:5
TLL2	5	Binding:5
TNFRSF10A	3	Binding:3
ST3GAL3	2	Binding:2
UPF1	1	Binding:1
TFEB	1	Binding:1
VAV1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UPF1	3.6.4.13	RNA helicase
CNNM4	7.2.2.14	P-type Mg2+ transporter
BMPR1B	2.7.10.2	non-specific protein-tyrosine kinase
SHMT2	2.1.2.1	glycine hydroxymethyltransferase
ST3GAL3	2.4.99.2, 2.4.99.6	beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminide alpha-2,3-sialyltransferase, N-acetyllactosaminide alpha-2,3-sialyltransferase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
DAGLA	3.1.1.116	sn-1-specific diacylglycerol lipase
UBE2D3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
UGT1A9	2.4.1.17	glucuronosyltransferase
KDM3B	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase
HDAC4	3.5.1.98	histone deacetylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MARK2	356
RXRG	193
BMPR1B	166
BRAF	1,442
SMARCA2	311
SRPK2	221
UGT1A9	153
CACNA1C	575
HDAC4	1,941

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
MOMELOTINIB	4	BMPR1B, MARK2
FEDRATINIB	4	BMPR1B, BRAF, MARK2, SRPK2
RUXOLITINIB	4	BMPR1B, BRAF, MARK2
BARICITINIB	4	MARK2
TOFACITINIB	4	MARK2
BRIGATINIB	4	MARK2
NINTEDANIB	4	MARK2, SRPK2
SUNITINIB	4	BMPR1B, CACNA1C, MARK2, SRPK2
MIDOSTAURIN	4	MARK2, SRPK2
GENTAMICIN SULFATE	4	RPL17, RPL23
BEXAROTENE	4	RXRG
OXAPROZIN	4	RXRG, SHMT2
TRETINOIN	4	RXRG
ALITRETINOIN	4	RXRG
AXITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B, BRAF
DASATINIB	4	BMPR1B, BRAF, CACNA1C
QUIZARTINIB	4	BMPR1B
CRIZOTINIB	4	BMPR1B
BORTEZOMIB	4	SEM1
CARFILZOMIB	4	SEM1
DULOXETINE	4	CACNA1C, SHMT2
PYRVINIUM	4	SHMT2
FLUPIRTINE	4	SHMT2
METHOTREXATE	4	SHMT2
PRIMAQUINE	4	SHMT2
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	17	MARK2, RPL17, RPL23, RXRG, BMPR1B, SEM1, SHMT2, BRAF, SLC6A9, SRPK2 (+7 more)
B	Phased (≥1) drug, not yet approved	2	SMARCA2, TCF4
C	Druggable family + PDB, no drug	6	UPF1, CNNM4, TNR, UBE2D3, KDM3B, CSMD1
D	Druggable family + AlphaFold only, no drug	8	CSMD2, SEMA3A, ST3GAL3, TLL2, UNC5B, FOLH1B, OR14J1, IMMP2L
E	Difficult family or no structure, no drug	41	TCF20, MAP1B, RGS6, CNNM2, RTN1, ATXN7, SOX5, SP4, STIP1, SUPT3H (+31 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
YWHAZ	23	BRAF
TCF20	0	—
CSMD2	0	—
MAP1B	10	—
UPF1	1	—
RGS6	0	—
CNNM2	0	—
RTN1	0	—
CNNM4	0	—
ATXN7	5	—
SEMA3A	0	—
ST3GAL3	2	—
SOX5	0	—
SP4	0	—
STIP1	13	—
SUPT3H	0	—
TBR1	0	—
ELOC	97	—
ELP4	0	—
TFAP2B	0	—
TFEB	1	—
FERRY3	0	—
TLL2	5	—
TNFRSF10A	3	—
TNFRSF10D	0	—
TNR	0	—
UBE2D3	18	—
UNC5B	0	—
VAV1	1	—
MIR99AHG	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,257.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	615
PHASE4	168
PHASE3	152
PHASE2	75
PHASE1	38
PHASE1/PHASE2	20
PHASE2/PHASE3	16
EARLY_PHASE1	16

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03420339	PHASE4	RECRUITING	Stimulant Effects on Disruptive Behavior
NCT03781752	PHASE4	RECRUITING	Carboxylesterase 1 Genetic Variation and Methylphenidate in ADHD
NCT03781765	PHASE4	RECRUITING	Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk
NCT04219280	PHASE4	RECRUITING	Evaluating Treatment of ADHD in Children with Down Syndrome
NCT04781140	PHASE4	RECRUITING	Evaluation of SPN-812 (Viloxazine Extended-release Capsule) in Preschool-age Children With ADHD
NCT05469386	PHASE4	ACTIVE_NOT_RECRUITING	Single and Combined Effects of Behavioral, Academic, and Medication Treatments for ADHD in the Classroom
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT06248229	PHASE4	RECRUITING	A Trial of Dyanavel XR in Treating Co-occurring Fatigue Symptoms in Adults With Attention Deficit Hyperactivity Disorder (ADHD).
NCT06577779	PHASE4	RECRUITING	An Open-Label Treatment With Randomization Observation, Investigator-Initiated Study, on the Duration and Efficacy of Jornay PM (Methylphenidate Hydrochloride Extended-Release Capsules) on Adult ADHD Symptoms and Executive Function and Emotional Regulation Throughout the Day Into Early Evening
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07044609	PHASE4	NOT_YET_RECRUITING	A Study to Assess the Effectiveness and Safety of Clonidine Extended-Release OnydaTM XR in Children With ADHD and ODD
NCT07121621	PHASE4	NOT_YET_RECRUITING	PHArmaCokinetics of methYLphenidate in Adult Patients With Attention-Deficit /Hyperactivity Disorder
NCT07169760	PHASE4	RECRUITING	R61/33 - VR Study Phase 4
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00181571	PHASE4	COMPLETED	A Double-Blind Comparison of Concerta and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181675	PHASE4	COMPLETED	A Double-Blind Comparison of Galantamine HBr and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181714	PHASE4	COMPLETED	Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta
NCT00181948	PHASE4	COMPLETED	Strattera Treatment in Children With ADHD Who Have Poor Response to Stimulant Therapy
NCT00181987	PHASE4	COMPLETED	Concerta in the Treatment of ADHD in Youth and Adults With Bipolar Disorder
NCT00190736	PHASE4	COMPLETED	Efficacy and Safety of Once-Daily Atomoxetine Hydrochloride in Adults With ADHD Over an Extended Period of Time (6 Months)
NCT00190775	PHASE4	COMPLETED	A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00190879	PHASE4	COMPLETED	Placebo-Controlled Study of Atomoxetine Hydrochloride in the Treatment of Adults With ADHD and Comorbid Social Anxiety Disorder
NCT00190957	PHASE4	COMPLETED	Atomoxetine Treatment of Adults With ADHD and Comorbid Alcohol Abuse
NCT00191035	PHASE4	COMPLETED	Maintenance of Benefit With Atomoxetine Hydrochloride in Adolescents With ADHD
NCT00191048	PHASE4	COMPLETED	Treatment With Atomoxetine Hydrochloride in Children and Adolescents With ADHD
NCT00191633	PHASE4	COMPLETED	Study of Atomoxetine in Children With ADHD to Assess Symptomatic and Functional Outcomes
NCT00191906	PHASE4	COMPLETED	Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD)
NCT00216918	PHASE4	COMPLETED	Neuropsychological Functioning in Children With Attention-Deficit/Hyperactivity Disorder.
NCT00221962	PHASE4	COMPLETED	Study of Aripiprazole (Abilify) in Children With ADHD (Attention Deficit Hyperactivity Disorder)
NCT00223561	PHASE4	COMPLETED	Methylphenidate and Driving Ability in Adult Patients With Attention-Deficit Hyperactivity Disorder
NCT00299234	PHASE4	TERMINATED	Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL
NCT00302406	PHASE4	COMPLETED	Naturalistic Substitution of Concerta in Adult Subject With ADHD Receiving Immediate Release Methylphenidate
NCT00305370	PHASE4	COMPLETED	Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD
NCT00381758	PHASE4	COMPLETED	The COMACS Study: A Comparison of Methylphenidates in an Analog Classroom Setting
NCT00406354	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany
NCT00434213	PHASE4	COMPLETED	Characterization of Dermal Reactions in Pediatric Patients With ADHD Using DAYTRANA
NCT00468143	PHASE4	COMPLETED	A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
NCT00471354	PHASE4	COMPLETED	A Study for Patients With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine
NCT00483106	PHASE4	COMPLETED	Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
NCT00485849	PHASE4	COMPLETED	A Study of Atomoxetine for Attention Deficit and Hyperactive/Impulsive Behaviour Problems in Children With ASD

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATOMOXETINE	4	155
METHYLPHENIDATE	4	134
LISDEXAMFETAMINE	4	44
GUANFACINE	4	15
NALTREXONE	4	12
VILOXAZINE HYDROCHLORIDE	4	9
AMPHETAMINE	4	6
BUPROPION	4	6
DEXMETHYLPHENIDATE	4	6
SOLRIAMFETOL	4	6
MOLINDONE	4	5
DEXTROAMPHETAMINE	4	4
MELATONIN	4	4
MEMANTINE	4	4
MODAFINIL	4	4
CARIPRAZINE	4	3
ARIPIPRAZOLE	4	2
CALCITRIOL	4	2
CLONIDINE HYDROCHLORIDE	4	2
ESZOPICLONE	4	2
LEVAMFETAMINE	4	2
PYRIDOXINE	4	2
VARENICLINE	4	2
ZOPICLONE	4	2
AMANTADINE	4	1
AMILORIDE	4	1
BREXPIPRAZOLE	4	1
CARBIDOPA	4	1
CARBIDOPA ANHYDROUS	4	1
CLONIDINE	4	1