Dementia

Summary

Dementia (MONDO:0001627) is a disease (an umbrella term covering 9 Mondo subtypes) with 25 cohort genes (1,207 GWAS associations across 51 studies) and 1,542 clinical trials. Top therapeutic interventions include galantamine, citalopram, and rivastigmine.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 25
• GWAS associations: 1,207
• ClinVar variants: 18
• Clinical trials: 1,542

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dementia
Mondo ID	MONDO:0001627
MeSH	D003704
DOID	DOID:1307
ICD-10-CM	F02
ICD-11	1468768235, 546689346
NCIT	C4786
SNOMED CT	52448006
UMLS	C0497327
MedGen	99229
Is cancer (heuristic)	no

Also known as: dementia · dementia (disease)

Data availability: 18 ClinVar variants · 1,207 GWAS associations (51 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

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

Subtypes (9): vascular dementia, Alzheimer disease, Lewy body dementia, hereditary dementia, dementia pugilistica, parkinsonism with dementia of Guadeloupe, AIDS dementia complex, progressive dementia with neuroserpin inclusion bodies, childhood-onset dementia

Genetics & variants

GWAS landscape

1,207 GWAS associations across 51 studies. Top hits map to 29 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6857	1e-323	LNCOB1, NECTIN2	C	0.55
rs429358	7e-305	APOE	C	1.17
rs4663105	6e-34	BIN1 - NIFKP9	C	0.16
chr19:45382034	3e-33		A
chr19:45242107	5e-19		A
rs10402524	1e-17	BCAM - NECTIN2	T	0.17
rs744373	2e-17	BIN1 - NIFKP9	A	0.14
rs12453	1e-16	MS4A6A	C	0.09
rs730482	1e-15	BIN1 - NIFKP9	A	0.09
rs2278867	2e-15	MS4A6A	A	0.11
rs1859788	3e-15	PILRA	A	0.94
rs10792832	8e-14	RNU6-560P - LINC02695	A	0.09
rs10948367	4e-13	CD2AP	G	0.09
rs7982	4e-13	CLU	A	0.95
rs526904	1e-12	PICALM - RNU6-560P	T	0.08
rs146791569	3e-12	OLFM1 - LINC02907	G	2.59
rs563910796	6e-12	MIAT, MIATNB	C	3.82
rs4844610	1e-11	CR1	A	0.1
rs4295	1e-11	ACE	C	0.08
rs556399519	1e-11	FGGY	A	4.27
rs192194010	1e-11	LINC01871	C	2.69
rs552140994	2e-11	LLPH	C	2.55
rs181412363	3e-11	DAW1	G	2.01
chr17:17728043	4e-11		A
rs592297	5e-11	PICALM	C	0.94
rs73505251	3e-10	ARHGAP45	A
rs1408077	5e-10	CR1	A	0.09
rs7738720	1e-09	B3GNTL1P2 - CD2AP-DT	T
rs570487962	2e-09	LINC02253, LINC00923	A
rs2208524	2e-09	RNU6-1018P - NEFHP2	T	0.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90449046	Le Borgne J	2024	115,841	613,671	X-chromosome-wide association study for Alzheimer’s disease.
GCST90449024	Fongang B	2024	44,009	466,606	A genome-wide association meta-analysis of all-cause and vascular dementia.
GCST90476496	Verma A	2024	19,855	423,191	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90551881	Casanova F	2024	8,040	443,191	MRI-derived brain iron, grey matter volume, and risk of dementia and Parkinson’s disease: Observational and genetic analysis in the UK Biobank cohort.
GCST90654661	Sherva R	2025	6,960	65,919	Genome-wide association studies of Alzheimer’s disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans.
GCST90267627	Sherva R	2022	6,796	69,627	African ancestry GWAS of dementia in a large military cohort identifies significant risk loci.
GCST90267628	Sherva R	2022	6,796	69,627	African ancestry GWAS of dementia in a large military cohort identifies significant risk loci.
GCST90558250	Zhang YR	2024	6,740	295,421	Whole exome sequencing analyses identified novel genes for Alzheimer’s disease and related dementia.
GCST90651180	Liu TY	2025	6,429	225,176	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90654662	Sherva R	2025	6,179	50,738	Genome-wide association studies of Alzheimer’s disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	5
Tier 2: splice/UTR	4
Tier 3: regulatory	0
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	32
low_freq (0.01-0.05)	2
rare (<0.01)	6
unknown	10

Functional consequences

Consequence	Count
intron_variant	21
unknown	10
intergenic_variant	10
missense_variant	5
3_prime_UTR_variant	2
splice_donor_region_variant	1
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6857	19	44888997	C>A,G,T	0.154	3_prime_UTR_variant	LNCOB1, NECTIN2	1e-323	Tier 2: splice/UTR
rs429358	19	44908684	T>C	0.151	missense_variant	APOE	7e-305	Tier 1: coding
rs4663105	2	127133851	A>C	0.415	intron_variant	BIN1 - NIFKP9	6e-34	Tier 4: intronic/intergenic
chr19:45382034							3e-33	Tier 4: intronic/intergenic
chr19:45242107							5e-19	Tier 4: intronic/intergenic
rs10402524	19	44826087	T>C	0.234	intergenic_variant	BCAM - NECTIN2	1e-17	Tier 4: intronic/intergenic
rs744373	2	127137039	A>C,G,T	0.358	intergenic_variant	BIN1 - NIFKP9	2e-17	Tier 4: intronic/intergenic
rs12453	11	60178272	T>C,G	0.4	missense_variant	MS4A6A	1e-16	Tier 1: coding
rs730482	2	127136908	A>T	0.28	intergenic_variant	BIN1 - NIFKP9	1e-15	Tier 4: intronic/intergenic
rs2278867	11	60175636	A>G,T	0.29	intron_variant	MS4A6A	2e-15	Tier 4: intronic/intergenic
rs1859788	7	100374211	A>C,G	0.319	missense_variant	PILRA	3e-15	Tier 1: coding
rs10792832	11	86156833	A>C,G,T	0.358	intergenic_variant	RNU6-560P - LINC02695	8e-14	Tier 4: intronic/intergenic
rs10948367	6	47617879	A>C,G	0.271	intron_variant	CD2AP	4e-13	Tier 4: intronic/intergenic
rs7982	8	27604964	A>C,G,T	0.404	missense_variant	CLU	4e-13	Tier 1: coding
rs526904	11	86100322	T>C	0.354	intergenic_variant	PICALM - RNU6-560P	1e-12	Tier 4: intronic/intergenic
rs146791569	9	135255256	G>A	0.003	intergenic_variant	OLFM1 - LINC02907	3e-12	Tier 4: intronic/intergenic
rs563910796	22	26662283	C>T	0	intron_variant	MIAT, MIATNB	6e-12	Tier 4: intronic/intergenic
rs4844610	1	207629207	A>C,G,T	0.185	intron_variant	CR1	1e-11	Tier 4: intronic/intergenic
rs4295	17	63478937	C>G	0.39	intron_variant	ACE	1e-11	Tier 4: intronic/intergenic
rs556399519	1	59786968	A>G	0	intron_variant	FGGY	1e-11	Tier 4: intronic/intergenic
rs192194010	2	7737491	C>T	0	intron_variant	LINC01871	1e-11	Tier 4: intronic/intergenic
rs552140994	12	66121827	C>T	0	3_prime_UTR_variant	LLPH	2e-11	Tier 2: splice/UTR
rs181412363	2	227921567	G>A	0.002	splice_donor_region_variant	DAW1	3e-11	Tier 2: splice/UTR
chr17:17728043							4e-11	Tier 4: intronic/intergenic
rs592297	11	86014894	C>A,G,T	0.197	missense_variant	PICALM	5e-11	Tier 1: coding
rs73505251	19	1068096	T>A	0.05	intron_variant	ARHGAP45	3e-10	Tier 4: intronic/intergenic
rs1408077	1	207630796	A>C,G,T	0.141	intron_variant	CR1	5e-10	Tier 4: intronic/intergenic
rs7738720	6	47427663	T>C	0.05	intergenic_variant	B3GNTL1P2 - CD2AP-DT	1e-09	Tier 4: intronic/intergenic
rs570487962	15	97449455	A>C,T		intron_variant	LINC02253, LINC00923	2e-09	Tier 4: intronic/intergenic
rs2208524	20	41794659	T>A,C,G	0.127	intergenic_variant	RNU6-1018P - NEFHP2	2e-09	Tier 4: intronic/intergenic

ClinVar germline variants

18 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity; risk factor, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
208584	NM_000158.4(GBE1):c.691+2T>C	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98222	NM_001377265.1(MAPT):c.2091+16C>T	MAPT	Pathogenic	criteria provided, multiple submitters, no conflicts
18157	NM_000021.4(PSEN1):c.236C>T (p.Ala79Val)	PSEN1	Pathogenic	criteria provided, multiple submitters, no conflicts
374134	NM_000021.4(PSEN1):c.314T>G (p.Phe105Cys)	PSEN1	Pathogenic	criteria provided, single submitter
98080	NM_000021.4(PSEN1):c.791C>T (p.Pro264Leu)	PSEN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98072	NM_000021.4(PSEN1):c.709T>C (p.Phe237Leu)	PSEN1	Likely pathogenic	criteria provided, single submitter
692155	NM_013386.5(SLC25A24):c.758G>C (p.Gly253Ala)	SLC25A24	Likely pathogenic	criteria provided, single submitter
199044	NM_000157.4(GBA1):c.1093G>A (p.Glu365Lys)	GBA1	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
548007	NM_000158.4(GBE1):c.1492G>A (p.Glu498Lys)	GBE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127974	NM_005591.4(MRE11):c.1727G>A (p.Arg576Gln)	MRE11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4075046	NM_001371904.1(APOA5):c.620A>C (p.Gln207Pro)	APOA5	Uncertain significance	criteria provided, single submitter
481777	NM_005591.4(MRE11):c.229G>A (p.Glu77Lys)	MRE11	Uncertain significance	criteria provided, multiple submitters, no conflicts
370053	NC_012920.1(MT-ND4):m.11815C>G	MT-ND4	Uncertain significance	no assertion criteria provided
370056	NC_012920.1(MT-ND4):m.12013A>G	MT-ND4	Uncertain significance	no assertion criteria provided
370057	NC_012920.1(MT-ND4):m.12018C>G	MT-ND4	Uncertain significance	no assertion criteria provided
692156	NM_013386.5(SLC25A24):c.1273C>A (p.Leu425Met)	SLC25A24	Uncertain significance	criteria provided, single submitter
374122	NM_003332.4(TYROBP):c.94G>A (p.Asp32Asn)	TYROBP	Uncertain significance	criteria provided, multiple submitters, no conflicts
779587	NM_020806.5(GPHN):c.1144+9A>G	GPHN	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 45 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BIN1	Orphanet:169186	Autosomal recessive centronuclear myopathy
BIN1	Orphanet:169189	Autosomal dominant centronuclear myopathy
TYROBP	Orphanet:2770	Nasu-Hakola disease
JPH3	Orphanet:98934	Huntington disease-like 2
GPHN	Orphanet:308400	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C
GPHN	Orphanet:3197	Hereditary hyperekplexia
APOA5	Orphanet:530849	Familial apolipoprotein A5 deficiency
SLC25A24	Orphanet:2095	Gorlin-Chaudhry-Moss syndrome
SLC25A24	Orphanet:2963	Progeroid syndrome, Petty type
CNTN1	Orphanet:210163	Congenital lethal myopathy, Compton-North type
GBA1	Orphanet:2072	Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
GBA1	Orphanet:411602	Hereditary late-onset Parkinson disease
GBA1	Orphanet:77259	Gaucher disease type 1
GBA1	Orphanet:77260	Gaucher disease type 2
GBA1	Orphanet:77261	Gaucher disease type 3
GBA1	Orphanet:85212	Fetal Gaucher disease
GBE1	Orphanet:206583	Adult polyglucosan body disease
GBE1	Orphanet:308621	Glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form
GBE1	Orphanet:308638	Glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form
GBE1	Orphanet:308655	Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form
GBE1	Orphanet:308670	Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form
GBE1	Orphanet:308684	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form
GBE1	Orphanet:308698	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form
GBE1	Orphanet:308712	Glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form
MAPT	Orphanet:100069	Semantic dementia
MAPT	Orphanet:100070	Progressive non-fluent aphasia
MAPT	Orphanet:240071	Classic progressive supranuclear palsy syndrome
MAPT	Orphanet:240085	Progressive supranuclear palsy-predominant parkinsonism syndrome
MAPT	Orphanet:240094	Progressive supranuclear palsy-pure akinesia with gait freezing syndrome
MAPT	Orphanet:240103	Progressive supranuclear palsy-corticobasal syndrome
MAPT	Orphanet:240112	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome
MAPT	Orphanet:275864	Behavioral variant of frontotemporal dementia
MRE11	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
MRE11	Orphanet:240760	Nijmegen breakage syndrome-like disorder
MRE11	Orphanet:251347	Ataxia-telangiectasia-like disorder
MT-ND4	Orphanet:104	Leber hereditary optic neuropathy
MT-ND4	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ND4	Orphanet:550	MELAS
MT-ND4	Orphanet:90641	Rare mitochondrial non-syndromic sensorineural deafness
MT-ND4	Orphanet:99718	Leber plus disease
PSEN1	Orphanet:100069	Semantic dementia
PSEN1	Orphanet:100070	Progressive non-fluent aphasia
PSEN1	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
PSEN1	Orphanet:154	Familial isolated dilated cardiomyopathy
PSEN1	Orphanet:275864	Behavioral variant of frontotemporal dementia

Cohort genes → proteins

25 cohort genes, 25 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	15
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BIN1	HGNC:1052	ENSG00000136717	O00499	Myc box-dependent-interacting protein 1	gwas
SLCO3A1	HGNC:10952	ENSG00000176463	Q9UIG8	Solute carrier organic anion transporter family member 3A1	gwas
TYROBP	HGNC:12449	ENSG00000011600	O43914	TYRO protein tyrosine kinase-binding protein	clinvar
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
JPH3	HGNC:14203	ENSG00000154118	Q8WXH2	Junctophilin-3	gwas
GPHN	HGNC:15465	ENSG00000171723	Q9NQX3	Gephyrin	clinvar
SMOX	HGNC:15862	ENSG00000088826	Q9NWM0	Spermine oxidase	gwas
OSBPL1A	HGNC:16398	ENSG00000141447	Q9BXW6	Oxysterol-binding protein-related protein 1	gwas
APOA5	HGNC:17288	ENSG00000110243	Q6Q788	Apolipoprotein A-V	clinvar
ARMH4	HGNC:19846	ENSG00000139971	Q86TY3	Armadillo-like helical domain-containing protein 4	gwas
SLC25A24	HGNC:20662	ENSG00000085491	Q6NUK1	Mitochondrial adenyl nucleotide antiporter SLC25A24	clinvar
CNTN1	HGNC:2171	ENSG00000018236	Q12860	Contactin-1	gwas
PHF21B	HGNC:25161	ENSG00000056487	Q96EK2	PHD finger protein 21B	gwas
ADSS2	HGNC:292	ENSG00000035687	P30520	Adenylosuccinate synthetase isozyme 2	gwas
DYNC1I1	HGNC:2963	ENSG00000158560	O14576	Cytoplasmic dynein 1 intermediate chain 1	gwas
GALNT2	HGNC:4124	ENSG00000143641	Q10471	Polypeptide N-acetylgalactosaminyltransferase 2	gwas
GBA1	HGNC:4177	ENSG00000177628	P04062	Lysosomal acid glucosylceramidase	clinvar
GBE1	HGNC:4180	ENSG00000114480	Q04446	1,4-alpha-glucan-branching enzyme	clinvar
MAPT	HGNC:6893	ENSG00000186868	P10636	Microtubule-associated protein tau	clinvar
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	clinvar
ABCG1	HGNC:73	ENSG00000160179	P45844	ATP-binding cassette sub-family G member 1	gwas
MTIF2	HGNC:7441	ENSG00000085760	P46199	Translation initiation factor IF-2, mitochondrial	gwas
MT-ND4	HGNC:7459	ENSG00000198886	C0HME5	Mitochondrial alternative ND4 protein	clinvar
PSEN1	HGNC:9508	ENSG00000080815	P49768	Presenilin-1	clinvar
NECTIN2	HGNC:9707	ENSG00000130202	Q92692	Nectin-2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BIN1	Myc box-dependent-interacting protein 1	Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling.
SLCO3A1	Solute carrier organic anion transporter family member 3A1	Putative organic anion antiporter with apparent broad substrate specificity.
TYROBP	TYRO protein tyrosine kinase-binding protein	Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
JPH3	Junctophilin-3	Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells.
GPHN	Gephyrin	Microtubule-associated protein involved in membrane protein-cytoskeleton interactions.
SMOX	Spermine oxidase	Flavoenzyme which catalyzes the oxidation of spermine to spermidine.
OSBPL1A	Oxysterol-binding protein-related protein 1	Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate.
APOA5	Apolipoprotein A-V	Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL.
ARMH4	Armadillo-like helical domain-containing protein 4	May modulate immune response and may play a role in inflammation.
SLC25A24	Mitochondrial adenyl nucleotide antiporter SLC25A24	Electroneutral antiporter that mediates the transport of adenyl nucleotides through the inner mitochondrial membrane.
CNTN1	Contactin-1	Contactins mediate cell surface interactions during nervous system development.
ADSS2	Adenylosuccinate synthetase isozyme 2	Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis.
DYNC1I1	Cytoplasmic dynein 1 intermediate chain 1	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function.
GALNT2	Polypeptide N-acetylgalactosaminyltransferase 2	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
GBA1	Lysosomal acid glucosylceramidase	Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose.
GBE1	1,4-alpha-glucan-branching enzyme	Glycogen-branching enzyme participates in the glycogen biosynthetic process along with glycogenin and glycogen synthase.
MAPT	Microtubule-associated protein tau	Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity.
MRE11	Double-strand break repair protein MRE11	Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
ABCG1	ATP-binding cassette sub-family G member 1	Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP.
MTIF2	Translation initiation factor IF-2, mitochondrial	One of the essential components for the initiation of protein synthesis.
MT-ND4	Mitochondrial alternative ND4 protein	Regulates mitochondrial respiration by decreasing oxygen consumption.
PSEN1	Presenilin-1	Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein).
NECTIN2	Nectin-2	Modulator of T-cell signaling.

Protein-family classification

Druggable: 10 · Difficult: 5 · Unknown: 10 · Druggable fraction: 0.4

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
Transporter	2	6.2×	0.210
Antibody/Immunoglobulin	3	3.5×	0.210
Complement	1	10.7×	0.238
Scaffold/PPI	3	2.1×	0.347
Enzyme (other)	3	1.4×	0.555
Protease	1	1.5×	0.666
Transcription factor	2	0.7×	0.942
Other/Unknown	10	0.7×	0.963

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BIN1	Scaffold/PPI	no		SH3_domain, Amphiphysin, Amphiphysin_2
SLCO3A1	Transporter	yes		Kazal_dom, OATP, Kazal_dom_sf
TYROBP	Other/Unknown	no		Tyrobp
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
JPH3	Other/Unknown	no		MORN, Junctophilin
GPHN	Other/Unknown	no		MoaB/Mog_dom, MoeA_linker/N, MoeA_C_domain_IV
SMOX	Enzyme (other)	yes	1.5.3.16	Amino_oxidase, FAD/NAD-bd_sf, Flavin_monoamine_oxidase
OSBPL1A	Scaffold/PPI	no		Oxysterol-bd, PH_domain, Ankyrin_rpt
APOA5	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E
ARMH4	Other/Unknown	no		ARMH4
SLC25A24	Other/Unknown	no		EF_hand_dom, MCP, GDC-like
CNTN1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
PHF21B	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
ADSS2	Other/Unknown	no		Adenylosuccinate_synthetase, Adenylosuccin_syn_GTP-bd, P-loop_NTPase
DYNC1I1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, DYNC1I1/DYNC1I2
GALNT2	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
GBA1	Enzyme (other)	yes	3.2.1.45	Glyco_hydro_30, GH_hydrolase_sf, GH30_C
GBE1	Antibody/Immunoglobulin	yes		Glyco_hydro_13_N, GH13_cat_dom, A-amylase/branching_C
MAPT	Other/Unknown	no		MAP_tubulin-bd_rpt, Tau, MAP2/MAP4/Tau
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd
ABCG1	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, Pigment_permease/Abcg
MTIF2	Transcription factor	no		TF_IF2_bacterial-like, T_Tr_GTP-bd_dom, Small_GTP-bd
MT-ND4	Other/Unknown	no		NADH4_N, ND/Mrp_TM, NADH_UbQ_OxRdtase
PSEN1	Protease	yes		Peptidase_A22A, Pept_A22A_PS1, Preselin/SPP
NECTIN2	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set

Expression context

Cohort genes with no expression data: 0.

22 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	25
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	4
C1 segment of cervical spinal cord	3
endothelial cell	3
skeletal muscle tissue of rectus abdominis	2
leukocyte	2
monocyte	2
mononuclear cell	2
Brodmann (1909) area 23	2
lower esophagus mucosa	2
corpus callosum	2
calcaneal tendon	2
islet of Langerhans	2
stromal cell of endometrium	2
biceps brachii	2
gastrocnemius	1
hindlimb stylopod muscle	1
buccal mucosa cell	1
middle temporal gyrus	1
primary visual cortex	1
parietal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BIN1	287	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
SLCO3A1	279	ubiquitous	marker	buccal mucosa cell, endothelial cell, C1 segment of cervical spinal cord
TYROBP	271	broad	marker	monocyte, mononuclear cell, leukocyte
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
JPH3	166	broad	yes	right frontal lobe, postcentral gyrus, parietal lobe
GPHN	270	ubiquitous	marker	cerebellar cortex, cerebellar hemisphere, right hemisphere of cerebellum
SMOX	258	ubiquitous	marker	amygdala, lower esophagus mucosa, C1 segment of cervical spinal cord
OSBPL1A	283	ubiquitous	marker	corpus callosum, medial globus pallidus, globus pallidus
APOA5	45	tissue_specific	yes	right lobe of liver, liver, skeletal muscle tissue of rectus abdominis
ARMH4	198	ubiquitous	marker	cortical plate, calcaneal tendon, adrenal tissue
SLC25A24	138	ubiquitous	yes	rectum, duodenum, islet of Langerhans
CNTN1	228	broad	marker	cortical plate, Brodmann (1909) area 23, endothelial cell
PHF21B	152	broad	marker	ganglionic eminence, adenohypophysis, pituitary gland
ADSS2	285	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
DYNC1I1	242	broad	marker	endothelial cell, pons, cortical plate
GALNT2	285	ubiquitous	marker	descending thoracic aorta, thoracic aorta, ascending aorta
GBA1	134	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, placenta
GBE1	293	ubiquitous	marker	gluteal muscle, tibialis anterior, biceps brachii
MAPT	141	broad	marker	cortical plate, superior frontal gyrus, prefrontal cortex
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte
ABCG1	270	ubiquitous	marker	right adrenal gland, left adrenal gland, right adrenal gland cortex
MTIF2	294	ubiquitous	marker	esophagus squamous epithelium, squamous epithelium, biceps brachii
MT-ND4	134	ubiquitous	marker	right uterine tube, apex of heart, zone of skin
PSEN1	287	ubiquitous	marker	middle frontal gyrus, corpus callosum, C1 segment of cervical spinal cord
NECTIN2	267	ubiquitous	marker	lower esophagus mucosa, stromal cell of endometrium, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPT	7,289
MTIF2	4,176
MRE11	3,932
PSEN1	3,732
BIN1	3,571
GBE1	3,402
TYROBP	2,723
CNTN1	2,717
ADSS2	2,681
GBA1	2,568

Intra-cohort edges

A	B	Sources
ADSS2	MAPT	intact
APOA5	GALNT2	string_interaction
MAPT	PSEN1	string_interaction

Structural data

PDB: 19 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPT	P10636	293
GBA1	P04062	58
PSEN1	P49768	27
GALNT2	Q10471	13
MTIF2	P46199	11
MRE11	P49959	10
BIN1	O00499	7
MT-ND4	C0HME5	7
NECTIN2	Q92692	7
OSBPL1A	Q9BXW6	6
TYROBP	O43914	5
ABCG1	P45844	5
SLC25A24	Q6NUK1	3
GBE1	Q04446	3
SMOX	Q9NWM0	2
CNTN1	Q12860	2
CSMD1	Q96PZ7	1
GPHN	Q9NQX3	1
ADSS2	P30520	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLCO3A1	Q9UIG8	75.19
APOA5	Q6Q788	72.38
DYNC1I1	O14576	71.20
JPH3	Q8WXH2	61.52
PHF21B	Q96EK2	60.69
ARMH4	Q86TY3	43.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 133. Enrichment computed across 25 evidence-associated genes (20 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 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Plasma lipoprotein remodeling	2	47.6×	0.061	APOA5, ABCG1
NOTCH2 Activation and Transmission of Signal to the Nucleus	2	43.9×	0.061	CNTN1, PSEN1
Activated NOTCH1 Transmits Signal to the Nucleus	2	35.7×	0.062	CNTN1, PSEN1
PAOs oxidise polyamines to amines	1	190.3×	0.100	SMOX
Glycogen storage disease type IV (GBE1)	1	190.3×	0.100	GBE1
Plasma lipoprotein assembly, remodeling, and clearance	2	22.8×	0.100	APOA5, ABCG1
COPI-independent Golgi-to-ER retrograde traffic	2	20.8×	0.100	DYNC1I1, GALNT2
Interconversion of polyamines	1	142.8×	0.108	SMOX
Sensing of DNA Double Strand Breaks	1	95.2×	0.108	MRE11
Molybdenum cofactor biosynthesis	1	81.6×	0.108	GPHN
Nectin/Necl trans heterodimerization	1	71.4×	0.108	NECTIN2
Neurofascin interactions	1	71.4×	0.108	CNTN1
Noncanonical activation of NOTCH3	1	71.4×	0.108	PSEN1
Chylomicron remodeling	1	57.1×	0.108	APOA5
HDL remodeling	1	57.1×	0.108	ABCG1
STING mediated induction of host immune responses	1	51.9×	0.108	MRE11
Regulated proteolysis of p75NTR	1	51.9×	0.108	PSEN1
Purine ribonucleoside monophosphate biosynthesis	1	51.9×	0.108	ADSS2
Organic anion transport by SLCO transporters	1	51.9×	0.108	SLCO3A1
NOTCH4 Activation and Transmission of Signal to the Nucleus	1	51.9×	0.108	PSEN1
Caspase-mediated cleavage of cytoskeletal proteins	1	47.6×	0.108	MAPT
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	47.6×	0.108	MRE11
TGFBR3 PTM regulation	1	47.6×	0.108	PSEN1
HDR through MMEJ (alt-NHEJ)	1	43.9×	0.108	MRE11
IRF3-mediated induction of type I IFN	1	40.8×	0.108	MRE11
Glycogen synthesis	1	40.8×	0.108	GBE1
Diseases of DNA Double-Strand Break Repair	1	40.8×	0.108	MRE11
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	40.8×	0.108	MRE11
MHC class II antigen presentation	2	8.9×	0.108	OSBPL1A, DYNC1I1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	2	8.7×	0.108	TYROBP, NECTIN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cholesterol metabolic process	4	32.7×	0.002	OSBPL1A, APOA5, GBA1, ABCG1
memory	4	30.5×	0.002	CSMD1, JPH3, MAPT, PSEN1
cerebellum development	3	44.8×	0.005	CNTN1, MT-ND4, PSEN1
locomotion	2	127.7×	0.008	JPH3, PSEN1
regulation of synaptic plasticity	3	32.4×	0.008	JPH3, MAPT, PSEN1
mitochondrial transport	2	100.3×	0.010	SLC25A24, PSEN1
amyloid precursor protein catabolic process	2	100.3×	0.010	ABCG1, PSEN1
phospholipid efflux	2	93.6×	0.010	APOA5, ABCG1
astrocyte activation	2	82.6×	0.011	MAPT, PSEN1
positive regulation of superoxide anion generation	2	73.9×	0.013	TYROBP, MAPT
brain morphogenesis	2	61.1×	0.017	GBA1, PSEN1
myeloid leukocyte activation	1	702.2×	0.025	TYROBP
coreceptor-mediated virion attachment to host cell	1	702.2×	0.025	NECTIN2
response to ammonium ion	1	702.2×	0.025	ADSS2
plus-end-directed organelle transport along microtubule	1	702.2×	0.025	MAPT
glycine receptor clustering	1	702.2×	0.025	GPHN
mitochondrial double-strand break repair via homologous recombination	1	702.2×	0.025	MRE11
regulation of TORC2 signaling	1	702.2×	0.025	ARMH4
negative regulation of ventricular cardiac muscle cell action potential	1	702.2×	0.025	BIN1
positive regulation of neuronal action potential	1	702.2×	0.025	GBA1
cholesterol efflux	2	43.9×	0.025	APOA5, ABCG1
negative regulation of neuron apoptotic process	3	13.9×	0.025	GBA1, GBE1, PSEN1
cellular response to amyloid-beta	2	32.7×	0.028	TYROBP, PSEN1
regulation of mitotic recombination	1	351.1×	0.029	MRE11
positive regulation of L-glutamate import across plasma membrane	1	351.1×	0.029	PSEN1
stimulatory killer cell immunoglobulin-like receptor signaling pathway	1	351.1×	0.029	TYROBP
establishment of synaptic specificity at neuromuscular junction	1	351.1×	0.029	GPHN
positive regulation of very-low-density lipoprotein particle remodeling	1	351.1×	0.029	APOA5
cerebellar Purkinje cell layer formation	1	351.1×	0.029	GBA1
Cajal-Retzius cell differentiation	1	351.1×	0.029	PSEN1

Therapeutics

Drugs indicated for this disease

9 approved, 94 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aducanumab	Approved (phase 4)
Donanemab	Approved (phase 4)
Donepezil	Approved (phase 4)
Galantamine	Approved (phase 4)
Ginkgo	Approved (phase 4)
Lecanemab	Approved (phase 4)
Memantine	Approved (phase 4)
Rivastigmine	Approved (phase 4)
Tacrine	Approved (phase 4)
Acamprosate	Phase 3 (in late-stage trials)
Agomelatine	Phase 3 (in late-stage trials)
Alprazolam	Phase 3 (in late-stage trials)
Amisulpride	Phase 3 (in late-stage trials)
Amitriptyline	Phase 3 (in late-stage trials)
Aripiprazole	Phase 3 (in late-stage trials)
Benperidol	Phase 3 (in late-stage trials)
Biperiden	Phase 3 (in late-stage trials)
Bromazepam	Phase 3 (in late-stage trials)
Bromperidol	Phase 3 (in late-stage trials)
Brotizolam	Phase 3 (in late-stage trials)
Bupropion	Phase 3 (in late-stage trials)
Buspirone	Phase 3 (in late-stage trials)
Carbamazepine	Phase 3 (in late-stage trials)
Chloral Hydrate	Phase 3 (in late-stage trials)
Chlorprothixene	Phase 3 (in late-stage trials)
Citalopram	Phase 3 (in late-stage trials)
Clobazam	Phase 3 (in late-stage trials)
Clomethiazole	Phase 3 (in late-stage trials)
Clomipramine	Phase 3 (in late-stage trials)
Clonazepam	Phase 3 (in late-stage trials)
Clozapine	Phase 3 (in late-stage trials)
Diazepam	Phase 3 (in late-stage trials)
Diphenhydramine	Phase 3 (in late-stage trials)
Doxepin	Phase 3 (in late-stage trials)
Duloxetine	Phase 3 (in late-stage trials)
Encenicline	Phase 3 (in late-stage trials)
Escitalopram	Phase 3 (in late-stage trials)
Fluoxetine	Phase 3 (in late-stage trials)
Flupentixol	Phase 3 (in late-stage trials)
Fluphenazine Enanthate	Phase 3 (in late-stage trials)
Flurazepam	Phase 3 (in late-stage trials)
Fluspirilene	Phase 3 (in late-stage trials)
Fluvoxamine	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Haloperidol	Phase 3 (in late-stage trials)
Hydroxyzine	Phase 3 (in late-stage trials)
Imipramine	Phase 3 (in late-stage trials)
Lacosamide	Phase 3 (in late-stage trials)
Lamotrigine	Phase 3 (in late-stage trials)
Levetiracetam	Phase 3 (in late-stage trials)
Levomepromazine	Phase 3 (in late-stage trials)
Lithium Carbonate	Phase 3 (in late-stage trials)
Lorazepam	Phase 3 (in late-stage trials)
Lormetazepam	Phase 3 (in late-stage trials)
Maprotiline	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Melperone	Phase 3 (in late-stage trials)
Methylphenidate	Phase 3 (in late-stage trials)
Mianserin	Phase 3 (in late-stage trials)
Midazolam	Phase 3 (in late-stage trials)
Mirtazapine	Phase 3 (in late-stage trials)
Moclobemide	Phase 3 (in late-stage trials)
Nicergoline	Phase 3 (in late-stage trials)
Nitrazepam	Phase 3 (in late-stage trials)
Nortriptyline	Phase 3 (in late-stage trials)
Olanzapine	Phase 3 (in late-stage trials)
Opipramol	Phase 3 (in late-stage trials)
Oxazepam	Phase 3 (in late-stage trials)
Oxcarbazepine	Phase 3 (in late-stage trials)
Paliperidone	Phase 3 (in late-stage trials)
Paroxetine	Phase 3 (in late-stage trials)
Perazine	Phase 3 (in late-stage trials)
Perphenazine	Phase 3 (in late-stage trials)
Phenobarbital	Phase 3 (in late-stage trials)
Phenytoin	Phase 3 (in late-stage trials)
Pimozide	Phase 3 (in late-stage trials)
Pipamperone	Phase 3 (in late-stage trials)
Piracetam	Phase 3 (in late-stage trials)
Pregabalin	Phase 3 (in late-stage trials)
Promethazine	Phase 3 (in late-stage trials)
Prothipendyl	Phase 3 (in late-stage trials)
Pyritinol	Phase 3 (in late-stage trials)
Quetiapine	Phase 3 (in late-stage trials)
Reboxetine	Phase 3 (in late-stage trials)
Risperidone	Phase 3 (in late-stage trials)
Sertindole	Phase 3 (in late-stage trials)
Sertraline	Phase 3 (in late-stage trials)
Sulpiride	Phase 3 (in late-stage trials)
Tarenflurbil	Phase 3 (in late-stage trials)
Temazepam	Phase 3 (in late-stage trials)
Thioridazine	Phase 3 (in late-stage trials)
Tiapride	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)
Tranylcypromine	Phase 3 (in late-stage trials)
Trazodone	Phase 3 (in late-stage trials)
Triazolam	Phase 3 (in late-stage trials)
Trimipramine	Phase 3 (in late-stage trials)
Valproic Acid	Phase 3 (in late-stage trials)
Zaleplon	Phase 3 (in late-stage trials)
Ziprasidone	Phase 3 (in late-stage trials)
Zolpidem	Phase 3 (in late-stage trials)
Zopiclone	Phase 3 (in late-stage trials)
Zuclopenthixol	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ambroxol, Cannabinol, Dronabinol, Fasudil, Intepirdine, Megestrol Acetate, Nicorandil, Onabotulinumtoxina, Ondansetron, Rimabotulinumtoxinb, Roflumilast, Sodium Chloride.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 4 · Undrugged: 21

Druggability breadth: 10 of 25 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
GBA1	MIGALASTAT
MAPT	BEPRIDIL
PSEN1	NIROGACESTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPT	449	4
GBA1	12	4
PSEN1	8	4
GALNT2	2	2
BIN1	0	0
SLCO3A1	0	0
TYROBP	0	0
CSMD1	0	0
JPH3	0	0
GPHN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MIGALASTAT	4	GBA1
GLUCONOLACTONE	4	GBA1
MIGLITOL	4	GBA1
MEXILETINE	4	GBA1
GENTIAN VIOLET	4	GBA1, MAPT
CHLORHEXIDINE	4	GBA1
TAMOXIFEN	4	GBA1, MAPT
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT
INDIGOTINDISULFONATE	4	MAPT
TRIHEXYPHENIDYL HYDROCHLORIDE	4	MAPT
IMIPRAMINE	4	MAPT
FURAZOLIDONE	4	MAPT
DROPERIDOL	4	MAPT
ARIPIPRAZOLE	4	MAPT
RALOXIFENE HYDROCHLORIDE	4	MAPT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PSEN1	557	Binding:538, Functional:12, ADMET:6, Unclassified:1
GBA1	436	Binding:403, Functional:33
MAPT	184	Binding:180, Functional:4
MRE11	36	Binding:36
GALNT2	19	Binding:19
SMOX	18	Binding:15, ADMET:3
SLCO3A1	9	Functional:9
ADSS2	2	Binding:2
CNTN1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SMOX	1.5.3.16	spermine oxidase
GALNT2	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
GBA1	3.2.1.45	glucosylceramidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GBA1	436
MAPT	184
PSEN1	557

Pharmacogenomics

Cohort genes with a PharmGKB record: 25; 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)
MIGALASTAT	4	GBA1
GLUCONOLACTONE	4	GBA1
MIGLITOL	4	GBA1
MEXILETINE	4	GBA1
GENTIAN VIOLET	4	GBA1, MAPT
CHLORHEXIDINE	4	GBA1
TAMOXIFEN	4	GBA1, MAPT
BEPRIDIL	4	MAPT
PHENYLBUTAZONE	4	MAPT
CEFOTAXIME SODIUM	4	MAPT
DIENESTROL	4	MAPT
PROGESTERONE	4	MAPT
CLOTRIMAZOLE	4	MAPT
CHOLECALCIFEROL	4	MAPT
LATANOPROST	4	MAPT
CHLORTHALIDONE	4	MAPT
FLUORESCEIN	4	MAPT
OXCARBAZEPINE	4	MAPT
NABUMETONE	4	MAPT
GLIPIZIDE	4	MAPT
AMIODARONE HYDROCHLORIDE	4	MAPT
TRICLABENDAZOLE	4	MAPT
MESORIDAZINE	4	MAPT
INDIGOTINDISULFONATE	4	MAPT
TRIHEXYPHENIDYL HYDROCHLORIDE	4	MAPT
IMIPRAMINE	4	MAPT
FURAZOLIDONE	4	MAPT
DROPERIDOL	4	MAPT
ARIPIPRAZOLE	4	MAPT
RALOXIFENE HYDROCHLORIDE	4	MAPT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	GBA1, MAPT, PSEN1
B	Phased (≥1) drug, not yet approved	1	GALNT2
C	Druggable family + PDB, no drug	6	CSMD1, SMOX, CNTN1, GBE1, ABCG1, NECTIN2
D	Druggable family + AlphaFold only, no drug	1	SLCO3A1
E	Difficult family or no structure, no drug	14	BIN1, TYROBP, JPH3, GPHN, OSBPL1A, APOA5, ARMH4, SLC25A24, PHF21B, ADSS2 (+4 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BIN1	0	—
SLCO3A1	9	—
TYROBP	0	—
CSMD1	0	—
JPH3	0	—
GPHN	0	—
SMOX	18	—
OSBPL1A	0	—
APOA5	0	—
ARMH4	0	—
SLC25A24	0	—
CNTN1	1	—
PHF21B	0	—
ADSS2	2	—
DYNC1I1	0	—
GBE1	0	—
MRE11	36	—
ABCG1	0	—
MTIF2	0	—
MT-ND4	0	—
NECTIN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,542.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	871
PHASE2	67
PHASE3	48
PHASE4	41
PHASE1	36
PHASE2/PHASE3	17
PHASE1/PHASE2	15
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01453127	PHASE4	ENROLLING_BY_INVITATION	DaTSCAN Imaging in Aging and Neurodegenerative Disease
NCT04262206	PHASE4	RECRUITING	Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults
NCT05514106	PHASE4	ENROLLING_BY_INVITATION	MIBG in Aging and Neurologic Disorders
NCT05855863	PHASE4	NOT_YET_RECRUITING	Clinical Study of GKT in Diabetes Related Dementia
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT06662526	PHASE4	NOT_YET_RECRUITING	Lithium for Prevention of Cognitive Declining in Mood Illnesses
NCT07485283	PHASE4	RECRUITING	Recombinant Herpes Zoster Vaccine for Prevention of Cardiovascular Events and Dementia
NCT00043849	PHASE4	COMPLETED	Treatment of Agitation/Psychosis in Dementia/Parkinsonism (TAP/DAP)
NCT00127114	PHASE4	WITHDRAWN	Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD)
NCT00164970	PHASE4	COMPLETED	Can Oral Vitamin B12 and Folate Supplementation Preserve Cognitive Function of Patients With Early Dementia?
NCT00177671	PHASE4	COMPLETED	Antidepressant Medication Plus Donepezil for Treating Late-life Depression
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00371059	PHASE4	COMPLETED	Memantine for Agitation in Dementia
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00433121	PHASE4	COMPLETED	Discontinuation of Antipsychotics and Antidepressants Among Patients With BPSD
NCT00450047	PHASE4	COMPLETED	Study on the Efficacy of Speed-Feedback Therapy for Elderly People With Dementia
NCT00495820	PHASE4	COMPLETED	Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study
NCT00594269	PHASE4	COMPLETED	Dementia Antipsychotics And Antidepressants Discontinuation Study
NCT00626613	PHASE4	UNKNOWN	The Relationship Between Risperdal Treatment and Quality of Life in Patients With Alzheimer’s Disease and Behavioural and Psychological Symptoms of Dementia (BPSD)
NCT00768261	PHASE4	COMPLETED	Corticolimbic Degeneration and Treatment of Dementia
NCT00792662	PHASE4	WITHDRAWN	Improving Function, Quality of Life, Glycemia in Diabetics With Dementia
NCT00814658	PHASE4	COMPLETED	The Use of Galantamine (Reminyl ER) in Patients With MIXed Dementia: Effects on Cognition and Quality of Life
NCT00914095	PHASE4	COMPLETED	Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson’s Disease (PARKGAIT-II)
NCT01012830	PHASE4	UNKNOWN	Huperzine-A to Help With Mental Problems and the Inability to Care for Onself in Patients With Schizophrenia
NCT01109836	PHASE4	COMPLETED	Austrian Polyintervention Study to Prevent Cognitive Decline After Ischemic Stroke
NCT01340950	PHASE4	COMPLETED	Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
NCT01799941	PHASE4	COMPLETED	Safety, Tolerability and Effectiveness of Nuedexta in the Treatment of Pseudobulbar Affect (PBA)
NCT01825577	PHASE4	TERMINATED	Exploring the Use of Transdermal Methylphenidate to Reduce Fall Risk in Patients With Dementia.
NCT01849042	PHASE4	UNKNOWN	Effect of Memantine Oral Pump on Language in Patients With Probable Alzheimer’s Disease
NCT02267057	PHASE4	COMPLETED	Efficacy of Pain Treatment on Depression in Patients With Dementia
NCT02782429	PHASE4	UNKNOWN	The Role of Ketamine in Preventing Cognitive Dysfunctions in Postoperative Period of Cardiac Surgery
NCT03061006	PHASE4	COMPLETED	Impact of Anticoagulation Therapy on the Cognitive Decline and Dementia in Patients With Non-Valvular Atrial Fibrillation
NCT03066518	PHASE4	COMPLETED	Effect of Melatonin on Sleep Quality in Patients Dementia
NCT03221751	PHASE4	TERMINATED	Prazosin and Cerebrospinal Fluid (CSF) Biomarkers in Mild Traumatic Brain Injury (mTBI)
NCT03817931	PHASE4	COMPLETED	Higher Neural Changes Following Anticholinergic, Beta 3 Agonist, or Placebo in Patients With Overactive Bladder
NCT04117178	PHASE4	COMPLETED	Monitoring Anti-Dementia Drugs by Serum Levels
NCT04294654	PHASE4	COMPLETED	Vortioxetine in Patients With Depression and Early Dementia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GALANTAMINE	4	16
CITALOPRAM	4	15
RIVASTIGMINE	4	9
DONEPEZIL	4	7
MEMANTINE	4	7
BUPROPION	4	6
VENLAFAXINE	4	6
METHYLPHENIDATE	4	5
RISPERIDONE	4	5
DONANEMAB	4	4
PAROXETINE	4	4
QUETIAPINE	4	4
DIVALPROEX SODIUM	4	3
ESCITALOPRAM	4	3
FLUTEMETAMOL	4	3
LECANEMAB	4	3
MIRTAZAPINE	4	3
OLANZAPINE	4	3
FLORBETABEN F18	4	2
FLORBETAPIR F 18	4	2
GINKGO	4	2
HALOPERIDOL	4	2
LORAZEPAM	4	2
MELATONIN	4	2
NICERGOLINE	4	2
PERPHENAZINE	4	2
PIRACETAM	4	2
ROFLUMILAST	4	2
ACAMPROSATE	4	1
ACETAMINOPHEN	4	1