PCSK2

Summary

PCSK2 (proprotein convertase subtilisin/kexin type 2, HGNC:8744) is a protein-coding gene on chromosome 20p12.1, encoding Neuroendocrine convertase 2 (P16519). Serine endopeptidase which is involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues.

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5126 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 55 total
• Druggable target: yes
• MANE Select transcript: NM_002594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8744
Approved symbol	PCSK2
Name	proprotein convertase subtilisin/kexin type 2
Location	20p12.1
Locus type	gene with protein product
Status	Approved
Aliases	PC2, SPC2
Ensembl gene	ENSG00000125851
Ensembl biotype	protein_coding
OMIM	162151
Entrez	5126

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000262545, ENST00000377899, ENST00000459871, ENST00000470007, ENST00000536609, ENST00000947703, ENST00000947704, ENST00000947705

RefSeq mRNA: 3 — MANE Select: NM_002594 NM_001201528, NM_001201529, NM_002594

CCDS: CCDS13125, CCDS56179, CCDS56180

Canonical transcript exons

ENST00000262545 — 12 exons

Exon	Start	End
ENSE00000859196	17409263	17409339
ENSE00000859197	17429435	17429523
ENSE00000859198	17436708	17436883
ENSE00000859199	17453742	17453957
ENSE00000859200	17456348	17456448
ENSE00000859201	17465326	17465553
ENSE00001163720	17481584	17484578
ENSE00001163726	17227040	17227482
ENSE00003475020	17260240	17260344
ENSE00003496377	17360532	17360640
ENSE00003530795	17358327	17358440
ENSE00003662645	17369240	17369277

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 97.81.

FANTOM5 (CAGE): breadth broad, TPM avg 14.1461 / max 1169.2853, expressed in 506 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183635	9.5638	476
183634	3.6547	276
183636	0.6878	146
183633	0.2398	92

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	97.81	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.06	gold quality
type B pancreatic cell	CL:0000169	95.44	gold quality
right lobe of thyroid gland	UBERON:0001119	94.59	gold quality
CA1 field of hippocampus	UBERON:0003881	94.44	gold quality
endothelial cell	CL:0000115	94.33	gold quality
middle temporal gyrus	UBERON:0002771	93.55	gold quality
superior frontal gyrus	UBERON:0002661	92.66	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.24	gold quality
orbitofrontal cortex	UBERON:0004167	91.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.58	gold quality
primary visual cortex	UBERON:0002436	91.40	gold quality
entorhinal cortex	UBERON:0002728	91.26	gold quality
postcentral gyrus	UBERON:0002581	91.17	gold quality
prefrontal cortex	UBERON:0000451	90.92	gold quality
parietal lobe	UBERON:0001872	90.71	gold quality
dorsal root ganglion	UBERON:0000044	90.50	gold quality
occipital lobe	UBERON:0002021	89.82	gold quality
frontal cortex	UBERON:0001870	88.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.13	gold quality
left lobe of thyroid gland	UBERON:0001120	87.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.82	gold quality
neocortex	UBERON:0001950	87.50	gold quality
cerebral cortex	UBERON:0000956	86.90	gold quality
sural nerve	UBERON:0015488	86.80	gold quality
thyroid gland	UBERON:0002046	86.15	gold quality
cortical plate	UBERON:0005343	85.41	gold quality
telencephalon	UBERON:0001893	85.07	gold quality
right frontal lobe	UBERON:0002810	84.51	gold quality
temporal lobe	UBERON:0001871	84.26	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	3459.68
E-GEOD-81547	yes	1981.98
E-GEOD-81608	yes	1850.50
E-GEOD-83139	yes	1436.72
E-HCAD-31	yes	1054.39
E-ENAD-20	yes	716.09
E-HCAD-35	yes	89.21
E-GEOD-137537	yes	34.59
E-MTAB-8142	yes	20.95
E-ENAD-27	yes	14.16
E-GEOD-84465	yes	7.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, PAX6

miRNA regulators (miRDB)

147 targeting PCSK2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115

Literature-anchored findings (GeneRIF, showing 18)

• prominently expressed in PTHrP-expressing human cancer cell lines originating from tumors of the breast, lung, prostate, as well as lymphoma (PMID:11720250)
• A marked decrease in the ratio of the PC2 precursor to the total enzymatic pool is observed in the frontal cortex of Alzheimer patients; however, the content and enzymatic activity of the PC2 mature form are similar in Alzheimer patients and controls. (PMID:14614908)
• concluded that there are two novel TRE-like sequences in the hPC2 promoter and that these regions act in concert in a unique manner to facilitate the effects of thyroid hormone and 9-cis-retinoic acid on PC2 (PMID:15585599)
• PC1 and PC2 in are abnormally expressed and processed in human colorectal liver metastases (PMID:16293189)
• Single nucleotide polymorphisms in PCSK2 is associated with type 2 diabetes (PMID:17618154)
• PC1/3 governs the endocrine, and PC2 the neuronal processing, of proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22. (PMID:18096669)
• PC1 and PC2 were primarily expressed in neurons, whereas PACE4 appeared to be largely restricted to glia. Thus, elevated PACE4 may modulate the bioactivity of proteins secreted in the ONH and retina. (PMID:19339735)
• The presence of PC and GOAT in the cells, as well as n-octanoic acid in the culture medium, was necessary to produce n-octanoyl ghrelin. (PMID:19628676)
• Data revealed that six polymorphisms of F10, PITRM1, PCSK2, JPH3, MYO7B, and AKAP12 were related (P<0.05) to the prevalence of chronic kidney disease. (PMID:19724895)
• SEMA3F, CLEC16A, LAMA3, and PCSK2 variants have roles in myocardial infarction in Japanese individuals (PMID:20036365)
• differential gene expression profiles revealed more abundant mRNA expression in ectopic ACTH syndrome than in Cushing disease of proprotein convertase-2 (PMID:21383526)
• The association of risk allele rs2021785 at PCSK2 with type 2 diabetes exists in a Han Chinese population (PMID:21437630)
• variant of the PCSK2 gene was associated with reduced glucose-stimulated insulin secretion, but also with lower glucagon levels, which could potentially counteract the effects of decreased insulin secretion on the risk of type 2 diabetes (PMID:23011353)
• in the processing of hypothalamic neuropeptides in huntington disease may partially arise from decreased PC1/3 and PC2 expressions. (PMID:24226266)
• FAM20C plays a role in 7B2-mediated proPC2 activation by phosphorylating residue Thr111; and that 7B2 function is regulated by alternative splicing. (PMID:25811241)
• PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes. (PMID:26607656)
• Revisiting Proinsulin Processing: Evidence That Human beta-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2. (PMID:32291281)
• PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin. (PMID:32794589)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcsk2	ENSDARG00000019451
mus_musculus	Pcsk2	ENSMUSG00000027419
rattus_norvegicus	Pcsk2	ENSRNOG00000005438
drosophila_melanogaster	amon	FBGN0023179
caenorhabditis_elegans		WBGENE00001172

Paralogs (9): PCSK5 (ENSG00000099139), PCSK4 (ENSG00000115257), TPP2 (ENSG00000134900), PCSK6 (ENSG00000140479), FURIN (ENSG00000140564), MBTPS1 (ENSG00000140943), PCSK7 (ENSG00000160613), PCSK9 (ENSG00000169174), PCSK1 (ENSG00000175426)

Protein

Protein identifiers

Neuroendocrine convertase 2 — P16519 (reviewed: P16519)

Alternative names: KEX2-like endoprotease 2, Prohormone convertase 2, Proprotein convertase 2

All UniProt accessions (1): P16519

UniProt curated annotations — full annotation on UniProt →

Function. Serine endopeptidase which is involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Secreted.

Similarity. Belongs to the peptidase S8 family. Furin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P16519-1	1	yes
P16519-2	2
P16519-3	3

RefSeq proteins (3): NP_001188457, NP_001188458, NP_002585* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000209	Peptidase_S8/S53_dom	Domain
IPR002884	P_dom	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR015500	Peptidase_S8_subtilisin-rel	Family
IPR022398	Peptidase_S8_His-AS	Active_site
IPR023827	Peptidase_S8_Asp-AS	Active_site
IPR023828	Peptidase_S8_Ser-AS	Active_site
IPR032815	S8_pro-domain	Domain
IPR034182	Kexin/furin	Domain
IPR036852	Peptidase_S8/S53_dom_sf	Homologous_superfamily
IPR038466	S8_pro-domain_sf	Homologous_superfamily

Pfam: PF00082, PF01483, PF16470

UniProt features (24 total): sequence variant 7, glycosylation site 3, disulfide bond 3, active site 3, splice variant 2, domain 2, signal peptide 1, propeptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16519-F1	92.42	0.83

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 (3): 167 (charge relay system); 208 (charge relay system); 384 (charge relay system)

Disulfide bonds (3): 225–376, 317–347, 468–494

Glycosylation sites (3): 524, 375, 514

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-264876	Insulin processing
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 182 (showing top): RNGTGGGC_UNKNOWN, CREL_01, TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, TGCGCANK_UNKNOWN, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, GCANCTGNY_MYOD_Q6, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, TGACCTY_ERR1_Q2, LHX3_01, CACCAGC_MIR138, GGGTGGRR_PAX4_03, GGAMTNNNNNTCCY_UNKNOWN

GO Biological Process (8): proteolysis (GO:0006508), nervous system development (GO:0007399), peptide hormone processing (GO:0016486), protein autoprocessing (GO:0016540), insulin processing (GO:0030070), enkephalin processing (GO:0034230), islet amyloid polypeptide processing (GO:0034231), protein processing (GO:0016485)

GO Molecular Function (6): serine-type endopeptidase activity (GO:0004252), endopeptidase activity (GO:0004175), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), membrane (GO:0016020), transport vesicle (GO:0030133), secretory granule (GO:0030141), neuron projection (GO:0043005), extracellular region (GO:0005576), cytoplasmic vesicle (GO:0031410), intracellular organelle lumen (GO:0070013)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide hormone metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptide hormone processing	3
cellular anatomical structure	3
peptidase activity	2
endomembrane system	2
protein metabolic process	1
system development	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
protein processing	1
insulin metabolic process	1
proteolysis	1
protein maturation	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine hydrolase activity	1
catalytic activity	1
nuclear lumen	1
cytoplasmic vesicle	1
secretory vesicle	1
plasma membrane bounded cell projection	1
cytoplasm	1
intracellular vesicle	1
intracellular organelle	1
organelle lumen	1

Protein interactions and networks

STRING

2271 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCSK2	SCG5	P01164	962
PCSK2	CPE	P16870	807
PCSK2	THBD	P07204	772
PCSK2	GCG	P01275	750
PCSK2	SST	P01166	649
PCSK2	SSTR5	P34988	646
PCSK2	PYGB	P11216	599
PCSK2	NKX6-1	P78426	584
PCSK2	SSTR4	P31391	581
PCSK2	POMC	P01189	580
PCSK2	INS	P01308	566
PCSK2	NEUROD1	Q13562	557
PCSK2	SLC30A8	Q8IWU4	556
PCSK2	CD226	Q15762	546
PCSK2	ABCC8	Q09428	541

IntAct

8 interactions, top by confidence:

A	B	Type	Score
BOD1	PCSK2	psi-mi:“MI:0915”(physical association)	0.560
PCSK2	PCSK2	psi-mi:“MI:0407”(direct interaction)	0.440
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DISC1	PCSK2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): PCSK2 (Affinity Capture-MS)

ESM2 similar proteins: A0A044RE18, B4F6N6, B5DF27, E1C3U7, F1QQC3, G5ECN9, O17798, O35548, O64481, P09231, P09958, P13134, P16519, P21661, P23188, P23377, P28840, P28841, P29119, P29120, P29122, P29145, P29146, P30432, P41413, P51512, P51559, P58022, P63239, P63240, P91863, Q03333, Q04592, Q08B63, Q09175, Q28193, Q5REC2, Q63415, Q8QGP3, Q8SQJ3

Diamond homologs: A0A044RE18, G5ECN9, O13359, O17798, P09231, P09958, P13134, P16519, P21661, P23188, P23377, P26016, P28840, P28841, P29119, P29120, P29121, P29122, P29141, P29145, P29146, P30430, P30432, P41413, P42781, P51559, P63239, P63240, P91863, Q03333, Q04592, Q09175, Q16549, Q28193, Q5REC2, Q61139, Q62849, Q63415, Q6UW60, Q78EH2

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	PCSK2	“transcriptional regulation”
PCSK2	“down-regulates quantity”	OXT	cleavage
PCSK2	“up-regulates quantity”	Oxytocin	cleavage
PCSK2	“up-regulates quantity”	“Neurophysin 1”	cleavage
PCSK2	“up-regulates activity”	IAPP	cleavage
PCSK2	“up-regulates quantity”	Corticotropin	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2835 predictions. Top by Δscore:

Variant	Effect	Δscore
20:17227479:AAAGG:A	donor_loss	1.0000
20:17227484:T:A	donor_loss	1.0000
20:17260343:GG:G	donor_gain	1.0000
20:17260344:GG:G	donor_gain	1.0000
20:17360524:T:A	acceptor_gain	1.0000
20:17360637:GATG:G	donor_gain	1.0000
20:17369278:G:GG	donor_gain	1.0000
20:17409257:TTTCA:T	acceptor_loss	1.0000
20:17409258:TTCAG:T	acceptor_loss	1.0000
20:17409259:TCA:T	acceptor_loss	1.0000
20:17409260:CAG:C	acceptor_loss	1.0000
20:17409261:A:AG	acceptor_gain	1.0000
20:17409261:AG:A	acceptor_loss	1.0000
20:17409262:G:GG	acceptor_gain	1.0000
20:17409262:G:T	acceptor_loss	1.0000
20:17409262:GA:G	acceptor_gain	1.0000
20:17409262:GAAT:G	acceptor_gain	1.0000
20:17409335:AACAG:A	donor_loss	1.0000
20:17409336:ACAG:A	donor_loss	1.0000
20:17409337:CAGGT:C	donor_loss	1.0000
20:17409338:AGGT:A	donor_loss	1.0000
20:17409339:G:GA	donor_loss	1.0000
20:17409341:T:G	donor_loss	1.0000
20:17429431:A:AG	acceptor_gain	1.0000
20:17429432:A:G	acceptor_gain	1.0000
20:17429433:A:AG	acceptor_gain	1.0000
20:17429434:G:GG	acceptor_gain	1.0000
20:17429434:GCCAC:G	acceptor_gain	1.0000
20:17436880:CAAGG:C	donor_loss	1.0000
20:17436882:AGG:A	donor_loss	1.0000

AlphaMissense

4227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:17358430:A:C	Q129P	1.000
20:17358432:T:A	W130R	1.000
20:17358432:T:C	W130R	1.000
20:17358434:G:C	W130C	1.000
20:17358434:G:T	W130C	1.000
20:17358439:T:C	L132P	1.000
20:17360589:T:A	W152R	1.000
20:17360589:T:C	W152R	1.000
20:17360591:G:C	W152C	1.000
20:17360591:G:T	W152C	1.000
20:17360607:G:A	G158R	1.000
20:17360607:G:C	G158R	1.000
20:17360607:G:T	G158W	1.000
20:17360608:G:A	G158E	1.000
20:17360608:G:T	G158V	1.000
20:17360634:G:C	D167H	1.000
20:17360634:G:T	D167Y	1.000
20:17360635:A:C	D167A	1.000
20:17360635:A:T	D167V	1.000
20:17360637:G:C	D168H	1.000
20:17360638:A:C	D168A	1.000
20:17360638:A:T	D168V	1.000
20:17360640:G:T	G169W	1.000
20:17369240:G:A	G169E	1.000
20:17369264:T:C	L177P	1.000
20:17409275:A:C	S186R	1.000
20:17409277:T:A	S186R	1.000
20:17409277:T:G	S186R	1.000
20:17409337:C:A	N206K	1.000
20:17409337:C:G	N206K	1.000

dbSNP variants (sampled 300 via entrez): RS1000008104 (20:17376331 C>A,T), RS1000010180 (20:17246313 G>T), RS1000039398 (20:17255135 C>A,T), RS1000046495 (20:17448616 A>G), RS1000056079 (20:17249307 C>T), RS1000083493 (20:17456673 G>A), RS1000087676 (20:17287939 C>G,T), RS1000088079 (20:17294337 A>C), RS1000097861 (20:17391679 C>G), RS1000109364 (20:17423145 A>G), RS1000118589 (20:17416357 T>C), RS1000124202 (20:17314640 A>G), RS1000129811 (20:17329640 A>T), RS1000135547 (20:17472551 A>G), RS1000153333 (20:17231566 G>A)

Disease associations

OMIM: gene MIM:162151 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000328_3	Biochemical measures	8.000000e-06
GCST000880_22	Menarche (age at onset)	3.000000e-08
GCST001066_21	Dialysis-related mortality	5.000000e-06
GCST001762_324	Obesity-related traits	8.000000e-08
GCST002362_13	Preschool internalizing problems	7.000000e-06
GCST002541_119	Menarche (age at onset)	1.000000e-13
GCST003488_10	Response to fenofibrate (triglyceride levels)	4.000000e-06
GCST003771_7	Loneliness	3.000000e-06
GCST006086_10	Familial lung cancer	4.000000e-06
GCST007565_40	Morning person	7.000000e-16
GCST007576_439	Chronotype	2.000000e-07
GCST007576_92	Chronotype	7.000000e-16
GCST010989_156	Body size at age 10	1.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0005119	antioxidant measurement
EFO:0005661	Child Behaviour Checklist assessment
EFO:0007681	triglyceride change measurement
EFO:0007865	loneliness measurement
EFO:0006953	family history of lung cancer
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2433 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S8: Subtilisin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
peptide 18 [PMID: 24350995]	Inhibition	9.62	pKi

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.62	Ki	0.24	nM	CHEMBL3115771
9.44	Ki	0.36	nM	CHEMBL3126388
8.77	Ki	1.7	nM	CHEMBL3115770
7.26	Ki	55	nM	CHEMBL568525
6.51	Ki	312	nM	CHEMBL566340
5.86	Ki	1388	nM	CHEMBL569918

PubChem BioAssay actives

6 with measured affinity, of 8 total; 6 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
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(4-carbamimidoylphenyl)methyl]hexanamide	1067773: Inhibition of human PC2 expressed in drosophila schneider 2 cells using pyroGlu-Arg-Thr-Lys-Arg-AMC as substrate after 1 hr	ki	0.0002	uM
137630787	1628272: Inhibition of recombinant C-terminal truncated human SPC2 expressed in drosophila Schneider 2 cells after 1 hr by spectrofluorometry	ki	0.0004	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-6-amino-N-[(E)-4-(diaminomethylideneamino)but-2-enyl]hexanamide	1067773: Inhibition of human PC2 expressed in drosophila schneider 2 cells using pyroGlu-Arg-Thr-Lys-Arg-AMC as substrate after 1 hr	ki	0.0017	uM
N-[(2S)-1-[[(2S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]decanamide	446390: Inhibition of human PC2 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	0.0550	uM
(2S)-N-[(2S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-5-(diaminomethylideneamino)-2-[(2-phenylacetyl)amino]pentanamide	446390: Inhibition of human PC2 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	0.3120	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-5-(diaminomethylideneamino)pentanamide	446390: Inhibition of human PC2 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	1.3880	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, affects cotreatment, decreases expression, increases methylation	3
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	affects cotreatment, decreases expression	1
butylbenzyl phthalate	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
imeglimin	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Alitretinoin	increases expression	1
Cocaine	decreases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Thimerosal	increases expression	1
Triclosan	decreases expression	1
Triiodothyronine	decreases expression	1
Crack Cocaine	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1049705	Binding	Inhibition of human PC2 expressed in Drosophila schneider 2 cells by fluorescence assay	Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.