PI15

Summary

PI15 (peptidase inhibitor 15, HGNC:8946) is a protein-coding gene on chromosome 8q21.13, encoding Peptidase inhibitor 15 (O43692). Serine protease inhibitor which displays weak inhibitory activity against trypsin.

This gene encodes a trypsin inhibitor. The protein shares similarity to insect venom allergens, mammalian testis-specific proteins and plant pathogenesis-related proteins. It is frequently expressed in human neuroblastoma and glioblastoma cell lines, and thus may play a role in the central nervous system.

Source: NCBI Gene 51050 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_015886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8946
Approved symbol	PI15
Name	peptidase inhibitor 15
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	P25TI
Ensembl gene	ENSG00000137558
Ensembl biotype	protein_coding
OMIM	607076
Entrez	51050

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000260113, ENST00000523773, ENST00000649643

RefSeq mRNA: 2 — MANE Select: NM_015886 NM_001324403, NM_015886

CCDS: CCDS6218

Canonical transcript exons

ENST00000260113 — 6 exons

Exon	Start	End
ENSE00000819700	74825210	74825522
ENSE00001087105	74843981	74844099
ENSE00001087106	74849118	74855029
ENSE00001087107	74845382	74845497
ENSE00001087108	74845128	74845260
ENSE00003835777	74824534	74824675

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 95.08.

FANTOM5 (CAGE): breadth broad, TPM avg 9.1339 / max 819.2842, expressed in 336 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89411	7.6453	287
89410	1.1876	165
89413	0.1626	81
89412	0.1384	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	95.08	gold quality
mammary duct	UBERON:0001765	94.35	gold quality
vermiform appendix	UBERON:0001154	92.40	gold quality
left uterine tube	UBERON:0001303	92.00	gold quality
epithelium of mammary gland	UBERON:0003244	91.45	gold quality
seminal vesicle	UBERON:0000998	87.86	gold quality
caecum	UBERON:0001153	86.82	gold quality
mammary gland	UBERON:0001911	86.70	gold quality
thoracic mammary gland	UBERON:0005200	86.68	gold quality
cartilage tissue	UBERON:0002418	86.52	gold quality
smooth muscle tissue	UBERON:0001135	86.25	gold quality
prostate gland	UBERON:0002367	84.98	gold quality
visceral pleura	UBERON:0002401	84.60	gold quality
urethra	UBERON:0000057	84.15	gold quality
superficial temporal artery	UBERON:0001614	83.90	gold quality
myometrium	UBERON:0001296	80.46	gold quality
pleura	UBERON:0000977	79.67	gold quality
islet of Langerhans	UBERON:0000006	78.63	gold quality
caput epididymis	UBERON:0004358	77.75	gold quality
parietal pleura	UBERON:0002400	77.74	gold quality
body of uterus	UBERON:0009853	77.21	gold quality
vagina	UBERON:0000996	76.63	gold quality
right ovary	UBERON:0002118	76.31	gold quality
colonic epithelium	UBERON:0000397	76.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.59	gold quality
ectocervix	UBERON:0012249	75.26	gold quality
rectum	UBERON:0001052	75.13	gold quality
corpus epididymis	UBERON:0004359	75.06	gold quality
endocervix	UBERON:0000458	73.50	gold quality
uterus	UBERON:0000995	73.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	1762.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

253 targeting PI15, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-7110-3P	100.00	73.18	2486
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-3064-3P	100.00	70.09	1254
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684

Literature-anchored findings (GeneRIF, showing 2)

• Human serine peptidase inhibitor PI15 as a potential host factor involved in the regulation of CPAF activation. Silencing expression as well as over expression of PI15 affected normal development of Chlamydia. (PMID:29900129)
• PI15 as a novel marker for predicting the diagnosis and follow-up of cholangiocarcinoma patients. (PMID:30638862)

Cross-species orthologs

48 orthologs

Organism	Symbol	Gene ID
danio_rerio	pi15a	ENSDARG00000045378
danio_rerio	pi15b	ENSDARG00000061292
mus_musculus	Pi15	ENSMUSG00000067780
rattus_norvegicus	Pi15	ENSRNOG00000017686
drosophila_melanogaster	Ag5r	FBGN0015010
drosophila_melanogaster	Ag5r2	FBGN0020508
drosophila_melanogaster	CG9400	FBGN0030562
drosophila_melanogaster	CG10651	FBGN0032853
drosophila_melanogaster	CG9822	FBGN0034623
drosophila_melanogaster	CG17974	FBGN0034624
drosophila_melanogaster	CG3640	FBGN0035042
drosophila_melanogaster	CG8072	FBGN0036070
drosophila_melanogaster	CG6628	FBGN0036072
drosophila_melanogaster	scpr-C	FBGN0037879
drosophila_melanogaster	scpr-B	FBGN0037888
drosophila_melanogaster	scpr-A	FBGN0037889
drosophila_melanogaster	CG8483	FBGN0038126
drosophila_melanogaster	CG30486	FBGN0050486
drosophila_melanogaster	antr	FBGN0050488
drosophila_melanogaster	CG31286	FBGN0051286
drosophila_melanogaster	CG32313	FBGN0052313
drosophila_melanogaster	CG32679	FBGN0052679
drosophila_melanogaster	CG34002	FBGN0054002
drosophila_melanogaster	CG17575	FBGN0250842
drosophila_melanogaster	CG42564	FBGN0260766
drosophila_melanogaster	CG42780	FBGN0261848
drosophila_melanogaster	CG43775	FBGN0264297
drosophila_melanogaster	CG43776	FBGN0264298
drosophila_melanogaster	CG43777	FBGN0264299
caenorhabditis_elegans		WBGENE00004742
caenorhabditis_elegans		WBGENE00007397
caenorhabditis_elegans		WBGENE00008027
caenorhabditis_elegans		WBGENE00008028
caenorhabditis_elegans		WBGENE00008029
caenorhabditis_elegans		WBGENE00008030
caenorhabditis_elegans		WBGENE00008625
caenorhabditis_elegans		WBGENE00009891
caenorhabditis_elegans		WBGENE00009895
caenorhabditis_elegans		WBGENE00009896
caenorhabditis_elegans		WBGENE00012816
caenorhabditis_elegans		WBGENE00013971
caenorhabditis_elegans		WBGENE00013972
caenorhabditis_elegans		WBGENE00015246
caenorhabditis_elegans		WBGENE00017055
caenorhabditis_elegans		WBGENE00017183
caenorhabditis_elegans		WBGENE00019178
caenorhabditis_elegans		WBGENE00019179
caenorhabditis_elegans		WBGENE00021780

Paralogs (13): CRISP3 (ENSG00000096006), R3HDML (ENSG00000101074), CRISPLD2 (ENSG00000103196), CRISPLD1 (ENSG00000121005), GLIPR2 (ENSG00000122694), CRISP2 (ENSG00000124490), CRISP1 (ENSG00000124812), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18A (ENSG00000157322), CLEC18C (ENSG00000157335), GLIPR1L1 (ENSG00000173401), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

Peptidase inhibitor 15 — O43692 (reviewed: O43692)

Alternative names: 25 kDa trypsin inhibitor, Cysteine-rich secretory protein 8, SugarCrisp

All UniProt accessions (1): O43692

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease inhibitor which displays weak inhibitory activity against trypsin. May play a role in facial patterning during embryonic development.

Subcellular location. Secreted.

Tissue specificity. Weakly expressed. Expressed at low level in prostate, mammary gland, salivary gland and thyroid gland.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the CRISP family.

RefSeq proteins (2): NP_001311332, NP_056970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001283	CRISP-related	Family
IPR014044	CAP_dom	Domain
IPR018244	Allrgn_V5/Tpx1_CS	Conserved_site
IPR035940	CAP_sf	Homologous_superfamily
IPR047832	PI15_CAP	Domain

Pfam: PF00188

UniProt features (7 total): glycosylation site 3, signal peptide 1, propeptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43692-F1	83.69	0.70

Functional residue map

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

Glycosylation sites (3): 26, 36, 124

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 172 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, WALLACE_PROSTATE_CANCER_RACE_UP, TAL1ALPHAE47_01, CHANDRAN_METASTASIS_DN, EVI1_05, GATA3_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, AML_Q6, TGANTCA_AP1_C, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, GATA1_04, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GFI1_01, SABATES_COLORECTAL_ADENOMA_DN, GATA4_Q3

GO Biological Process (0):

GO Molecular Function (1): peptidase inhibitor activity (GO:0030414)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PI15	SERPINI2	O75830	694
PI15	RPE65	Q16518	571
PI15	FAM180A	Q6UWF9	566
PI15	FHAD1	B1AJZ9	540
PI15	CEP290	O15078	524
PI15	SMNDC1	O75940	515
PI15	KLHL8	Q9P2G9	506
PI15	SLC25A29	Q8N8R3	496
PI15	KLHL35	Q6PF15	491
PI15	GCC2	Q8IWJ2	474
PI15	SERPINB4	P48594	471
PI15	RNF222	A6NCQ9	455
PI15	MMP9	P14780	453
PI15	ANKS1A	Q92625	449
PI15	TCP11	Q8WWU5	442

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PI15	GLS	psi-mi:“MI:0914”(association)	0.350
MRM2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
PI15	CCN2	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): KIAA0319L (Affinity Capture-MS), PI15 (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), ALG11 (Affinity Capture-MS), CCNH (Affinity Capture-MS), MNAT1 (Affinity Capture-MS), TRIM37 (Affinity Capture-MS), GLS (Affinity Capture-MS), MTMR1 (Affinity Capture-MS), MIB2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), EDEM3 (Affinity Capture-MS), CERCAM (Affinity Capture-MS), HLA-DQB1 (Affinity Capture-MS), CHID1 (Affinity Capture-MS)

ESM2 similar proteins: A2A5I3, A5D8T8, B2RY83, D3ZE85, O19116, O43692, O75882, P16562, P24786, P52848, P78539, P97401, Q01973, Q02353, Q08DW9, Q16288, Q3KPV7, Q3UHN9, Q4R766, Q58D84, Q5IFJ9, Q5IS37, Q5IS82, Q5RF67, Q5VV63, Q5VWW1, Q5ZIN0, Q62632, Q63769, Q6A051, Q6AYT7, Q6UXF7, Q6VNS1, Q7T141, Q80ZF8, Q8BS03, Q8C4U3, Q8N2K0, Q8N474, Q8NCF0

Diamond homologs: A0A182GL09, A0A1S4EWW7, A0A218QX58, A9YME1, B9URJ1, C0ITL3, C8YJ99, D4P2Y4, O43692, P0DMB9, P0DPU0, P0DPU1, P0DPU2, P0DPU5, P0DPV2, P0DSI3, P10736, P10737, P35759, P35760, P35778, P35779, P35780, P35781, P35782, P35784, P35785, P35786, P35787, P81656, P81657, P83377, P85840, P86686, P86870, Q05108, Q05109, Q2L6Z1, Q32LB5, Q3KPV7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

782 predictions. Top by Δscore:

Variant	Effect	Δscore
8:74825520:ATGGT:A	donor_loss	1.0000
8:74825521:TGG:T	donor_loss	1.0000
8:74825522:GGTAA:G	donor_loss	1.0000
8:74825523:GTAAG:G	donor_loss	1.0000
8:74825524:T:G	donor_loss	1.0000
8:74845376:TCACA:T	acceptor_loss	1.0000
8:74845377:CACAG:C	acceptor_loss	1.0000
8:74845378:ACAGA:A	acceptor_loss	1.0000
8:74845379:CAGA:C	acceptor_loss	1.0000
8:74845380:AGA:A	acceptor_loss	1.0000
8:74845380:AGAT:A	acceptor_gain	1.0000
8:74845381:GATG:G	acceptor_gain	1.0000
8:74845495:AAAGT:A	donor_loss	1.0000
8:74845498:G:GG	donor_gain	1.0000
8:74845499:TAA:T	donor_loss	1.0000
8:74845500:AAGTA:A	donor_loss	1.0000
8:74824673:GAG:G	donor_gain	0.9900
8:74825209:GCAAA:G	acceptor_gain	0.9900
8:74825523:G:GG	donor_gain	0.9900
8:74844096:GAAGG:G	donor_loss	0.9900
8:74844097:AAGG:A	donor_loss	0.9900
8:74844098:AG:A	donor_loss	0.9900
8:74844099:GG:G	donor_loss	0.9900
8:74844100:GT:G	donor_loss	0.9900
8:74844101:T:G	donor_loss	0.9900
8:74844104:G:GT	donor_gain	0.9900
8:74845379:C:G	acceptor_gain	0.9900
8:74845380:A:AG	acceptor_gain	0.9900
8:74845380:AGATG:A	acceptor_gain	0.9900
8:74845381:G:GG	acceptor_gain	0.9900

AlphaMissense

1680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:74843984:T:A	W93R	1.000
8:74843984:T:C	W93R	1.000
8:74843986:G:C	W93C	1.000
8:74843986:G:T	W93C	1.000
8:74844019:G:C	W104C	1.000
8:74844019:G:T	W104C	1.000
8:74844029:T:A	C108S	1.000
8:74844029:T:C	C108R	1.000
8:74844030:G:A	C108Y	1.000
8:74844030:G:C	C108S	1.000
8:74844031:C:G	C108W	1.000
8:74844035:T:A	W110R	1.000
8:74844035:T:C	W110R	1.000
8:74844037:G:C	W110C	1.000
8:74844037:G:T	W110C	1.000
8:74844043:T:A	H112Q	1.000
8:74844043:T:G	H112Q	1.000
8:74844071:G:T	G122C	1.000
8:74844075:A:C	Q123P	1.000
8:74844079:T:A	N124K	1.000
8:74844079:T:G	N124K	1.000
8:74844081:T:C	L125P	1.000
8:74845159:T:A	W142R	1.000
8:74845159:T:C	W142R	1.000
8:74845161:G:C	W142C	1.000
8:74845161:G:T	W142C	1.000
8:74845169:A:T	E145V	1.000
8:74845243:T:A	C170S	1.000
8:74845243:T:C	C170R	1.000
8:74845244:G:A	C170Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000109332 (8:74846726 A>T), RS1000198713 (8:74849013 C>A,T), RS1000272812 (8:74843374 A>G), RS1000375017 (8:74849902 A>G), RS1000501422 (8:74855073 A>G,T), RS1000599210 (8:74829809 C>T), RS1000656134 (8:74836314 G>A), RS1000710080 (8:74848317 C>A,T), RS1000713433 (8:74830105 C>A), RS1000821953 (8:74848058 A>C), RS1000904413 (8:74824473 A>C), RS1000907009 (8:74823731 C>A,T), RS1000920963 (8:74829741 C>G), RS1000943251 (8:74835918 G>A), RS1000957950 (8:74855395 C>A)

Disease associations

OMIM: gene MIM:607076 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000189_43	Protein quantitative trait loci	8.000000e-07
GCST003927_4	Dysmenorrheic pain	7.000000e-07
GCST007242_1	Normal body mass index vs. thin	5.000000e-07
GCST010002_305	Refractive error	2.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005057	myoglobin measurement
EFO:0007889	dysmenorrheic pain measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Phenylmercuric Acetate	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
bisphenol A	increases methylation	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
mercuric bromide	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	increases expression, affects cotreatment	1
Methotrexate	increases expression	1
Nickel	increases expression	1
Niclosamide	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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