Delirium

Summary

Delirium (MONDO:0045057) is a disease with 45 cohort genes (31 GWAS associations across 11 studies) and 854 clinical trials. The dominant Reactome pathway is Chylomicron remodeling (4 cohort genes). Top therapeutic interventions include haloperidol, dexmedetomidine, and rivastigmine.

At a glance

• Cohort genes: 45
• GWAS associations: 31
• Clinical trials: 854

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	delirium
Mondo ID	MONDO:0045057
EFO	EFO:0009267
MeSH	D003693
ICD-11	897917531
NCIT	C2981
SNOMED CT	2776000
UMLS	C0011206
MedGen	41445
Is cancer (heuristic)	no

Also known as: OBS syndrome

Data availability: 31 GWAS associations (11 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › delirium

Related subtypes (5): amnestic disorder, dementia, alexia, psychotic disorder, subjective cognitive decline

Subtypes (1): subacute delirium

Genetics & variants

GWAS landscape

31 GWAS associations across 11 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs429358	8e-24	APOE	T	0.22
rs889945293	2e-11	LINC01500	A	2.31
chr2:103117777	1e-08		T	4.26
chr2:195210106	1e-07		C	3.92
chr7:112660783	1e-07		G	3.23
chr6:136207021	1e-07		T	4.25
chr19:5331297	2e-07		?
chr10:132654411	5e-07		A	1.98
chr20:58629940	5e-07		A	2.78
chr21:46223727	8e-07		C	2.87
chr15:27902427	8e-07		T	2.6
chr10:9361099	8e-07		T	1.55
chr9:27486453	9e-07		G	1.64
chr3:144544936	1e-06		C	1.85
chr8:125540043	1e-06		G	2.99
chr22:30558994	1e-06		A	2.68
chr2:64791014	1e-06		G	7.56
chr20:56336051	1e-06		C	2.1
chr9:80076247	1e-06		A	1.43
chr11:116579473	3e-06		T	2.89
chr11:94271846	3e-06		T	2.29
chr12:82288694	3e-06		T	2.78
chr10:117894879	3e-06		T	2.16
chr6:151635146	3e-06		G	2.16
chr5:121652214	3e-06		T	2.78
chr1:225773031	4e-06		G	3.19
chr6:153879321	4e-06		G	2.66
chr11:116988389	5e-06		A	3.4
chr17:56369857	5e-06		A	2.75
chr7:43366306	5e-06		A	2.57

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90473243	UK Biobank Whole-Genome Sequencing Consortium	2025	8,461	449,979	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90476503	Verma A	2024	5,690	438,267	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480735	Verma A	2024	1,406	118,362	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481680	Verma A	2024	1,406	118,362	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079785	Backman JD	2021	1,083	386,847	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083771	Backman JD	2021	1,083	386,847	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90651982	Liu TY	2025	969	225,176	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90435839	Zhou W	2018	654	402,383	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90481679	Verma A	2024	609	58,407	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST005851	McCoy TH Jr.	2018	421	5,614	Genome-wide association identifies a novel locus for delirium risk.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	29

MAF distribution

Bucket	Variants
common (>=0.05)	4
low_freq (0.01-0.05)	18
rare (<0.01)	7
unknown	1

Functional consequences

Consequence	Count
unknown	28
missense_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs429358	19	44908684	T>C	0.152	missense_variant	APOE	8e-24	Tier 1: coding
rs889945293	14	58726286	A>G	0.001	intron_variant	LINC01500	2e-11	Tier 4: intronic/intergenic
chr2:103117777				0.01			1e-08	Tier 4: intronic/intergenic
chr2:195210106				0.009			1e-07	Tier 4: intronic/intergenic
chr7:112660783				0.011			1e-07	Tier 4: intronic/intergenic
chr6:136207021				0.008			1e-07	Tier 4: intronic/intergenic
chr19:5331297							2e-07	Tier 4: intronic/intergenic
chr10:132654411				0.045			5e-07	Tier 4: intronic/intergenic
chr20:58629940				0.017			5e-07	Tier 4: intronic/intergenic
chr21:46223727				0.009			8e-07	Tier 4: intronic/intergenic
chr15:27902427				0.017			8e-07	Tier 4: intronic/intergenic
chr10:9361099				0.173			8e-07	Tier 4: intronic/intergenic
chr9:27486453				0.109			9e-07	Tier 4: intronic/intergenic
chr3:144544936				0.049			1e-06	Tier 4: intronic/intergenic
chr8:125540043				0.016			1e-06	Tier 4: intronic/intergenic
chr22:30558994				0.014			1e-06	Tier 4: intronic/intergenic
chr2:64791014				0.005			1e-06	Tier 4: intronic/intergenic
chr20:56336051				0.031			1e-06	Tier 4: intronic/intergenic
chr9:80076247				0.345			1e-06	Tier 4: intronic/intergenic
chr11:116579473				0.011			3e-06	Tier 4: intronic/intergenic
chr11:94271846				0.024			3e-06	Tier 4: intronic/intergenic
chr12:82288694				0.01			3e-06	Tier 4: intronic/intergenic
chr10:117894879				0.025			3e-06	Tier 4: intronic/intergenic
chr6:151635146				0.025			3e-06	Tier 4: intronic/intergenic
chr5:121652214				0.013			3e-06	Tier 4: intronic/intergenic
chr1:225773031				0.009			4e-06	Tier 4: intronic/intergenic
chr6:153879321				0.01			4e-06	Tier 4: intronic/intergenic
chr11:116988389				0.01			5e-06	Tier 4: intronic/intergenic
chr17:56369857				0.012			5e-06	Tier 4: intronic/intergenic
chr7:43366306				0.016			5e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APOA5	Orphanet:530849	Familial apolipoprotein A5 deficiency
CCM2	Orphanet:221061	Familial cerebral cavernous malformation
C9orf72	Orphanet:100069	Semantic dementia
C9orf72	Orphanet:100070	Progressive non-fluent aphasia
C9orf72	Orphanet:275864	Behavioral variant of frontotemporal dementia
C9orf72	Orphanet:275872	Frontotemporal dementia with motor neuron disease
C9orf72	Orphanet:401901	Huntington disease-like syndrome due to C9ORF72 expansions
C9orf72	Orphanet:803	Amyotrophic lateral sclerosis
GFRA1	Orphanet:1848	Renal agenesis, bilateral
GNA14	Orphanet:1063	Tufted angioma
GNA14	Orphanet:2122	Kaposiform hemangioendothelioma
GNA14	Orphanet:675359	Anastomosing haemangioma
APOA1	Orphanet:425	Apolipoprotein A-I deficiency
APOA1	Orphanet:93560	AApoAI amyloidosis
APOC3	Orphanet:181428	Familial Hyperalphalipoproteinemia
LBR	Orphanet:1426	Greenberg dysplasia
LBR	Orphanet:448267	Regressive spondylometaphyseal dysplasia
LBR	Orphanet:779	Reynolds syndrome

Cohort genes → proteins

45 cohort genes, 41 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	45

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SF3A1	HGNC:10765	ENSG00000099995	Q15459	Splicing factor 3A subunit 1	gwas
SLC9A2	HGNC:11072	ENSG00000115616	Q9UBY0	Sodium/hydrogen exchanger 2	gwas
SLC9A4	HGNC:11077	ENSG00000180251	Q6AI14	Sodium/hydrogen exchanger 4	gwas
SUMO3	HGNC:11124	ENSG00000184900	P55854	Small ubiquitin-related modifier 3	gwas
SNCAIP	HGNC:11139	ENSG00000064692	Q9Y6H5	Synphilin-1	gwas
SYCP2	HGNC:11490	ENSG00000196074	Q9BX26	Synaptonemal complex protein 2	gwas
ZPR1	HGNC:13051	ENSG00000109917	O75312	Zinc finger protein ZPR1	gwas
PTTG1IP	HGNC:13524	ENSG00000183255	P53801	Pituitary tumor-transforming gene 1 protein-interacting protein	gwas
CDH26	HGNC:15902	ENSG00000124215	Q8IXH8	Cadherin-like protein 26	gwas
FAM217B	HGNC:16170	ENSG00000196227	Q9NTX9	Protein FAM217B	gwas
APOA5	HGNC:17288	ENSG00000110243	Q6Q788	Apolipoprotein A-V	gwas
ENAH	HGNC:18271	ENSG00000154380	Q8N8S7	Protein enabled homolog	gwas
CCM2	HGNC:21708	ENSG00000136280	Q9BSQ5	Cerebral cavernous malformations 2 protein	gwas
IFNK	HGNC:21714	ENSG00000147896	Q9P0W0	Interferon kappa	gwas
HECW1	HGNC:22195	ENSG00000002746	Q76N89	E3 ubiquitin-protein ligase HECW1	gwas
TBC1D10A	HGNC:23609	ENSG00000099992	Q9BXI6	TBC1 domain family member 10A	gwas
MOB3B	HGNC:23825	ENSG00000120162	Q86TA1	MOB kinase activator 3B	gwas
TATDN1	HGNC:24220	ENSG00000147687	Q6P1N9	Deoxyribonuclease TATDN1	gwas
AFTPH	HGNC:25951	ENSG00000119844	Q6ULP2	Aftiphilin	gwas
SAMTOR	HGNC:26475	ENSG00000164603	Q1RMZ1	S-adenosylmethionine sensor upstream of mTORC1	gwas
MIR646HG	HGNC:27659	ENSG00000228340		MIR646 host gene	gwas
BUD13	HGNC:28199	ENSG00000137656	Q9BRD0	BUD13 homolog	gwas
C9orf72	HGNC:28337	ENSG00000147894	Q96LT7	Guanine nucleotide exchange factor C9orf72	gwas
HORMAD2	HGNC:28383	ENSG00000176635	Q8N7B1	HORMA domain-containing protein 2	gwas
SIK3	HGNC:29165	ENSG00000160584	Q9Y2K2	Serine/threonine-protein kinase SIK3	gwas
DNAH14	HGNC:2945	ENSG00000185842	Q0VDD8	Dynein axonemal heavy chain 14	gwas
CASTOR1	HGNC:34423	ENSG00000239282	Q8WTX7	Cytosolic arginine sensor for mTORC1 subunit 1	gwas
AKAP12	HGNC:370	ENSG00000131016	Q02952	A-kinase anchor protein 12	gwas
MIR4772	HGNC:41741	ENSG00000264764		microRNA 4772	gwas
MIR4434	HGNC:41832	ENSG00000283204		microRNA 4434	gwas
GFRA1	HGNC:4243	ENSG00000151892	P56159	GDNF family receptor alpha-1	gwas
GNA14	HGNC:4382	ENSG00000156049	O95837	Guanine nucleotide-binding protein subunit alpha-14	gwas
MIR6818	HGNC:49940	ENSG00000275818		microRNA 6818	gwas
IL18R1	HGNC:5988	ENSG00000115604	Q13478	Interleukin-18 receptor 1	gwas
IL18RAP	HGNC:5989	ENSG00000115607	O95256	Interleukin-18 receptor accessory protein	gwas
IL1RL1	HGNC:5998	ENSG00000115602	Q01638	Interleukin-1 receptor-like 1	gwas
APOA1	HGNC:600	ENSG00000118137	P02647	Apolipoprotein A-I	gwas
APOA4	HGNC:602	ENSG00000110244	P06727	Apolipoprotein A-IV	gwas
APOC3	HGNC:610	ENSG00000110245	P02656	Apolipoprotein C-III	gwas
LBR	HGNC:6518	ENSG00000143815	Q14739	Delta(14)-sterol reductase LBR	gwas
LIF	HGNC:6596	ENSG00000128342	P15018	Leukemia inhibitory factor	gwas
MTMR3	HGNC:7451	ENSG00000100330	Q13615	Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3	gwas
PDE7B	HGNC:8792	ENSG00000171408	Q9NP56	3’,5’-cyclic-AMP phosphodiesterase 7B	gwas
PPFIA2	HGNC:9246	ENSG00000139220	O75334	Liprin-alpha-2	gwas
PPP1R3D	HGNC:9294	ENSG00000132825	O95685	Protein phosphatase 1 regulatory subunit 3D	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SF3A1	Splicing factor 3A subunit 1	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
SLC9A2	Sodium/hydrogen exchanger 2	Plasma membrane Na(+)/H(+) antiporter.
SLC9A4	Sodium/hydrogen exchanger 4	Electroneutral antiporter that exchanges sodium for protons or ammonium ions at the basolateral membrane of epithelia to regulate cell volume and intracellular pH upon hypertonic conditions.
SUMO3	Small ubiquitin-related modifier 3	Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer.
SNCAIP	Synphilin-1	Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins.
SYCP2	Synaptonemal complex protein 2	Major component of the axial/lateral elements of synaptonemal complexes (SCS) during meiotic prophase.
ZPR1	Zinc finger protein ZPR1	Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus.
PTTG1IP	Pituitary tumor-transforming gene 1 protein-interacting protein	May facilitate PTTG1 nuclear translocation.
CDH26	Cadherin-like protein 26	Cadherins are calcium-dependent cell adhesion proteins.
APOA5	Apolipoprotein A-V	Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL.
ENAH	Protein enabled homolog	Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells.
CCM2	Cerebral cavernous malformations 2 protein	Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity.
IFNK	Interferon kappa	May play a role in the regulation of immune cell function.
HECW1	E3 ubiquitin-protein ligase HECW1	E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1.
TBC1D10A	TBC1 domain family member 10A	GTPase-activating protein (GAP) specific for RAB27A and RAB35.
MOB3B	MOB kinase activator 3B	Modulates LATS1 expression in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
TATDN1	Deoxyribonuclease TATDN1	Exhibits 3’-5’ exonuclease and apurinic/apyrimidinic (AP) endonuclease activities (in vitro).
AFTPH	Aftiphilin	Component of clathrin-coated vesicles.
SAMTOR	S-adenosylmethionine sensor upstream of mTORC1	S-adenosyl-L-methionine-binding protein that acts as an inhibitor of mTORC1 signaling via interaction with the GATOR1 and KICSTOR complexes.
BUD13	BUD13 homolog	Involved in pre-mRNA splicing as component of the activated spliceosome.
C9orf72	Guanine nucleotide exchange factor C9orf72	Acts as a guanine-nucleotide releasing factor (GEF) for Rab GTPases by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
HORMAD2	HORMA domain-containing protein 2	Essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity.
SIK3	Serine/threonine-protein kinase SIK3	Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor.
DNAH14	Dynein axonemal heavy chain 14	Force generating protein of respiratory cilia.
CASTOR1	Cytosolic arginine sensor for mTORC1 subunit 1	Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway.
AKAP12	A-kinase anchor protein 12	Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).
GFRA1	GDNF family receptor alpha-1	Coreceptor for GDNF, a neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
GNA14	Guanine nucleotide-binding protein subunit alpha-14	Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
IL18R1	Interleukin-18 receptor 1	Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B.
IL18RAP	Interleukin-18 receptor accessory protein	Within the IL18 receptor complex, does not mediate IL18-binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation.
IL1RL1	Interleukin-1 receptor-like 1	Receptor for interleukin-33 (IL-33) which plays crucial roles in innate and adaptive immunity, contributing to tissue homeostasis and responses to environmental stresses together with coreceptor IL1RAP.
APOA1	Apolipoprotein A-I	Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT).
APOA4	Apolipoprotein A-IV	May have a role in chylomicrons and VLDL secretion and catabolism.
APOC3	Apolipoprotein C-III	Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma.
LBR	Delta(14)-sterol reductase LBR	Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis.
LIF	Leukemia inhibitory factor	LIF has the capacity to induce terminal differentiation in leukemic cells.
MTMR3	Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3	Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate.
PDE7B	3’,5’-cyclic-AMP phosphodiesterase 7B	Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
PPFIA2	Liprin-alpha-2	Alters PTPRF cellular localization and induces PTPRF clustering.
PPP1R3D	Protein phosphatase 1 regulatory subunit 3D	Seems to act as a glycogen-targeting subunit for PP1.

Protein-family classification

Druggable: 7 · Difficult: 4 · Unknown: 34 · Druggable fraction: 0.16

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	34	1.4×	0.035
Antibody/Immunoglobulin	3	1.9×	0.698
Phosphatase	1	1.9×	0.851
Kinase	2	1.2×	0.851
Scaffold/PPI	2	0.8×	0.980
Transcription factor	2	0.4×	0.980
Enzyme (other)	1	0.3×	0.980

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SF3A1	Other/Unknown	no		Surp, Ubiquitin-like_dom, SF3A1_dom
SLC9A2	Other/Unknown	no		NHE-2/4, NaH_exchanger, Cation/H_exchanger_TM
SLC9A4	Other/Unknown	no		NHE-2/4, NaH_exchanger, Cation/H_exchanger_TM
SUMO3	Other/Unknown	no		Ubiquitin-like_dom, Rad60/SUMO-like_dom, Ubiquitin-like_domsf
SNCAIP	Scaffold/PPI	no		Ankyrin_rpt, SNCAIP_SNCA-bd, Ankyrin_rpt-contain_sf
SYCP2	Other/Unknown	no		SYCP2-like, SYCP2_SLD, SYCP2_ARLD
ZPR1	Transcription factor	no		Znf_ZPR1, ZPR1, ZPR1_A/B_dom
PTTG1IP	Other/Unknown	no		PSI, PTTG1IP
CDH26	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
FAM217B	Other/Unknown	no		FAM217
APOA5	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E
ENAH	Other/Unknown	no		WH1/EVH1_dom, PH-like_dom_sf, VASP_tetra
CCM2	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, Malcavernin
IFNK	Other/Unknown	no		Interferon_alpha/beta/delta, 4_helix_cytokine-like_core
HECW1	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_dom
TBC1D10A	Other/Unknown	no		Rab-GAP-TBC_dom, Rab-GAP_TBC_sf, Rab_GAP_TBC_domain
MOB3B	Kinase	yes		MOB_kinase_act_fam, MOB_kinase_act_sf
TATDN1	Other/Unknown	no		TatD-like, DNase_TatD-rel_CS, Metal_Hydrolase
AFTPH	Other/Unknown	no		Clathrin-bd, Aftin-like
SAMTOR	Other/Unknown	no		Bmt2/SAMTOR, SAM-dependent_MTases_sf
MIR646HG	Other/Unknown	no
BUD13	Other/Unknown	no		Bud13, CWC26_splicing_factor
C9orf72	Other/Unknown	no		C9orf72
HORMAD2	Other/Unknown	no		HORMA_dom, HORMA_dom_sf, HORMA_MeioticProgression
SIK3	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
DNAH14	Other/Unknown	no		Dhc_D4, Dynein_HC_stalk, DHC
CASTOR1	Other/Unknown	no		CASTOR_fam, CASTOR_ACT_dom, CASTOR1_N
AKAP12	Other/Unknown	no		AKAP_WSK, RII-bd_1, AKAP12
MIR4772	Other/Unknown	no
MIR4434	Other/Unknown	no
GFRA1	Other/Unknown	no		GDNF_rcpt, GDNF_rcpt_A1, GDNF/GAS1
GNA14	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
MIR6818	Other/Unknown	no
IL18R1	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub, IL-1_rcpt_I/II-typ
IL18RAP	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub, Ig-like_dom
IL1RL1	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub2, Ig_sub
APOA1	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E
APOA4	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E
APOC3	Other/Unknown	no		Apo-CIII, Apo_CIII_sf
LBR	Enzyme (other)	yes	1.3.1.70	ERG24_DHCR-like, Tudor, Sterol_reductase_CS
LIF	Other/Unknown	no		Leukemia_IF/oncostatin, Leukemia_IF, 4_helix_cytokine-like_core
MTMR3	Phosphatase	yes	3.1.3.95	Znf_FYVE, Tyr_Pase_cat, Myotubularin-like_Pase_dom
PDE7B	Transcription factor	no	3.1.4.53	PDEase_catalytic_dom, HD/PDEase_dom, PDEase
PPFIA2	Other/Unknown	no		SAM, SAM/pointed_sf, Liprin
PPP1R3D	Other/Unknown	no		CBM21_dom, Pase-1_reg-su_3B/C/D_met, CBM21_dom_sf

Expression context

Cohort genes with no expression data: 0.

39 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)	44
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	6
secondary oocyte	5
blood	5
endothelial cell	4
right testis	4
bone marrow	4
sperm	3
male germ line stem cell (sensu Vertebrata) in testis	3
left testis	3
cortical plate	3
liver	3
right lobe of liver	3
calcaneal tendon	3
lateral globus pallidus	3
jejunal mucosa	3
male germ cell	2
tibia	2
ganglionic eminence	2
germinal epithelium of ovary	2
ventricular zone	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SF3A1	300	ubiquitous	marker	sperm, male germ cell, sural nerve
SLC9A2	144	broad	marker	rectum, male germ line stem cell (sensu Vertebrata) in testis, mucosa of transverse colon
SLC9A4	67	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, stomach, body of stomach
SUMO3	294	ubiquitous	marker	endothelial cell, tibia, parietal pleura
SNCAIP	240	broad	marker	ventricular zone, ganglionic eminence, germinal epithelium of ovary
SYCP2	192	broad	marker	right testis, oocyte, left testis
ZPR1	267	ubiquitous	marker	cortical plate, ganglionic eminence, right testis
PTTG1IP	295	ubiquitous	marker	visceral pleura, tibia, pleura
CDH26	180	tissue_specific	marker	bronchial epithelial cell, bronchus, lower esophagus mucosa
FAM217B	247	ubiquitous	marker	endothelial cell, middle temporal gyrus, postcentral gyrus
APOA5	45	tissue_specific	yes	right lobe of liver, liver, skeletal muscle tissue of rectus abdominis
ENAH	292	ubiquitous	marker	saphenous vein, blood vessel layer, colonic epithelium
CCM2	243	ubiquitous	marker	putamen, nucleus accumbens, anterior cingulate cortex
IFNK	43	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, cartilage tissue, calcaneal tendon
HECW1	172	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
TBC1D10A	229	ubiquitous	marker	nasal cavity epithelium, upper arm skin, skin of leg
MOB3B	260	ubiquitous	marker	inferior vagus X ganglion, ventricular zone, lateral globus pallidus
TATDN1	134	ubiquitous	marker	body of pancreas, calcaneal tendon, gastrocnemius
AFTPH	292	ubiquitous	marker	renal medulla, male germ cell, sperm
SAMTOR	240	ubiquitous	yes	secondary oocyte, cortical plate, oocyte
MIR646HG	183	broad	marker	buccal mucosa cell, thymus, sperm
BUD13	246	ubiquitous	marker	secondary oocyte, oocyte, tendon of biceps brachii
C9orf72	250	ubiquitous	marker	monocyte, leukocyte, mucosa of paranasal sinus
HORMAD2	66	tissue_specific	marker	right testis, left testis, testis
SIK3	290	ubiquitous	marker	lateral globus pallidus, corpus callosum, lateral nuclear group of thalamus
DNAH14	172	ubiquitous	marker	left testis, right testis, adrenal tissue
CASTOR1	134	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, vagina
AKAP12	287	ubiquitous	marker	pons, lateral nuclear group of thalamus, dorsal root ganglion
MIR4772	71		yes	bone marrow, vermiform appendix, blood
MIR4434	77		yes	monocyte, bone marrow, granulocyte

Protein interactions among cohort

Intra-cohort edges: 20.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SF3A1	4,038
APOA1	3,608
C9orf72	3,126
LBR	2,789
ZPR1	2,581
LIF	2,339
BUD13	2,107
APOA5	1,919
APOC3	1,895
AKAP12	1,810

Intra-cohort edges

A	B	Sources
APOA1	APOA4	string_interaction
APOA1	APOC3	intact, string_interaction
APOA4	APOC3	string_interaction
APOA5	APOC3	string_interaction
APOA5	BUD13	string_interaction
APOA5	SIK3	string_interaction
APOA5	ZPR1	string_interaction
BUD13	SIK3	string_interaction
BUD13	ZPR1	string_interaction
C9orf72	MOB3B	string_interaction
CASTOR1	SAMTOR	string_interaction
FAM217B	PPP1R3D	string_interaction
FAM217B	SYCP2	string_interaction
HORMAD2	MTMR3	string_interaction
HORMAD2	SYCP2	biogrid_interaction, string_interaction
IFNK	MOB3B	string_interaction
IL18R1	IL18RAP	string_interaction
IL18R1	SLC9A4	string_interaction
IL1RL1	SLC9A4	string_interaction
PPP1R3D	SYCP2	string_interaction

Structural data

PDB: 22 · AlphaFold-only: 19 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SF3A1	Q15459	51
APOA1	P02647	31
ENAH	Q8N8S7	27
BUD13	Q9BRD0	11
CASTOR1	Q8WTX7	10
SUMO3	P55854	8
CCM2	Q9BSQ5	8
PPFIA2	O75334	7
SIK3	Q9Y2K2	5
LIF	P15018	5
C9orf72	Q96LT7	4
IL18R1	Q13478	3
IL18RAP	O95256	3
TATDN1	Q6P1N9	2
APOA4	P06727	2
SNCAIP	Q9Y6H5	1
HECW1	Q76N89	1
SAMTOR	Q1RMZ1	1
GFRA1	P56159	1
IL1RL1	Q01638	1
APOC3	P02656	1
LBR	Q14739	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GNA14	O95837	93.68
MOB3B	Q86TA1	90.13
IFNK	Q9P0W0	82.77
ZPR1	O75312	80.11
PDE7B	Q9NP56	79.84
TBC1D10A	Q9BXI6	78.06
PTTG1IP	P53801	77.51
CDH26	Q8IXH8	72.84
HORMAD2	Q8N7B1	72.61
APOA5	Q6Q788	72.38
PPP1R3D	O95685	71.03
MTMR3	Q13615	66.94
SLC9A4	Q6AI14	66.73
SLC9A2	Q9UBY0	66.40
FAM217B	Q9NTX9	57.78
SYCP2	Q9BX26	54.36
AFTPH	Q6ULP2	46.36
AKAP12	Q02952	40.98
DNAH14	Q0VDD8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 152. Enrichment computed across 45 evidence-associated genes (27 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 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chylomicron remodeling	4	169.2×	8e-07	APOA5, APOA1, APOA4, APOC3
Plasma lipoprotein remodeling	4	70.5×	2e-05	APOA5, APOA1, APOA4, APOC3
Chylomicron assembly	3	126.9×	7e-05	APOA1, APOA4, APOC3
Plasma lipoprotein assembly	3	79.3×	2e-04	APOA1, APOA4, APOC3
Plasma lipoprotein assembly, remodeling, and clearance	4	33.8×	2e-04	APOA5, APOA1, APOA4, APOC3
Metabolism of fat-soluble vitamins	3	42.3×	0.001	APOA1, APOA4, APOC3
Interleukin-18 signaling	2	105.7×	0.003	IL18R1, IL18RAP
Visual phototransduction	3	28.8×	0.003	APOA1, APOA4, APOC3
Retinoid metabolism and transport	3	27.6×	0.003	APOA1, APOA4, APOC3
Sodium/Proton exchangers	2	94.0×	0.003	SLC9A2, SLC9A4
HDL remodeling	2	84.6×	0.003	APOA1, APOC3
Transport of small molecules	6	5.6×	0.007	SLC9A2, SLC9A4, APOA5, APOA1, APOA4, APOC3
Assembly of active LPL and LIPC lipase complexes	2	44.5×	0.010	APOA5, APOA4
Metabolism of vitamins and cofactors	3	12.9×	0.017	APOA1, APOA4, APOC3
Amyloid fiber formation	3	11.4×	0.022	SNCAIP, APOA1, APOA4
Sensory Perception	3	10.6×	0.026	APOA1, APOA4, APOC3
Defective ABCA1 causes TGD	1	211.5×	0.042	APOA1
Interleukin-33 signaling	1	141.0×	0.060	IL1RL1
RHOD GTPase cycle	2	15.1×	0.060	AKAP12, LBR
Amino acids regulate mTORC1	2	14.8×	0.060	SAMTOR, CASTOR1
Metabolism of lipids	4	4.7×	0.071	APOA5, APOA1, LBR, MTMR3
SUMO is conjugated to E1 (UBA2:SAE1)	1	84.6×	0.075	SUMO3
HDL clearance	1	84.6×	0.075	APOA1
Cellular response to starvation	2	12.3×	0.075	SAMTOR, CASTOR1
SUMO is proteolytically processed	1	70.5×	0.086	SUMO3
Regulation of lipid metabolism by PPARalpha	2	10.4×	0.091	APOA5, APOA1
SUMO is transferred from E1 to E2 (UBE2I, UBC9)	1	60.4×	0.092	SUMO3
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	52.9×	0.092	GNA14
Interleukin-6 family signaling	1	52.9×	0.092	LIF
HDL assembly	1	52.9×	0.092	APOA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 39 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phospholipid efflux	4	115.2×	1e-05	APOA5, APOA1, APOA4, APOC3
acylglycerol homeostasis	3	259.3×	2e-05	APOA5, APOA1, APOA4
cholesterol efflux	4	54.0×	9e-05	APOA5, APOA1, APOA4, APOC3
lipoprotein metabolic process	3	72.0×	6e-04	APOA5, APOA4, APOC3
reverse cholesterol transport	3	72.0×	6e-04	APOA1, APOA4, APOC3
high-density lipoprotein particle remodeling	3	61.7×	8e-04	APOA1, APOA4, APOC3
regulation of intestinal cholesterol absorption	2	216.1×	0.001	APOA1, APOA4
negative regulation of very-low-density lipoprotein particle remodeling	2	144.0×	0.003	APOA1, APOC3
interleukin-18-mediated signaling pathway	2	144.0×	0.003	IL18R1, IL18RAP
triglyceride homeostasis	3	37.0×	0.003	APOA5, APOA1, APOC3
cholesterol homeostasis	4	16.0×	0.003	APOA5, APOA1, APOA4, APOC3
positive regulation of triglyceride catabolic process	2	108.0×	0.004	APOA5, APOA4
regulation of TORC1 signaling	2	86.4×	0.006	SAMTOR, C9orf72
positive regulation of TORC1 signaling	3	22.7×	0.007	SAMTOR, SIK3, CASTOR1
regulation of Cdc42 protein signal transduction	2	72.0×	0.007	APOA1, APOC3
positive regulation of fatty acid biosynthetic process	2	66.5×	0.008	APOA5, APOA4
regulation of autophagosome assembly	2	57.6×	0.010	C9orf72, MTMR3
triglyceride catabolic process	2	41.1×	0.018	APOA5, APOC3
cholesterol metabolic process	3	15.1×	0.018	APOA5, APOA1, APOA4
negative regulation of high-density lipoprotein particle clearance	1	432.1×	0.027	APOC3
DNA endoreduplication	1	432.1×	0.027	ZPR1
protein-lipid complex assembly	1	432.1×	0.027	APOA4
regulation of protein kinase C signaling	1	432.1×	0.027	AKAP12
pre-mRNA catabolic process	1	432.1×	0.027	ZPR1
sodium ion import across plasma membrane	2	32.0×	0.027	SLC9A2, SLC9A4
U2-type prespliceosome assembly	2	32.0×	0.027	SF3A1, BUD13
regulation of intracellular pH	2	30.9×	0.027	SLC9A2, SLC9A4
natural killer cell activation	2	29.8×	0.027	IFNK, IL18R1
macrophage differentiation	2	24.0×	0.035	IL1RL1, LIF
regulation of glycogen catabolic process	1	216.1×	0.036	PPP1R3D

Therapeutics

Drugs indicated for this disease

0 approved, 21 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetaminophen	Phase 3 (in late-stage trials)
Clonidine	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Fospropofol	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Guanfacine	Phase 3 (in late-stage trials)
Haloperidol	Phase 3 (in late-stage trials)
Ketamine	Phase 3 (in late-stage trials)
Liraglutide	Phase 3 (in late-stage trials)
Loxapine	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Methylphenidate	Phase 3 (in late-stage trials)
Midazolam	Phase 3 (in late-stage trials)
Nalbuphine	Phase 3 (in late-stage trials)
Physostigmine	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Quetiapine	Phase 3 (in late-stage trials)
Rivastigmine	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Suvorexant	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Chlorpromazine, Donepezil, Fentanyl, Haloperidol Decanoate, Lorazepam, Olanzapine, Sevoflurane, Xenon.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 42

Druggability breadth: 14 of 45 evidence-associated genes (31%) 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
SIK3	MOMELOTINIB
PDE7B	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SIK3	25	4
SLC9A2	3	2
PDE7B	3	4
SF3A1	0	0
SLC9A4	0	0
SUMO3	0	0
SNCAIP	0	0
SYCP2	0	0
ZPR1	0	0
PTTG1IP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	SIK3
FEDRATINIB	4	SIK3
RUXOLITINIB	4	SIK3
DABRAFENIB	4	SIK3
VANDETANIB	4	SIK3
BOSUTINIB	4	SIK3
DASATINIB	4	SIK3
MIDOSTAURIN	4	SIK3
VARDENAFIL	4	PDE7B
DIPYRIDAMOLE	4	PDE7B
CRENOLANIB	3	SIK3
SARACATINIB	3	SIK3
CANERTINIB	3	SIK3
LESTAURTINIB	3	SIK3
ZONIPORIDE	2	SLC9A2
CARIPORIDE	2	SLC9A2
ENIPORIDE	2	SLC9A2
ZOTIRACICLIB	2	SIK3
TANZISERTIB	2	SIK3
OSI-632	2	SIK3
SONOLISIB	2	SIK3
AT-9283	2	SIK3
MILCICLIB	2	SIK3
UCN-01	2	SIK3
KW-2449	1	SIK3
AZD-7762	1	SIK3
XL-019	1	SIK3
PF-03814735	1	SIK3
CYC-116	1	SIK3
Y-39983	1	SIK3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
SIK3	173	Binding:173
PDE7B	89	Binding:83, ADMET:4, Functional:1, Toxicity:1
SLC9A2	10	Binding:8, Functional:2
SF3A1	7	Binding:7
GFRA1	2	Binding:2
APOA1	2	Binding:2
SUMO3	1	Binding:1
SNCAIP	1	Binding:1
AKAP12	1	Binding:1
APOC3	1	Binding:1
LBR	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HECW1	2.3.2.26	HECT-type E3 ubiquitin transferase
LBR	1.3.1.70	DELTA14-sterol reductase
MTMR3	3.1.3.95	phosphatidylinositol-3,5-bisphosphate 3-phosphatase
PDE7B	3.1.4.53	3’,5’-cyclic-AMP phosphodiesterase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SIK3	173

Pharmacogenomics

Cohort genes with a PharmGKB record: 41; 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	SIK3
FEDRATINIB	4	SIK3
RUXOLITINIB	4	SIK3
DABRAFENIB	4	SIK3
VANDETANIB	4	SIK3
BOSUTINIB	4	SIK3
DASATINIB	4	SIK3
MIDOSTAURIN	4	SIK3
VARDENAFIL	4	PDE7B
DIPYRIDAMOLE	4	PDE7B
CRENOLANIB	3	SIK3
SARACATINIB	3	SIK3
CANERTINIB	3	SIK3
LESTAURTINIB	3	SIK3
ZONIPORIDE	2	SLC9A2
CARIPORIDE	2	SLC9A2
ENIPORIDE	2	SLC9A2
ZOTIRACICLIB	2	SIK3
TANZISERTIB	2	SIK3
OSI-632	2	SIK3
SONOLISIB	2	SIK3
AT-9283	2	SIK3
MILCICLIB	2	SIK3
UCN-01	2	SIK3
KW-2449	1	SIK3
AZD-7762	1	SIK3
XL-019	1	SIK3
PF-03814735	1	SIK3
CYC-116	1	SIK3
Y-39983	1	SIK3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SIK3, PDE7B
B	Phased (≥1) drug, not yet approved	1	SLC9A2
C	Druggable family + PDB, no drug	4	IL18R1, IL18RAP, IL1RL1, LBR
D	Druggable family + AlphaFold only, no drug	2	MOB3B, MTMR3
E	Difficult family or no structure, no drug	36	SF3A1, SLC9A4, SUMO3, SNCAIP, SYCP2, ZPR1, PTTG1IP, CDH26, FAM217B, APOA5 (+26 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SF3A1	7	—
SLC9A4	0	—
SUMO3	1	—
SNCAIP	1	—
SYCP2	0	—
ZPR1	0	—
PTTG1IP	0	—
CDH26	0	—
FAM217B	0	—
APOA5	0	—
ENAH	0	—
CCM2	0	—
IFNK	0	—
HECW1	0	—
TBC1D10A	0	—
MOB3B	0	—
TATDN1	0	—
AFTPH	0	—
SAMTOR	0	—
MIR646HG	0	—
BUD13	0	—
C9orf72	0	—
HORMAD2	0	—
DNAH14	0	—
CASTOR1	0	—
AKAP12	1	—
MIR4772	0	—
MIR4434	0	—
GFRA1	2	—
GNA14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 854.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	666
PHASE4	95
PHASE3	37
PHASE2	32
PHASE2/PHASE3	8
EARLY_PHASE1	6
PHASE1/PHASE2	5
PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03480061	PHASE4	ACTIVE_NOT_RECRUITING	Dexmedetomidine to Reduce the Incidence of POCD After Open Cardiac Surgery
NCT04289142	PHASE4	RECRUITING	Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients
NCT04532606	PHASE4	RECRUITING	Impact of Remimazolam on Prognosis After Bladder Cancer Surgery
NCT05069428	PHASE4	RECRUITING	Delirium Reduction With Ramelteon
NCT05823844	PHASE4	RECRUITING	Efficacy of Suvorexant on Post-operative Sleep Disturbance
NCT05990790	PHASE4	RECRUITING	The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium
NCT06579001	PHASE4	RECRUITING	Effect of Nasal Spray Dexmedetomidine on Emergence Delirium Prevention in Total Hip Replacement
NCT07066111	PHASE4	NOT_YET_RECRUITING	The Effect of Bupivacaine Liposome Preemptive Analgesia on Postoperative Pain and Delirium in Elderly Patients Undergoing Hip Fracture Surgery
NCT07151716	PHASE4	RECRUITING	Sedation With Dexmedetomidine-esketamine Combination and Delirium in ICU Patients
NCT07235995	PHASE4	NOT_YET_RECRUITING	Paracetamol and Mannitol Injection and Postoperative Delirium
NCT07265128	PHASE4	NOT_YET_RECRUITING	Remimazolam vs Midazolam to Reduce Delirium in Adults ≥65 Undergoing CPB Valve Surgery
NCT07277881	PHASE4	NOT_YET_RECRUITING	The Effect of Reversal of Remimazolam Sedation With Flumazenil on Cognitive Function in Patients Undergoing Hip Arthroplasty Under Spinal Anesthesia
NCT07407400	PHASE4	NOT_YET_RECRUITING	Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients
NCT07523334	PHASE4	NOT_YET_RECRUITING	Impact of Esketamine on Delayed Neurocognitive Recovery in Older Patients
NCT00182845	PHASE4	COMPLETED	Donepezil in the Prevention of Post-Operative Cognitive Decline
NCT00182884	PHASE4	COMPLETED	Donepezil in Preventing Delirium in Hospitalized Elderly
NCT00286936	PHASE4	TERMINATED	Incidence of Delirium in Hip Fracture Patients Randomized to Regular Hypnotics vs Placebo
NCT00303433	PHASE4	TERMINATED	Namenda to Prevent Post-Operative Delirium
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT00622011	PHASE4	TERMINATED	Risperidone and Zotepine in the Treatment of Delirium
NCT00693121	PHASE4	COMPLETED	Amantadine for Treatment of Symptoms of the Post-traumatic Confusional State
NCT00704301	PHASE4	TERMINATED	Rivastigmine for Intensive Care Unit (ICU) Delirium
NCT00786318	PHASE4	WITHDRAWN	Ziprasidone vs Standard Therapy for Agitated Patients in the ED
NCT00835159	PHASE4	COMPLETED	Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial
NCT01139996	PHASE4	TERMINATED	Use of Transdermal Clonidine in Trauma Patients
NCT01353378	PHASE4	WITHDRAWN	Use of Dexmedetomidine in Children Undergoing Oral Maxillofacial Surgery to Decrease Emergence Delirium
NCT01362959	PHASE4	COMPLETED	Nicotine Replacement Therapy in the Intensive Care Unit
NCT01530308	PHASE4	COMPLETED	Haloperidol Prophylaxis in Older Emergency Department Patients
NCT01785290	PHASE4	COMPLETED	pRophylactic halopEriDol Use for Delirium in iCu patiEnts With a High Risk for Delirium
NCT01791296	PHASE4	COMPLETED	Does Nightly Dexmedetomidine Improve Sleep and Reduce Delirium in ICU Patients?
NCT01904760	PHASE4	COMPLETED	Dexmedetomidine to Prevent Agitation After Free Flap Surgery
NCT01934049	PHASE4	UNKNOWN	Postoperative Recovery in Elderly Patients Undergoing Hip Hemi-arthroplasty
NCT01993836	PHASE4	COMPLETED	Markers of Alzheimers Disease and Cognitive Outcomes After Perioperative Care
NCT02025855	PHASE4	TERMINATED	Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit
NCT02078583	PHASE4	UNKNOWN	The Effect of Analgesia Based Sedation Protocol on Brain Function of Critical Care Patients
NCT02080169	PHASE4	UNKNOWN	Safety and Efficacy of Combined Sedation With Midazolam and Dexmedetomidine in ICU Patients
NCT02096068	PHASE4	COMPLETED	Neuroprotection With Dexmedetomidine in Patients Undergoing Elective Cardiac or Abdominal Surgery (Neuprodex)
NCT02109081	PHASE4	TERMINATED	Dexamethasone and Postoperative Delirium
NCT02117726	PHASE4	UNKNOWN	Impact of Various Sedation Regimens on the Incidence of Delirium

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HALOPERIDOL	4	22
DEXMEDETOMIDINE	4	20
RIVASTIGMINE	4	15
ZIPRASIDONE	4	9
CLONIDINE	4	8
CHLORPROMAZINE	4	6
GUANFACINE	4	6
MELATONIN	4	6
METHYLENE BLUE CATION	4	6
RAMELTEON	4	6
TROPISETRON	4	6
DONEPEZIL	4	5
DESFLURANE	4	4
FENTANYL	4	4
SUFENTANIL	4	4
SUVOREXANT	4	4
THIAMINE ION	4	4
TRAZODONE	4	3
DARIDOREXANT	4	2
LORAZEPAM	4	2
MIDAZOLAM	4	2
PREGABALIN	4	2
REMIMAZOLAM	4	2
SEVOFLURANE	4	2
AMANTADINE HYDROCHLORIDE	4	1
BUPIVACAINE HYDROCHLORIDE	4	1
CAFFEINE CITRATE	4	1
CYANOCOBALAMIN	4	1
DEXAMETHASONE	4	1
ESKETAMINE	4	1