Insomnia

Summary

Insomnia (MONDO:0013600) is a disease with 30 cohort genes (3,958 GWAS associations across 56 studies) and 1,190 clinical trials. Top therapeutic interventions include zopiclone, eszopiclone, and zolpidem.

At a glance

• Cohort genes: 30
• GWAS associations: 3,958
• ClinVar variants: 1
• Clinical trials: 1,190

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	insomnia
Mondo ID	MONDO:0013600
EFO	EFO:0004698
MeSH	D007319
ICD-10-CM	G47.0
NCIT	C28286
SNOMED CT	193462001
UMLS	C0917801
MedGen	214589
Is cancer (heuristic)	no

Also known as: delayed sleep phase syndrome, susceptibility to · DSPD · DSPS · insomnia · insomnia (disease)

Data availability: 1 ClinVar variant · 3,958 GWAS associations (56 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › insomnia

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cluster headache syndrome, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (1): fatal familial insomnia

Genetics & variants

GWAS landscape

3,958 GWAS associations across 56 studies. Top hits map to 15 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6742078	3e-69	UGT1A9, UGT1A6, UGT1A4, UGT1A5, UGT1A1, UGT1A3, UGT1A8, UGT1A7, UGT1A10	?
rs887829	5e-69	UGT1A6, UGT1A7, UGT1A8, UGT1A5, UGT1A10, UGT1A9, UGT1A4, UGT1A3	?
chr2:234664586	1e-67		?
rs34983651	1e-67	UGT1A9, UGT1A7, UGT1A10, UGT1A6, UGT1A4, UGT1A8, UGT1A3, UGT1A5	?
rs17863787	2e-59	UGT1A6, UGT1A9, UGT1A7, UGT1A8, UGT1A10	?
rs28899170	2e-58	UGT1A8, UGT1A7, UGT1A10, UGT1A6, UGT1A9	?
rs6714634	8e-58	UGT1A6, UGT1A4, UGT1A3, UGT1A9, UGT1A5, UGT1A7, UGT1A10, UGT1A8	?
rs10929302	1e-57	UGT1A9, UGT1A3, UGT1A8, UGT1A5, UGT1A6, UGT1A7, UGT1A10, UGT1A4	?
rs3771341	2e-57	UGT1A6, UGT1A7, UGT1A5, UGT1A1, UGT1A8, UGT1A9, UGT1A4, UGT1A10, UGT1A3	?
rs2885296	3e-57	UGT1A5, UGT1A4, UGT1A3, UGT1A9, UGT1A7, UGT1A10, UGT1A8, UGT1A6	?
rs6747843	3e-57	UGT1A6, UGT1A10, UGT1A3, UGT1A9, UGT1A7, UGT1A4, UGT1A8, UGT1A5	?
rs17864701	1e-56	UGT1A3, UGT1A7, UGT1A10, UGT1A5, UGT1A6, UGT1A9, UGT1A8, UGT1A4	?
rs11695484	1e-56	UGT1A9, UGT1A8, UGT1A7, UGT1A3, UGT1A5, UGT1A6, UGT1A10, UGT1A4	?
rs7567468	2e-56	UGT1A4, UGT1A5, UGT1A3, UGT1A8, UGT1A6, UGT1A10, UGT1A7, UGT1A9	?
rs17862875	2e-56	UGT1A7, UGT1A5, UGT1A4, UGT1A3, UGT1A9, UGT1A6, UGT1A8, UGT1A10	?
rs34352510	2e-56	UGT1A10, UGT1A6, UGT1A5, UGT1A4, UGT1A9, UGT1A3, UGT1A8, UGT1A7	?
rs6722076	4e-55	UGT1A6, UGT1A8, UGT1A3, UGT1A7, UGT1A5, UGT1A10, UGT1A9, UGT1A4	?
rs773965339	8e-55	UGT1A6, UGT1A10, UGT1A8, UGT1A7, UGT1A9	?
rs112132688	1e-53	UGT1A10, UGT1A5, UGT1A7, UGT1A4, UGT1A8, UGT1A6, UGT1A9	?
rs10168416	7e-48	UGT1A8, UGT1A7, UGT1A10, UGT1A9	?
rs747484438	8e-48	UGT1A8, UGT1A9, UGT1A10, UGT1A7	?
rs2070959	1e-47	UGT1A7, UGT1A10, UGT1A8, UGT1A9, UGT1A6	?
rs7571915	1e-47	UGT1A9, UGT1A10, UGT1A8	?
rs11692664	2e-47	UGT1A9, UGT1A8, UGT1A10	?
rs10202865	2e-47	UGT1A9, UGT1A10, UGT1A8	?
chr2:234604068	3e-46		?
rs75444879	1e-44	UGT1A9, UGT1A8, UGT1A10	?
rs35984508	1e-44	UGT1A10, UGT1A8, UGT1A9	?
rs1105880	2e-44	UGT1A9, UGT1A6, UGT1A10, UGT1A7, UGT1A8	?
rs1105879	3e-44	UGT1A10, UGT1A8, UGT1A6, UGT1A9, UGT1A7	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90131901	Watanabe K	2022	593,724	1,771,286	Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways.
GCST90131903	Watanabe K	2022	390,751	1,018,386	Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways.
GCST90131902	Watanabe K	2022	222,753	993,280	Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways.
GCST90026657	Chu X	2021	101,922	84,871	Insomnia affects the levels of plasma bilirubin and protein metabolism: an observational study and GWGEIS in UK Biobank cohort.
GCST90026658	Chu X	2021	93,452	78,122	Insomnia affects the levels of plasma bilirubin and protein metabolism: an observational study and GWGEIS in UK Biobank cohort.
GCST90026656	Chu X	2021	85,121	74,733	Insomnia affects the levels of plasma bilirubin and protein metabolism: an observational study and GWGEIS in UK Biobank cohort.
GCST90475826	Verma A	2024	78,566	329,572	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90134531	Yin B	2022	64,717	264,954	Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis.
GCST004702	Hammerschlag AR	2017	32,384	27,128	Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.
GCST90477493	Verma A	2024	24,423	83,343	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	7

Functional consequences

Consequence	Count
intron_variant	41
unknown	3
non_coding_transcript_exon_variant	2
missense_variant	2
synonymous_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6742078	2	233763993	G>T	0.05	intron_variant	UGT1A9, UGT1A6, UGT1A4, UGT1A5, UGT1A1, UGT1A3, UGT1A8, UGT1A7, UGT1A10	3e-69	Tier 4: intronic/intergenic
rs887829	2	233759924	C>A,G,T	0.05	intron_variant	UGT1A6, UGT1A7, UGT1A8, UGT1A5, UGT1A10, UGT1A9, UGT1A4, UGT1A3	5e-69	Tier 4: intronic/intergenic
chr2:234664586							1e-67	Tier 4: intronic/intergenic
rs34983651	2	233760234	C>CTA		intron_variant	UGT1A9, UGT1A7, UGT1A10, UGT1A6, UGT1A4, UGT1A8, UGT1A3, UGT1A5	1e-67	Tier 4: intronic/intergenic
rs17863787	2	233702448	T>G	0.05	intron_variant	UGT1A6, UGT1A9, UGT1A7, UGT1A8, UGT1A10	2e-59	Tier 4: intronic/intergenic
rs28899170	2	233695584	C>A,T	0.05	intron_variant	UGT1A8, UGT1A7, UGT1A10, UGT1A6, UGT1A9	2e-58	Tier 4: intronic/intergenic
rs6714634	2	233756119	T>C	0.05	intron_variant	UGT1A6, UGT1A4, UGT1A3, UGT1A9, UGT1A5, UGT1A7, UGT1A10, UGT1A8	8e-58	Tier 4: intronic/intergenic
rs10929302	2	233757136	G>A	0.05	intron_variant	UGT1A9, UGT1A3, UGT1A8, UGT1A5, UGT1A6, UGT1A7, UGT1A10, UGT1A4	1e-57	Tier 4: intronic/intergenic
rs3771341	2	233764593	G>A,T	0.05	intron_variant	UGT1A6, UGT1A7, UGT1A5, UGT1A1, UGT1A8, UGT1A9, UGT1A4, UGT1A10, UGT1A3	2e-57	Tier 4: intronic/intergenic
rs2885296	2	233750415	A>C	0.05	intron_variant	UGT1A5, UGT1A4, UGT1A3, UGT1A9, UGT1A7, UGT1A10, UGT1A8, UGT1A6	3e-57	Tier 4: intronic/intergenic
rs6747843	2	233755708	G>A	0.05	intron_variant	UGT1A6, UGT1A10, UGT1A3, UGT1A9, UGT1A7, UGT1A4, UGT1A8, UGT1A5	3e-57	Tier 4: intronic/intergenic
rs17864701	2	233744071	C>G,T	0.05	intron_variant	UGT1A3, UGT1A7, UGT1A10, UGT1A5, UGT1A6, UGT1A9, UGT1A8, UGT1A4	1e-56	Tier 4: intronic/intergenic
rs11695484	2	233745803	A>G	0.05	intron_variant	UGT1A9, UGT1A8, UGT1A7, UGT1A3, UGT1A5, UGT1A6, UGT1A10, UGT1A4	1e-56	Tier 4: intronic/intergenic
rs7567468	2	233734192	C>T	0.05	intron_variant	UGT1A4, UGT1A5, UGT1A3, UGT1A8, UGT1A6, UGT1A10, UGT1A7, UGT1A9	2e-56	Tier 4: intronic/intergenic
rs17862875	2	233740656	G>A	0.05	intron_variant	UGT1A7, UGT1A5, UGT1A4, UGT1A3, UGT1A9, UGT1A6, UGT1A8, UGT1A10	2e-56	Tier 4: intronic/intergenic
rs34352510	2	233741916	T>C	0.05	non_coding_transcript_exon_variant	UGT1A10, UGT1A6, UGT1A5, UGT1A4, UGT1A9, UGT1A3, UGT1A8, UGT1A7	2e-56	Tier 4: intronic/intergenic
rs6722076	2	233738671	G>A,C	0.05	intron_variant	UGT1A6, UGT1A8, UGT1A3, UGT1A7, UGT1A5, UGT1A10, UGT1A9, UGT1A4	4e-55	Tier 4: intronic/intergenic
rs773965339	2	233703808			intron_variant	UGT1A6, UGT1A10, UGT1A8, UGT1A7, UGT1A9	8e-55	Tier 4: intronic/intergenic
rs112132688	2	233725006	G>A	0.05	intron_variant	UGT1A10, UGT1A5, UGT1A7, UGT1A4, UGT1A8, UGT1A6, UGT1A9	1e-53	Tier 4: intronic/intergenic
rs10168416	2	233688441	C>A,G,T	0.05	intron_variant	UGT1A8, UGT1A7, UGT1A10, UGT1A9	7e-48	Tier 4: intronic/intergenic
rs747484438	2	233684957			intron_variant	UGT1A8, UGT1A9, UGT1A10, UGT1A7	8e-48	Tier 4: intronic/intergenic
rs2070959	2	233693545	A>G	0.05	missense_variant	UGT1A7, UGT1A10, UGT1A8, UGT1A9, UGT1A6	1e-47	Tier 1: coding
rs7571915	2	233677928	G>A	0.05	intron_variant	UGT1A9, UGT1A10, UGT1A8	1e-47	Tier 4: intronic/intergenic
rs11692664	2	233678562	A>G	0.05	intron_variant	UGT1A9, UGT1A8, UGT1A10	2e-47	Tier 4: intronic/intergenic
rs10202865	2	233679061	C>G,T	0.05	intron_variant	UGT1A9, UGT1A10, UGT1A8	2e-47	Tier 4: intronic/intergenic
chr2:234604068							3e-46	Tier 4: intronic/intergenic
rs75444879	2	233679202	G>A,C	0.05	intron_variant	UGT1A9, UGT1A8, UGT1A10	1e-44	Tier 4: intronic/intergenic
rs35984508	2	233679206	G>A,T	0.05	intron_variant	UGT1A10, UGT1A8, UGT1A9	1e-44	Tier 4: intronic/intergenic
rs1105880	2	233693319	A>C,G,T	0.05	synonymous_variant	UGT1A9, UGT1A6, UGT1A10, UGT1A7, UGT1A8	2e-44	Tier 4: intronic/intergenic
rs1105879	2	233693556	A>C,G,T	0.05	missense_variant	UGT1A10, UGT1A8, UGT1A6, UGT1A9, UGT1A7	3e-44	Tier 1: coding

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
16190	NM_000814.6(GABRB3):c.650G>A (p.Arg217His)	GABRB3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXP2	Orphanet:209908	Isolated childhood apraxia of speech
FOXP2	Orphanet:251061	7q31 microdeletion syndrome
CACNA1D	Orphanet:324321	Sinoatrial node dysfunction and deafness
CACNA1D	Orphanet:369929	Primary hyperaldosteronism-seizures-neurological abnormalities syndrome
SATB2	Orphanet:251019	2q32q33 deletion syndrome
SATB2	Orphanet:251028	SATB2-associated syndrome due to a chromosomal rearrangement
SATB2	Orphanet:576283	SATB2-associated syndrome due to a pathogenic variant
ANO6	Orphanet:806	Scott syndrome
CEP152	Orphanet:2512	Autosomal recessive primary microcephaly
CEP152	Orphanet:808	Seckel syndrome
LIN28B	Orphanet:635	Neuroblastoma
GABRB3	Orphanet:2382	Lennox-Gastaut syndrome
GABRB3	Orphanet:64280	Childhood absence epilepsy

Cohort genes → proteins

30 cohort genes, 25 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	29
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRAV8-3	HGNC:12148	ENSG00000211787	A0A0A6YYJ7	T cell receptor alpha variable 8-3	gwas
FOXP2	HGNC:13875	ENSG00000128573	O15409	Forkhead box protein P2	gwas
CACNA1D	HGNC:1391	ENSG00000157388	Q01668	Voltage-dependent L-type calcium channel subunit alpha-1D	gwas
WDR17	HGNC:16661	ENSG00000150627	Q8IZU2	WD repeat-containing protein 17	gwas
MDGA2	HGNC:19835	ENSG00000139915	Q7Z553	MAM domain-containing glycosylphosphatidylinositol anchor protein 2	gwas
WDR27	HGNC:21248	ENSG00000184465	A2RRH5	WD repeat-containing protein 27	gwas
SATB2	HGNC:21637	ENSG00000119042	Q9UPW6	DNA-binding protein SATB2	gwas
ENPP6	HGNC:23409	ENSG00000164303	Q6UWR7	Glycerophosphocholine cholinephosphodiesterase ENPP6	gwas
DELEC1	HGNC:23658	ENSG00000173077	Q9P2X7	Deleted in esophageal cancer 1	gwas
HEXIM1	HGNC:24953	ENSG00000186834	O94992	Protein HEXIM1	gwas
ANO6	HGNC:25240	ENSG00000177119	Q4KMQ2	Anoctamin-6	gwas
ZNF841	HGNC:27611	ENSG00000197608	Q6ZN19	Zinc finger protein 841	gwas
ZNF616	HGNC:28062	ENSG00000204611	Q08AN1	Zinc finger protein 616	gwas
CNIH2	HGNC:28744	ENSG00000174871	Q6PI25	Protein cornichon homolog 2	gwas
CEP152	HGNC:29298	ENSG00000103995	O94986	Centrosomal protein of 152 kDa	gwas
SCFD2	HGNC:30676	ENSG00000184178	Q8WU76	Sec1 family domain-containing protein 2	gwas
LIN28B	HGNC:32207	ENSG00000187772	Q6ZN17	Protein lin-28 homolog B	gwas
RPP40P2	HGNC:39770	ENSG00000271190		ribonuclease P/MRP subunit p40 pseudogene 2	gwas
GABRB3	HGNC:4083	ENSG00000166206	P28472	Gamma-aminobutyric acid receptor subunit beta-3	clinvar
LINC00917	HGNC:48607	ENSG00000168367		long intergenic non-protein coding RNA 917	gwas
LINC00989	HGNC:48918	ENSG00000250334		long intergenic non-protein coding RNA 989	gwas
LINC01065	HGNC:49103	ENSG00000237092		long intergenic non-protein coding RNA 1065	gwas
LINC01122	HGNC:49267	ENSG00000233723		long intergenic non-protein coding RNA 1122	gwas
IL15	HGNC:5977	ENSG00000164136	P40933	Interleukin-15	gwas
MEIS1	HGNC:7000	ENSG00000143995	O00470	Homeobox protein Meis1	gwas
MSRA	HGNC:7377	ENSG00000175806	Q9UJ68	Mitochondrial peptide methionine sulfoxide reductase	gwas
NTF3	HGNC:8023	ENSG00000185652	P20783	Neurotrophin-3	gwas
PCDH9	HGNC:8661	ENSG00000184226	Q9HC56	Protocadherin-9	gwas
PSMC3	HGNC:9549	ENSG00000165916	P17980	26S proteasome regulatory subunit 6A	gwas
RFX3	HGNC:9984	ENSG00000080298	P48380	Transcription factor RFX3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAV8-3	T cell receptor alpha variable 8-3	V region of the variable domain of T cell receptor (TR) alpha chain that participates in the antigen recognition.
FOXP2	Forkhead box protein P2	Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium.
CACNA1D	Voltage-dependent L-type calcium channel subunit alpha-1D	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
MDGA2	MAM domain-containing glycosylphosphatidylinositol anchor protein 2	May be involved in cell-cell interactions.
SATB2	DNA-binding protein SATB2	Binds to DNA, at nuclear matrix- or scaffold-associated regions.
ENPP6	Glycerophosphocholine cholinephosphodiesterase ENPP6	Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells.
DELEC1	Deleted in esophageal cancer 1	Candidate tumor suppressor.
HEXIM1	Protein HEXIM1	Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor.
ANO6	Anoctamin-6	Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets and osteoblasts.
ZNF841	Zinc finger protein 841	May be involved in transcriptional regulation.
ZNF616	Zinc finger protein 616	May be involved in transcriptional regulation.
CNIH2	Protein cornichon homolog 2	Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs).
CEP152	Centrosomal protein of 152 kDa	Necessary for centrosome duplication; the function also seems to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication.
SCFD2	Sec1 family domain-containing protein 2	May be involved in protein transport.
LIN28B	Protein lin-28 homolog B	Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c.
GABRB3	Gamma-aminobutyric acid receptor subunit beta-3	Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
IL15	Interleukin-15	Cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems.
MEIS1	Homeobox protein Meis1	Acts as a transcriptional regulator of PAX6.
MSRA	Mitochondrial peptide methionine sulfoxide reductase	Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.
NTF3	Neurotrophin-3	Seems to promote the survival of visceral and proprioceptive sensory neurons.
PCDH9	Protocadherin-9	Potential calcium-dependent cell-adhesion protein.
PSMC3	26S proteasome regulatory subunit 6A	Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
RFX3	Transcription factor RFX3	Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development.

Protein-family classification

Druggable: 5 · Difficult: 8 · Unknown: 17 · Druggable fraction: 0.17

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	1	3.7×	0.529
Phosphatase	1	2.8×	0.529
Antibody/Immunoglobulin	2	1.9×	0.529
Transcription factor	6	1.6×	0.529
Scaffold/PPI	2	1.1×	0.628
Other/Unknown	17	1.0×	0.628
Enzyme (other)	1	0.4×	0.927

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRAV8-3	Antibody/Immunoglobulin	yes		Ig-like_dom, Ig_V-set, Ig-like_fold
FOXP2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC
CACNA1D	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, LVDCC_a1dsu
WDR17	Scaffold/PPI	no		WD40_rpt, Quinoprotein_ADH-like_sf, WD40/YVTN_repeat-like_dom_sf
MDGA2	Antibody/Immunoglobulin	yes		MAM_dom, Ig_sub2, Ig_sub
WDR27	Scaffold/PPI	no		WD40_rpt, Quinoprotein_ADH-like_sf, WD40/YVTN_repeat-like_dom_sf
SATB2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
ENPP6	Phosphatase	yes	3.1.4.3	Phosphodiest/P_Trfase, Alkaline_phosphatase_core_sf
DELEC1	Other/Unknown	no		DEC1
HEXIM1	Other/Unknown	no		HEXIM
ANO6	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
ZNF841	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger_PRDM4/PRDM1/PRDM14
ZNF616	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
CNIH2	Other/Unknown	no		Cornichon, Cornichon_conserved
CEP152	Other/Unknown	no		CEP152/SHC-Transforming, CEP152_CC, CEP152_PLK4_bind
SCFD2	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
LIN28B	Transcription factor	no		Znf_CCHC, CSP_DNA-bd, CSD
RPP40P2	Other/Unknown	no
GABRB3	Other/Unknown	no		GABAAb_rcpt, GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM
LINC00917	Other/Unknown	no
LINC00989	Other/Unknown	no
LINC01065	Other/Unknown	no
LINC01122	Other/Unknown	no
IL15	Other/Unknown	no		IL-15/IL-21_fam, 4_helix_cytokine-like_core, IL-15
MEIS1	Transcription factor	no		HD, KN_HD, Homeodomain-like_sf
MSRA	Enzyme (other)	yes	1.8.4.11	Met_Sox_Rdtase_MsrA_dom, Met_Sox_Rdtase_MsrA_sf, MsrA_MetSO_reductase
NTF3	Other/Unknown	no		Nerve_growth_factor-rel, Neurotrophin-3, Nerve_growth_factor_CS
PCDH9	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Protocadherin
PSMC3	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
RFX3	Other/Unknown	no		DNA-bd_RFX, RFX1_trans_act, WH-like_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

23 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)	1
broad (>20)	29
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	8
primordial germ cell in gonad	5
male germ line stem cell (sensu Vertebrata) in testis	5
granulocyte	3
buccal mucosa cell	3
tibialis anterior	3
adrenal tissue	3
mucosa of paranasal sinus	2
right uterine tube	2
corpus callosum	2
secondary oocyte	2
calcaneal tendon	2
ganglionic eminence	2
sperm	2
Brodmann (1909) area 23	2
left testis	2
right testis	2
monocyte	2
lymph node	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAV8-3	149		marker	granulocyte, lymph node, primordial germ cell in gonad
FOXP2	237	broad	marker	buccal mucosa cell, tibialis anterior, mucosa of paranasal sinus
CACNA1D	219	broad	marker	buccal mucosa cell, adrenal tissue, right lung
WDR17	203	broad	marker	endothelial cell, cortical plate, prefrontal cortex
MDGA2	85	broad	marker	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
WDR27	227	ubiquitous	marker	right uterine tube, left ovary, left lobe of thyroid gland
SATB2	235	ubiquitous	marker	periodontal ligament, cortical plate, mucosa of sigmoid colon
ENPP6	186	tissue_specific	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
DELEC1	154	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, granulocyte
HEXIM1	290	ubiquitous	marker	esophagus squamous epithelium, granulocyte, gingival epithelium
ANO6	254	ubiquitous	marker	epithelial cell of pancreas, secondary oocyte, tibialis anterior
ZNF841	134	ubiquitous	yes	calcaneal tendon, corpus callosum, adrenal tissue
ZNF616	194	ubiquitous	yes	sural nerve, adrenal tissue, cortical plate
CNIH2	172	broad	marker	cortical plate, ganglionic eminence, anterior cingulate cortex
CEP152	218	ubiquitous	marker	secondary oocyte, oocyte, sperm
SCFD2	251	ubiquitous	yes	pancreatic ductal cell, ileal mucosa, tibialis anterior
LIN28B	52	broad	marker	placenta, buccal mucosa cell, primordial germ cell in gonad
RPP40P2	6		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, colonic epithelium
GABRB3	219	broad	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23
LINC00917	67	tissue_specific	yes	sperm, left testis, right testis
LINC00989	128	tissue_specific	yes	monocyte, leukocyte, calcaneal tendon
LINC01065	74		yes	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
LINC01122	142	broad	marker	cortical plate, ganglionic eminence, male germ line stem cell (sensu Vertebrata) in testis
IL15	233	ubiquitous	marker	decidua, monocyte, mononuclear cell
MEIS1	264	ubiquitous	marker	right uterine tube, mucosa of stomach, body of uterus
MSRA	134	ubiquitous	marker	cortical plate, adult mammalian kidney, right lobe of liver
NTF3	177	broad	marker	popliteal artery, tibial artery, aorta
PCDH9	253	broad	marker	inferior vagus X ganglion, superior vestibular nucleus, subthalamic nucleus
PSMC3	289	ubiquitous	marker	apex of heart, gastrocnemius, muscle of leg
RFX3	253	ubiquitous	marker	bronchial epithelial cell, mucosa of paranasal sinus, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSMC3	4,843
HEXIM1	3,613
IL15	3,126
LIN28B	2,829
FOXP2	2,557
MSRA	2,363
MEIS1	2,354
CACNA1D	2,318
SATB2	2,254
GABRB3	1,972

Intra-cohort edges

A	B	Sources
MSRA	PCDH9	string_interaction

Structural data

PDB: 13 · AlphaFold-only: 12 · No structure: 5

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSMC3	P17980	130
GABRB3	P28472	95
CNIH2	Q6PI25	7
CACNA1D	Q01668	6
NTF3	P20783	5
IL15	P40933	4
SATB2	Q9UPW6	3
CEP152	O94986	3
FOXP2	O15409	2
HEXIM1	O94992	2
MEIS1	O00470	2
LIN28B	Q6ZN17	1
PCDH9	Q9HC56	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ENPP6	Q6UWR7	93.06
SCFD2	Q8WU76	92.33
TRAV8-3	A0A0A6YYJ7	90.41
MSRA	Q9UJ68	89.13
WDR17	Q8IZU2	85.42
MDGA2	Q7Z553	84.96
ANO6	Q4KMQ2	82.00
WDR27	A2RRH5	81.09
ZNF616	Q08AN1	71.02
ZNF841	Q6ZN19	69.52
RFX3	P48380	67.90
DELEC1	Q9P2X7	62.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 142. Enrichment computed across 30 evidence-associated genes (15 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 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ANO6 does not expose PS, PE on the platelet membrane	1	761.3×	0.124	ANO6
NTF3 activates NTRK2 (TRKB) signaling	1	380.7×	0.124	NTF3
NTF3 activates NTRK3 signaling	1	380.7×	0.124	NTF3
Activated NTRK3 signals through PLCG1	1	253.8×	0.140	NTF3
Protein repair	1	126.9×	0.150	MSRA
Activated NTRK3 signals through PI3K	1	126.9×	0.150	NTF3
Glycerophospholipid catabolism	1	108.8×	0.150	ENPP6
Activated NTRK3 signals through RAS	1	84.6×	0.150	NTF3
Signaling by NTRK3 (TRKC)	1	76.1×	0.150	NTF3
Positive Regulation of CDH1 Gene Transcription	1	63.4×	0.150	FOXP2
Induction of Cell-Cell Fusion	1	58.6×	0.150	ANO6
RUNX2 regulates bone development	1	54.4×	0.150	SATB2
Interleukin-15 signaling	1	50.8×	0.150	IL15
Amplification and propagation of coagulation cascade	1	42.3×	0.150	ANO6
RUNX2 regulates osteoblast differentiation	1	30.4×	0.150	SATB2
Activation of HOX genes during differentiation	1	29.3×	0.150	MEIS1
Adrenaline,noradrenaline inhibits insulin secretion	1	26.2×	0.150	CACNA1D
Cargo concentration in the ER	1	22.4×	0.150	CNIH2
GABA receptor activation	1	21.1×	0.150	GABRB3
Sensory processing of sound	1	20.6×	0.150	CACNA1D
Late SARS-CoV-2 Infection Events	1	19.5×	0.150	ANO6
Regulation of activated PAK-2p34 by proteasome mediated degradation	1	18.6×	0.150	PSMC3
Signaling by ERBB4	1	18.1×	0.150	GABRB3
Regulation of ornithine decarboxylase (ODC)	1	18.1×	0.150	PSMC3
NCAM signaling for neurite out-growth	1	18.1×	0.150	CACNA1D
Vpu mediated degradation of CD4	1	17.7×	0.150	PSMC3
Autodegradation of the E3 ubiquitin ligase COP1	1	17.7×	0.150	PSMC3
Ubiquitin-dependent degradation of Cyclin D	1	17.7×	0.150	PSMC3
Cross-presentation of soluble exogenous antigens (endosomes)	1	16.9×	0.150	PSMC3
Vif-mediated degradation of APOBEC3G	1	16.9×	0.150	PSMC3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
reproductive behavior	1	732.7×	0.031	GABRB3
caudate nucleus development	1	732.7×	0.031	FOXP2
putamen development	1	732.7×	0.031	FOXP2
circadian sleep/wake cycle, REM sleep	1	732.7×	0.031	GABRB3
host-mediated perturbation of viral transcription	1	732.7×	0.031	PSMC3
phosphatidylserine exposure on blood platelet	1	732.7×	0.031	ANO6
embryonic pattern specification	2	47.3×	0.031	SATB2, MEIS1
cell maturation	2	38.6×	0.031	IL15, RFX3
positive regulation of monoatomic ion transmembrane transport	1	366.4×	0.038	ANO6
NK T cell proliferation	1	244.2×	0.038	IL15
activation of blood coagulation via clotting cascade	1	244.2×	0.038	ANO6
choline metabolic process	1	244.2×	0.038	ENPP6
extrathymic T cell selection	1	244.2×	0.038	IL15
positive regulation of potassium ion export across plasma membrane	1	244.2×	0.038	ANO6
positive regulation of type B pancreatic cell development	1	244.2×	0.038	RFX3
negative regulation of pre-miRNA processing	1	244.2×	0.038	LIN28B
purinergic nucleotide receptor signaling pathway	1	183.2×	0.038	ANO6
RNA destabilization	1	183.2×	0.038	LIN28B
calcium activated phosphatidylserine scrambling	1	183.2×	0.038	ANO6
type B pancreatic cell maturation	1	183.2×	0.038	RFX3
positive regulation of miRNA catabolic process	1	183.2×	0.038	LIN28B
negative regulation of primary miRNA processing	1	183.2×	0.038	LIN28B
natural killer cell proliferation	1	146.5×	0.038	IL15
positive regulation of adenylate cyclase activity	1	146.5×	0.038	CACNA1D
negative regulation of cell volume	1	146.5×	0.038	ANO6
epithelial cell proliferation involved in lung morphogenesis	1	146.5×	0.038	FOXP2
calcium activated phosphatidylcholine scrambling	1	146.5×	0.038	ANO6
membrane depolarization during SA node cell action potential	1	146.5×	0.038	CACNA1D
de novo centriole assembly involved in multi-ciliated epithelial cell differentiation	1	146.5×	0.038	CEP152
roof of mouth development	2	21.6×	0.038	SATB2, GABRB3

Therapeutics

Drugs indicated for this disease

12 approved, 19 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Estazolam	Approved (phase 4)
Eszopiclone	Approved (phase 4)
Lemborexant	Approved (phase 4)
Melatonin	Approved (phase 4)
Mirtazapine	Approved (phase 4)
Pentobarbital	Approved (phase 4)
Quazepam	Approved (phase 4)
Ramelteon	Approved (phase 4)
Suvorexant	Approved (phase 4)
Temazepam	Approved (phase 4)
Triazolam	Approved (phase 4)
Zaleplon	Approved (phase 4)
Almorexant	Phase 3 (in late-stage trials)
Amitriptyline	Phase 3 (in late-stage trials)
Brotizolam	Phase 3 (in late-stage trials)
Cannabidiol	Phase 3 (in late-stage trials)
Daridorexant	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Eplivanserin	Phase 3 (in late-stage trials)
Esmirtazapine	Phase 3 (in late-stage trials)
Fazamorexant	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Gaboxadol	Phase 3 (in late-stage trials)
Indiplon	Phase 3 (in late-stage trials)
ORN-0829 HYDRATE	Phase 3 (in late-stage trials)
Pregabalin	Phase 3 (in late-stage trials)
Sertraline	Phase 3 (in late-stage trials)
Tasimelteon	Phase 3 (in late-stage trials)
Trazodone	Phase 3 (in late-stage trials)
Zolpidem	Phase 3 (in late-stage trials)
Zopiclone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Armodafinil, Cannabinol, Casopitant, Quetiapine, Seltorexant.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 27

Druggability breadth: 9 of 30 evidence-associated genes (30%) 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
CACNA1D	BEPRIDIL
GABRB3	LINDANE
PSMC3	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1D	48	4
GABRB3	32	4
PSMC3	2	4
TRAV8-3	0	0
FOXP2	0	0
WDR17	0	0
MDGA2	0	0
WDR27	0	0
SATB2	0	0
ENPP6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	CACNA1D
IMIPRAMINE	4	CACNA1D
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D
SAQUINAVIR	4	CACNA1D
DULOXETINE	4	CACNA1D
DIAZEPAM	4	CACNA1D, GABRB3
SERTINDOLE	4	CACNA1D
QUINIDINE	4	CACNA1D
LAMIVUDINE	4	CACNA1D
PIMOZIDE	4	CACNA1D
PHENYTOIN	4	CACNA1D
TERFENADINE	4	CACNA1D
CISAPRIDE	4	CACNA1D
SOLIFENACIN	4	CACNA1D
NIFEDIPINE	4	CACNA1D
DILTIAZEM	4	CACNA1D
NILOTINIB	4	CACNA1D
ASTEMIZOLE	4	CACNA1D
TERODILINE	4	CACNA1D
CLOZAPINE	4	CACNA1D
MIBEFRADIL	4	CACNA1D
DOFETILIDE	4	CACNA1D
THIORIDAZINE	4	CACNA1D
PAROXETINE	4	CACNA1D
DONEPEZIL	4	CACNA1D
IBUTILIDE	4	CACNA1D
SUNITINIB	4	CACNA1D
HALOPERIDOL	4	CACNA1D
DASATINIB	4	CACNA1D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
GABRB3	887	Binding:722, Functional:156, ADMET:6, Toxicity:3
CACNA1D	233	Binding:145, Functional:81, Toxicity:5, ADMET:2
LIN28B	27	Binding:27
PSMC3	27	Binding:27
IL15	9	Binding:9
HEXIM1	8	Binding:8
ENPP6	7	Binding:7
SATB2	6	Binding:6
MEIS1	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ENPP6	3.1.4.3	phospholipase C
MSRA	1.8.4.11	peptide-methionine (S)-S-oxide reductase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1D	233
GABRB3	887

Pharmacogenomics

Cohort genes with a PharmGKB record: 24; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	CACNA1D
IMIPRAMINE	4	CACNA1D
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D
SAQUINAVIR	4	CACNA1D
DULOXETINE	4	CACNA1D
DIAZEPAM	4	CACNA1D, GABRB3
SERTINDOLE	4	CACNA1D
QUINIDINE	4	CACNA1D
LAMIVUDINE	4	CACNA1D
PIMOZIDE	4	CACNA1D
PHENYTOIN	4	CACNA1D
TERFENADINE	4	CACNA1D
CISAPRIDE	4	CACNA1D
SOLIFENACIN	4	CACNA1D
NIFEDIPINE	4	CACNA1D
DILTIAZEM	4	CACNA1D
NILOTINIB	4	CACNA1D
ASTEMIZOLE	4	CACNA1D
TERODILINE	4	CACNA1D
CLOZAPINE	4	CACNA1D
MIBEFRADIL	4	CACNA1D
DOFETILIDE	4	CACNA1D
THIORIDAZINE	4	CACNA1D
DONEPEZIL	4	CACNA1D
IBUTILIDE	4	CACNA1D
SUNITINIB	4	CACNA1D
HALOPERIDOL	4	CACNA1D
DASATINIB	4	CACNA1D

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CACNA1D, GABRB3, PSMC3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	4	TRAV8-3, MDGA2, ENPP6, MSRA
E	Difficult family or no structure, no drug	23	FOXP2, WDR17, WDR27, SATB2, DELEC1, HEXIM1, ANO6, ZNF841, ZNF616, CNIH2 (+13 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TRAV8-3	0	—
FOXP2	0	—
WDR17	0	—
MDGA2	0	—
WDR27	0	—
SATB2	6	—
ENPP6	7	—
DELEC1	0	—
HEXIM1	8	—
ANO6	0	—
ZNF841	0	—
ZNF616	0	—
CNIH2	0	—
CEP152	0	—
SCFD2	0	—
LIN28B	27	—
RPP40P2	0	—
LINC00917	0	—
LINC00989	0	—
LINC01065	0	—
LINC01122	0	—
IL15	9	—
MEIS1	5	—
MSRA	0	—
NTF3	0	—
PCDH9	0	—
RFX3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,190.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	791
PHASE4	91
PHASE3	85
PHASE2	72
PHASE1	38
EARLY_PHASE1	9
PHASE2/PHASE3	7
PHASE1/PHASE2	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04627480	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of a Neurostimulation Device for Insomnia: A Randomized Trial
NCT05823844	PHASE4	RECRUITING	Efficacy of Suvorexant on Post-operative Sleep Disturbance
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT06306404	PHASE4	NOT_YET_RECRUITING	Sleeping Through Menopause
NCT06435520	PHASE4	RECRUITING	Enhancing Hypnotic Medication Discontinuation in Primary Care
NCT06497894	PHASE4	RECRUITING	No More Sleepless Nights in Perimenopause
NCT06787976	PHASE4	NOT_YET_RECRUITING	Effect of Dolutegravir Compared With Darunavir/Cobicistat on the Severity of Neuropsychiatric Effects al 12 Weeks in Antirretroviral Treatment-Naive Adults.
NCT06788522	PHASE4	NOT_YET_RECRUITING	The Effects of Orexin Antagonism on Fear Extinction in PTSD
NCT07018557	PHASE4	RECRUITING	Impact of Eszopiclone on Blood Pressure in Patients With Insomnia and Hypertension (PRYSMA-HTN)
NCT07136415	PHASE4	RECRUITING	Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms
NCT07328594	PHASE4	NOT_YET_RECRUITING	Impact of Daridorexant on Sleep, Daytime Alertness, and Smoking
NCT07384429	PHASE4	RECRUITING	Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson’s Disease
NCT07542756	PHASE4	NOT_YET_RECRUITING	A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia
NCT07555743	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder and Insomnia
NCT00124384	PHASE4	COMPLETED	The Effects of Modafinil on Waking Function and on Sleep in Individuals With Primary Insomnia
NCT00156533	PHASE4	COMPLETED	Long Term Treatment With Zolpidem: Nightly and Intermittent Dosing
NCT00178048	PHASE4	COMPLETED	Paroxetine in the Treatment of Chronic Primary Insomnia
NCT00235508	PHASE4	COMPLETED	Safety and Efficacy of Eszopiclone in Patients With Generalized Anxiety Disorder
NCT00252278	PHASE4	UNKNOWN	Effect of Atomoxetine on ADHD-Related Insomnia in Children and Adolescents
NCT00283790	PHASE4	COMPLETED	Residual Effects of Zolpidem Tartrate Extended Release and Eszopiclone Vs Placebo
NCT00287391	PHASE4	COMPLETED	Sleep Disorders and Gastroesophageal Reflux Disease (GERD)
NCT00295386	PHASE4	COMPLETED	Cognitive-Behavioural and Hypnotic Treatment of Chronic Primary Insomnia Among the Elderly
NCT00296179	PHASE4	COMPLETED	Ambien CR For Treatment Of Insomnia Associated With Depression When Used Concomitantly With Lexapro
NCT00296790	PHASE4	COMPLETED	Ambien CR vs. Placebo For Treatment Of Insomnia Associated With Anxiety When Used Concomitantly With Escitalopram (Lexapro)
NCT00337272	PHASE4	TERMINATED	Treating Chronic Insomnia in Breast Cancer Patients
NCT00359229	PHASE4	COMPLETED	Stilnox Treatment in Elderly Patients With Insomnia
NCT00365976	PHASE4	COMPLETED	Study of the Insomnia in Patients With Low Back Pain
NCT00386334	PHASE4	COMPLETED	A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly With Primary Chronic Insomnia
NCT00392041	PHASE4	COMPLETED	Eszopiclone in the Treatment of Insomnia and Fibromyalgia
NCT00414037	PHASE4	TERMINATED	How do Sleeping Pills Affect Pain in the Brain?
NCT00414102	PHASE4	COMPLETED	Subjective Efficacy of Ramelteon on Sleep in Adults With Chronic Insomnia.
NCT00432198	PHASE4	COMPLETED	Zolpidem Postmarketing Study in Adolescent Patients With Insomnia
NCT00465972	PHASE4	COMPLETED	The Treatment of Insomnia in Patients With HIV Disease
NCT00492232	PHASE4	COMPLETED	Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia
NCT00507546	PHASE4	COMPLETED	Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia
NCT00511134	PHASE4	TERMINATED	Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban
NCT00566371	PHASE4	COMPLETED	The Effect of a Once Daily Dose of Atomoxetine (ATX) on ADHD-Related Insomnia in Children and Adolescents
NCT00568789	PHASE4	COMPLETED	Safety of Ramelteon in Elderly Subjects
NCT00626210	PHASE4	TERMINATED	Modafinil Treatment for Sleep/Wake Disturbances in Older Adults
NCT00628914	PHASE4	UNKNOWN	Brain Mechanisms and Targeting Insomnia in Major Depression

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ZOPICLONE	4	45
ESZOPICLONE	4	39
ZOLPIDEM	4	39
RAMELTEON	4	31
SUVOREXANT	4	28
LEMBOREXANT	4	11
TRAZODONE	4	11
ATOMOXETINE	4	6
DARIDOREXANT	4	6
DEXMEDETOMIDINE HYDROCHLORIDE	4	5
ARMODAFINIL	4	3
BUPROPION	4	3
DARUNAVIR	4	3
DOXEPIN	4	3
ESCITALOPRAM	4	3
GUANFACINE	4	3
SOLRIAMFETOL	4	3
TEMAZEPAM	4	3
VENLAFAXINE	4	3
ESTAZOLAM	4	2
MIRTAZAPINE	4	2
MODAFINIL	4	2
PAROXETINE	4	2
PIMAVANSERIN	4	2
QUETIAPINE	4	2
TASIMELTEON	4	2
ALCOHOL	4	1
AMINOLEVULINIC ACID	4	1
AMITRIPTYLINE	4	1
AMITRIPTYLINE HYDROCHLORIDE	4	1