Alzheimer disease type 1

disease

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Also known as ADAD1Alzheimer disease 1Alzheimer disease 1, familialAlzheimer disease, familial, 1early-onset familial form of Alzheimer disease

Summary

Alzheimer disease type 1 (MONDO:0007088) is a disease caused by APP (GenCC Strong), with 10 cohort genes and 21 clinical trials. Top therapeutic interventions include donepezil, methylene blue cation, and phenazopyridine.

At a glance

Causal gene: APP (GenCC Strong)
Cohort genes: 10
ClinVar variants: 59
Clinical trials: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Alzheimer disease type 1
Mondo ID	MONDO:0007088
MeSH	C536594
OMIM	104300
DOID	DOID:0080348
UMLS	C1863052
MedGen	354892
GARD	0009465
Is cancer (heuristic)	no

Also known as: AD · AD1 · Alzheimer disease 1 · Alzheimer disease 1, familial · Alzheimer disease, familial, 1 · early-onset familial form of Alzheimer disease

Data availability: 59 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › early-onset autosomal dominant Alzheimer disease › Alzheimer disease type 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

59 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 10 pathogenic, 7 conflicting classifications of pathogenicity, 6 likely pathogenic, 5 pathogenic/likely pathogenic, 5 benign/likely benign, 2 benign, 1 likely benign, 1 conflicting classifications of pathogenicity; other; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
18088	NM_000484.4(APP):c.2149G>A (p.Val717Ile)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18089	NM_000484.4(APP):c.2149G>T (p.Val717Phe)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18090	NM_000484.4(APP):c.2150T>G (p.Val717Gly)	APP	Pathogenic	criteria provided, single submitter
18091	NM_000484.4(APP):c.2075C>G (p.Ala692Gly)	APP	Pathogenic	no assertion criteria provided
18093	NM_000484.4(APP):c.2010_2011inv (p.Lys670_Met671delinsAsnLeu)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18096	NM_000484.4(APP):c.2146A>G (p.Ile716Val)	APP	Pathogenic	criteria provided, single submitter
18097	NM_000484.4(APP):c.2143G>A (p.Val715Met)	APP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18098	NM_000484.4(APP):c.2078A>G (p.Glu693Gly)	APP	Pathogenic	no assertion criteria provided
18100	NM_000484.4(APP):c.2141C>T (p.Thr714Ile)	APP	Pathogenic	criteria provided, single submitter
18102	NM_000484.4(APP):c.2140A>G (p.Thr714Ala)	APP	Pathogenic	criteria provided, multiple submitters, no conflicts
18105	NM_000484.4(APP):c.2149G>C (p.Val717Leu)	APP	Pathogenic	criteria provided, single submitter
1065637	NM_000410.4(HFE):c.1006+1G>A	HFE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
407079	NM_000410.4(HFE):c.546_547del (p.Leu183fs)	HFE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3626	NM_000250.2(MPO):c.1705C>T (p.Arg569Trp)	LOC106694316	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3632	NM_000250.2(MPO):c.2031-2A>C	LPO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342870	NM_000484.4(APP):c.2155A>C (p.Thr719Pro)	APP	Likely pathogenic	criteria provided, single submitter
18094	NM_000484.4(APP):c.2137G>A (p.Ala713Thr)	APP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2628367	NM_000484.4(APP):c.2061A>C (p.Lys687Asn)	APP	Likely pathogenic	criteria provided, single submitter
3382968	NM_000484.4(APP):c.2059A>C (p.Lys687Gln)	APP	Likely pathogenic	criteria provided, single submitter
1685344	NM_000410.4(HFE):c.76+2T>C	HFE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324732	NM_000250.2(MPO):c.249-2A>G	LOC106694315	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1359826	NM_000484.4(APP):c.2020G>C (p.Glu674Gln)	APP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1372949	NM_000484.4(APP):c.1580G>A (p.Arg527Gln)	APP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1522518	NM_000484.4(APP):c.1450C>T (p.Pro484Ser)	APP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300739	NM_002658.6(PLAU):c.17C>A (p.Ala6Glu)	C10orf55	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
11	NM_000410.4(HFE):c.193A>T (p.Ser65Cys)	HFE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9	NM_000410.4(HFE):c.845G>A (p.Cys282Tyr)	HFE	Conflicting classifications of pathogenicity; other; risk factor	criteria provided, conflicting classifications
3627	NM_000250.2(MPO):c.518A>G (p.Tyr173Cys)	MPO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
489145	NM_000250.2(MPO):c.604G>T (p.Glu202Ter)	MPO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18095	NM_000484.4(APP):c.1995G>C (p.Glu665Asp)	APP	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
APP	Strong	Autosomal dominant	Alzheimer disease type 1	11
A2M	No Known Disease Relationship	Unknown	Alzheimer disease type 1

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APP	Orphanet:100006	ABeta amyloidosis, Dutch type
APP	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
APP	Orphanet:324703	ABetaL34V amyloidosis
APP	Orphanet:324708	ABeta amyloidosis, Iowa type
APP	Orphanet:324713	ABeta amyloidosis, Italian type
APP	Orphanet:324718	ABetaA21G amyloidosis
APP	Orphanet:324723	ABeta amyloidosis, Arctic type
HFE	Orphanet:443057	Sporadic porphyria cutanea tarda
HFE	Orphanet:443062	Familial porphyria cutanea tarda
HFE	Orphanet:465508	Symptomatic form of HFE-related hemochromatosis
HFE	Orphanet:586	Cystic fibrosis
HFE	Orphanet:648581	Digenic hemochromatosis
MPO	Orphanet:2587	Myeloperoxidase deficiency

Cohort genes → proteins

10 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
APP	HGNC:620	ENSG00000142192	P05067	Amyloid-beta precursor protein	gencc,clinvar
A2M	HGNC:7	ENSG00000175899	P01023	Alpha-2-macroglobulin	gencc
BLMH	HGNC:1059	ENSG00000108578	Q13867	Bleomycin hydrolase	clinvar
NANOS3	HGNC:22048	ENSG00000187556	P60323	Nanos homolog 3	clinvar
C10orf55	HGNC:31008	ENSG00000222047		chromosome 10 putative open reading frame 55	clinvar
HFE	HGNC:4886	ENSG00000010704	Q30201	Hereditary hemochromatosis protein	clinvar
HFE-AS1	HGNC:55168			HFE antisense RNA 1	clinvar
LPO	HGNC:6678	ENSG00000167419	P22079	Lactoperoxidase	clinvar
MPO	HGNC:7218	ENSG00000005381	P05164	Myeloperoxidase	clinvar
NOS3	HGNC:7876	ENSG00000164867	P29474	Nitric oxide synthase 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APP	Amyloid-beta precursor protein	Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.
A2M	Alpha-2-macroglobulin	Is able to inhibit all four classes of proteinases by a unique ’trapping’ mechanism.
BLMH	Bleomycin hydrolase	The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and maligna…
NANOS3	Nanos homolog 3	Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase.
HFE	Hereditary hemochromatosis protein	Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.
LPO	Lactoperoxidase	Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2).
MPO	Myeloperoxidase	Part of the host defense system of polymorphonuclear leukocytes.
NOS3	Nitric oxide synthase 3	Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.5

Family distribution

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

Family	Genes	Fold	FDR
Complement	1	26.8×	0.220
Protease	1	3.7×	0.442
Antibody/Immunoglobulin	1	2.9×	0.442
Enzyme (other)	2	2.4×	0.442
Transcription factor	1	0.8×	0.870
Other/Unknown	4	0.7×	0.907

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APP	Other/Unknown	no		Kunitz_BPTI, Amyloid_glyco_extra, Amyloid_glyco
A2M	Complement	yes		Macroglobln_a2, MG2, Terpenoid_cyclase/PrenylTrfase
BLMH	Protease	yes	3.4.22.40	Pept_cys_AS, Peptidase_C1B, Papain-like_cys_pep_sf
NANOS3	Transcription factor	no		Nanos/Xcar2, Znf_nanos-typ, Nanos_sf
C10orf55	Other/Unknown	no
HFE	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HFE-AS1	Other/Unknown	no
LPO	Other/Unknown	no		Haem_peroxidase_sf, Haem_peroxidase_animal, Haem_peroxidase_sf_animal
MPO	Enzyme (other)	yes	1.11.2.2	Haem_peroxidase_sf, Haem_peroxidase_animal, Haem_peroxidase_sf_animal
NOS3	Enzyme (other)	yes	1.14.13.39	Flavdoxin-like, OxRdtase_FAD/NAD-bd, Flavoprot_Pyr_Nucl_cyt_Rdtase

Expression context

Cohort genes with no expression data: 1.

8 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)	9
unknown	1

Top tissues across cohort

Tissue	Cohort genes
prefrontal cortex	2
Brodmann (1909) area 9	1
renal medulla	1
lower lobe of lung	1
upper lobe of left lung	1
upper lobe of lung	1
skin of abdomen	1
skin of leg	1
upper arm skin	1
amygdala	1
primordial germ cell in gonad	1
left testis	1
right testis	1
sperm	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
olfactory segment of nasal mucosa	1
parotid gland	1
trachea	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APP	295	ubiquitous	marker	prefrontal cortex, renal medulla, Brodmann (1909) area 9
A2M	282	broad	marker	lower lobe of lung, upper lobe of lung, upper lobe of left lung
BLMH	271	ubiquitous	marker	upper arm skin, skin of leg, skin of abdomen
NANOS3	129	broad	yes	primordial germ cell in gonad, prefrontal cortex, amygdala
C10orf55	122		marker	sperm, left testis, right testis
HFE	238	ubiquitous	marker	type B pancreatic cell, olfactory bulb, stromal cell of endometrium
HFE-AS1
LPO	105	tissue_specific	marker	parotid gland, olfactory segment of nasal mucosa, trachea
MPO	157	broad	marker	trabecular bone tissue, bone marrow cell, bone marrow
NOS3	168	broad	marker	spleen, apex of heart, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APP	11,686
NOS3	3,606
MPO	3,383
A2M	3,063
BLMH	1,616
HFE	1,569
NANOS3	932
LPO	677
C10orf55	0
HFE-AS1	0

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APP	P05067	256
NOS3	P29474	105
MPO	P05164	49
A2M	P01023	13
BLMH	Q13867	6
HFE	Q30201	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LPO	P22079	92.43
NANOS3	P60323	71.75

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 94. Enrichment computed across 10 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Events associated with phagocytolytic activity of PMN cells	2	1427.5×	4e-05	LPO, MPO
NOSIP mediated eNOS trafficking	1	713.8×	0.033	NOS3
Aggregated β-amyloid induces FXII autocatalysis	1	713.8×	0.033	APP
Response to elevated platelet cytosolic Ca2+	2	40.8×	0.033	APP, A2M
Aggregated β-amyloid interacts with fibrinogen	1	356.9×	0.041	APP
NOSTRIN mediated eNOS trafficking	1	285.5×	0.041	NOS3
R-HSA-140837	1	178.4×	0.041	A2M
Formyl peptide receptors bind formyl peptides and many other ligands	1	178.4×	0.041	APP
HDL assembly	1	178.4×	0.041	A2M
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	1	142.8×	0.041	NOS3
Inflammasomes	1	142.8×	0.041	APP
Cell recruitment (pro-inflammatory response)	1	142.8×	0.041	APP
Regulation of FXIIa and plasma kallikrein activity	1	142.8×	0.041	A2M
Platelet activation, signaling and aggregation	2	26.4×	0.041	APP, A2M
Platelet degranulation	2	22.0×	0.041	APP, A2M
Extracellular matrix organization	2	15.8×	0.041	APP, A2M
R-HSA-140877	1	119.0×	0.043	A2M
eNOS activation	1	109.8×	0.043	NOS3
Neurodegenerative Diseases	1	109.8×	0.043	APP
Specification of primordial germ cells	1	109.8×	0.043	NANOS3
Nitric oxide stimulates guanylate cyclase	1	102.0×	0.044	NOS3
Defective Intrinsic Pathway for Apoptosis	1	95.2×	0.044	APP
Advanced glycosylation endproduct receptor signaling	1	89.2×	0.044	APP
Plasma lipoprotein assembly	1	89.2×	0.044	A2M
The NLRP3 inflammasome	1	84.0×	0.045	APP
Diseases of programmed cell death	1	79.3×	0.045	APP
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	64.9×	0.053	APP
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	59.5×	0.056	APP
TRAF6 mediated NF-kB activation	1	57.1×	0.056	APP
Purinergic signaling in leishmaniasis infection	1	52.9×	0.057	APP

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
removal of superoxide radicals	2	263.3×	0.004	MPO, NOS3
hydrogen peroxide catabolic process	2	168.5×	0.005	LPO, MPO
hypochlorous acid biosynthetic process	1	2106.5×	0.011	MPO
negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I	1	2106.5×	0.011	HFE
negative regulation of complement activation, lectin pathway	1	1053.2×	0.011	A2M
regulation of the force of heart contraction by chemical signal	1	1053.2×	0.011	NOS3
negative regulation of muscle hyperplasia	1	1053.2×	0.011	NOS3
smooth muscle hyperplasia	1	1053.2×	0.011	NOS3
regulation of iron ion transport	1	1053.2×	0.011	HFE
tetrahydrobiopterin metabolic process	1	1053.2×	0.011	NOS3
response to gold nanoparticle	1	1053.2×	0.011	MPO
regulation of translation	2	54.7×	0.011	APP, NANOS3
calcium ion transport	2	45.3×	0.011	APP, NOS3
positive regulation of gene expression	3	14.5×	0.011	APP, HFE, NOS3
regulation of nervous system process	1	702.2×	0.012	NOS3
L-homocysteine catabolic process	1	702.2×	0.012	BLMH
collateral sprouting in absence of injury	1	702.2×	0.012	APP
response to iron ion starvation	1	702.2×	0.012	HFE
astrocyte activation involved in immune response	1	526.6×	0.012	APP
respiratory burst involved in defense response	1	526.6×	0.012	MPO
axo-dendritic transport	1	526.6×	0.012	APP
microglia development	1	526.6×	0.012	APP
cellular response to norepinephrine stimulus	1	526.6×	0.012	APP
regulation of spontaneous synaptic transmission	1	526.6×	0.012	APP
negative regulation of CD8-positive, alpha-beta T cell activation	1	526.6×	0.012	HFE
response to oxidative stress	2	32.7×	0.012	LPO, MPO
response to lipopolysaccharide	2	31.2×	0.012	MPO, NOS3
axon midline choice point recognition	1	421.3×	0.013	APP
swimming behavior	1	421.3×	0.013	APP
hippocampal neuron apoptotic process	1	421.3×	0.013	APP

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 6

Druggability breadth: 6 of 10 evidence-associated genes (60%) 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
APP	FLORBETAPIR F 18
LPO	METHIMAZOLE
MPO	DAPSONE
NOS3	CHLORZOXAZONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APP	40	4
MPO	19	4
NOS3	6	4
LPO	4	4
A2M	0	0
BLMH	0	0
NANOS3	0	0
C10orf55	0	0
HFE	0	0
HFE-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLORBETAPIR F 18	4	APP
FLORBETAPIR	4	APP
METHYLENE BLUE CATION	4	APP
FLUTEMETAMOL F 18	4	APP
TRETINOIN	4	APP
METHYLENE BLUE ANHYDROUS	4	APP
CLIOQUINOL	4	APP
DONEPEZIL	4	APP
FLORBETABEN F18	4	APP
NIACIN	4	APP
FLUTEMETAMOL	4	APP
GENTIAN VIOLET	4	APP
AMODIAQUINE	4	APP
CARVEDILOL	4	APP
CHLOROQUINE	4	APP
TACRINE	4	APP
RETINOL	4	APP
METHIMAZOLE	4	LPO
PROPYLTHIOURACIL	4	LPO, MPO
CARBIMAZOLE	4	LPO
DAPSONE	4	MPO
HYDRALAZINE	4	MPO
MELATONIN	4	MPO
PAROXETINE	4	MPO
TRYPTOPHAN	4	MPO
NIMESULIDE	4	MPO
ISONIAZID	4	MPO
MEFENAMIC ACID	4	MPO
METOCLOPRAMIDE	4	MPO
CHLORZOXAZONE	4	NOS3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
APP	1,744	Binding:1699, Functional:44, ADMET:1
NOS3	188	Binding:178, ADMET:6, Functional:4
MPO	178	Binding:165, Functional:9, ADMET:4
LPO	6	Binding:6
BLMH	4	ADMET:4
A2M	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLMH	3.4.22.40	bleomycin hydrolase
MPO	1.11.2.2	myeloperoxidase
NOS3	1.14.13.39	nitric-oxide synthase (NADPH)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
APP	1,744
MPO	178
NOS3	188

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 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)
FLORBETAPIR F 18	4	APP
FLORBETAPIR	4	APP
FLUTEMETAMOL F 18	4	APP
TRETINOIN	4	APP
METHYLENE BLUE ANHYDROUS	4	APP
CLIOQUINOL	4	APP
FLORBETABEN F18	4	APP
NIACIN	4	APP
FLUTEMETAMOL	4	APP
GENTIAN VIOLET	4	APP
AMODIAQUINE	4	APP
CARVEDILOL	4	APP
CHLOROQUINE	4	APP
TACRINE	4	APP
RETINOL	4	APP
METHIMAZOLE	4	LPO
PROPYLTHIOURACIL	4	LPO, MPO
CARBIMAZOLE	4	LPO
DAPSONE	4	MPO
HYDRALAZINE	4	MPO
MELATONIN	4	MPO
PAROXETINE	4	MPO
TRYPTOPHAN	4	MPO
NIMESULIDE	4	MPO
ISONIAZID	4	MPO
MEFENAMIC ACID	4	MPO
METOCLOPRAMIDE	4	MPO
CHLORZOXAZONE	4	NOS3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	APP, LPO, MPO, NOS3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	A2M, BLMH, HFE
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	NANOS3, C10orf55, HFE-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
A2M	1	—
BLMH	4	—
NANOS3	0	—
C10orf55	0	—
HFE	0	—
HFE-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 21.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE2	4
EARLY_PHASE1	2
PHASE1	2
PHASE4	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04520308	PHASE4	UNKNOWN	An Open-label, Single-arm Longitudinal Study With Dupilumab for Patients With Atopic Dermatitis
NCT07011706	PHASE2	ACTIVE_NOT_RECRUITING	ATI-045 Versus Placebo in Patients With Moderate-to-Severe Atopic Dermatitis
NCT07252440	PHASE2	RECRUITING	A Study to Evaluate the Efficacy and Safety of TTYP01 Tablets in Early Symptomatic Alzheimer’s Disease
NCT02380573	PHASE2	COMPLETED	Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer’s Disease
NCT03806478	PHASE2	UNKNOWN	Study of APH-1105 in Patients With Mild to Moderate Alzheimer’s Disease
NCT05984784	PHASE1/PHASE2	TERMINATED	A Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of IMG-007 in Adults With Atopic Dermatitis (AD)
NCT03932916	PHASE1	COMPLETED	Safety and Pharmacokinetic of Donepezil Pamoate in Healthy Subjects
NCT06593626	PHASE1	COMPLETED	A Phase I Clinical Study on the Safety and Pharmacokinetics of [18F]Florbetazine Injection
NCT05469009	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer’s Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy
NCT01733355	EARLY_PHASE1	TERMINATED	A Phase 0, Open Label, Multi-center Exploratory and Safety Study of [F-18]T807
NCT05637801	Not specified	ACTIVE_NOT_RECRUITING	A Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (HOPE Study)
NCT06245031	Not specified	ENROLLING_BY_INVITATION	Extension to a Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (OLE Hope Study, CA-0015)
NCT06335836	Not specified	RECRUITING	The Effects of Social Isolation and Social Interaction on the Risk of Dementia Progression and Brain Function in SCD (Subjective Cognitive Decline, SCD)
NCT07100470	Not specified	NOT_YET_RECRUITING	Metabolic Characterization of Alzheimer’s Disease and Frontotemporal Dementia by 23Na-MRI and FDG-PET
NCT01190904	Not specified	COMPLETED	Hormones and Sexual Function Predict Outcomes in Revascularized Men With Diabetes
NCT02273895	Not specified	COMPLETED	The Use of EEG in Alzheimer’s Disease, With and Without Scopolamine - A Pilot Study
NCT04100889	Not specified	WITHDRAWN	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Alzheimer’s Disease
NCT05078944	Not specified	COMPLETED	Progress of Mild Alzheimer’s Disease in Participants on Acupuncture Versus Sham Acupuncture
NCT05372458	Not specified	UNKNOWN	The Mechanism Study of Diabetic Pancreatic Amyloid Deposition on Cognitive Dysfunction in Alzheimer’s Disease
NCT06039267	Not specified	COMPLETED	Brain Health & the Microbiome
NCT06155201	Not specified	UNKNOWN	Development and Application of Intelligent Diagnosis and Treatment Norms for Children and Adolescents With Mental Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DONEPEZIL	4	3
METHYLENE BLUE CATION	4	3
PHENAZOPYRIDINE	4	3
ADUCANUMAB	4	1
FLORTAUCIPIR	4	1
LECANEMAB	4	1
SCOPOLAMINE	4	1
CHEMBL1187846	0	1
CHEMBL3084722	0	1

Cohort genes: APP, A2M, BLMH, NANOS3, HFE, HFE-AS1, LPO, MPO, NOS3
Drugs: Donepezil, Methylene Blue Cation, Phenazopyridine, Aducanumab, Flortaucipir, Lecanemab, Scopolamine