PCSK7

Summary

PCSK7 (proprotein convertase subtilisin/kexin type 7, HGNC:8748) is a protein-coding gene on chromosome 11q23.3, encoding Proprotein convertase subtilisin/kexin type 7 (Q16549). Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif.

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. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It can process proalbumin and is thought to be responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene has been implicated in the transcriptional regulation of housekeeping genes and plays a role in the regulation of iron metabolism. A t(11;14)(q23;q32) chromosome translocation associated with B-cell lymphoma occurs between this gene and its inverted counterpart.

Source: NCBI Gene 9159 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 128 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8748
Approved symbol	PCSK7
Name	proprotein convertase subtilisin/kexin type 7
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	PC7, PC8, LPC, SPC7
Ensembl gene	ENSG00000160613
Ensembl biotype	protein_coding
OMIM	604872
Entrez	9159

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 26 protein_coding, 7 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000320934, ENST00000524507, ENST00000525027, ENST00000527037, ENST00000527861, ENST00000528217, ENST00000528973, ENST00000529458, ENST00000530269, ENST00000531573, ENST00000532301, ENST00000532810, ENST00000533135, ENST00000534529, ENST00000676339, ENST00000852286, ENST00000852287, ENST00000852288, ENST00000852289, ENST00000852290, ENST00000852291, ENST00000852292, ENST00000852293, ENST00000852294, ENST00000852295, ENST00000852296, ENST00000852297, ENST00000852298, ENST00000928997, ENST00000928998, ENST00000928999, ENST00000929000, ENST00000950973, ENST00000950974, ENST00000950975

RefSeq mRNA: 1 — MANE Select: NM_004716 NM_004716

CCDS: CCDS8382

Canonical transcript exons

ENST00000320934 — 17 exons

Exon	Start	End
ENSE00001053373	117227157	117227322
ENSE00001053375	117224701	117224755
ENSE00001053378	117230349	117230468
ENSE00001053381	117223208	117223308
ENSE00001053385	117224078	117224216
ENSE00001053388	117228216	117228350
ENSE00001131013	117225931	117226021
ENSE00001241963	117229377	117229856
ENSE00002155293	117232027	117232073
ENSE00002166729	117204337	117206356
ENSE00003490035	117219057	117219164
ENSE00003554685	117206681	117206798
ENSE00003571416	117207970	117208064
ENSE00003608175	117208897	117209053
ENSE00003624780	117218466	117218568
ENSE00003636926	117219591	117219758
ENSE00003643769	117207067	117207160

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9519 / max 96.7959, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122477	11.3758	1793
122478	1.5760	646

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.59	gold quality
sural nerve	UBERON:0015488	96.55	gold quality
mucosa of transverse colon	UBERON:0004991	95.32	gold quality
transverse colon	UBERON:0001157	94.78	gold quality
mucosa of stomach	UBERON:0001199	94.32	gold quality
left uterine tube	UBERON:0001303	94.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.25	gold quality
body of stomach	UBERON:0001161	93.81	gold quality
colonic epithelium	UBERON:0000397	93.63	gold quality
buccal mucosa cell	CL:0002336	93.48	gold quality
lymph node	UBERON:0000029	93.45	gold quality
rectum	UBERON:0001052	93.28	gold quality
small intestine	UBERON:0002108	93.21	gold quality
spleen	UBERON:0002106	92.92	gold quality
stomach	UBERON:0000945	92.62	gold quality
blood	UBERON:0000178	92.58	gold quality
apex of heart	UBERON:0002098	92.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.53	gold quality
cerebellar hemisphere	UBERON:0002245	92.42	gold quality
cerebellar cortex	UBERON:0002129	92.36	gold quality
colon	UBERON:0001155	92.24	gold quality
intestine	UBERON:0000160	92.05	gold quality
large intestine	UBERON:0000059	92.01	gold quality
stromal cell of endometrium	CL:0002255	91.99	gold quality
leukocyte	CL:0000738	91.67	gold quality
adenohypophysis	UBERON:0002196	91.59	gold quality
monocyte	CL:0000576	91.56	gold quality
mononuclear cell	CL:0000842	91.46	gold quality
lower esophagus mucosa	UBERON:0035834	91.39	gold quality
upper lobe of left lung	UBERON:0008952	91.31	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	3603.56
E-GEOD-137537	yes	1064.36
E-MTAB-7407	yes	1018.12
E-MTAB-8142	yes	79.77
E-CURD-46	yes	37.15
E-HCAD-1	yes	16.88
E-ANND-3	yes	11.68
E-HCAD-6	no	1379.51
E-GEOD-149689	no	1019.06
E-MTAB-9067	no	4.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting PCSK7, 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-4692	100.00	67.32	2066
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3153	99.55	67.59	2337

Literature-anchored findings (GeneRIF, showing 22)

• we investigated the specificity and potency of complete prodomains and short C-terminal prodomain peptides of each SPC on highly purified, soluble enzyme preparations of human SPC1, SPC6, and SPC7. (PMID:11723118)
• in binding VEGFR-2, furin and PC5 promote cleavage of N-and C-terminal VEGF-D propeptides, whereas PC7 promotes cleavage of the C-terminal propeptide only (PMID:17242158)
• Mass spectrometry analysis provides evidence that the HLA-B51-presented peptide profile is altered in the absence of peptide-loading complex quality control or lack of PC7 function in major histocompatibility (MHC) class I-mediated antigen presentation. (PMID:20164418)
• PC7 is distinct from other proprotein convertases in its zymogen activation, subcellular localization, and trafficking. (PMID:21075846)
• PCSK7 is involved in sTfR generation and iron homeostasis. (PMID:21149283)
• Proprotein convertase PC7 enhances the activation of the EGF receptor pathway through processing of the EGF precursor. (PMID:21209099)
• Region encoded by amino acids ala713-asp730 is essential and sufficient for endocytosis. (PMID:22294700)
• Among the PC family members, only furin activates hepcidin in hepatocytes, and uniquely the full-length membrane-bound PC7 can directly shed hTfR1 by cleavage at Arg100 (PMID:23390091)
• overexpression of PCs, furin and PC5, but not PC7, which are all expressed in SMC, increase PKGI cleavage in a dose-dependent manner (PMID:23686857)
• Furin and PC7 siRNAs induced HIF-1alpha protein by increasing its translation, resulting in upregulation of VEGF-A. (PMID:24436242)
• Results demonstrate that PCSK7 variation is a strong host risk factor of liver cirrhosis in hereditary hemochromatosis patients homozygous for HFE C282Y. (PMID:24556216)
• The data suggest that PCSK7 genotypes may interact with dietary CHO intake on changes in insulin sensitivity in the white Americans. (PMID:25504030)
• Our present data suggest that PCSK7 as well as PCSK9 may be associated with lipids, especially triglyceride, and may serve as a candidate for a new drug target to treat lipid abnormality syndromes. (PMID:26763881)
• PCSK7 rs236918 C allele is a risk factor for cirrhosis development in Italian patients with HFE-Hemochromatosis. (PMID:26868056)
• PCSK7 gene variation is associated with dyslipidemia and more severe liver disease in high risk individuals, likely by modulating PCSK7 expression/activity. (PMID:30918065)
• The motif EXEXXXL in the cytosolic tail of the secretory human proprotein convertase PC7 regulates its trafficking and cleavage activity. (PMID:31915245)
• Proprotein convertase 7 (PCSK7) reduces apoA-V levels. (PMID:31945259)
• Network Medicine Approach in Prevention and Personalized Treatment of Dyslipidemias. (PMID:33118184)
• Variants in PCSK7, PNPLA3 and TM6SF2 are risk factors for the development of cirrhosis in hereditary haemochromatosis. (PMID:33565643)
• The rs508487, rs236911, and rs236918 Genetic Variants of the Proprotein Convertase Subtilisin-Kexin Type 7 (PCSK7) Gene Are Associated with Acute Coronary Syndrome and with Plasma Concentrations of HDL-Cholesterol and Triglycerides. (PMID:34207761)
• Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver transplantation: a cross-sectional study. (PMID:34876018)
• Dysregulation of the LPC-ATX-LPA axis in autoimmune hepatitis is associated with monocyte activation. (PMID:37392838)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcsk7	ENSDARG00000069968
mus_musculus	Pcsk7	ENSMUSG00000035382
rattus_norvegicus	Pcsk7	ENSRNOG00000017478

Paralogs (9): PCSK5 (ENSG00000099139), PCSK4 (ENSG00000115257), PCSK2 (ENSG00000125851), TPP2 (ENSG00000134900), PCSK6 (ENSG00000140479), FURIN (ENSG00000140564), MBTPS1 (ENSG00000140943), PCSK9 (ENSG00000169174), PCSK1 (ENSG00000175426)

Protein

Protein identifiers

Proprotein convertase subtilisin/kexin type 7 — Q16549 (reviewed: Q16549)

Alternative names: Lymphoma proprotein convertase, Prohormone convertase 7, Proprotein convertase 7, Proprotein convertase 8, Subtilisin/kexin-like protease PC7

All UniProt accessions (5): Q16549, A0A1B0GX40, E9PIW7, E9PLM0, E9PMC0

UniProt curated annotations — full annotation on UniProt →

Function. Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive secretory pathway.

Subcellular location. Golgi apparatus. trans-Golgi network membrane.

Tissue specificity. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocyte.

Post-translational modifications. Cysteine residues in the cytoplasmic tail are probably palmitoylated. N-glycosylated.

Activity regulation. Inhibited by zinc and copper.

Similarity. Belongs to the peptidase S8 family.

RefSeq proteins (1): NP_004707* (*=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
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

Enzyme classification (BRENDA):

• EC 3.4.21.B27 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (27 total): sequence variant 5, glycosylation site 4, sequence conflict 4, active site 3, topological domain 2, domain 2, region of interest 2, signal peptide 1, propeptide 1, site 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16549-F1	81.92	0.66

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 (4): 187 (charge relay system); 228 (charge relay system); 406 (charge relay system); 141–142 (cleavage; by autolysis)

Glycosylation sites (4): 167, 175, 241, 511

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane

MSigDB gene sets: 160 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, HASLINGER_B_CLL_WITH_MUTATED_VH_GENES, GOBP_REGULATION_OF_HORMONE_LEVELS, HASLINGER_B_CLL_WITH_11Q23_DELETION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, BROWNE_HCMV_INFECTION_48HR_DN, MODULE_120, RICKMAN_METASTASIS_DN, GOBP_PROTEIN_MATURATION, GOCC_TRANS_GOLGI_NETWORK, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_AMIDE_METABOLIC_PROCESS, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_23, ZAMORA_NOS2_TARGETS_UP

GO Biological Process (3): protein processing (GO:0016485), peptide hormone processing (GO:0016486), proteolysis (GO:0006508)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), protein binding (GO:0005515), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (6): Golgi membrane (GO:0000139), trans-Golgi network (GO:0005802), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH1 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
proteolysis	1
protein maturation	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
binding	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
Golgi apparatus subcompartment	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCSK7	ITM2C	Q9NQX7	748
PCSK7	PCSK9	Q8NBP7	681
PCSK7	MBTPS1	Q14703	679
PCSK7	PTPRC	P08575	631
PCSK7	NCAM1	P13591	607
PCSK7	CD19	P15391	606
PCSK7	CD4	P01730	580
PCSK7	FCGR3A	P08637	574
PCSK7	FCGR3B	O75015	571
PCSK7	CD8A	P01732	570
PCSK7	KRT6B	P04259	512
PCSK7	CD38	P28907	505
PCSK7	TMPRSS2	O15393	495
PCSK7	TNF	P01375	474
PCSK7	CD34	P28906	473

IntAct

34 interactions, top by confidence:

A	B	Type	Score
PCSK7	SERPINH1	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	GFAP	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	NDUFV2	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	NOS3	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	KLK6	psi-mi:“MI:0915”(physical association)	0.560
	PCSK7	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
PCSK7	JPH3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (9): PCSK7 (Two-hybrid), PCSK7 (Co-localization), PCSK7 (Positive Genetic), PCSK7 (Negative Genetic), PCSK7 (Co-fractionation), PCSK7 (Co-fractionation), PRKAA1 (Co-fractionation), TRIM28 (Co-fractionation), PCSK7 (Affinity Capture-RNA)

ESM2 similar proteins: A0JPF9, A2VE29, A6QPN6, A8T658, B3SP85, E7E2N8, F1QVU0, H2N4I1, O00391, O08841, O95479, P06802, P07911, P13284, P20062, P23276, P48733, P55104, P56201, P59996, Q13219, Q16549, Q499T2, Q4R7M2, Q5R5C1, Q5REL7, Q5RER0, Q5RJG7, Q5U2X4, Q5XWD5, Q62849, Q6IUU3, Q6P6S4, Q80W65, Q86UX2, Q8BND5, Q8CFX1, Q8NCG5, Q92179, Q924C3

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

12 interactions.

A	Effect	B	Mechanism
PCSK7	up-regulates	PPP2CA	phosphorylation
PCSK7	down-regulates	CDC25B	phosphorylation
PCSK7	down-regulates	KHSRP	phosphorylation
(-)-anisomycin	up-regulates	PCSK7	“chemical activation”
PCSK7	down-regulates	DDB2
PCSK7	down-regulates	CEBPA	phosphorylation
PCSK7	up-regulates	ELK4	phosphorylation
SB-202190	down-regulates	PCSK7	“chemical inhibition”
PCSK7	up-regulates	ATF6	phosphorylation
PCSK7	down-regulates	ETV6	phosphorylation
PCSK7	up-regulates	RELA
PCSK7	down-regulates	NFKBIA

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3367 predictions. Top by Δscore:

Variant	Effect	Δscore
11:117206675:TAGTA:T	donor_loss	1.0000
11:117206677:GTACC:G	donor_loss	1.0000
11:117206678:TACC:T	donor_loss	1.0000
11:117206679:A:AG	donor_loss	1.0000
11:117206680:CCT:C	donor_loss	1.0000
11:117206715:T:TA	donor_gain	1.0000
11:117206794:ACAGC:A	acceptor_gain	1.0000
11:117206795:CAGC:C	acceptor_gain	1.0000
11:117206795:CAGCC:C	acceptor_gain	1.0000
11:117206796:AGC:A	acceptor_gain	1.0000
11:117206797:GC:G	acceptor_gain	1.0000
11:117206798:CCTG:C	acceptor_gain	1.0000
11:117206799:C:CC	acceptor_gain	1.0000
11:117206801:G:C	acceptor_gain	1.0000
11:117206801:G:GC	acceptor_gain	1.0000
11:117208895:A:AC	donor_gain	1.0000
11:117208896:C:CC	donor_gain	1.0000
11:117218462:TTACC:T	donor_loss	1.0000
11:117218463:TA:T	donor_loss	1.0000
11:117218464:A:AC	donor_gain	1.0000
11:117218464:AC:A	donor_gain	1.0000
11:117218465:C:CT	donor_gain	1.0000
11:117218465:CC:C	donor_gain	1.0000
11:117218465:CCA:C	donor_gain	1.0000
11:117218465:CCATT:C	donor_gain	1.0000
11:117218564:CAGAT:C	acceptor_gain	1.0000
11:117218566:GATCT:G	acceptor_loss	1.0000
11:117218567:ATCTA:A	acceptor_loss	1.0000
11:117218568:TCTAT:T	acceptor_loss	1.0000
11:117218569:C:CC	acceptor_gain	1.0000

AlphaMissense

5157 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:117219700:G:A	T405I	1.000
11:117224121:G:C	C337W	1.000
11:117224122:C:T	C337Y	1.000
11:117224128:T:A	D335V	1.000
11:117224128:T:G	D335A	1.000
11:117224129:C:G	D335H	1.000
11:117224143:C:A	G330V	1.000
11:117224143:C:T	G330E	1.000
11:117224145:G:C	N329K	1.000
11:117224145:G:T	N329K	1.000
11:117224149:C:A	G328V	1.000
11:117224149:C:T	G328D	1.000
11:117224150:C:A	G328C	1.000
11:117224740:G:C	D292E	1.000
11:117224740:G:T	D292E	1.000
11:117224741:T:A	D292V	1.000
11:117224741:T:C	D292G	1.000
11:117224741:T:G	D292A	1.000
11:117224742:C:G	D292H	1.000
11:117224747:G:T	P290Q	1.000
11:117224750:C:T	G289E	1.000
11:117224751:C:G	G289R	1.000
11:117224751:C:T	G289R	1.000
11:117224752:C:A	W288C	1.000
11:117224752:C:G	W288C	1.000
11:117224754:A:G	W288R	1.000
11:117224754:A:T	W288R	1.000
11:117224755:G:C	S287R	1.000
11:117224755:G:T	S287R	1.000
11:117225932:T:G	S287R	1.000

dbSNP variants (sampled 300 via entrez): RS1000098848 (11:117220060 C>G), RS1000233876 (11:117213875 A>C), RS1000348462 (11:117230936 A>C), RS1000400902 (11:117231271 A>G), RS1000444655 (11:117229257 G>A,C), RS1000684904 (11:117229997 C>T), RS1000914807 (11:117224403 G>A), RS1000988515 (11:117204965 A>G), RS1001070802 (11:117218252 A>C,G), RS1001089159 (11:117211790 G>C), RS1001234666 (11:117218743 G>A,C), RS1001243935 (11:117211935 G>T), RS1001334623 (11:117224609 G>C,T), RS1001467673 (11:117220170 T>G), RS1001795940 (11:117226380 C>T)

Disease associations

OMIM: gene MIM:604872 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): corpus callosum lipoma (MONDO:0003845), skin tag (MONDO:0004026), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): Median facial cleft (Orphanet:141234), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000913_1	Iron status biomarkers	1.000000e-27
GCST001247_18	Cardiovascular disease risk factors	2.000000e-10
GCST003364_3	Triglyceride levels	8.000000e-09
GCST007849_5	Triglycerides	2.000000e-09
GCST007850_4	HDL cholesterol	3.000000e-20
GCST007850_9	HDL cholesterol	5.000000e-20
GCST008141_2	HDL cholesterol	7.000000e-06
GCST010002_199	Refractive error	3.000000e-34

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004460	soluble transferrin receptor measurement
EFO:0004461	iron biomarker measurement
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2232 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 81,995 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1464	WARFARIN	4	69,797
CHEMBL1466	DICUMAROL	4	12,198

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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
peptide 18 [PMID: 24350995]	Inhibition	7.86	pKi
furin inhibitor peptide	Inhibition	6.82	pKi

ChEMBL bioactivities

14 potent at pChembl≥5 of 15 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.92	Ki	0.12	nM	CHEMBL3126388
7.86	Ki	13.8	nM	CHEMBL3115771
7.14	Ki	72	nM	CHEMBL3115770
6.87	Ki	135	nM	CHEMBL525748
6.87	Ki	135	nM	CHEMBL502642
6.76	Ki	172	nM	CHEMBL503520
6.69	Ki	206	nM	CHEMBL455792
6.33	IC50	462	nM	XYLARENONE C
6.01	Ki	968	nM	CHEMBL568525
5.95	Ki	1133	nM	CHEMBL500184
5.91	Ki	1220	nM	CHEMBL499438
5.89	IC50	1300	nM	DICUMAROL
5.29	Ki	5131	nM	CHEMBL569918
5.21	Ki	6154	nM	CHEMBL566340

PubChem BioAssay actives

14 with measured affinity, of 39 total; 14 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
137630787	1628276: Inhibition of recombinant C-terminal truncated human SPC7 expressed in drosophila Schneider 2 cells after 1 hr by spectrofluorometry	ki	0.0001	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-[(4-carbamimidoylphenyl)methyl]hexanamide	1067774: Inhibition of human PC7 expressed in drosophila schneider 2 cells using pyroGlu-Arg-Thr-Lys-Arg-AMC as substrate after 1 hr	ki	0.0138	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	1067774: Inhibition of human PC7 expressed in drosophila schneider 2 cells using pyroGlu-Arg-Thr-Lys-Arg-AMC as substrate after 1 hr	ki	0.0720	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carboxamide	360138: Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.1350	uM
(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carboxamide	360138: Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.1350	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	360138: Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.1720	uM
(2S,3R)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoic acid	360138: Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	0.2060	uM
[(1aR,4R,7S,7aR,7bR)-1a-(3-hydroxyprop-1-en-2-yl)-7,7a-dimethyl-2-oxo-5,6,7,7b-tetrahydro-4H-naphtho[1,2-b]oxiren-4-yl] 2,4,6-trimethyloctanoate	610485: Inhibition of recombinant type 8 subtilisin using Arg-Glu-(EDANS)- Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-Lys-(DALBCYL)-Arg fluorogenic substrate preincubated for 1 hr measured after 1 hr at 1 min interval by fluorescence assay	ic50	0.4620	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	446388: Inhibition of human PC7 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	0.9680	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoic acid	360138: Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	1.1330	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	360138: Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	ki	1.2200	uM
4-hydroxy-3-[(4-hydroxy-2-oxochromen-3-yl)methyl]chromen-2-one	610485: Inhibition of recombinant type 8 subtilisin using Arg-Glu-(EDANS)- Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-Lys-(DALBCYL)-Arg fluorogenic substrate preincubated for 1 hr measured after 1 hr at 1 min interval by fluorescence assay	ic50	1.3000	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	446388: Inhibition of human PC7 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	5.1310	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	446388: Inhibition of human PC7 expressed in Drosophila schneider 2 cells by fluorescence assay	ki	6.1540	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
tanshinone	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Aspirin	decreases expression	1
Atrazine	increases expression	1
Catechin	affects cotreatment, increases expression	1
Selenium	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vincristine	increases expression	1
Vitamin E	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008225	Binding	Inhibition of human recombinant PC7 assessed as fluorescent Pyr-RTKR-AMC substrate cleavage	Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. — J Biol Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT00520078	Not specified	UNKNOWN	Clinicopathological and Molecular Correlation of Acrochordon in Relation to Human Papillomavirus Infection
NCT04161274	Not specified	COMPLETED	Randomized Clinical Trial on Skin Tags Approachment.
NCT05353374	Not specified	COMPLETED	Effectiveness of Sodium Fusidate Ointment Compared to Petrolatum for Wound Healing Following Cauterization
NCT06315946	Not specified	COMPLETED	Efficacy of a Cryogenic Medical Device on Skin Tags Versus a Comparator Product.
NCT07355543	Not specified	RECRUITING	Evaluate the Effectiveness and Safety of a Cryogenic Pen to Treat Skin Tags Versus a Comparator.
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment