BACE1

Summary

BACE1 (beta-secretase 1, HGNC:933) is a protein-coding gene on chromosome 11q23.3, encoding Beta-secretase 1 (P56817). Responsible for the proteolytic processing of the amyloid precursor protein (APP).

This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer’s disease patients.

Source: NCBI Gene 23621 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 69 total
• GTEx eGene: eQTL in 13 tissues, sQTL in 3 (q < 0.05)
• Drug target: yes — 4 curated mechanism-of-action drugs; 26 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Constraint (gnomAD): pLI 0.76 (intermediate), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_012104
• Interaction hub: 2,210 STRING partners (top 6% of genes corpus-wide)
• Notable: 69 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:933
Approved symbol	BACE1
Name	beta-secretase 1
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	Asp2
Ensembl gene	ENSG00000186318
Ensembl biotype	protein_coding
OMIM	604252
Entrez	23621

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000313005

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 3, TSL 3: 1, TSL 5: 2

ENST00000313005, ENST00000392937, ENST00000428381, ENST00000445823, ENST00000509916, ENST00000510630, ENST00000510915, ENST00000513780, ENST00000514464, ENST00000528053, ENST00000530824, ENST00000679585, ENST00000680271, ENST00000680681, ENST00000680800, ENST00000680971, ENST00000681714, ENST00000681753, ENST00000896512, ENST00000927849, ENST00001027691, ENST00001142847

RefSeq mRNA: 7 — MANE Select: NM_012104 NM_001207048, NM_001207049, NM_001411039, NM_012104, NM_138971, NM_138972, NM_138973

CCDS: CCDS44739, CCDS44740, CCDS44741, CCDS55786, CCDS55787, CCDS8383, CCDS91601

Canonical transcript exons

ENST00000313005 — 9 exons

Exon	Start	End
ENSE00002041784	117285698	117289807
ENSE00002719959	117315535	117316256
ENSE00003694855	117296873	117296961
ENSE00003695531	117290488	117290659
ENSE00003696159	117295131	117295347
ENSE00003698958	117293054	117293188
ENSE00003699113	117293871	117294008
ENSE00003700609	117290900	117291049
ENSE00003701731	117291712	117291813

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.2558 / max 762.3993, expressed in 1636 samples.

Highest expression (Bgee): inferior vagus X ganglion, body of pancreas, C1 segment of cervical spinal cord, spinal cord, corpus callosum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BACE1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	1.5e-88	+1.09	11:117293108:C:G
Testis	sqtl	1.6e-78	-1.31	11:117293108:C:G
Brain Cerebellar Hemisphere	eqtl	1.3e-15	+0.96	11:117300759:C:G
Whole Blood	eqtl	1.7e-13	+0.29	11:117318500:G:A
Adrenal Gland	eqtl	5.8e-12	+0.41	11:117312934:C:T
Brain Cerebellum	eqtl	8.6e-12	+1.01	11:117300759:C:G
Cells Cultured fibroblasts	eqtl	6.0e-04	+0.13	11:117297848:A:G
Minor Salivary Gland	eqtl	7.1e-04	+1.09	11:117251191:C:A
Thyroid	eqtl	1.3e-03	-0.63	11:118285138:C:T
Adipose Visceral Omentum	eqtl	1.8e-02	+0.10	11:117321018:C:T
Brain Cerebellum	sqtl	2.1e-02	-2.90	11:117594680:C:G
Nerve Tibial	eqtl	2.2e-02	+0.33	11:117271909:C:G
Adipose Subcutaneous	eqtl	3.3e-02	-0.15	11:117982616:G:A
Brain Anterior cingulate cortex BA24	eqtl	4.1e-02	+0.15	11:117679093:G:A
Nerve Tibial	sqtl	4.3e-02	-0.57	11:117050268:G:A
Esophagus Mucosa	eqtl	4.4e-02	-0.21	11:117261599:T:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
122486	24.3303	1635
122483	0.5370	74
122480	0.2667	124
122484	0.0629	24
122482	0.0572	34
122481	0.0017	1

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	97.98	gold quality
body of pancreas	UBERON:0001150	97.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.86	gold quality
spinal cord	UBERON:0002240	97.78	gold quality
corpus callosum	UBERON:0002336	97.00	gold quality
stromal cell of endometrium	CL:0002255	96.96	gold quality
subthalamic nucleus	UBERON:0001906	96.88	gold quality
medulla oblongata	UBERON:0001896	96.16	gold quality
pancreas	UBERON:0001264	95.95	gold quality
ventral tegmental area	UBERON:0002691	95.77	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.72	gold quality
inferior olivary complex	UBERON:0002127	95.57	gold quality
superior vestibular nucleus	UBERON:0007227	95.53	gold quality
midbrain	UBERON:0001891	95.29	gold quality
substantia nigra	UBERON:0002038	95.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.89	gold quality
pons	UBERON:0000988	94.88	gold quality
cranial nerve II	UBERON:0000941	94.68	gold quality
prefrontal cortex	UBERON:0000451	94.66	gold quality
globus pallidus	UBERON:0001875	94.39	gold quality
medial globus pallidus	UBERON:0002477	94.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.18	gold quality
islet of Langerhans	UBERON:0000006	93.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.47	gold quality
cortical plate	UBERON:0005343	93.40	gold quality
substantia nigra pars compacta	UBERON:0001965	93.10	gold quality
adrenal tissue	UBERON:0018303	93.06	gold quality
Ammon’s horn	UBERON:0001954	92.97	gold quality
parietal lobe	UBERON:0001872	92.84	gold quality
frontal cortex	UBERON:0001870	92.78	gold quality
postcentral gyrus	UBERON:0002581	92.72	gold quality
lateral globus pallidus	UBERON:0002476	92.59	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	92.23	gold quality
entorhinal cortex	UBERON:0002728	92.18	gold quality
neocortex	UBERON:0001950	92.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.09	gold quality
orbitofrontal cortex	UBERON:0004167	91.94	gold quality
cerebral cortex	UBERON:0000956	91.91	gold quality
superior frontal gyrus	UBERON:0002661	91.84	gold quality
temporal lobe	UBERON:0001871	91.71	gold quality
telencephalon	UBERON:0001893	91.60	gold quality
amygdala	UBERON:0001876	91.44	gold quality
hypothalamus	UBERON:0001898	91.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.12	gold quality
brain	UBERON:0000955	91.02	gold quality
putamen	UBERON:0001874	90.98	gold quality
smooth muscle tissue	UBERON:0001135	90.97	gold quality
forebrain	UBERON:0001890	90.91	gold quality
right frontal lobe	UBERON:0002810	90.88	gold quality
CA1 field of hippocampus	UBERON:0003881	90.78	gold quality
occipital lobe	UBERON:0002021	90.72	gold quality
tendon of biceps brachii	UBERON:0008188	90.55	gold quality
cingulate cortex	UBERON:0003027	90.40	gold quality
anterior cingulate cortex	UBERON:0009835	90.40	gold quality
caudate nucleus	UBERON:0001873	90.29	gold quality
nucleus accumbens	UBERON:0001882	90.05	gold quality
gall bladder	UBERON:0002110	90.02	gold quality
right coronary artery	UBERON:0001625	89.93	gold quality
cerebellar cortex	UBERON:0002129	89.82	gold quality
cerebellar hemisphere	UBERON:0002245	89.79	gold quality
primary visual cortex	UBERON:0002436	89.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.66	gold quality
cerebellum	UBERON:0002037	89.57	gold quality
right ovary	UBERON:0002118	89.44	gold quality
endothelial cell	CL:0000115	89.25	gold quality
descending thoracic aorta	UBERON:0002345	89.20	gold quality
left ovary	UBERON:0002119	89.17	gold quality
cerebellar vermis	UBERON:0004720	89.17	gold quality
ganglionic eminence	UBERON:0004023	89.15	gold quality
thoracic aorta	UBERON:0001515	88.99	gold quality
ascending aorta	UBERON:0001496	88.94	gold quality
aorta	UBERON:0000947	88.79	gold quality
popliteal artery	UBERON:0002250	88.71	gold quality
tibial artery	UBERON:0007610	88.70	gold quality
middle temporal gyrus	UBERON:0002771	88.66	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.51	gold quality
body of uterus	UBERON:0009853	88.48	gold quality
ventricular zone	UBERON:0003053	88.07	gold quality
colonic epithelium	UBERON:0000397	87.99	gold quality
left uterine tube	UBERON:0001303	87.93	gold quality
ovary	UBERON:0000992	87.89	gold quality
endocervix	UBERON:0000458	87.80	gold quality
left adrenal gland	UBERON:0001234	87.76	gold quality
coronary artery	UBERON:0001621	87.76	gold quality
left coronary artery	UBERON:0001626	87.72	gold quality
adrenal gland	UBERON:0002369	87.63	gold quality
left adrenal gland cortex	UBERON:0035825	87.59	gold quality
dorsal root ganglion	UBERON:0000044	87.58	gold quality
right adrenal gland cortex	UBERON:0035827	87.52	gold quality
tibial nerve	UBERON:0001323	87.49	gold quality
sperm	CL:0000019	87.47	gold quality
right adrenal gland	UBERON:0001233	87.31	gold quality
ectocervix	UBERON:0012249	87.28	gold quality
adrenal cortex	UBERON:0001235	87.20	gold quality
trigeminal ganglion	UBERON:0001675	86.94	gold quality
right lobe of liver	UBERON:0001114	86.87	gold quality
right uterine tube	UBERON:0001302	86.85	gold quality
saphenous vein	UBERON:0007318	86.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.80	gold quality
lower esophagus	UBERON:0013473	86.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	22.51

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	243.6	medium
Locus coeruleus	tissue	79.1
Nucleus accumbens	tissue	74.1
Hippocampus	tissue	70.7	medium
Postcentral gyrus	tissue	65.9
Cerebellum	tissue	57.2	high
Hippocampal formation	tissue	50.5
Cerebral cortex	tissue	44.3	medium
Somatosensory cortex	tissue	44.3
Prefrontal cortex	tissue	43.5
Motor cortex	tissue	42.1
Occipital cortex	tissue	41.8
Retina	tissue	41.4
Retrosplenial and cingulate cortex	tissue	40.8
Pons	tissue	40.0
Thalamus	tissue	39.3
Entorhinal cortex	tissue	39.1
Midbrain	tissue	38.6
Retrosplenial cortex	tissue	38.6
Insular cortex	tissue	38.5
Temporal cortex	tissue	37.9
Choroid plexus	tissue	36.7
Amygdala	tissue	36.3
Superior colliculi	tissue	34.5
Spinal cord	tissue	33.4
Medulla oblongata	tissue	32.9
Corpus callosum	tissue	32.7
Substantia nigra	tissue	32.3
Septum	tissue	31.8
Hypothalamus	tissue	31.0
Ventral forebrain	tissue	30.9
Putamen	tissue	26.9
Periaqueductal gray	tissue	26.8
Olfactory bulb	tissue	25.6
Basal ganglia	tissue	25.1	medium
Caudate putamen	tissue	24.9
Liver	tissue	23.1	medium
Frontal cortex	tissue	22.0
Ovary	tissue	21.8	not detected
Smooth muscle	tissue	19.5	not detected
Gallbladder	tissue	17.4	medium
Parathyroid gland	tissue	17.1	low
Cervix	tissue	16.7	not detected
Seminal vesicle	tissue	16.4	low
Endometrium 1	tissue	15.6	medium
Fallopian tube	tissue	13.7	medium
Kidney	tissue	13.3	medium
Lung	tissue	13.1	medium
Adrenal gland	tissue	13.1	medium
Placenta	tissue	12.6	medium
Adipose tissue	tissue	12.3	not detected
Esophagus	tissue	12.3	low
Prostate	tissue	12.0	low
Thyroid gland	tissue	11.3	not detected
Spleen	tissue	11.2	medium
Skeletal muscle	tissue	11.0	low
Urinary bladder	tissue	10.8	low
Skin 1	tissue	10.3	low
Salivary gland	tissue	10.2	not detected
Heart muscle	tissue	10.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (242.6), Dorsal funiculus (white matter) (213.8), Lateral funiculus (white matter) (199.2), Nucleus raphe obscurus (193.9), Temporal white matter (193.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CTNNB1, FLOT2, GATA1, HIF1A, HSF1, IFNGR1, NCOR1, NFATC2, NFIA, NFKB1, NFKB, PPARG, RELA, SP1, SPI1, STAT1, STAT3, TCF3, TCF7L2, TFAP2A, TNF, YY1

miRNA regulators (miRDB)

Targeting BACE1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 236 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6845-3P	99.94	66.88	1439

Functional genomics

gnomAD constraint: pLI 0.762, LOEUF 0.556, missense Z 2.21 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000313005 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:117,289,569–117,315,591	407 / 565.7	0.72	no
11:117,315,592–117,315,795	104 / 95.5	1.09	no

Literature-anchored findings (GeneRIF, showing 40)

• BACE1 is in the distal Golgi membrane with a minor presence in the endoplasmic reticulum, endosomes, and plasma membrane in human neuroblastoma SHEP cells and in mouse Neuro-2a cell lines (PMID:11466313)
• BACE has a loose substrate specificity and the substrate recognition site in BACE extends over several amino acids (PMID:11741910)
• beta-Secretase cleavage of the amyloid precursor protein mediates neuronal apoptosis caused by familial ALzheimer’s disease mutations. (PMID:11744168)
• Intracellular localization of BACE affects sleavage site specificity; processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer’s disease brain (PMID:11847218)
• Our data are consistent with a role for the cytoplasmic domain in regulating BACE trafficking and localization. (PMID:11860271)
• A model of the three-dimensional structure of the beta-secretase zymogen has been constructed. (PMID:11922623)
• BACE1 interacts with nicastrin (PMID:12054507)
• Splice variants of the beta-site APP-cleaving enzyme BACE1 are found in human brain and pancreas (BACE1) (PMID:12054559)
• Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity (PMID:12093293)
• Results show an increase in protein expression of BACE in the cortex of Alzheimer’s disease patients compared to age-matched controls (PMID:12112088)
• endocytosis and intracellular transport of memapsin 2, mediated by its cytosolic domain, may involve the binding of GGA1 and GGA2 (PMID:12135764)
• Crystal structure analysis of memapsin-2 catalytic unit complexed with its inhibitor OM00-3 defines locations and functions of new binding pockets S3’ and S4’. (PMID:12206667)
• Activity levels are increased in brain regions affected by amyloid deposition and remain increased despite significant neuronal and synaptic loss in Alzheimer disease (PMID:12223024)
• Oxidative stress induces increased BACE protein levels and activity in NT2 neurons accompanied by an increase in amyloid beta protein precursor. (PMID:12270690)
• BACE mRNA amounts were similar in the hippocampus and cerebellum of Alzheimer’s patients and controls. (PMID:12438920)
• Results describe a decrease in alpha-secretase (81% of normal) and a large increase in beta-secretase activity (185%) in sporadic Alzheimer’s disease temporal cortex. (PMID:12445809)
• An isoenzyme specifically truncates amyloid beta-peptide after its presenilin-dependent generation. (PMID:12471021)
• elevated expression and enzymatic activity in the brain of sporadic Alzheimer disease patients (PMID:12514700)
• The association of beta-site APP cleaving enzyme (BACE) C786G polymorphism with Alzheimer’s disease. No significant association of this polymorphism with the occurrence of AD can be established. (PMID:12535780)
• Identification of domains for PLSCR1 and BACE binding and their colocalization in the Golgi area and endosomal compartments suggest involvement of PLSCR1 in the intracellular distribution and/or recruitment of BACE into the lipid raft. (PMID:12586838)
• BACE1 and BACE2 (a) are expressed in normal adult muscle at the postsynaptic domain of neuromuscular junctions, and in cultured human muscle; (b) accumulate in the form of plaque-like inclusions in myositis vacuolated and necrotic muscle fibers (PMID:12618121)
• gamma-secretase cleavage of CT99 is a prerequisite for BACE-mediated processing at Abeta-34 site and therefore, BACE and gamma-secretase activity can be mutually dependent. (PMID:12665519)
• sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; but, a combination of a specific BACE1 allele and APOE epsilon 4 may increase the risk for Alzheimer disease over and above that attributed to APOE epsilon 4 alone. (PMID:12707937)
• antagonistic effect with beta-site amyloid precursor protein-cleaving enzyme 2 on beta-amyloid peptide production in cells (PMID:12801932)
• BACE exon 5 polymorphism plays an important role in the development of Alzheimer’s disease, possibly by influencing Abeta(42) protein levels. (PMID:12824768)
• BACE1 sheddase is distinct from alpha-secretase and, inhibition of BACE1 shedding does not influence amyloid precursor protein processing at the beta-site (PMID:12857759)
• These data suggest a possible genetic relation between BACE1 and AD. (PMID:12928915)
• acts on the P-selectin glycoprotein ligand 1, which mediates leukocyte adhesion in inflammatory reactions (PMID:14507929)
• BACE 1 cleavage regulates a common function of APP and APLPs in neurons (PMID:14699153)
• BACE1 gene expression is tightly regulated at the transcriptional level, and transcription factor Sp1 plays an important role in regulation of BACE1 to process APP generating Abeta in Alzheimer’s disease. (PMID:14701757)
• Homology models of alternatively spliced isoforms B (BACEI-476), C (BACEI-457) and D(BACEI-432) suggest that these should have diminished enzyme activity due to the the loss of key complexing residues (PMID:14748006)
• beta-Secretase activity is enhanced by cellular targeting into intracellular cholesterol-rich microdomains (PMID:14748707)
• BACE elevation may lead to increased amyloid beta peptide production and enhanced deposition of amyloid plaques in sporadic Alzheimer disease patients. (PMID:14978286)
• BACE overexpression is not sufficient to produce beta-amyloid plaques, but simultaneous expression of BACE and its substrate (SwAPP) leads to an accelerated amyloid plaque formation. (PMID:14991462)
• Alternative splicing in the BACE-1 5’UTR affects the efficiency of translation initiation (PMID:15034149)
• promotor and 5’ UTR sequence analysis (PMID:15059975)
• transcription response element analysis of 5’ flanking region (PMID:15059977)
• The major structural difference in the bound and unbound memapsin 2 is a large movement of the flap of about 4.5 angstroms at the tip; the flap in the unbound memapsin 2 appears in a novel “open” position permitting access to the active-site cleft. (PMID:15096037)
• memapsin 2 and APP, immunoprecipitated together from cell lysates, suggested that the interaction of these two proteins is part of the native cellular processes [memapsin-2] (PMID:15197182)
• Stimulation of cells with muscarinic agonists increased BACE1 expression up to twofold over basal levels. Similar effects of BACE1 up-regulation were observed when protein kinase C was directly activated by phorbol esters. (PMID:15211591)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	bace1	ENSDARG00000101716
mus_musculus	Bace1	ENSMUSG00000032086
rattus_norvegicus	Bace1	ENSRNOG00000016847
drosophila_melanogaster	Bace	FBGN0032049
drosophila_melanogaster	CG6508	FBGN0032303
drosophila_melanogaster	CG17134	FBGN0032304
drosophila_melanogaster	CG33128	FBGN0053128
caenorhabditis_elegans		WBGENE00000214
caenorhabditis_elegans		WBGENE00000218
caenorhabditis_elegans		WBGENE00012681
caenorhabditis_elegans		WBGENE00012682
caenorhabditis_elegans		WBGENE00012683
caenorhabditis_elegans		WBGENE00013973
caenorhabditis_elegans		WBGENE00017678
caenorhabditis_elegans		WBGENE00019104
caenorhabditis_elegans		WBGENE00019105
caenorhabditis_elegans		WBGENE00077655

Paralogs (9): PGC (ENSG00000096088), CTSD (ENSG00000117984), NAPSA (ENSG00000131400), REN (ENSG00000143839), BACE2 (ENSG00000182240), CTSE (ENSG00000196188), PGA4 (ENSG00000229183), PGA3 (ENSG00000229859), PGA5 (ENSG00000256713)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1346542) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 36 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased anxiety-related response	2
abnormal spatial working memory	2
abnormal myelination	1
demyelination	1
decreased body weight	1
abnormal anxiety-related response	1
hyperactivity	1
impaired coordination	1
abnormal gait	1
decreased exploration in new environment	1
abnormal spatial learning	1
abnormal startle reflex	1
postnatal growth retardation	1
abnormal long-term depression	1
abnormal muscle physiology	1
improved righting response	1
enhanced paired-pulse facilitation	1
abnormal locomotor activation	1
abnormal response to novel object	1
abnormal channel response	1
abnormal nervous system physiology	1
abnormal myelin sheath morphology	1
decreased thermal nociceptive threshold	1
impaired passive avoidance behavior	1
abnormal muscle spindle morphology	1

+11 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q2HJ40	98.2%	Diamond
Cavia porcellus	Q1KLR6	92.0%	Diamond
Strongylocentrotus purpuratus	W8W138	49.8%	Diamond
Irpex lacteus	P17576	35.7%	Diamond
Malassezia globosa CBS 7966	A8PZM4	31.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
BACE1-AS	ncRNA	100379571
FXYD6-FXYD2	protein-coding	100533181
CEP164	protein-coding	22897
RNF214	protein-coding	257160
FXYD2	protein-coding	486
DSCAML1	protein-coding	57453
TAGLN	protein-coding	6876
PCSK7	protein-coding	9159
FXYD6-AS1	ncRNA	123706543
FXYD6	protein-coding	53826
SIDT2	protein-coding	51092
PAFAH1B2	protein-coding	5049

Protein

Protein identifiers

Beta-secretase 1 — P56817 (reviewed: P56817)

Alternative names: Aspartyl protease 2, Beta-site amyloid precursor protein cleaving enzyme 1, Memapsin-2, Membrane-associated aspartic protease 2

All UniProt accessions (8): A0A7P0T924, A0A7P0TAB4, B7Z3K2, B7Z3Z4, E9PJG7, P56817, Q76KP0, U3KPS1

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves CHL1.

Subunit / interactions. Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498. Interacts with RTN1; RTN2; RTN3 and RTN4; the interaction leads to inhibition of amyloid precursor protein processing. Interacts with SNX6. Interacts with PCSK9. Interacts with NAT8 and NAT8B. Interacts with BIN1. Interacts (via extracellular domain) with ADAM10 (via extracellular domain). Interacts with SORL1; this interaction may affect binding with APP and hence reduce APP cleavage. Interacts with NRDC AND NRG1.

Subcellular location. Cell membrane. Golgi apparatus. trans-Golgi network. Endoplasmic reticulum. Endosome. Cell surface. Cytoplasmic vesicle membrane. Membrane raft. Lysosome. Late endosome. Early endosome. Recycling endosome. Cell projection. Axon. Dendrite.

Tissue specificity. Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.

Post-translational modifications. N-Glycosylated. Addition of a bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting, further degradation and is required for maintaining stability under stress conditions. Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307. Acetylation by NAT8 and NAT8B is transient and deacetylation probably occurs in the Golgi. Acetylation regulates the maturation, the transport to the plasma membrane, the stability and the expression of the protein. Palmitoylation mediates lipid raft localization. Ubiquitinated at Lys-501, ubiquitination leads to lysosomal degradation. Monoubiquitinated and ‘Lys-63’-linked polyubitinated. Deubiquitnated by USP8; inhibits lysosomal degradation. Phosphorylation at Ser-498 is required for interaction with GGA1 and retrograded transport from endosomal compartments to the trans-Golgi network. Non-phosphorylated BACE1 enters a direct recycling route to the cell surface.

Activity regulation. Inhibited by RTN3 and RTN4.

Domain organisation. DXXLL motif is required for a proper endocytosis and retrograde transport to the trans-Golgi network, as well as for regulation of lysosomal degradation. The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP.

Induction. Up-regulated by the Ca(2+)-regulated transcription factor NFATC4.

Similarity. Belongs to the peptidase A1 family.

Isoforms (6)

UniProt ID	Names	Canonical?
P56817-1	A, BACE-1A, BAC-501	yes
P56817-2	B, BACE-1B, BACE-I-476
P56817-3	C, BACE-1C, BACE-I-457
P56817-4	D, BACE-1D, BACE-I-432
P56817-5	5
P56817-6	6

RefSeq proteins (7): NP_001193977, NP_001193978, NP_001397968, NP_036236, NP_620427, NP_620428, NP_620429 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001461	Aspartic_peptidase_A1	Family
IPR001969	Aspartic_peptidase_AS	Active_site
IPR009119	BACE	Family
IPR009120	BACE1	Family
IPR021109	Peptidase_aspartic_dom_sf	Homologous_superfamily
IPR033121	PEPTIDASE_A1	Domain
IPR033874	Memapsin-like	Domain

Pfam: PF00026

Enzyme classification (BRENDA)

• EC 3.4.23.46 — memapsin 2 (BRENDA: 7 organisms, 189 substrates, 722 inhibitors, 12 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
EEISEVNLDAEFRG	1.71	2
M-2420 PEPTIDE	0.0019–0.0083	2
SEVNLDAEFR	4.07	2
((7-METHOXYCOUMARIN-4-YL)ACETYL)-SER-GLU-VAL-ASN	0.0045	1
7-METHOXYCOUMARIN-4-YL-SEVNLDAEFK-2,4-DINITROPHE	0.055	1
ARG-GLU(5-[(2-AMINOETHYL)AMINO]-NAPHTHALENE-1-SU	0.0054	1
RE(EDANS)EVNLDAEFK(DABCYL)R-NH2	12.8	1

UniProt features (100 total): strand 31, helix 17, modified residue 8, turn 8, mutagenesis site 6, lipid moiety-binding region 4, glycosylation site 4, splice variant 4, disulfide bond 3, active site 2, topological domain 2, sequence variant 2, region of interest 2, signal peptide 1, propeptide 1, chain 1, cross-link 1, transmembrane region 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

showing 30 of 431 structures by resolution:

PDB	Title	Method	Resolution (Å)
7MYI	BACE-1 in complex with compound #6	X-RAY DIFFRACTION	1.25
6UWP	BACE-1 in complex with compound #32	X-RAY DIFFRACTION	1.29
6EQM	Crystal Structure of Human BACE-1 in Complex with CNP520	X-RAY DIFFRACTION	1.35
4L7G	Diethylaminosulfur Trifluoride-Mediated Intramolecular Cyclization of …	X-RAY DIFFRACTION	1.38
6EJ2	BACE1 compound 28	X-RAY DIFFRACTION	1.46
6UWV	BACE-1 in complex with compound #34	X-RAY DIFFRACTION	1.47
3VF3	Crystal Structure of Human Beta Secretase in Complex with NVP-BQQ711	X-RAY DIFFRACTION	1.48
5HDZ	BACE-1 in complex with …	X-RAY DIFFRACTION	1.49
2QP8	Structure of BACE Bound to SCH734723	X-RAY DIFFRACTION	1.5
4B78	Aminoimidazoles as BACE-1 Inhibitors: From De Novo Design to Ab- lowering in Brain	X-RAY DIFFRACTION	1.5
4DJX	Structure of BACE Bound to …	X-RAY DIFFRACTION	1.5
5HU1	BACE1 in complex with …	X-RAY DIFFRACTION	1.5
6BFE	BACE crystal structure with hydroxy pyrrolidine inhibitor	X-RAY DIFFRACTION	1.51
3VEU	Crystal Structure of Human Beta Secretase in Complex with NVP-AVI326	X-RAY DIFFRACTION	1.52
5F01	CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH …	X-RAY DIFFRACTION	1.52
3L5E	Structure of BACE Bound to SCH736062	X-RAY DIFFRACTION	1.53
5HE4	BACE-1 in complex with …	X-RAY DIFFRACTION	1.53
6FGY	Crystal Structure of Human BACE-1 in Complex with amino-1,4-oxazine compound 4	X-RAY DIFFRACTION	1.54
5HE5	BACE-1 in complex with …	X-RAY DIFFRACTION	1.55
4FM7	Crystal Structure of BACE with Compound 14g	X-RAY DIFFRACTION	1.56
6UVP	BACE-1 in complex with compound #3	X-RAY DIFFRACTION	1.56
4R91	BACE-1 in complex with …	X-RAY DIFFRACTION	1.58
5HDU	BACE-1 incomplex with …	X-RAY DIFFRACTION	1.58
4FGX	Crystal structure of bace1 with novel inhibitor	X-RAY DIFFRACTION	1.59
2VIJ	Human BACE-1 in complex with 3-(1,1-dioxidotetrahydro-2H-1,2-thiazin- …	X-RAY DIFFRACTION	1.6
2VIZ	Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- …	X-RAY DIFFRACTION	1.6
2VJ7	Human BACE-1 in complex with …	X-RAY DIFFRACTION	1.6
2VJ9	Human BACE-1 in complex with N-((1S,2R)-3-(cyclohexylamino)-2-hydroxy- …	X-RAY DIFFRACTION	1.6
2WF0	Human BACE-1 in complex with …	X-RAY DIFFRACTION	1.6
2WF1	Human BACE-1 in complex with …	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56817-F1	87.75	0.74

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 3R1G

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Aspartic-type peptidases, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
93
289

Post-translational modifications (13)

Type	Positions
N6-acetyllysine	126, 275, 279, 285, 299, 300, 307
Phosphoserine	498
S-palmitoyl cysteine	474, 478, 482, 485
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	501

Disulfide bonds (3)

Type	Positions
Disulfide bond	216–420, 278–443, 330–380

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	153, 172, 223, 354

Mutagenesis-validated functional residues (6)

Position	Phenotype
93	decreases beta-cleaved soluble app production.
284	almost abolishes beta-cleaved soluble app production.
498	no effect on endocytosis from the cell surface. increases recycling from endosomes to the cell surface.
498	no effect on endocytosis form the cell surface. decreases recycling from endosomes to the cell surface.
499–500	impairs endocytosis and produces a delayed retrograde transport to the trans-golgi network and delivery to the lysosomes, decreasing its …
501	inhibits ubiquitination. no effect on endocytosis rate. induced protein stability and accumulation in early and late endosomes, lysosomes …

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 2; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

2 pathways:

ID	Pathway	Evidence
R-HSA-977225	Amyloid fiber formation	curated
R-HSA-392499	Metabolism of proteins	—

MSigDB gene sets: 277 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_BEHAVIOR, GCM_PTPRD, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, AAGTCCA_MIR422B_MIR422A, LFA1_Q6, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_CELL_SURFACE, TATTATA_MIR374, GOBP_RESPONSE_TO_COPPER_ION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (20): proteolysis (GO:0006508), membrane protein ectodomain proteolysis (GO:0006509), response to lead ion (GO:0010288), protein processing (GO:0016485), amyloid-beta formation (GO:0034205), swimming behavior (GO:0036269), amyloid precursor protein catabolic process (GO:0042987), positive regulation of neuron apoptotic process (GO:0043525), amyloid-beta metabolic process (GO:0050435), detection of mechanical stimulus involved in sensory perception of pain (GO:0050966), prepulse inhibition (GO:0060134), cellular response to copper ion (GO:0071280), cellular response to manganese ion (GO:0071287), presynaptic modulation of chemical synaptic transmission (GO:0099171), signaling receptor ligand precursor processing (GO:0140448), cellular response to amyloid-beta (GO:1904646), amyloid fibril formation (GO:1990000), response to insulin-like growth factor stimulus (GO:1990418), regulation of neuron apoptotic process (GO:0043523), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (9): amyloid-beta binding (GO:0001540), endopeptidase activity (GO:0004175), aspartic-type endopeptidase activity (GO:0004190), peptidase activity (GO:0008233), beta-aspartyl-peptidase activity (GO:0008798), enzyme binding (GO:0019899), protein serine/threonine kinase binding (GO:0120283), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (25): lysosome (GO:0005764), endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), multivesicular body (GO:0005771), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), neuronal cell body (GO:0043025), membrane raft (GO:0045121), recycling endosome (GO:0055037), Golgi-associated vesicle lumen (GO:0070931), hippocampal mossy fiber to CA3 synapse (GO:0098686), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), presynapse (GO:0098793)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

showing 60 of 70 GO namespaces:

Category	Terms
endosome	4
protein metabolic process	2
neuron apoptotic process	2
cellular response to metal ion	2
presynapse	2
endomembrane system	2
cellular anatomical structure	2
neuron projection	2
membrane protein proteolysis	1
response to metal ion	1
proteolysis	1
protein maturation	1
amyloid precursor protein catabolic process	1
amyloid-beta metabolic process	1
locomotory behavior	1
amyloid precursor protein metabolic process	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
metabolic process	1
sensory perception of pain	1
detection of mechanical stimulus involved in sensory perception	1
startle response	1
negative regulation of response to external stimulus	1
response to copper ion	1
response to manganese ion	1
modulation of chemical synaptic transmission	1
protein processing	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to amyloid-beta	1
supramolecular fiber organization	1
response to hormone	1
regulation of apoptotic process	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
peptide binding	1
peptidase activity	1
endopeptidase activity	1
aspartic-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
omega peptidase activity	1
threonine-type peptidase activity	1
protein binding	1
protein kinase binding	1
binding	1
catalytic activity	1
lytic vacuole	1
cytoplasmic vesicle	1
late endosome	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
exocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 22 of 54 annotations. The rest are phylogenetic / computational / electronic (IEA).

22 experimentally-supported GO terms:

GO term	NS	Evidence
amyloid-beta formation	BP	direct assay
amyloid-beta metabolic process	BP	direct assay
membrane protein ectodomain proteolysis	BP	direct assay
positive regulation of neuron apoptotic process	BP	genetic interaction
protein processing	BP	direct assay
proteolysis	BP	direct assay
Golgi apparatus	CC	direct assay
cell surface	CC	direct assay
early endosome	CC	direct assay
endosome	CC	direct assay
late endosome	CC	direct assay
lysosome	CC	direct assay
multivesicular body	CC	direct assay
plasma membrane	CC	direct assay
recycling endosome	CC	direct assay
trans-Golgi network	CC	direct assay
amyloid-beta binding	MF	physical interaction
aspartic-type endopeptidase activity	MF	direct assay
endopeptidase activity	MF	direct assay
enzyme binding	MF	physical interaction
peptidase activity	MF	direct assay
protein serine/threonine kinase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,210 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BACE1	APP	P05067	975
BACE1	PSEN1	P49768	939
BACE1	ADAM10	O14672	869
BACE1	MMEL1	Q495T6	843
BACE1	PSEN2	P49810	830
BACE1	NCSTN	Q92542	796
BACE1	IDE	P14735	783
BACE1	MME	P08473	781
BACE1	CDK5	Q00535	780
BACE1	APLP1	P51693	773
BACE1	APH1A	Q96BI3	769
BACE1	PSENEN	Q9NZ42	769
BACE1	BCHE	P06276	763
BACE1	MAPT	P10636	756
BACE1	APOE	P02649	750

IntAct

Human interaction partners of BACE1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

17 partners by confidence:

Partner	Interaction type	MIscore	Records
APP	protein cleavage	0.870	9
GGA1	physical association	0.670	4
PSEN1	physical association	0.640	6
ITM2B	physical association	0.560	4
IAPP	protein cleavage	0.560	2
GGA2	physical association	0.540	2
GGA3	physical association	0.540	2
KCNC4	physical association	0.520	3
SNX6	physical association	0.500	1
ADAM10	physical association	0.450	2
FLOT2	association	0.420	2
ADRB2	physical association	0.370	1
SLC25A5	association	0.350	1
TUBB8B	association	0.350	1
CSNK1D	proximity	0.270	1
FLOT1	proximity	0.270	1
MMP2	proximity	0.270	1

BioGRID (67 interactions; top human partners by supporting records): GGA1 (Affinity Capture-Western; 12 records), APP (Affinity Capture-Western; 3 records), GGA2 (Affinity Capture-Western; 3 records), GGA3 (Affinity Capture-Western; 3 records), HYOU1 (FRET; 3 records), EDEM1 (Affinity Capture-Western; 2 records), FBXO2 (Affinity Capture-Western; 2 records), KCNC4 (Affinity Capture-Western; 2 records), KCNQ1 (Affinity Capture-Western; 2 records), NGFR (Affinity Capture-Western; 2 records), PCSK9 (Biochemical Activity; 2 records), RTN3 (Affinity Capture-Western; 2 records), SCGB1D4 (Affinity Capture-MS; 2 records), SORT1 (Affinity Capture-Western; 2 records), STUB1 (Biochemical Activity; 2 records)

SIGNOR signaling

showing 9 of 10 signaling interactions:

A	Effect	B	Mechanism
CSNK1D	unknown	BACE1	phosphorylation
USP8	“up-regulates quantity by stabilization”	BACE1	deubiquitination
BACE1	“up-regulates activity”	APP	cleavage
USP8	“up-regulates quantity”	BACE1	deubiquitination
CDK5	“up-regulates activity”	BACE1	phosphorylation
STUB1	“down-regulates quantity”	BACE1	ubiquitination
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	BACE1	polyubiquitination
FBXO2	“down-regulates quantity by destabilization”	BACE1	binding
CDK5/CDK5R1	“up-regulates activity”	BACE1	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ BACE1-CHRM1 complex	2	BACE1, CHRM1
PAR4-BACE1 complex	2	BACE1, PAWR

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Amyloid fiber formation	7	45.0×	2e-08

Disease & clinical

Genetic variants

Variant evidence for BACE1: 69 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

69 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 737):

Position(s)	Effect	Δscore	Sites
11:117290486–117290487	donor_loss	1.0000	5
11:117291814–117291815	acceptor_loss	1.0000	6
11:117293052–117293053	donor_loss	1.0000	2
11:117293190	acceptor_loss	1.0000	2
11:117295169	donor_gain	1.0000
11:117295348–117295349	acceptor_loss	1.0000	4
11:117296848	donor_gain	1.0000
11:117290484	donor_gain	0.9900
11:117290486	donor_loss	0.9900
11:117290660–117290661	acceptor_loss	0.9900	6

AlphaMissense

1,563 missense substitutions predicted likely pathogenic (of 3,266 scored), across 349 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M399	9	0.905	0.999
D93	8	1.000	1.000
D289	8	1.000	1.000
S96	8	0.998	1.000
D144	8	0.995	1.000
F169	8	0.993	1.000
F211	8	0.992	0.999
F322	8	0.990	1.000
F341	8	0.989	0.998
N98	8	0.988	1.000
F99	8	0.988	0.999
F415	8	0.988	1.000
S97	8	0.986	1.000
F406	8	0.986	1.000
N282	8	0.983	1.000
F383	8	0.974	0.999
F170	8	0.968	1.000
F357	8	0.965	0.998
F198	8	0.962	0.997
S290	8	0.957	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.18e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	7.73e-05

Disease associations

OMIM: gene MIM:604252 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST90002395_693	Mean platelet volume	8e-18
GCST001157_5	Cardiovascular disease risk factors	8e-7
GCST007637_53	Diffusing capacity of carbon monoxide	9e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009369	diffusing capacity of the lung for carbon monoxide

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111390 (PROTEIN FAMILY), CHEMBL4822 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the BACE1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

4 curated-mechanism drugs:

Drug	Modality	Max phase
ELENBECESTAT	Small molecule	3
LANABECESTAT	Small molecule	3
VERUBECESTAT	Small molecule	3
ATABECESTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 701,814 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

26 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL76	CHLOROQUINE	4	59,347
CHEMBL311498	CIANIDANOL	4	60,179
CHEMBL502	DONEPEZIL	4	43,884
CHEMBL939	GEFITINIB	4	119,425
CHEMBL4204869	ELENBECESTAT	3	202
CHEMBL3989948	LANABECESTAT	3	348
CHEMBL3301601	VERUBECESTAT	3	615
CHEMBL145	CAFFEIC ACID	3	36,727
CHEMBL140	CURCUMIN	3	95,185
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	23,201
CHEMBL1950045	HYDROXYTYROSOL	3	6,767
CHEMBL473159	PHLOROGLUCINOL	3	35,544
CHEMBL50	QUERCETIN	3	75,572
CHEMBL226335	RUTIN	3	58,533
CHEMBL11608	TYRAMINE	3	38,560
CHEMBL3916243	ATABECESTAT	2	224
CHEMBL129482	(+)-EPICATECHIN	2	134
CHEMBL583912	(-)-EPICATECHIN	2	20,191
CHEMBL444478	ACETOSIDE	2	3,737
CHEMBL6246	ELLAGIC ACID	2	23,439
CHEMBL151	LUTEOLIN	2
CHEMBL1483796	SPICLOMAZINE	2
CHEMBL2177913	AZD-3839	1
CHEMBL150	KAEMPFEROL	1
CHEMBL2333941	LY-2811376	1
CHEMBL2396989	LY-2886721	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — A1: Pepsin

Most potent curated ligand interactions (33 total), top 25:

Ligand	Action	Affinity	Parameter
compound 6 [PMID: 34553947]	Inhibition	9.89	pKi
compound 15 [PMID: 25699151]	Inhibition	9.52	pIC50
verubecestat	Competitive	9.47	pKi
AM-6494	Inhibition	9.4	pIC50
AMG-8718	Inhibition	9.15	pIC50
PF-06684511	Inhibition	9.15	pIC50
atabecestat	Inhibition	9.1	pKi
compound 16 [PMID: 23412139]	Competitive	8.77	pKi
AZ-4217	Competitive	8.74	pKi
lanabecestat	Competitive	8.66	pIC50
JNJ-67569762	Inhibition	8.57	pIC50
compound 11d [PMID: 23981898]	Competitive	8.4	pIC50
FAH65E(-)	Inhibition	8.3	pIC50
compound 9 [PMID: 26937601]	Inhibition	8.3	pKi
NB-360	Inhibition	8.3	pIC50
compound 2 [PMID: 22911925]	Competitive	8.26	pIC50
elenbecestat	Inhibition	8.15	pIC50
PF-06751979	Inhibition	8.14	pIC50
compound 13 [PMID: 23412139]	Inhibition	8.11	pKi
umibecestat	Inhibition	7.96	pIC50
oxazine 89	Competitive	7.92	pIC50
compound J [PMID: 21907142]	Inhibition	7.74	pIC50
LY2886721	Competitive	7.7	pIC50
example 2 [WO2013004676]	Inhibition	7.59	pIC50
AZD3839	Competitive	7.58	pKi

Binding affinities (BindingDB)

5787 measured of 6081 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	IC50	0.0002 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide	IC50	0.0009 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide	IC50	0.0009 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(8R)-10-amino-8-methyl-6,6-dioxo-6lambda6-thia-9-azaspiro[4.5]dec-9-en-8-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	IC50	0.001 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-5-(difluoromethyl)pyrazine-2-carboxamide	IC50	0.0018 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(3R)-5-amino-3-methyl-1,1-dioxo-2,6-dihydro-1,4-thiazin-3-yl]-4-fluorophenyl]-5-(difluoromethoxy)pyridine-2-carboxamide	IC50	0.0057 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
(4aR,6R,8aS)-8a-[2,4-difluoro-5-[(2,2,2-trifluoroethylamino)methyl]phenyl]-6-(fluoromethyl)-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-2-amine	IC50	0.006 nM	US-9045498: Hexahydropyrano[3,4-d][1,3]thiazin-2-amine compounds
N-[3-[(3R)-5-amino-3-methyl-1,1-dioxo-2,6-dihydro-1,4-thiazin-3-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide	IC50	0.0061 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(3R)-5-amino-3-methyl-1,1-dioxo-2,6-dihydro-1,4-thiazin-3-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	IC50	0.0082 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[3-[(3R)-5-amino-3-methyl-2,6-dihydro-1,4-thiazin-3-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	IC50	0.011 nM	US-9273042: 5-amino[1,4]thiazines as BACE 1 inhibitors
N-[2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-1,3-thiazol-4-yl]-5-methoxypyridine-2-carboxamide	IC50	0.014 nM	US-9315520: 2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
N-[3-[(4R,5R)-2-amino-5-fluoro-4,5-dimethyl-6H-1,3-oxazin-4-yl]-4-fluorophenyl]-5-but-2-ynoxypyrazine-2-carboxamide	IC50	0.1 nM	US-8754075: 1,3-oxazines as BACE1 and/or BACE2 inhibitors
N2-[(2R,4S,5S)-5-{[N-{[(2,5-dimethyl-1,3-oxazol-4-yl)methoxy]carbonyl}-3-(methylsulfonyl)-L-alanyl]amino}-4-hydroxy-2,7-dimethyloctanoyl]-N-(2-methylpropyl)-L-valinamide	KI	0.12 nM
US8865911, 114	IC50	0.14 nM	US-10231967: Compounds and their use as BACE inhibitors
US8975415, 221	IC50	0.16 nM	US-9242973: Chromane compounds
(5S)-2-amino-4’-fluoro-7’-(2-fluoro-3-pyridinyl)-2’-(2-fluoro-4-pyridinyl)-3-methylspiro[imidazole-5,9’-xanthene]-4-one	IC50	0.2 nM	US-8957083: Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use
N-[3-[(1R,10R)-8-amino-10-methyl-1-oxo-1lambda6-thia-2,7,9-triazabicyclo[5.4.0]undeca-1,8-dien-10-yl]-4-fluorophenyl]-5-but-2-ynoxypyrazine-2-carboxamide	IC50	0.2 nM	US-9605006: 5-aryl-1-imino-1-oxo-[1,2,4]thiadiazines
(1R,5S,6S)-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-1-(methylsulfonyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-3-amine	IC50	0.2 nM	US-10246429: Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
CHEMBL3260839	IC50	0.2 nM
CHEMBL3261045	IC50	0.2 nM
US8865911, 92 Isomer 2	IC50	0.27 nM	US-10231967: Compounds and their use as BACE inhibitors
(5S)-2-amino-7’-(3-chlorophenyl)-2’-(3,6-dihydro-2H-pyran-4-yl)-4’-fluoro-3-methylspiro[imidazole-5,9’-xanthene]-4-one	IC50	0.3 nM	US-8957083: Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use
(7R)-4’-fluoro-7’-(2-fluoro-3-pyridinyl)-2’-(2-fluoro-4-pyridinyl)spiro[imidazo[1,2-c]imidazole-7,9’-xanthene]-5-amine	IC50	0.3 nM	US-8962859: Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use
(3,5-dimethyl-1H-pyrazol-1-yl)methyl N-[(1R)-1-{[(1R,3S,4S)-3-hydroxy-1,6-dimethyl-1-{[(1S)-2-methyl-1-[(2-methylpropyl)carbamoyl]propyl]carbamoyl}heptan-4-yl]carbamoyl}-2-methanesulfonylethyl]carbamate	KI	0.3 nM
N-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-5-chloro-3-methylpyridine-2-carboxamide	IC50	0.3 nM	US-9556135: Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
CHEMBL3260838	IC50	0.3 nM
CHEMBL3354718	IC50	0.3 nM
(3R,6R)-3-[5-[(3-chloro-1,7-naphthyridin-8-yl)amino]-2-fluorophenyl]-6-fluoro-3,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine	IC50	0.33 nM	US-9556135: Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
N-[3-[(4aR,7aS)-2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-isocyanopyridine-2-carboxamide	IC50	0.358 nM	US-8987254: Tetrahydropyrrolothiazine compounds
N-[3-[(4aR,7aS)-2-Amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-cyano-pyridine-2-carboxamide hydrochloride	IC50	0.358 nM	US-9999624: Combination Alzheimer therapy using anti-N3pGlu Abeta antibodies + a BACE inhibitor
(3R,6R)-3-[5-[(3-chloro-5-fluoro-1,7-naphthyridin-8-yl)amino]-2-fluorophenyl]-6-fluoro-3,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-amine	IC50	0.38 nM	US-9556135: Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
N-[3-[(4R,5R)-2-amino-5-fluoro-4-methyl-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide	IC50	0.4 nM	US-8754075: 1,3-oxazines as BACE1 and/or BACE2 inhibitors
N-[3-[(4R,5R)-2-amino-5-fluoro-4,5-dimethyl-6H-1,3-oxazin-4-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	IC50	0.4 nM	US-8754075: 1,3-oxazines as BACE1 and/or BACE2 inhibitors
(7S)-2’-(3,6-dihydro-2H-pyran-5-yl)-4’-fluoro-7’-(2-fluoro-3-pyridinyl)spiro[imidazo[1,2-c]imidazole-7,9’-xanthene]-5-amine	IC50	0.4 nM	US-8962859: Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use
(7S)-4’-fluoro-7’-(2-fluoro-3-pyridinyl)-2’-(4-methylphenyl)spiro[imidazo[1,2-c]imidazole-7,9’-xanthene]-5-amine	IC50	0.4 nM	US-8962859: Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use
N-(2-amino-3’-chloro-1’-fluorospiro[5,6-dihydro-1,3-oxazine-4,5’-chromeno[2,3-c]pyridine]-7’-yl)-5-but-2-ynoxypyrazine-2-carboxamide	IC50	0.4 nM	US-9296759: Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use
N-[2-amino-1’-fluoro-3’-(2-fluoro-4-pyridinyl)spiro[5,6-dihydro-1,3-thiazine-4,5’-chromeno[2,3-c]pyridine]-7’-yl]-5-methoxypyridine-2-carboxamide	IC50	0.4 nM	US-9296759: Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use
N-[3-[(3R)-5-amino-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-3-yl]-4-fluorophenyl]-5-but-2-ynoxypyridine-2-carboxamide	IC50	0.4 nM	US-9556135: Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide	IC50	0.4 nM	US-10246429: Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
(1S,5S,6S)-3-amino-5-(5-((Z)-2-(5-(but-2-yn-1-yloxy)pyrazin-2-yl)-2-fluorovinyl)-2-fluorophenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carbonitrile	IC50	0.4 nM	US-10246429: Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)(morpholino)methanone	IC50	0.4 nM	US-10246429: Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
((1S,5S,6S)-3-amino-5-(2-fluoro-5-((Z)-2-fluoro-2-(5-(prop-2-yn-1-yloxy)pyrazin-2-yl)vinyl)phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl)((S)-3-fluoropyrrolidin-1-yl)methanone	IC50	0.4 nM	US-10246429: Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use
N-[3-[(5R)-3-amino-2,5-dimethyl-1,1-dioxo-6H-1,2,4-thiadiazin-5-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide	IC50	0.4 nM	US-9687494: Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use
CHEMBL3359749	IC50	0.4 nM
CHEMBL3354715	IC50	0.4 nM
N-[3-[(5R,6R)-8-amino-5-fluoro-6-methyl-4,4-dioxo-4lambda6-thia-7-azaspiro[2.5]oct-7-en-6-yl]-4-fluorophenyl]-5-chloro-3-methylpyridine-2-carboxamide	IC50	0.44 nM	US-9556135: Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
N-[3-[(4aR,7aS)-2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-isocyanopyridine-2-carboxamide	IC50	0.45 nM	US-8987254: Tetrahydropyrrolothiazine compounds
N-[3-[(4aR,7aS)-2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-cyanopyridine-2-carboxamide	IC50	0.45 nM	US-9999624: Combination Alzheimer therapy using anti-N3pGlu Abeta antibodies + a BACE inhibitor
N-[3-[(5R,6R)-8-amino-5-fluoro-6-methyl-4,4-dioxo-4lambda6-thia-7-azaspiro[2.5]oct-7-en-6-yl]-4-fluorophenyl]-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide	IC50	0.48 nM	US-9556135: Amino-dihydrothiazine and amino-dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use
N-[3-[(4aR,7aS)-2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]phenyl]-5-(hydroxymethyl)pyrazine-2-carboxamide	IC50	0.482 nM	US-8987254: Tetrahydropyrrolothiazine compounds

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.96	IC50	0.011	nM	CHEMBL3982593
10.85	IC50	0.014	nM	CHEMBL3922902
10.77	Ki	0.017	nM	CHEMBL2179131
10.62	IC50	0.024	nM	CHEMBL4088234
10.51	IC50	0.031	nM	CHEMBL2408786
10.48	IC50	0.033	nM	CHEMBL4212046
10.47	IC50	0.034	nM	CHEMBL4217023
10.44	Ki	0.036	nM	CHEMBL2179138
10.05	IC50	0.09	nM	CHEMBL4561849
10.00	IC50	0.1	nM	CHEMBL3680900
9.96	IC50	0.11	nM	CHEMBL4203860
9.92	Ki	0.12	nM	CHEMBL449300
9.92	Ki	0.12	nM	CHEMBL254740
9.89	Ki	0.13	nM	ATABECESTAT
9.83	IC50	0.149	nM	CHEMBL5863499
9.82	IC50	0.15	nM	CHEMBL2047041
9.82	IC50	0.15	nM	CHEMBL2177305
9.80	IC50	0.16	nM	CHEMBL2152903
9.80	IC50	0.16	nM	CHEMBL3650848
9.80	IC50	0.157	nM	CHEMBL4564324
9.73	IC50	0.186	nM	CHEMBL6009196
9.70	IC50	0.2	nM	CHEMBL2152903
9.70	IC50	0.2	nM	CHEMBL3260839
9.70	IC50	0.2	nM	CHEMBL3349234
9.70	IC50	0.2	nM	CHEMBL3394218
9.70	IC50	0.2	nM	CHEMBL3394226
9.70	IC50	0.2	nM	CHEMBL3394227
9.70	IC50	0.2	nM	CHEMBL3741617
9.70	IC50	0.2	nM	CHEMBL3695737
9.70	IC50	0.2	nM	CHEMBL4588608
9.70	IC50	0.2	nM	CHEMBL4437161
9.70	IC50	0.2	nM	CHEMBL4577527
9.70	EC50	0.2	nM	CHEMBL409875
9.70	IC50	0.2	nM	CHEMBL6043173
9.68	Ki	0.21	nM	CHEMBL5092328
9.68	IC50	0.211	nM	CHEMBL5197518
9.62	IC50	0.241	nM	CHEMBL6020648
9.60	Ki	0.25	nM	CHEMBL3352906
9.60	IC50	0.25	nM	CHEMBL4861687
9.55	IC50	0.28	nM	CHEMBL2152914
9.54	IC50	0.287	nM	CHEMBL5857457
9.52	IC50	0.3	nM	CHEMBL3260838
9.52	Ki	0.3	nM	CHEMBL363255
9.52	Ki	0.3	nM	CHEMBL448008
9.52	IC50	0.3	nM	CHEMBL3354718
9.52	IC50	0.3	nM	CHEMBL3394211
9.52	IC50	0.3	nM	CHEMBL3394216
9.52	IC50	0.3	nM	CHEMBL3394220
9.52	IC50	0.3	nM	CHEMBL3394221
9.52	IC50	0.3	nM	CHEMBL3394224

PubChem BioAssay actives

3561 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-1,3-thiazol-4-yl]-5-methoxypyridine-2-carboxamide	1369218: Inhibition of BACE1 in human H4 cells transfected with wild type APP assessed as reduction in soluble portion of APPbeta level in cells incubated for overnight by ELISA	ic50	<0.0001	uM
(4S,6R)-4-[2,4-difluoro-5-[[[1-(trifluoromethyl)cyclopropyl]amino]methyl]phenyl]-4,6-dimethyl-5,6-dihydro-1,3-thiazin-2-amine	1460172: Inhibition of BACE1 in human H4 cells expressing wild type APP695 assessed as reduction in soluble APPbeta level after 18 hrs by ELISA	ic50	<0.0001	uM
2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-N-(6-methoxy-2-pyridinyl)-1,3-thiazole-5-carboxamide	1369218: Inhibition of BACE1 in human H4 cells transfected with wild type APP assessed as reduction in soluble portion of APPbeta level in cells incubated for overnight by ELISA	ic50	<0.0001	uM
N-[2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-1,3-thiazol-4-yl]-4-methoxybenzamide	1369218: Inhibition of BACE1 in human H4 cells transfected with wild type APP assessed as reduction in soluble portion of APPbeta level in cells incubated for overnight by ELISA	ic50	<0.0001	uM
(2,5-dimethyl-1,3-oxazol-4-yl)methyl N-[(2R)-1-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-[[(2S)-3-methyl-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-8-oxooctan-4-yl]amino]-3-methylsulfonyl-1-oxopropan-2-yl]carbamate	1797486: Enzyme Inhibition Measurements from Article 10.1021/ja058636j: “Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitors.”	ki	0.0001	uM
N-[3-[(1R,5R,6S)-3-amino-2,2,5-trimethyl-1-oxo-1lambda6-thia-4,9-diazabicyclo[4.3.0]nona-1(9),3-dien-5-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide	1545230: Inhibition of BACE1 in HEK293 cells harboring APP assessed as reduction in amyloidbeta 40 level incubated for 18 to 20 hrs by AlphaLISA Assay	ic50	0.0001	uM
2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-N-(3-methoxyphenyl)-1,3-thiazole-5-carboxamide	1369218: Inhibition of BACE1 in human H4 cells transfected with wild type APP assessed as reduction in soluble portion of APPbeta level in cells incubated for overnight by ELISA	ic50	0.0001	uM
(2,5-dimethyl-1,3-oxazol-4-yl)methyl N-[(2R)-1-[[(4S,5S,7R)-8-[[(2S)-1-(tert-butylamino)-3-methyl-1-oxobutan-2-yl]amino]-5-hydroxy-2,7-dimethyl-8-oxooctan-4-yl]amino]-3-methylsulfonyl-1-oxopropan-2-yl]carbamate	314082: Binding affinity to recombinant memapsin 2	ki	0.0001	uM
N-[(2S)-3-butylsulfonyl-1-[[(2S,3R)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]amino]-1-oxopropan-2-yl]pyrazine-2-carboxamide	292707: Inhibition of BACE expressed in HEK293 cells	ec50	0.0002	uM
(4S)-3’-(3,4-dihydro-2H-pyran-5-yl)-1’-fluoro-7’-(2-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1191077: Inhibition of human recombinant BACE1 pre-incubated with enzyme for 60 mins before fluorescent substrate addition FRET method	ic50	0.0002	uM
N-[3-[(1S,5S,6S)-3-amino-1-(fluoromethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0002	uM
N-[3-[(1S,5S,6S)-3-amino-1-(difluoromethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0002	uM
N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1545213: Inhibition of BACE1 in human SH-SY5Y cells transfected with APP695 assessed as reduction in amyloidbeta (1 to 40 residues) incubated for 24 hrs by sandwich ELlSA	ic50	0.0002	uM
N-[3-[(10R)-8-amino-7,10-dimethyl-1-oxo-1lambda6-thia-2,9-diazabicyclo[5.4.0]undeca-1,8-dien-10-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide	1545230: Inhibition of BACE1 in HEK293 cells harboring APP assessed as reduction in amyloidbeta 40 level incubated for 18 to 20 hrs by AlphaLISA Assay	ic50	0.0002	uM
N-[3-[(2S,5R)-6-amino-5-ethylsulfonyl-2-(fluoromethyl)-5-methyl-3,4-dihydropyridin-2-yl]-4-fluorophenyl]-2,2-difluoro-[1,3]dioxolo[4,5-c]pyridine-6-carboxamide	1807509: Displacement of [3H]-JNJ962 from BACE1 (unknown origin) expressed in HEK293 cell membrane assessed as inhibition constant by scintillation counting analysis	ki	0.0002	uM
2-methoxy-4-[(E)-2-[5-[4-(trifluoromethoxy)phenyl]-1,3,4-oxadiazol-2-yl]ethenyl]phenol	1938216: Inhibition of BACE1 (unknown origin)	ic50	0.0002	uM
(4S)-1’-fluoro-7’-(2-fluoro-3-pyridinyl)-3’-(6-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1191077: Inhibition of human recombinant BACE1 pre-incubated with enzyme for 60 mins before fluorescent substrate addition FRET method	ic50	0.0003	uM
(4S)-1’-fluoro-7’-(2-fluoro-3-pyridinyl)-3’-(3-methyl-1,2-oxazol-5-yl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1191077: Inhibition of human recombinant BACE1 pre-incubated with enzyme for 60 mins before fluorescent substrate addition FRET method	ic50	0.0003	uM
(1S,5S,6S)-3-amino-5-[2,3-difluoro-5-[(5-prop-2-ynoxypyrazine-2-carbonyl)amino]phenyl]-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0003	uM
(4S)-3’-(3,6-dihydro-2H-pyran-4-yl)-7’-(5-prop-1-ynyl-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1416139: Inhibition of recombinant human BACE1 using fluorophore/quencher-tagged peptide as substrate pretreated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay	ic50	0.0003	uM
2-methoxy-4-[(E)-2-[5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]ethenyl]phenol	1938216: Inhibition of BACE1 (unknown origin)	ic50	0.0003	uM
(4S)-4-amino-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(4S,5S,7R)-8-[[(2S)-1-[[(2S)-4-carboxy-1-[(1-carboxy-2-phenylethyl)amino]-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-hydroxy-2,7-dimethyl-8-oxooctan-4-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	42091: Binding affinity for human brain memapsin 2 beta-Secretase (BACE)	ki	0.0003	uM
(2R,5S)-5-[[(2S)-2-[[(2R,4S,5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-hydroxy-2,7-dimethyloctanoyl]amino]-3-methylbutanoyl]amino]-2-benzyl-4-oxooctanedioic acid	238396: Binding affinity against Beta-secretase	ki	0.0003	uM
(4S)-4-amino-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(4S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-hydroxy-6-methyl-3-oxoheptan-4-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	239175: Binding affinity towards Beta-secretase determined using continuum electrostatics solvation	ki	0.0003	uM
N-[3-[(4R,4aR,7aS)-2-amino-7,7-difluoro-4-methyl-6,7a-dihydro-4aH-furo[2,3-e][1,3]oxazin-4-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1545221: Inhibition of BACE1 in human SH-SY5Y cells expressing betaAPP assessed as reduction in amyloidbeta (1 to 40 residues) level incubated for 24 hrs by HTRF assay	ic50	0.0004	uM
(4S)-1’-fluoro-7’-(2-fluoro-3-pyridinyl)-3’-pyridin-4-ylspiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1191077: Inhibition of human recombinant BACE1 pre-incubated with enzyme for 60 mins before fluorescent substrate addition FRET method	ic50	0.0004	uM
(4S)-3’-(3,4-dihydro-2H-pyran-6-yl)-1’-fluoro-7’-(2-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1191077: Inhibition of human recombinant BACE1 pre-incubated with enzyme for 60 mins before fluorescent substrate addition FRET method	ic50	0.0004	uM
N-[6-[2-[2-[2-amino-3-[3-(3,3-dimethylbutylamino)-3-oxopropyl]quinolin-6-yl]phenyl]ethyl]-3-pyridinyl]-4-fluorobenzamide	1301518: Binding affinity to BACE1 (unknown origin) by surface plasmon resonance spectroscopic analysis	kd	0.0004	uM
N-[3-[(1S,5S,6S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0004	uM
(1S,5S,6S)-3-amino-5-[5-[(5-chloropyridine-2-carbonyl)amino]-2,3-difluorophenyl]-N,N,5-trimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0004	uM
N-[3-[(4aS,5S,7aS)-2-amino-5-(1,1-difluoroethyl)-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-(1,2,4-triazol-1-yl)pyrazine-2-carboxamide	1545213: Inhibition of BACE1 in human SH-SY5Y cells transfected with APP695 assessed as reduction in amyloidbeta (1 to 40 residues) incubated for 24 hrs by sandwich ELlSA	ic50	0.0004	uM
(4S)-3’-(2-fluoro-4-pyridinyl)-7’-(5-prop-1-ynyl-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1416139: Inhibition of recombinant human BACE1 using fluorophore/quencher-tagged peptide as substrate pretreated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay	ic50	0.0004	uM
(1S,5S,6S)-3-amino-5-[5-[(5-chloropyridine-2-carbonyl)amino]-2,3-difluorophenyl]-N,5-dimethyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0004	uM
N-[3-[(3S)-1-amino-5-fluoro-3-methyl-4H-2,6-naphthyridin-3-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1758845: Inhibition of BACE1 in human SH-SY5Y cells expressing APP assessed as reduction in Abeta40 by HTRF assay	ic50	0.0004	uM
N-[3-[(1S,5S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide	1807507: Inhibition of BACE1 (1 to 454 residues) (unknown origin) using APP harboring Swedish Lys-Met/Asn-Leu mutant-derived peptide as substrate by FRET assay	ic50	0.0004	uM
3-N-[(2S,3R)-3-hydroxy-4-[(3-methoxyphenyl)methylamino]-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-1-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide	778924: Inhibition of BACE1 (unknown origin) assessed as inhibition of cellular amyloid beta level	ic50	0.0004	uM
(4S)-7’-(2-fluoro-3-pyridinyl)-3’-[(3R)-3-fluoropyrrolidin-1-yl]spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1190882: Inhibition of BACE1 (unknown origin) by fluorescence assay	ic50	0.0005	uM
(4S)-3’-(3,6-dihydro-2H-pyran-5-yl)-7’-(5-prop-1-ynyl-3-pyridinyl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-2-amine	1416139: Inhibition of recombinant human BACE1 using fluorophore/quencher-tagged peptide as substrate pretreated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay	ic50	0.0005	uM
4-[(E)-2-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]ethenyl]-2-methoxyphenol	1938216: Inhibition of BACE1 (unknown origin)	ic50	0.0005	uM
pyridin-3-ylmethyl N-[(2S)-3-butylsulfonyl-1-[[(2S,3R)-1-(3,5-difluorophenyl)-4-[(3-ethylphenyl)methylamino]-3-hydroxybutan-2-yl]amino]-1-oxopropan-2-yl]carbamate	292707: Inhibition of BACE expressed in HEK293 cells	ec50	0.0006	uM
N-[2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-1,3-thiazol-4-yl]-1-(difluoromethyl)pyrazole-3-carboxamide	1369218: Inhibition of BACE1 in human H4 cells transfected with wild type APP assessed as reduction in soluble portion of APPbeta level in cells incubated for overnight by ELISA	ic50	0.0006	uM
N-[3-[(9S)-7-amino-2,2-difluoro-9-methyl-6-oxa-8-azaspiro[3.5]non-7-en-9-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide	1545221: Inhibition of BACE1 in human SH-SY5Y cells expressing betaAPP assessed as reduction in amyloidbeta (1 to 40 residues) level incubated for 24 hrs by HTRF assay	ic50	0.0006	uM
(1S,5S,6S)-3-amino-5-[5-[(5-chloropyridine-2-carbonyl)amino]-2,3-difluorophenyl]-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-ene-1-carboxamide	1546012: Inhibition of BACE1 (unknown origin) using FRET peptide substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0006	uM
N-[3-[(1S,5S,6S)-3-amino-5-(fluoromethyl)-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl]-5-prop-2-ynoxypyrazine-2-carboxamide	1545217: Inhibition of C-terminal His6-tagged human BACE1 expressed in mammalian expression system preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay	ic50	0.0006	uM
N-[6-[(1R,5R,6S)-3-amino-2,2,5-trimethyl-1-oxo-1lambda6-thia-4,9-diazabicyclo[4.3.0]nona-1(9),3-dien-5-yl]-5-fluoro-2-pyridinyl]-5-cyano-3-methylpyridine-2-carboxamide	1545230: Inhibition of BACE1 in HEK293 cells harboring APP assessed as reduction in amyloidbeta 40 level incubated for 18 to 20 hrs by AlphaLISA Assay	ic50	0.0006	uM
N-[2-amino-7’-(3,6-dihydro-2H-pyran-5-yl)spiro[5H-1,3-oxazole-4,9’-xanthene]-2’-yl]-5-chloropyridine-2-carboxamide	1301518: Binding affinity to BACE1 (unknown origin) by surface plasmon resonance spectroscopic analysis	kd	0.0006	uM
N-[(4S)-2-amino-3’-(3,6-dihydro-2H-pyran-5-yl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-7’-yl]-5-chloropyridine-2-carboxamide	1416139: Inhibition of recombinant human BACE1 using fluorophore/quencher-tagged peptide as substrate pretreated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay	ic50	0.0006	uM
3-[5-[(4S)-2-amino-3’-(3,6-dihydro-2H-pyran-4-yl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-7’-yl]-3-pyridinyl]prop-2-yn-1-ol	1416139: Inhibition of recombinant human BACE1 using fluorophore/quencher-tagged peptide as substrate pretreated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay	ic50	0.0006	uM
N-[(4S)-2-amino-3’-(oxan-4-yl)spiro[5H-1,3-oxazole-4,5’-chromeno[2,3-c]pyridine]-7’-yl]-5-chloropyridine-2-carboxamide	1416139: Inhibition of recombinant human BACE1 using fluorophore/quencher-tagged peptide as substrate pretreated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay	ic50	0.0006	uM
N-[3-[(1S,5R)-3-amino-5-methyl-1-methylimino-1-oxo-2-(2,2,2-trifluoroethyl)-6H-1,2,4-thiadiazin-5-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide	1704650: Inhibition of BACE1 in HEK293 cells harboring APP assessed as reduction in amyloidbeta 40 level measured after 18 to 20 hrs by AlphaLISA Assay	ic50	0.0006	uM

CTD chemical–gene interactions

85 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Tretinoin	affects localization, decreases expression, increases expression	4
Lead	increases expression, increases reaction, affects cotreatment, decreases reaction, increases abundance	3
methylmercuric chloride	decreases expression	2
bisphenol A	affects binding, decreases methylation	2
potassium chromate(VI)	affects cotreatment, increases expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Curcumin	increases expression, decreases reaction	2
DDT	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation, decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
4-((alpha-L-rhamnosyloxy)benzyl)isothiocyanate	decreases reaction, increases expression	1
oxyphylla A	decreases reaction, increases expression	1
PF-06840003	affects expression, affects reaction	1
pimagedine	affects cotreatment, decreases reaction, increases expression	1
ferulic acid	decreases reaction, increases expression	1
naringenin	decreases activity	1
triphenyl phosphate	affects expression	1
lead acetate	increases abundance, increases expression, increases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
Azure B	decreases activity	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
dinophysistoxin 1	decreases expression	1
chromium hexavalent ion	affects expression	1
27-hydroxycholesterol	increases expression	1
Go 6976	affects localization, decreases reaction	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

1237 unique, capped per target: 1230 binding, 6 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2388914	Binding	Inhibition of BACE1/BACE2 (unknown origin) transfected in CHO cells assessed as release of amyloid beta (1 to 40) after 24 hrs by immunoassay	Dihydrooxazines As Inhibitors of BACE-1 or BACE-2. — *ACS Med Chem Lett*
CHEMBL832508	Functional	Beta-secretase inhibitory activity as inhibition of secreted alkaline phosphatase in HEK293 cells expressing SEAP-APP fusion protein	Discovery of cell-permeable non-peptide inhibitors of beta-secretase by high-throughput docking and continuum electrostatics calculations. — *J Med Chem*
CHEMBL4727125	ADMET	Inhibition human BACE1 expressed in baculovirus expression system at 5 uM using Panvera peptide as substrate measured after 60 mins by fluorescence assay relative to control	Centrally Active Multitarget Anti-Alzheimer Agents Derived from the Antioxidant Lead CR-6. — *J Med Chem*

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8ZX	Ubigene HEK293 BACE1 KO	Transformed cell line	Female
CVCL_D9YE	Ubigene HeLa BACE1 KO	Cancer cell line	Female
CVCL_SE58	HAP1 BACE1 (-) 1	Cancer cell line	Male
CVCL_XB48	FC33	Transformed cell line	Female
CVCL_XL92	HAP1 BACE1 (-) 2	Cancer cell line	Male
CVCL_YK22	HEK293 tGFP-BACE1	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BACE1 across ~30M SureChEMBL compounds — explore on Sugi Predict.