Mood disorder

Summary

Mood disorder (MONDO:0005371) is a disease (an umbrella term covering 5 Mondo subtypes) with 65 cohort genes (275 GWAS associations across 29 studies) and 285 clinical trials. Top therapeutic interventions include brexpiprazole, prucalopride, and valproic acid.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 65
• GWAS associations: 275
• Clinical trials: 285

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mood disorder
Mondo ID	MONDO:0005371
EFO	EFO:0004247
MeSH	D019964
DOID	DOID:3324
ICD-10-CM	F30-F39
NCIT	C92200
SNOMED CT	46206005
UMLS	C0525045
MedGen	99866
Is cancer (heuristic)	no

Also known as: episodic mood disorder

Data availability: 275 GWAS associations (29 studies).

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › mood disorder

Related subtypes (13): akinetopsia, cortical deafness, pain agnosia, tactile agnosia, visual agnosia, psychosexual disorder, drug-induced mental disorder, alcohol-induced mental disorder, adjustment disorder, psychotic disorder, developmental disorder of mental health, anxiety disorder, disruptive behavior disorder

Subtypes (5): dysthymic disorder, atypical depressive disorder, depressive disorder, cyclothymic disorder, bipolar disorder

Genetics & variants

GWAS landscape

275 GWAS associations across 29 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs62057061	2e-22	LINC02210-CRHR1	G	0.03
chr11:113377488	8e-22		C	0.04
rs199505	1e-18	WNT3	?	0.02
rs190783615	2e-17	RNA5SP516 - SPANXN4	?	15.18
rs599550	4e-17	TCF4	?	0.03
rs1560312	1e-16	MAPT	?	0.02
chr7:2074122	1e-16		A	0.04
chr14:42143231	1e-14		A	0.03
chr1:73736562	2e-14		G	0.03
rs4936271	2e-14	DRD2	T	0.04
chr11:28625357	5e-14		A	0.04
rs11039149	6e-14	NR1H3	G	0.02
rs17781288	1e-13	LRFN5-DT	C	0.03
rs7107356	2e-13	MTCH2 - AGBL2	?	0.02
rs35738585	2e-13	DRD2 - TMPRSS5	?	0.02
chr6:152225383	2e-13		T	0.04
rs10156548	3e-13	LINC03142	G	0.02
rs34186148	7e-13	LINC02210-CRHR1	?	0.02
rs4800995	7e-13	TCF4 - LINC01415	?	0.02
rs8067056	1e-12	MAPT	?	0.02
chr3:49236439	1e-12		T	0.03
rs12967855	2e-12	CELF4	A	0.02
rs17487484	2e-12	DCC	T	0.02
chr18:50552965	3e-12		A	0.03
rs2678670	4e-12	CAPZBP1 - LINC01965	A	0.03
rs1055447	6e-12	ARFGAP2	?	0.02
rs1261070	6e-12	TCF4	?	0.03
rs611439	6e-12	TCF4	?	0.03
rs1533827	6e-12	MAD1L1	C	0.04
chr9:140258802	7e-12		G	0.05

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476510	Verma A	2024	191,200	234,387	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480751	Verma A	2024	65,347	48,451	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481736	Verma A	2024	65,347	48,451	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
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.
GCST90481734	Verma A	2024	31,196	24,578	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435857	Zhou W	2018	12,560	365,476	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST003813	Li QS	2016	7,795	191,173	Analysis of 23andMe antidepressant efficacy survey data: implication of circadian rhythm and neuroplasticity in bupropion response.
GCST000570	McMahon FJ	2010	6,686	9,068	Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.
GCST003809	Li QS	2016	6,348	191,357	Analysis of 23andMe antidepressant efficacy survey data: implication of circadian rhythm and neuroplasticity in bupropion response.
GCST90708783	Antonsdottir IM	2024	5,606	4,382	Genetic associations with psychosis and affective disturbance in Alzheimer’s disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
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	31
unknown	11
intergenic_variant	5
3_prime_UTR_variant	1
non_coding_transcript_exon_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs62057061	17	45779273	C>G	0.05	intron_variant	LINC02210-CRHR1	2e-22	Tier 4: intronic/intergenic
chr11:113377488				0.365			8e-22	Tier 4: intronic/intergenic
rs199505	17	46782044	A>C,G,T	0.05	intron_variant	WNT3	1e-18	Tier 4: intronic/intergenic
rs190783615	X	142772620	T>C		intergenic_variant	RNA5SP516 - SPANXN4	2e-17	Tier 4: intronic/intergenic
rs599550	18	55585157	G>A,T	0.05	intron_variant	TCF4	4e-17	Tier 4: intronic/intergenic
rs1560312	17	45901622	A>G	0.05	intron_variant	MAPT	1e-16	Tier 4: intronic/intergenic
chr7:2074122				0.198			1e-16	Tier 4: intronic/intergenic
chr14:42143231				0.477			1e-14	Tier 4: intronic/intergenic
chr1:73736562				0.486			2e-14	Tier 4: intronic/intergenic
rs4936271	11	113447983	T>C	0.488	intron_variant	DRD2	2e-14	Tier 4: intronic/intergenic
chr11:28625357				0.375			5e-14	Tier 4: intronic/intergenic
rs11039149	11	47255124	A>G	0.05	intron_variant	NR1H3	6e-14	Tier 4: intronic/intergenic
rs17781288	14	41603205	C>G	0.424	intron_variant	LRFN5-DT	1e-13	Tier 4: intronic/intergenic
rs7107356	11	47654618	A>G,T	0.05	intergenic_variant	MTCH2 - AGBL2	2e-13	Tier 4: intronic/intergenic
rs35738585	11	113515625	T>G	0.05	intergenic_variant	DRD2 - TMPRSS5	2e-13	Tier 4: intronic/intergenic
chr6:152225383				0.358			2e-13	Tier 4: intronic/intergenic
rs10156548	9	23318435	G>A,C,T	0.05	intron_variant	LINC03142	3e-13	Tier 4: intronic/intergenic
rs34186148	17	45777289	G>A,C,T	0.05	intron_variant	LINC02210-CRHR1	7e-13	Tier 4: intronic/intergenic
rs4800995	18	55748146	G>A,C	0.05	intron_variant	TCF4 - LINC01415	7e-13	Tier 4: intronic/intergenic
rs8067056	17	46006582	T>A,C,G	0.05	intron_variant	MAPT	1e-12	Tier 4: intronic/intergenic
chr3:49236439				0.281			1e-12	Tier 4: intronic/intergenic
rs12967855	18	37558282	A>C,G,T	0.05	intron_variant	CELF4	2e-12	Tier 4: intronic/intergenic
rs17487484	18	53196913	T>A,G	0.05	intron_variant	DCC	2e-12	Tier 4: intronic/intergenic
chr18:50552965				0.422			3e-12	Tier 4: intronic/intergenic
rs2678670	2	103853106	A>T	0.494	intron_variant	CAPZBP1 - LINC01965	4e-12	Tier 4: intronic/intergenic
rs1055447	11	47164873	C>A,T	0.05	3_prime_UTR_variant	ARFGAP2	6e-12	Tier 2: splice/UTR
rs1261070	18	55235854	A>G	0.05	intron_variant	TCF4	6e-12	Tier 4: intronic/intergenic
rs611439	18	55537633	C>A,G,T	0.05	intron_variant	TCF4	6e-12	Tier 4: intronic/intergenic
rs1533827	7	2034655	C>G,T	0.166	intron_variant	MAD1L1	6e-12	Tier 4: intronic/intergenic
chr9:140258802				0.119			7e-12	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 31 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN8A	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SCN8A	Orphanet:306	Self-limited infantile epilepsy
SCN8A	Orphanet:352582	Familial infantile myoclonic epilepsy
SCN8A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SORL1	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
POT1	Orphanet:251627	Oligodendroglioma
POT1	Orphanet:251630	Anaplastic oligodendroglioma
POT1	Orphanet:618	Familial melanoma
POT1	Orphanet:67038	B-cell chronic lymphocytic leukemia
FANCL	Orphanet:84	Fanconi anemia
AGK	Orphanet:1369	Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome
AGK	Orphanet:98994	Total early-onset cataract
CUL3	Orphanet:300530	Pseudohypoaldosteronism type 2E
CUL3	Orphanet:528084	Non-specific syndromic intellectual disability
BPNT2	Orphanet:280586	Chondrodysplasia with joint dislocations, gPAPP type
PBRM1	Orphanet:404511	Clear cell papillary renal cell carcinoma
ERG	Orphanet:319	Skeletal Ewing sarcoma
ERG	Orphanet:370334	Extraskeletal Ewing sarcoma
FLRT3	Orphanet:478	Kallmann syndrome
FOXC1	Orphanet:250923	Isolated aniridia
FOXC1	Orphanet:708	Peters anomaly
FOXC1	Orphanet:782	Axenfeld-Rieger syndrome
FOXC1	Orphanet:91483	Rieger anomaly
FOXC1	Orphanet:98978	Axenfeld anomaly
FYB1	Orphanet:566192	Congenital autosomal recessive small-platelet thrombocytopenia
HCN1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
HCN1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
TNC	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYT1L	Orphanet:647799	MYT1L-related developmental delay-intellectual disability-obesity syndrome
MYT1L	Orphanet:699850	2p25.3 microduplication syndrome
NT5C2	Orphanet:320396	Autosomal recessive spastic paraplegia type 45

Cohort genes → proteins

65 cohort genes, 65 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	65

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPLP1	HGNC:10372	ENSG00000137818	P05386	Large ribosomal subunit protein P1	gwas
SCN8A	HGNC:10596	ENSG00000196876	Q9UQD0	Sodium channel protein type 8 subunit alpha	gwas
SLC24A3	HGNC:10977	ENSG00000185052	Q9HC58	Sodium/potassium/calcium exchanger 3	gwas
SLC4A8	HGNC:11034	ENSG00000050438	Q2Y0W8	Electroneutral sodium bicarbonate exchanger 1	gwas
SNCAIP	HGNC:11139	ENSG00000064692	Q9Y6H5	Synphilin-1	gwas
SORL1	HGNC:11185	ENSG00000137642	Q92673	Sortilin-related receptor	gwas
TAF1B	HGNC:11533	ENSG00000115750	Q53T94	TATA box-binding protein-associated factor RNA polymerase I subunit B	gwas
TLE3	HGNC:11839	ENSG00000140332	Q04726	Transducin-like enhancer protein 3	gwas
EIPR1	HGNC:12383	ENSG00000032389	Q53HC9	EARP and GARP complex-interacting protein 1	gwas
UBE2H	HGNC:12484	ENSG00000186591	P62256	Ubiquitin-conjugating enzyme E2 H	gwas
YWHAQ	HGNC:12854	ENSG00000134308	P27348	14-3-3 protein theta	gwas
MAGEC2	HGNC:13574	ENSG00000046774	Q9UBF1	Melanoma-associated antigen C2	gwas
RASGRP3	HGNC:14545	ENSG00000152689	Q8IV61	Ras guanyl-releasing protein 3	gwas
ZHX3	HGNC:15935	ENSG00000174306	Q9H4I2	Zinc fingers and homeoboxes protein 3	gwas
NAV3	HGNC:15998	ENSG00000067798	Q8IVL0	Neuron navigator 3	gwas
SCP2D1-AS1	HGNC:16210	ENSG00000149443	Q9BR46	Putative uncharacterized protein SCP2D1-AS1	gwas
BHLHE41	HGNC:16617	ENSG00000123095	Q9C0J9	Class E basic helix-loop-helix protein 41	gwas
POT1	HGNC:17284	ENSG00000128513	Q9NUX5	Protection of telomeres protein 1	gwas
CDH19	HGNC:1758	ENSG00000071991	Q9H159	Cadherin-19	gwas
CDH8	HGNC:1767	ENSG00000150394	P55286	Cadherin-8	gwas
DSEL	HGNC:18144	ENSG00000171451	Q8IZU8	Dermatan-sulfate epimerase-like protein	gwas
ERRFI1	HGNC:18185	ENSG00000116285	Q9UJM3	ERBB receptor feedback inhibitor 1	gwas
PIWIL4	HGNC:18444	ENSG00000134627	Q7Z3Z4	Piwi-like protein 4	gwas
DCLK2	HGNC:19002	ENSG00000170390	Q8N568	Serine/threonine-protein kinase DCLK2	gwas
FANCL	HGNC:20748	ENSG00000115392	Q9NW38	E3 ubiquitin-protein ligase FANCL	gwas
LINC02901	HGNC:21179	ENSG00000203711	Q4VX62	Putative uncharacterized protein LINC02901	gwas
FSTL4	HGNC:21389	ENSG00000053108	Q6MZW2	Follistatin-related protein 4	gwas
AGK	HGNC:21869	ENSG00000006530	Q53H12	Acylglycerol kinase, mitochondrial	gwas
ADAMTS6	HGNC:222	ENSG00000049192	Q9UKP5	A disintegrin and metalloproteinase with thrombospondin motifs 6	gwas
BRINP3	HGNC:22393	ENSG00000162670	Q76B58	BMP/retinoic acid-inducible neural-specific protein 3	gwas
CORO1B	HGNC:2253	ENSG00000172725	Q9BR76	Coronin-1B	gwas
ENPP6	HGNC:23409	ENSG00000164303	Q6UWR7	Glycerophosphocholine cholinephosphodiesterase ENPP6	gwas
DOCK10	HGNC:23479	ENSG00000135905	Q96BY6	Dedicator of cytokinesis protein 10	gwas
GPR152	HGNC:23622	ENSG00000175514	Q8TDT2	Probable G-protein coupled receptor 152	gwas
RASL11B	HGNC:23804	ENSG00000128045	Q9BPW5	Ras-like protein family member 11B	gwas
E2F7	HGNC:23820	ENSG00000165891	Q96AV8	Transcription factor E2F7	gwas
CSE1L	HGNC:2431	ENSG00000124207	P55060	Exportin-2	gwas
FAM98A	HGNC:24520	ENSG00000119812	Q8NCA5	Protein FAM98A	gwas
MICAL2	HGNC:24693	ENSG00000133816	O94851	[F-actin]-monooxygenase MICAL2	gwas
CSTF3	HGNC:2485	ENSG00000176102	Q12996	Cleavage stimulation factor subunit 3	gwas
STOX2	HGNC:25450	ENSG00000173320	Q9P2F5	Storkhead-box protein 2	gwas
NDC1	HGNC:25525	ENSG00000058804	Q9BTX1	Nucleoporin NDC1	gwas
CUL3	HGNC:2553	ENSG00000036257	Q13618	Cullin-3	gwas
BPNT2	HGNC:26019	ENSG00000104331	Q9NX62	Golgi-resident adenosine 3’,5’-bisphosphate 3’-phosphatase	gwas
DGKG	HGNC:2853	ENSG00000058866	P49619	Diacylglycerol kinase gamma	gwas
DKK3	HGNC:2893	ENSG00000050165	Q9UBP4	Dickkopf-related protein 3	gwas
KAZN	HGNC:29173	ENSG00000189337	Q674X7	Kazrin	gwas
NLK	HGNC:29858	ENSG00000087095	Q9UBE8	Serine/threonine-protein kinase NLK	gwas
PBRM1	HGNC:30064	ENSG00000163939	Q86U86	Protein polybromo-1	gwas
SPANXN4	HGNC:33177	ENSG00000189326	Q5MJ08	Sperm protein associated with the nucleus on the X chromosome N4	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPLP1	Large ribosomal subunit protein P1	Plays an important role in the elongation step of protein synthesis.
SCN8A	Sodium channel protein type 8 subunit alpha	Pore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively pass along their electrochemical gradie…
SLC24A3	Sodium/potassium/calcium exchanger 3	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
SLC4A8	Electroneutral sodium bicarbonate exchanger 1	Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1.
SNCAIP	Synphilin-1	Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins.
SORL1	Sortilin-related receptor	Sorting receptor that directs several proteins to their correct location within the cell.
TAF1B	TATA box-binding protein-associated factor RNA polymerase I subunit B	Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment ev…
TLE3	Transducin-like enhancer protein 3	Transcriptional coregulator that binds to a number of transcription factors.
EIPR1	EARP and GARP complex-interacting protein 1	Acts as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network.
UBE2H	Ubiquitin-conjugating enzyme E2 H	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
YWHAQ	14-3-3 protein theta	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
MAGEC2	Melanoma-associated antigen C2	Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases.
RASGRP3	Ras guanyl-releasing protein 3	Guanine nucleotide exchange factor (GEF) for Ras and Rap1.
ZHX3	Zinc fingers and homeoboxes protein 3	Acts as a transcriptional repressor.
NAV3	Neuron navigator 3	Is involved in microtubule cytoskeleton organization and plays a role in cell migration.
BHLHE41	Class E basic helix-loop-helix protein 41	Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.
POT1	Protection of telomeres protein 1	Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
CDH19	Cadherin-19	Cadherins are calcium-dependent cell adhesion proteins.
CDH8	Cadherin-8	Cadherins are calcium-dependent cell adhesion proteins.
ERRFI1	ERBB receptor feedback inhibitor 1	Negative regulator of EGFR signaling in skin morphogenesis.
PIWIL4	Piwi-like protein 4	Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity.
DCLK2	Serine/threonine-protein kinase DCLK2	Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family.
FANCL	E3 ubiquitin-protein ligase FANCL	Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway.
AGK	Acylglycerol kinase, mitochondrial	Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively.
BRINP3	BMP/retinoic acid-inducible neural-specific protein 3	Inhibits neuronal cell proliferation by negative regulation of the cell cycle transition.
CORO1B	Coronin-1B	Regulates leading edge dynamics and cell motility in fibroblasts.
ENPP6	Glycerophosphocholine cholinephosphodiesterase ENPP6	Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells.
DOCK10	Dedicator of cytokinesis protein 10	Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP.
GPR152	Probable G-protein coupled receptor 152	Orphan receptor.
E2F7	Transcription factor E2F7	Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response.
CSE1L	Exportin-2	Export receptor for importin-alpha.
FAM98A	Protein FAM98A	Positively stimulates PRMT1-induced protein arginine methylation.
MICAL2	[F-actin]-monooxygenase MICAL2	Methionine monooxygenase that promotes depolymerization of F-actin by mediating oxidation of residues ‘Met-44’ and ‘Met-47’ on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization.
CSTF3	Cleavage stimulation factor subunit 3	One of the multiple factors required for polyadenylation and 3’-end cleavage of mammalian pre-mRNAs.
NDC1	Nucleoporin NDC1	Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope.
CUL3	Cullin-3	Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
BPNT2	Golgi-resident adenosine 3’,5’-bisphosphate 3’-phosphatase	Exhibits 3’-nucleotidase activity toward adenosine 3’,5’-bisphosphate (PAP), namely hydrolyzes adenosine 3’,5’-bisphosphate into adenosine 5’-monophosphate (AMP) and a phosphate.
DGKG	Diacylglycerol kinase gamma	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
DKK3	Dickkopf-related protein 3	Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6.
KAZN	Kazrin	Component of the cornified envelope of keratinocytes.
NLK	Serine/threonine-protein kinase NLK	Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination.
PBRM1	Protein polybromo-1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
ERG	Transcriptional regulator ERG	Transcriptional regulator.
FLRT3	Leucine-rich repeat transmembrane protein FLRT3	Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners.
FOXC1	Forkhead box protein C1	DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development.
FOXF2	Forkhead box protein F2	Probable transcription activator for a number of lung-specific genes.
FYB1	FYN-binding protein 1	Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells.
ERVMER34-1	Endogenous retroviral envelope protein HEMO	Endogenous envelope proteins originate from retroviral envelope proteins, which mediate receptor recognition and membrane fusion during early infection.
GRM8	Metabotropic glutamate receptor 8	G-protein coupled receptor for glutamate.
HCN1	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1	Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions.

Protein-family classification

Druggable: 22 · Difficult: 15 · Unknown: 28 · 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
Ion channel	3	5.2×	0.227
Phosphatase	3	3.9×	0.234
Kinase	5	2.1×	0.312
Complement	1	4.1×	0.396
Antibody/Immunoglobulin	4	1.8×	0.396
Scaffold/PPI	6	1.6×	0.396
Transcription factor	9	1.1×	0.610
Other/Unknown	28	0.8×	0.986
GPCR	2	0.7×	0.986
Protease	1	0.6×	0.986
Enzyme (other)	3	0.6×	0.986

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPLP1	Other/Unknown	no		Ribosomal_P1/P2, P1/P2_N_sf
SCN8A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SLC24A3	Other/Unknown	no		K/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
SLC4A8	Other/Unknown	no		HCO3_transpt_euk, Na/HCO3_transpt, HCO3_transpt-like_TM_dom
SNCAIP	Scaffold/PPI	no		Ankyrin_rpt, SNCAIP_SNCA-bd, Ankyrin_rpt-contain_sf
SORL1	Antibody/Immunoglobulin	yes		LDLR_classB_rpt, LDrepeatLR_classA_rpt, FN3_dom
TAF1B	Transcription factor	no		TF_Rrn7_Zf, TAF1B/Rrn7, Rrn7_cyclin_C
TLE3	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
EIPR1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
UBE2H	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
YWHAQ	Other/Unknown	no		14-3-3, 14-3-3_CS, 14-3-3_domain
MAGEC2	Other/Unknown	no		MHD_dom, MAGE, MAGE_WH1
RASGRP3	Other/Unknown	no		Ras-like_Gua-exchang_fac_N, RASGEF_cat_dom, EF_hand_dom
ZHX3	Transcription factor	no		HD, Homeodomain-like_sf, Znf_C2H2_type
NAV3	Other/Unknown	no		CH_dom, AAA+_ATPase, ATPase_AAA_core
SCP2D1-AS1	Other/Unknown	no
BHLHE41	Transcription factor	no		Orange_dom, bHLH_dom, HLH_DNA-bd_sf
POT1	Other/Unknown	no		Telomer_end-bd_POT1/Cdc13, NA-bd_OB-fold, POT1
CDH19	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
CDH8	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
DSEL	Enzyme (other)	yes	5.1.3.19	Sulfotransferase_dom, Chondroitin_lyas, P-loop_NTPase
ERRFI1	Kinase	yes		Cdc42-bd-like, EGFR_SigReg_Kinase
PIWIL4	Other/Unknown	no		PAZ_dom, Piwi, RNaseH-like_sf
DCLK2	Kinase	yes		Prot_kinase_dom, Doublecortin_dom, Ser/Thr_kinase_AS
FANCL	Transcription factor	no	2.3.2.27	Znf_RING/FYVE/PHD, UBQ-conjugating_enzyme/RWD, FancL_WD-rpt_cont_dom
LINC02901	Other/Unknown	no
FSTL4	Antibody/Immunoglobulin	yes		EF_hand_dom, Kazal_dom, Ig_sub2
AGK	Kinase	yes	2.7.1.94	Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N
ADAMTS6	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
BRINP3	Complement	yes		Growth_fac_rcpt_cys_sf, MACPF, BRINP
CORO1B	Scaffold/PPI	no		WD40_rpt, DUF1899, Coronin
ENPP6	Phosphatase	yes	3.1.4.3	Phosphodiest/P_Trfase, Alkaline_phosphatase_core_sf
DOCK10	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, DOCK_C/D_N
GPR152	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, MRGPCRFAMILY
RASL11B	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
E2F7	Other/Unknown	no		E2F_WHTH_DNA-bd_dom, E2F, WH-like_DNA-bd_sf
CSE1L	Other/Unknown	no		Importin-beta_N, XPO2_C, ARM-like
FAM98A	Other/Unknown	no		FAM98
MICAL2	Transcription factor	no		CH_dom, Znf_LIM, FAD-bd
CSTF3	Other/Unknown	no		HAT, Suf, TPR-like_helical_dom_sf
STOX2	Other/Unknown	no		Storkhead-box_WHD, STOX1/2
NDC1	Other/Unknown	no		Nucleoporin_prot_Ndc1/Nup
CUL3	Other/Unknown	no		Cullin_N, Cullin_CS, Cullin_homology
BPNT2	Phosphatase	yes		Inositol_monophosphatase-like, Inositol_monophosphatase_CS, CysQ/Inositol_MonoPase
DGKG	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, EF_hand_dom
DKK3	Other/Unknown	no		Dickkopf_N, DKK1-4, Dkk3_Cys2
KAZN	Other/Unknown	no		SAM, SAM/pointed_sf, Kazrin_SAM_rpt_1
NLK	Kinase	yes		Prot_kinase_dom, MAP_kinase_CS, Ser/Thr_kinase_AS
PBRM1	Other/Unknown	no		BAH_dom, Bromodomain, HMG_box_dom
SPANXN4	Other/Unknown	no		SPAN-X_fam

Expression context

Cohort genes with no expression data: 0.

59 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)	2
broad (>20)	63
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	9
endothelial cell	9
male germ line stem cell (sensu Vertebrata) in testis	8
primordial germ cell in gonad	8
cortical plate	8
secondary oocyte	5
calcaneal tendon	5
left testis	5
middle temporal gyrus	4
adrenal tissue	4
oocyte	4
corpus callosum	4
cerebellar hemisphere	4
ganglionic eminence	3
adenohypophysis	3
male germ cell	3
sperm	3
right testis	3
C1 segment of cervical spinal cord	3
inferior vagus X ganglion	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPLP1	156	ubiquitous	marker	epithelium of bronchus, thymus, trachea
SCN8A	194	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
SLC24A3	272	broad	marker	lateral nuclear group of thalamus, tongue squamous epithelium, saphenous vein
SLC4A8	219	ubiquitous	marker	pons, Brodmann (1909) area 23, superior vestibular nucleus
SNCAIP	240	broad	marker	ventricular zone, ganglionic eminence, germinal epithelium of ovary
SORL1	293	ubiquitous	marker	frontal pole, paraflocculus, middle frontal gyrus
TAF1B	256	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, adrenal tissue
TLE3	248	ubiquitous	marker	blood, cortical plate, ganglionic eminence
EIPR1	249	ubiquitous	marker	prefrontal cortex, adenohypophysis, nucleus accumbens
UBE2H	282	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
YWHAQ	303	ubiquitous	marker	sperm, male germ cell, endothelial cell
MAGEC2	28	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right testis
RASGRP3	255	ubiquitous	marker	corpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord
ZHX3	287	ubiquitous	marker	sural nerve, mucosa of stomach, calcaneal tendon
NAV3	232	ubiquitous	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23
SCP2D1-AS1	69		yes	male germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
BHLHE41	282	ubiquitous	marker	right uterine tube, inferior vagus X ganglion, calcaneal tendon
POT1	279	ubiquitous	marker	secondary oocyte, germinal epithelium of ovary, calcaneal tendon
CDH19	240	broad	marker	trigeminal ganglion, dorsal root ganglion, olfactory bulb
CDH8	188	broad	marker	endothelial cell, Brodmann (1909) area 23, prefrontal cortex
DSEL	132	ubiquitous	marker	stromal cell of endometrium, corpus callosum, cortical plate
ERRFI1	256	ubiquitous	marker	body of pancreas, vena cava, right lobe of liver
PIWIL4	211	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, bone marrow
DCLK2	183	ubiquitous	marker	oocyte, secondary oocyte, cortical plate
FANCL	293	ubiquitous	marker	pituitary gland, adenohypophysis, calcaneal tendon
LINC02901	154	broad	marker	left testis, right testis, testis
FSTL4	159	broad	marker	oocyte, secondary oocyte, primordial germ cell in gonad
AGK	161	ubiquitous	marker	adrenal tissue, cerebellar hemisphere, cerebellar cortex
ADAMTS6	185	ubiquitous	marker	tibia, calcaneal tendon, mucosa of stomach
BRINP3	172	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CUL3	9,954
YWHAQ	7,604
CSTF3	3,678
PBRM1	3,540
RPLP1	3,497
PTPRD	3,052
CSE1L	2,983
FOXC1	2,896
CORO1B	2,758
SORL1	2,524

Intra-cohort edges

A	B	Sources
BPNT2	ENPP6	intact
CDH19	CDH8	string_interaction
CUL3	ERG	biogrid_interaction
DCLK2	YWHAQ	biogrid_interaction
HCN1	SLC4A8	intact
MAGEC2	UBE2H	intact
NLK	ZHX3	biogrid_interaction, intact
RASGRP3	YWHAQ	intact
STOX2	YWHAQ	intact

Structural data

PDB: 28 · AlphaFold-only: 37 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NT5C2	P49902	43
CUL3	Q13618	30
PBRM1	Q86U86	30
TNC	P24821	21
HCN1	O60741	17
POT1	Q9NUX5	14
YWHAQ	P27348	9
PENK	P01210	9
FANCL	Q9NW38	8
ERG	P11308	8
GRM8	O00222	8
PTPRD	P23468	8
SCN8A	Q9UQD0	7
SORL1	Q92673	7
ERRFI1	Q9UJM3	7
CORO1B	Q9BR76	6
MICAL2	O94851	5
DOCK10	Q96BY6	4
RPLP1	P05386	3
CSTF3	Q12996	3
FLRT3	Q9NZU0	3
FYB1	O15117	3
UBE2H	P62256	2
ZHX3	Q9H4I2	2
NDC1	Q9BTX1	2
SLC4A8	Q2Y0W8	1
SNCAIP	Q9Y6H5	1
AGK	Q53H12	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ENPP6	Q6UWR7	93.06
CSE1L	P55060	91.22
EIPR1	Q53HC9	89.26
BPNT2	Q9NX62	88.55
PIWIL4	Q7Z3Z4	85.84
KCNJ15	Q99712	85.84
DSEL	Q8IZU8	85.75
FSTL4	Q6MZW2	81.18
RASL11B	Q9BPW5	79.69
TAF1B	Q53T94	79.35
CDH19	Q9H159	78.14
DGKG	P49619	77.53
ADAMTS6	Q9UKP5	77.45
CDH8	P55286	77.26
BRINP3	Q76B58	77.13
NLK	Q9UBE8	76.46
DKK3	Q9UBP4	74.08
GPR152	Q8TDT2	71.72
KAZN	Q674X7	71.09
RASGRP3	Q8IV61	70.51
DCLK2	Q8N568	70.37
SLC24A3	Q9HC58	70.31
SPANXN4	Q5MJ08	69.71
FAM98A	Q8NCA5	68.95
TLE3	Q04726	68.65
MAGEC2	Q9UBF1	66.43
FOXF2	Q12947	58.04
BHLHE41	Q9C0J9	56.72
NFE2L1	Q14494	56.19
FOXC1	Q12948	56.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 270. Enrichment computed across 65 evidence-associated genes (41 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 41 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of Homotypic Cell-Cell Adhesion	2	32.8×	0.223	CDH19, CDH8
Regulation of Expression and Function of Type II Classical Cadherins	2	32.8×	0.223	CDH19, CDH8
Export of Viral Ribonucleoproteins from Nucleus	1	92.8×	0.315	NDC1
HCN channels	1	69.6×	0.315	HCN1
Interactions of Rev with host cellular proteins	1	69.6×	0.315	NDC1
Abacavir metabolism	1	69.6×	0.315	NT5C2
Activation of RAS in B cells	1	55.7×	0.315	RASGRP3
Transport of Mature mRNAs Derived from Intronless Transcripts	1	39.8×	0.315	NDC1
Glycerophospholipid catabolism	1	39.8×	0.315	ENPP6
CDH11 homotypic and heterotypic interactions	1	39.8×	0.315	CDH8
Interactions of Vpr with host cellular proteins	1	34.8×	0.315	NDC1
Abacavir ADME	1	34.8×	0.315	NT5C2
Formation of intermediate mesoderm	1	34.8×	0.315	FOXC1
Regulation of CDH19 Expression and Function	1	34.8×	0.315	CDH19
Nucleotide catabolism	1	30.9×	0.315	NT5C2
G protein gated Potassium channels	1	27.9×	0.315	KCNJ15
Bicarbonate transporters	1	27.9×	0.315	SLC4A8
RHOBTB3 ATPase cycle	1	27.9×	0.315	CUL3
Sodium/Calcium exchangers	1	25.3×	0.315	SLC24A3
Purine catabolism	1	25.3×	0.315	NT5C2
Ribavirin ADME	1	25.3×	0.315	NT5C2
Regulation of CDH11 function	1	25.3×	0.315	CDH8
DS-GAG biosynthesis	1	23.2×	0.315	DSEL
Regulation of localization of FOXO transcription factors	1	23.2×	0.315	YWHAQ
Glucose metabolism	1	21.4×	0.315	NDC1
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	1	21.4×	0.315	YWHAQ
Telomere C-strand synthesis initiation	1	19.9×	0.315	POT1
Regulation of CDH11 Expression and Function	1	19.9×	0.315	CDH8
Activation of BAD and translocation to mitochondria	1	18.6×	0.315	YWHAQ
Processive synthesis on the C-strand of the telomere	1	18.6×	0.315	POT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 61 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
chondroitin sulfate proteoglycan metabolic process	2	138.1×	0.020	DSEL, BPNT2
cell migration	7	7.1×	0.020	SORL1, CDH19, CDH8, ERRFI1, CORO1B, CUL3, FOXC1
general adaptation syndrome, behavioral process	2	110.5×	0.022	HCN1, PENK
positive regulation of endocytic recycling	2	92.1×	0.024	SORL1, EIPR1
sodium ion transmembrane transport	4	13.3×	0.024	SCN8A, SLC24A3, SLC4A8, HCN1
glycerolipid metabolic process	2	69.1×	0.031	AGK, DGKG
lipid phosphorylation	2	55.2×	0.042	AGK, DGKG
cellular response to vitamin D	2	50.2×	0.045	TNC, PENK
proepicardium cell migration involved in pericardium morphogenesis	1	276.3×	0.081	FLRT3
obsolete GMP catabolic process to guanine	1	276.3×	0.081	NT5C2
negative regulation of brain-derived neurotrophic factor receptor signaling pathway	1	276.3×	0.081	FSTL4
positive regulation of DNA strand elongation	1	276.3×	0.081	POT1
glomerular epithelium development	1	276.3×	0.081	FOXC1
actin filament branching	1	276.3×	0.081	CORO1B
positive regulation of hematopoietic stem cell differentiation	1	276.3×	0.081	FOXC1
negative regulation of anti-Mullerian hormone signaling pathway	1	276.3×	0.081	DKK3
positive regulation of membrane hyperpolarization	1	276.3×	0.081	HCN1
regulation of protein polyubiquitination	1	276.3×	0.081	FOXF2
obsolete positive regulation of early endosome to recycling endosome transport	1	276.3×	0.081	SORL1
negative regulation of neurofibrillary tangle assembly	1	276.3×	0.081	SORL1
response to 1-oleoyl-sn-glycerol 3-phosphate	1	276.3×	0.081	ERRFI1
positive regulation of telomeric D-loop disassembly	1	276.3×	0.081	POT1
negative regulation of mitotic cell cycle	2	26.3×	0.081	BRINP3, FOXC1
trophectodermal cellular morphogenesis	1	138.1×	0.083	CUL3
apoptotic process involved in outflow tract morphogenesis	1	138.1×	0.083	FOXC1
sulfur oxidation	1	138.1×	0.083	MICAL2
negative regulation of protein autophosphorylation	1	138.1×	0.083	ERRFI1
positive regulation of DNA endoreduplication	1	138.1×	0.083	E2F7
uterine epithelium development	1	138.1×	0.083	ERRFI1
mesenchymal-epithelial cell signaling involved in prostate gland development	1	138.1×	0.083	TNC

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Lamotrigine	Phase 3 (in late-stage trials)
Paliperidone	Phase 3 (in late-stage trials)
Quetiapine	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Epoetin Beta, Haloperidol, Oxytocin, Sertraline, Ziprasidone.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 9 · Undrugged: 56

Druggability breadth: 26 of 65 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RPLP1	GENTAMICIN SULFATE
SCN8A	IMIPRAMINE
DCLK2	FEDRATINIB
NLK	SORAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN8A	25	4
NLK	17	4
DCLK2	9	4
GRM8	3	3
PBRM1	2	2
RPLP1	1	4
TAF1B	1	2
RASGRP3	1	2
CSE1L	1	2
SLC24A3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPLP1
IMIPRAMINE	4	SCN8A
SERTINDOLE	4	SCN8A
PIMOZIDE	4	SCN8A
NIFEDIPINE	4	SCN8A
DILTIAZEM	4	SCN8A
MIBEFRADIL	4	SCN8A
HALOPERIDOL	4	SCN8A
MEXILETINE	4	SCN8A
AMITRIPTYLINE	4	SCN8A
AMIODARONE	4	SCN8A
CHLORPROMAZINE	4	SCN8A
TETRACAINE	4	SCN8A
FEDRATINIB	4	DCLK2
RUXOLITINIB	4	DCLK2
SUNITINIB	4	DCLK2
CRIZOTINIB	4	DCLK2
SORAFENIB	4	NLK
BOSUTINIB	4	NLK
ENCORAFENIB	4	NLK
PAZOPANIB	4	NLK
DASATINIB	4	NLK
GEFITINIB	4	NLK
TEDISAMIL	3	SCN8A
NITRENDIPINE	3	SCN8A
AJMALINE	3	SCN8A
VIXOTRIGINE	3	SCN8A
ELECLAZINE	3	SCN8A
TETRODOTOXIN	3	SCN8A
LESTAURTINIB	3	DCLK2, NLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
DCLK2	216	Binding:216
NLK	204	Binding:203, Functional:1
PBRM1	193	Binding:193
SCN8A	173	Binding:148, Functional:16, ADMET:7, Toxicity:2
GRM8	111	Functional:57, Binding:54
RPLP1	90	Binding:90
HCN1	21	Binding:12, Functional:8, ADMET:1
RASGRP3	20	Binding:20
AGK	19	Binding:19
ERG	14	Binding:10, Functional:3, ADMET:1
ENPP6	7	Binding:7
CSE1L	7	Binding:7
CUL3	7	Binding:7
NT5C2	7	Binding:7
TAF1B	6	Binding:6
DGKG	5	Binding:5
YWHAQ	3	Binding:3
GPR152	2	Binding:2
SNCAIP	1	Binding:1
UBE2H	1	Binding:1
POT1	1	Binding:1
NDC1	1	Binding:1
FYB1	1	Binding:1
PTPRD	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBE2H	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
DSEL	5.1.3.19	chondroitin-glucuronate 5-epimerase
FANCL	2.3.2.27	RING-type E3 ubiquitin transferase
AGK	2.7.1.94	acylglycerol kinase
ENPP6	3.1.4.3	phospholipase C
DGKG	2.7.1.107	diacylglycerol kinase (ATP)
NT5C2	3.1.3.5	5’-nucleotidase
PTPRD	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN8A	173
DCLK2	216
NLK	204
PBRM1	193
GRM8	111

Pharmacogenomics

Cohort genes with a PharmGKB record: 63; 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)
GENTAMICIN SULFATE	4	RPLP1
IMIPRAMINE	4	SCN8A
SERTINDOLE	4	SCN8A
PIMOZIDE	4	SCN8A
NIFEDIPINE	4	SCN8A
DILTIAZEM	4	SCN8A
MIBEFRADIL	4	SCN8A
HALOPERIDOL	4	SCN8A
MEXILETINE	4	SCN8A
AMITRIPTYLINE	4	SCN8A
AMIODARONE	4	SCN8A
CHLORPROMAZINE	4	SCN8A
TETRACAINE	4	SCN8A
FEDRATINIB	4	DCLK2
RUXOLITINIB	4	DCLK2
SUNITINIB	4	DCLK2
CRIZOTINIB	4	DCLK2
SORAFENIB	4	NLK
BOSUTINIB	4	NLK
ENCORAFENIB	4	NLK
PAZOPANIB	4	NLK
DASATINIB	4	NLK
GEFITINIB	4	NLK
TEDISAMIL	3	SCN8A
NITRENDIPINE	3	SCN8A
AJMALINE	3	SCN8A
VIXOTRIGINE	3	SCN8A
ELECLAZINE	3	SCN8A
TETRODOTOXIN	3	SCN8A
LESTAURTINIB	3	DCLK2, NLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	RPLP1, SCN8A, DCLK2, NLK
B	Phased (≥1) drug, not yet approved	5	TAF1B, RASGRP3, CSE1L, PBRM1, GRM8
C	Druggable family + PDB, no drug	9	SORL1, UBE2H, ERRFI1, AGK, FLRT3, HCN1, TNC, NT5C2, PTPRD
D	Druggable family + AlphaFold only, no drug	9	DSEL, FSTL4, ADAMTS6, BRINP3, ENPP6, GPR152, BPNT2, DGKG, KCNJ15
E	Difficult family or no structure, no drug	38	SLC24A3, SLC4A8, SNCAIP, TLE3, EIPR1, YWHAQ, MAGEC2, ZHX3, NAV3, SCP2D1-AS1 (+28 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC24A3	0	—
SLC4A8	0	—
SNCAIP	1	—
SORL1	0	—
TLE3	0	—
EIPR1	0	—
UBE2H	1	—
YWHAQ	3	—
MAGEC2	0	—
ZHX3	0	—
NAV3	0	—
SCP2D1-AS1	0	—
BHLHE41	0	—
POT1	1	—
CDH19	0	—
CDH8	0	—
DSEL	0	—
ERRFI1	0	—
PIWIL4	0	—
FANCL	0	—
LINC02901	0	—
FSTL4	0	—
AGK	19	—
ADAMTS6	0	—
BRINP3	0	—
CORO1B	0	—
ENPP6	7	—
DOCK10	0	—
GPR152	2	—
RASL11B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 285.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	223
PHASE2	22
PHASE3	12
PHASE1	11
PHASE4	9
PHASE1/PHASE2	4
PHASE2/PHASE3	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06009289	PHASE4	NOT_YET_RECRUITING	Light and Sleep Fragmentation
NCT00137306	PHASE4	COMPLETED	Facilitating the Adoption of Evidence-Based Depression Management in Substance Use Treatment Programs
NCT00211250	PHASE4	COMPLETED	Comparing Compliance, Tolerability, Efficacy and Adverse Events in Bipolar Tients From Valproic Acid to Depakote ER
NCT00288782	PHASE4	COMPLETED	PET Neuroimaging of [11C]Mirtazapine
NCT01903096	PHASE4	COMPLETED	Treating Emotional Disorders in Primary Care With Psychological Techniques
NCT02263872	PHASE4	COMPLETED	Minocycline as an Adjunct for the Treatment of Depressive Symptoms: Pilot Randomized Controlled Trial
NCT02845453	PHASE4	COMPLETED	Treatment With Quetiapine for Youth With Substance Use Disorders and Severe Mood Dysregulation
NCT03911414	PHASE4	COMPLETED	A Clinical Trial Via Telepsychiatry of Treatments for the Management of Emotional Dysregulation in Youth
NCT04685642	PHASE4	UNKNOWN	Anti-inflmmation Treatment in Mood Disorder and Deep Learning Prediction Model
NCT00035802	PHASE3	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Topiramate Compared to Placebo in the Treatment of Patients With Bipolar I Disorder
NCT00202514	PHASE2/PHASE3	COMPLETED	Placebo Controlled Trial of Depakote ER in Alcohol Dependent Patients With Mood and/or Anxiety Symptoms
NCT00221468	PHASE3	COMPLETED	A Study of Quetiapine for the Treatment of Mood Disorders in Adolescents
NCT00240721	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Topiramate in the Treatment of Patients With Bipolar Disorder
NCT00299715	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Three Fixed Doses of Extended-release Paliperidone in Subjects With Bipolar I Disorder
NCT00309699	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Flexible Doses of Extended-release (ER) Paliperidone Compared With Flexible Doses of Quetiapine and Placebo in Patients With Bipolar I Disorder
NCT00423462	PHASE2/PHASE3	COMPLETED	First Experimental Study of Transference-Interpretations (FEST)
NCT00579982	PHASE3	COMPLETED	An Open-Label Trial Measuring Satisfaction And Convenience Of Two Formulations Of Lamotrigine In Subjects With A Mood Disorder
NCT01360632	PHASE3	COMPLETED	Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)
NCT01360645	PHASE3	COMPLETED	Study of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Pyxis Trial)
NCT01360866	PHASE3	COMPLETED	Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adults With Major Depressive Disorder (the Orion Trial)
NCT01727726	PHASE3	COMPLETED	A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
NCT02196506	PHASE3	COMPLETED	Study of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder With and Without Anxious Distress
NCT02703363	PHASE3	COMPLETED	Minocycline and Celecoxib as Adjunctive Treatments of Bipolar Depression
NCT05680727	PHASE2	ACTIVE_NOT_RECRUITING	Individualized Functional Connectivity Targeting in aiTBS for Depression
NCT06341426	PHASE2	RECRUITING	Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin
NCT06376734	PHASE2	RECRUITING	Search for Novel Transcranial Magnetic Stimulation (TMS) Targets for Mental Illness
NCT06511908	PHASE2	RECRUITING	Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression
NCT00001146	PHASE2	COMPLETED	Omega-3 Fatty Acids in the Treatment of Bipolar Disorder: A Double-Blind, Placebo-Controlled Trial
NCT00001482	PHASE2	COMPLETED	New Drugs in the Treatment of Mood Disorders
NCT00001487	PHASE2	COMPLETED	Treatment of Mid-Life-Related Mood Disorders
NCT00001545	PHASE2	COMPLETED	Evaluation of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Mood Disorders
NCT00055575	PHASE2	TERMINATED	Cholinergic Modulation of Condition and Emotion in Mood Disorders: Functional Neuroimaging Studies
NCT00088699	PHASE1/PHASE2	COMPLETED	Rapid Antidepressant Effects of Ketamine in Major Depression
NCT00149617	PHASE2	COMPLETED	Effectiveness of Buspirone and Motivational Enhancement Therapy for the Treatment of Marijuana Dependence - 1
NCT00217932	PHASE2	COMPLETED	Effectiveness of Divalproex Sodium (Depakote) in Treating Children With Temper Outbursts and Severe Mood Swings
NCT00291031	PHASE1/PHASE2	COMPLETED	Study of the Effect of Imagery Rehearsal Therapy (IRT) of Nightmares
NCT00521417	PHASE2	UNKNOWN	Short- and Long-term Group Psychotherapy
NCT00700609	PHASE2	TERMINATED	Family Based Treatment of Depressed Adolescents
NCT00748956	PHASE2	COMPLETED	Intranasal Administration of Neuropeptide Y in Healthy Male Volunteers
NCT00794040	PHASE2	COMPLETED	A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BREXPIPRAZOLE	4	5
PRUCALOPRIDE	4	4
VALPROIC ACID	4	4
DOXAZOSIN	4	3
FLUOXETINE	4	3
PRAZOSIN	4	3
GANAXOLONE	4	2
MINOCYCLINE	4	2
QUETIAPINE	4	2
TOPIRAMATE	4	2
ACETIC ACID	4	1
ACETYLCYSTEINE	4	1
BIOTIN	4	1
BUSPIRONE	4	1
ESTRADIOL	4	1
FISH OIL	4	1
LAMOTRIGINE	4	1
MIRTAZAPINE	4	1
NITROUS OXIDE	4	1
OMEGA-3-ACID ETHYL ESTERS	4	1
PALIPERIDONE	4	1
PALIPERIDONE PALMITATE	4	1
PINDOLOL	4	1
PRASTERONE	4	1
REBOXETINE	4	1
MIDOMAFETAMINE	3	7
ESREBOXETINE	3	1
ESTROGEN	3	1
INOSITOL	3	1
LITHIUM	3	1