SLPI

Summary

SLPI (secretory leukocyte peptidase inhibitor, HGNC:11092) is a protein-coding gene on chromosome 20q13.12, encoding Antileukoproteinase (P03973). Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G.

This gene encodes a secreted inhibitor which protects epithelial tissues from serine proteases. It is found in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. Its inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes. This antimicrobial protein has antibacterial, antifungal and antiviral activity.

Source: NCBI Gene 6590 — RefSeq curated summary.

At a glance

• Gene–disease (curated): otitis media (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 28 total — 1 pathogenic
• MANE Select transcript: NM_003064

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11092
Approved symbol	SLPI
Name	secretory leukocyte peptidase inhibitor
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	HUSI-I, ALK1, ALP, BLPI, HUSI, WAP4, WFDC4
Ensembl gene	ENSG00000124107
Ensembl biotype	protein_coding
OMIM	107285
Entrez	6590

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000338380

RefSeq mRNA: 1 — MANE Select: NM_003064 NM_003064

CCDS: CCDS13347

Canonical transcript exons

ENST00000338380 — 4 exons

Exon	Start	End
ENSE00000844924	45253575	45253733
ENSE00000906900	45252239	45252419
ENSE00001388145	45254459	45254564
ENSE00001433533	45253002	45253151

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.99.

FANTOM5 (CAGE): breadth broad, TPM avg 96.2843 / max 13554.6782, expressed in 799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187417	96.2003	795
187415	0.0451	14
187416	0.0389	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	99.99	gold quality
bronchus	UBERON:0002185	99.98	gold quality
bronchial epithelial cell	CL:0002328	99.97	gold quality
epithelium of bronchus	UBERON:0002031	99.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.97	gold quality
nasal cavity mucosa	UBERON:0001826	99.96	gold quality
nasal cavity epithelium	UBERON:0005384	99.95	gold quality
minor salivary gland	UBERON:0001830	99.92	gold quality
saliva-secreting gland	UBERON:0001044	99.91	gold quality
palpebral conjunctiva	UBERON:0001812	99.90	gold quality
mouth mucosa	UBERON:0003729	99.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.85	gold quality
parotid gland	UBERON:0001831	99.80	gold quality
seminal vesicle	UBERON:0000998	99.77	gold quality
pharyngeal mucosa	UBERON:0000355	99.75	gold quality
lower lobe of lung	UBERON:0008949	99.74	gold quality
right uterine tube	UBERON:0001302	99.68	gold quality
right lung	UBERON:0002167	99.66	gold quality
tongue squamous epithelium	UBERON:0006919	99.64	gold quality
pericardium	UBERON:0002407	99.63	gold quality
body of tongue	UBERON:0011876	99.61	gold quality
oral cavity	UBERON:0000167	99.59	gold quality
epithelium of nasopharynx	UBERON:0001951	99.52	gold quality
esophagus mucosa	UBERON:0002469	99.48	gold quality
lower esophagus mucosa	UBERON:0035834	99.45	gold quality
periodontal ligament	UBERON:0008266	99.19	gold quality
gingiva	UBERON:0001828	99.18	gold quality
metanephros cortex	UBERON:0010533	99.05	gold quality
gall bladder	UBERON:0002110	99.04	gold quality
gingival epithelium	UBERON:0001949	98.95	gold quality

Single-cell (SCXA)

Detected in 36 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	87371.16
E-CURD-114	yes	51686.70
E-HCAD-15	yes	32150.56
E-HCAD-13	yes	23069.85
E-MTAB-8530	yes	19023.76
E-HCAD-1	yes	17097.48
E-GEOD-130148	yes	13802.88
E-MTAB-6653	yes	12340.99
E-CURD-126	yes	11535.31
E-MTAB-6308	yes	9989.40
E-MTAB-10287	yes	9189.86
E-MTAB-10855	yes	8240.96
E-MTAB-8221	yes	7083.71
E-CURD-122	yes	5805.07
E-HCAD-24	yes	5702.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, KLF9, NFE2L2, NR3C1, PGR, RUNX2, STAT1, STAT3, STAT5A, STAT5B

miRNA regulators (miRDB)

8 targeting SLPI, 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-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-5094	98.63	67.11	1062

Literature-anchored findings (GeneRIF, showing 40)

• Synthesized locally at mucosal sites. Efficiently inhibit target enzymes released into interstitium. Might be important in controlling excessive neutrophil elastase release in chronic obstructive pulmonary disease and cystic fibrosis. (review) (PMID:11667971)
• Secretory leukocyte protease inhibitor in punch biopsies from human colonic mucosa. (PMID:11759111)
• possible role in the defence against ascending urinary tract infections; establishing a source of SLPI in renal tubuli cells. (PMID:11817677)
• Secretory leukocyte proteinase inhibitor and elafin are resistant to degradation by MMP-8. (PMID:11868825)
• results indicate that menstrual status (pre- vs. postmenopausal) influences the production of SLPI and bactericidal activity by uterine epithelial cells (PMID:12023766)
• mediates proliferation of human endometrial epithelial cells by positive and negative regulation of growth-associated genes (PMID:12023969)
• Streptococcal inhibitor of complement inhibits two additional components of the mucosal innate immune system: secretory leukocyte proteinase inhibitor and lysozyme. (PMID:12183536)
• secretory leukocyte protease inhibitor transcripts were expressed in the fallopian tube and prevented the reduction of the sperm acrosome reaction by elastase (PMID:12351521)
• SLPI has a role in wound healing and innate immunity (PMID:12526812)
• a causal role for SLPI in the malignant behavior of cancer cells, underscoring the potential malignancy-promoting activities of SPIs (PMID:12732717)
• in community acquired pneumonia, both A1AT and SLPI were cleaved or complexed in infected lobes and A1AT was oxidized; conclude that mean elastase levels are increased and that mean anti-elastase capacity is decreased in pneumonic lobes (PMID:12934194)
• Levels of alpha1-antitrypsin and alpha1-antichymotrypsin were higher by 1.47-fold, p<0.001 and 2.27-fold, p<0.001, respectively in lung cancer cases with metastasis compared to localized tumor. (PMID:15015603)
• Expression of secretory leukocyte protease inhibitor is increased during mitosis in keratinocytes. (PMID:15020232)
• key role in the oral mucosal defense against Candida albicans; the antimicrobial mucosal protein may serve as an indicator of previous oropharyngeal candidiasis infection among Hiv-1 infected persons (PMID:15039315)
• Antral SLPI levels were inversely correlated with inflammatory scores of antrum-predominant Helicobacter pylori gastritis. (PMID:15039364)
• impairs lipoteichokc acid and LPS induced proinflammatory gene expression in monocytes and macrophages in vitro. However, oxidation and elastase complex formation of SLPI diminished its anti-inflammatory effects (PMID:15155685)
• SLPI is not more highly expressed in squamous cell metaplasia as compared to areas with intact or damaged epithelium (PMID:15167969)
• ALP exerts variety of blocking effects on neutrophil functions, probably due to modulation of cytoskeletal changes, that may contribute to this inhibitor’s antiarthritis potential and qualify it as multifunctional regulator of inflammatory responses. (PMID:15248236)
• SLPI localizes in part along the megakaaryocyte and platelet cytoskeleton by virtue of specific interactions with beta1 tubulin. (PMID:15315966)
• Lower SLPI expression is associated with cervical adenocarcinomas (PMID:15492784)
• Secretory leukocyte protease inhibitor has a role in cancer development (PMID:15650263)
• Local down-regulation of SLPI in antral mucosa is a general phenomenon of Hp-related diseases. (PMID:15812165)
• The five genes, and three of the encoded proteins, were shown differentially expressed between a group of keratoconus patients and a reference group using different techniques (PMID:16015083)
• SLPI has antiprotease activity and antimicrobial activity against bacteria and fungi. SLPI is an important molecule in the functioning of the innate immune system. (PMID:16336202)
• Adenoviral E1A significantly suppressed SLPI and elafin/SKALP secretion by A549 cells upon interleukin (IL)-1beta stimulation. (PMID:16355004)
• Progesterone receptor transactivation of the secretory leukocyte protease inhibitor gene in Ishikawa endometrial epithelial cells involves recruitment of Kruppel-like factor 9/basic transcription element binding protein-1. (PMID:16384861)
• Newly uncovered properties of ALP to interfere with cytokine signalling and upregulation of adhesion molecules in endothelial cells are likely to contribute to the therapeutic potential of ALP in immune-complex-induced tissue injury. (PMID:16776851)
• Levels of mRNA and immunostaining of the antiproteases elafin and SLPI were enhanced strongly in inflamed versus noninflamed UC. Elafin and SLPI may be added to the list of defensin-like peptides with diminished induction in CD versus UC. (PMID:17200145)
• SLPI (secretory leucoprotease inhibitor) has important role in protecting the host from infection and injury. [secretory leucoprotease inhibitor] (PMID:17371258)
• secretory leukocyte protease inhibitor can inhibit interferon-gamma-induced cathepsin S production by macrophages (PMID:17878156)
• This review focuses on recent findings revealing that SLPI has many biological functions as diverse as anti-bacterial, anti-fungal, anti-viral, anti-inflammatory and immuno-modulatory functions. (PMID:17964057)
• Secretory leucoprotease inhibitor (SLPI) is a prominent innate immune protein of the respiratory tract, possessing serine protease inhibitor activity, antibacterial activity, and anti-inflammatory/immunomodulatory activity [review] (PMID:18075823)
• There was higher expression of SLPI in AIDS patients with CMV infection compared with all groups. There were no differences between controls and AIDS patients without histologic changes with chronic nonspecific sialadenitis or mycobacterial infection. (PMID:18173453)
• Neutrophil-derived SLPI protects secondary granule proteins against proteolytic activation and/or degradation by proteases. (PMID:18285402)
• Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer (PMID:18425362)
• Herpes simplex virus 1 and 2 downregulate secretory leukocyte protease inhibitor through a novel immune evasion mechanism (PMID:18667508)
• SLPI mRNA transcripts and protein were overexpressed in gastric cancer cells, and the depth of wall invasion was significantly greater in serosa-invading (T3 and T4) cancers compared to the serosa-free (T1 and T2) cancers. (PMID:18688858)
• SLPI inhibited the expression of MMP-9 and IL-8 in normal human bronchial epithelial cells induced by cigarette smoke extract. (PMID:18953959)
• hK7 and ALP were decreased in malignant prostate epithelium. (PMID:18976018)
• Chlamydia trachomatis and Chlamydophila abortus were found to induce SLPI mRNA and peptide expression in HeLa and JEG-3 cells respectively. (PMID:19039956)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slpi	ENSMUSG00000017002
rattus_norvegicus	Slpi-ps1	ENSRNOG00000029508
rattus_norvegicus	Slpi-ps2	ENSRNOG00000046350
rattus_norvegicus	Slpi	ENSRNOG00000046699
rattus_norvegicus	Slpi-ps2	ENSRNOG00000055534
drosophila_melanogaster	CG5639	FBGN0039527
caenorhabditis_elegans		WBGENE00015620

Paralogs (9): PI3 (ENSG00000124102), WFDC3 (ENSG00000124116), WFDC13 (ENSG00000168634), WFDC12 (ENSG00000168703), WFDC5 (ENSG00000175121), WFDC11 (ENSG00000180083), WFDC9 (ENSG00000180205), WFDC10A (ENSG00000180305), WFDC10B (ENSG00000182931)

Protein

Protein identifiers

Antileukoproteinase — P03973 (reviewed: P03973)

Alternative names: BLPI, HUSI-1, Mucus proteinase inhibitor, Protease inhibitor WAP4, Secretory leukocyte protease inhibitor, Seminal proteinase inhibitor, WAP four-disulfide core domain protein 4

All UniProt accessions (1): P03973

UniProt curated annotations — full annotation on UniProt →

Function. Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. Modulates the inflammatory and immune responses after bacterial infection, and after infection by the intracellular parasite L.major. Down-regulates responses to bacterial lipopolysaccharide (LPS). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses. Has antimicrobial activity against mycobacteria, but not against salmonella. Contributes to normal resistance against infection by M.tuberculosis. Required for normal resistance to infection by L.major. Required for normal wound healing, probably by preventing tissue damage by limiting protease activity. Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells.

Subunit / interactions. Interacts with GRN; interaction protects progranulin from proteolysis.

Subcellular location. Secreted.

Tissue specificity. Detected in blood plasma. Detected in bone marrow myeloid cells. Detected in airway sputum. Detected in parotid gland secretions. Detected in seminal plasma (at protein level). Detected in uterus cervix.

Induction. Down-regulated in response to low ELANE activity. Up-regulated by ELANE treatment in bone marrow cells.

Miscellaneous. The pathologies of several chronic and acute diseases of the respiratory tract involve an imbalance between the proteases of cells involved in inflammatory responses and the inhibitors of these proteases. The inflammation-mediated release of neutrophil elastase in the lungs of patients whose levels of active alpha-1-antiprotease are compromised by genetic background, cigarette smoking, air pollutants, or a combination of all three can result in severe lung damage and a decreased lifespan. The relatively small size of this protein, its lack of glycosylation and its stability make this protein a candidate for use as a therapeutic agent in diseases mediated by leukocyte elastase-antielastase imbalances.

RefSeq proteins (1): NP_003055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008197	WAP_dom	Domain
IPR036645	Elafin-like_sf	Homologous_superfamily
IPR050514	WAP_four-disulfide_core	Family

Pfam: PF00095

UniProt features (26 total): disulfide bond 8, mutagenesis site 7, strand 4, domain 2, signal peptide 1, chain 1, helix 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2Z7F	X-RAY DIFFRACTION	1.7
4DOQ	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P03973-F1	85.19	0.64

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 (1): 97–98 (reactive bond for chymotrypsin, trypsin and elastase)

Disulfide bonds (8): 89–118, 96–122, 105–117, 111–126, 35–64, 43–68, 51–63, 57–72

Mutagenesis-validated functional residues (7):

Position	Phenotype
45	no significant effect on inhibition of elastase, trypsin and chymotrypsin.
97	increases inhibition of chymotrypsin.
97	reduced inhibition of elastase. strongly reduced inhibition of chymotrypsin and trypsin.
97	strongly reduced inhibition of elastase. abolishes inhibition of trypsin.
98	no significant effect on inhibition of elastase, trypsin and chymotrypsin.
99	no significant effect on inhibition of elastase, trypsin and chymotrypsin.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 363 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MCLACHLAN_DENTAL_CARIES_UP, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, MODULE_45, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, HUMMERICH_BENIGN_SKIN_TUMOR_UP

GO Biological Process (9): immune response (GO:0006955), antibacterial humoral response (GO:0019731), negative regulation of protein binding (GO:0032091), response to lipopolysaccharide (GO:0032496), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), host-mediated perturbation of symbiont process (GO:0051851), immune system process (GO:0002376), defense response to bacterium (GO:0042742)

GO Molecular Function (7): DNA binding (GO:0003677), mRNA binding (GO:0003729), endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), enzyme binding (GO:0019899), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), extracellular matrix (GO:0031012), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Lineages of the Mammary Gland	2
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
immune system process	1
response to stimulus	1
antimicrobial humoral response	1
defense response to bacterium	1
regulation of protein binding	1
negative regulation of binding	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
modulation of process of another organism	1
biological_process	1
defense response	1
response to bacterium	1
nucleic acid binding	1
RNA binding	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
external encapsulating structure	1
secretory granule lumen	1
specific granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

2052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLPI	ELANE	P08246	981
SLPI	GRN	P23781	909
SLPI	CTSG	P08311	888
SLPI	DEFB103A	P81534	837
SLPI	LCN2	P30150	822
SLPI	CTRB2	Q6GPI1	795
SLPI	LTF	P02788	790
SLPI	CTRB1	P17538	782
SLPI	TUBB1	Q9H4B7	692
SLPI	HBEGF	Q99075	680
SLPI	SEMG2	Q02383	670
SLPI	CXCL8	P10145	669
SLPI	SEMG1	P04279	666
SLPI	DEFB4A	O15263	647
SLPI	WFDC1	Q9HC57	646

IntAct

60 interactions, top by confidence:

A	B	Type	Score
SGTA	SLPI	psi-mi:“MI:0915”(physical association)	0.720
FAM9B	SLPI	psi-mi:“MI:0915”(physical association)	0.720
SLPI	SGTA	psi-mi:“MI:0915”(physical association)	0.720
SLPI	FAM9B	psi-mi:“MI:0915”(physical association)	0.720
SLPI	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SLPI	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
SLPI	EFEMP1	psi-mi:“MI:0915”(physical association)	0.560
SLPI	NBL1	psi-mi:“MI:0915”(physical association)	0.560
SLPI	SGTB	psi-mi:“MI:0915”(physical association)	0.560
SLPI	MKRN3	psi-mi:“MI:0915”(physical association)	0.560
SLPI	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
SLPI	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
SLPI	CIB3	psi-mi:“MI:0915”(physical association)	0.560
SLPI	SMIM14	psi-mi:“MI:0915”(physical association)	0.560
LAT	SLPI	psi-mi:“MI:0915”(physical association)	0.560
SLPI	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
SLPI	CALN1	psi-mi:“MI:0915”(physical association)	0.560
SLPI	ELANE	psi-mi:“MI:0407”(direct interaction)	0.440
SLPI	TRIM11	psi-mi:“MI:0915”(physical association)	0.400
MAPK8IP2	SLPI	psi-mi:“MI:0915”(physical association)	0.370
PA	SLPI	psi-mi:“MI:0915”(physical association)	0.370
SRPK1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): SLPI (Two-hybrid), FAM9B (Two-hybrid), SLPI (Two-hybrid), SLPI (Affinity Capture-MS), SLPI (Affinity Capture-MS), SLPI (Affinity Capture-MS), SLPI (Two-hybrid), SLPI (Two-hybrid), SLPI (Two-hybrid), UBQLN1 (Two-hybrid), CIB3 (Two-hybrid), PIH1D2 (Two-hybrid), WDYHV1 (Two-hybrid), NBL1 (Two-hybrid), SMIM14 (Two-hybrid)

ESM2 similar proteins: A6NCL2, D3ZTT2, O19131, O46655, O70280, P01177, P01178, P01179, P01180, P01183, P01185, P01186, P03973, P13389, P19438, P22298, P22934, P25118, P35454, P35455, P50555, P58658, P58659, Q02509, Q14AE4, Q32LD3, Q3URS3, Q5T700, Q68US5, Q6UWE3, Q6UWL2, Q6V9X0, Q6WN34, Q76LW6, Q86Y78, Q8BPP5, Q8BVP6, Q8N6Q3, Q8VEA6, Q8WXA2

Diamond homologs: A4K2M6, A4K2P0, A4K2P8, A4K2R5, A4K2S4, A4K2T3, A4K2U1, A4K2V4, A4K2W8, A4K2X6, A4K2Y4, P01173, P03973, Q6IE40, Q6V9X0, Q8WWY7, Q9JHY3, P22298, Q868Z9, Q8MI69, A4K2M5, A4K2N9, A4K2P7, A4K2Q7, A4K2R4, A4K2S3, A4K2T2, A4K2U0, A4K2V3, A4K2W7, A4K2X5, A4K2Y3, Q8IUA0, Q8TCV5, P09837, O46655, P19957, A7X4M7, P16225, P23352

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2572174	NM_003064.4(SLPI):c.394+1G>T	Pathogenic

SpliceAI

385 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45253573:A:AC	donor_gain	1.0000
20:45253574:C:CC	donor_gain	1.0000
20:45253737:T:C	acceptor_gain	1.0000
20:45254457:A:AC	donor_gain	1.0000
20:45254458:C:CC	donor_gain	1.0000
20:45254458:CA:C	donor_gain	1.0000
20:45252416:CAAG:C	acceptor_gain	0.9900
20:45253088:T:TC	acceptor_gain	0.9900
20:45253569:GCTTA:G	donor_loss	0.9900
20:45253571:TTA:T	donor_loss	0.9900
20:45253572:TAC:T	donor_loss	0.9900
20:45253573:A:T	donor_loss	0.9900
20:45253734:C:CC	acceptor_gain	0.9900
20:45253735:T:C	acceptor_gain	0.9900
20:45253736:T:TC	acceptor_gain	0.9900
20:45253737:T:TC	acceptor_gain	0.9900
20:45254452:AACTT:A	donor_loss	0.9900
20:45254454:CTTA:C	donor_loss	0.9900
20:45254455:TTAC:T	donor_loss	0.9900
20:45254456:T:TG	donor_loss	0.9900
20:45254457:ACAC:A	donor_loss	0.9900
20:45254458:CACT:C	donor_gain	0.9900
20:45254463:T:A	donor_gain	0.9900
20:45252415:TCAAG:T	acceptor_gain	0.9800
20:45252416:CAAGC:C	acceptor_gain	0.9800
20:45253574:CTTGG:C	donor_gain	0.9800
20:45253642:C:A	donor_gain	0.9800
20:45253733:GCT:G	acceptor_loss	0.9800
20:45253734:C:T	acceptor_loss	0.9800
20:45253735:T:G	acceptor_loss	0.9800

AlphaMissense

865 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45253082:C:G	C105S	0.983
20:45253083:A:T	C105S	0.983
20:45253046:C:G	C117S	0.981
20:45253047:A:T	C117S	0.981
20:45253064:C:G	C111S	0.981
20:45253065:A:T	C111S	0.981
20:45253130:C:G	C89S	0.977
20:45253131:A:T	C89S	0.977
20:45253649:C:G	C57S	0.975
20:45253650:A:T	C57S	0.975
20:45253082:C:T	C105Y	0.973
20:45253667:C:G	C51S	0.970
20:45253668:A:T	C51S	0.970
20:45253048:C:A	K116N	0.968
20:45253048:C:G	K116N	0.968
20:45253109:C:G	C96S	0.968
20:45253110:A:T	C96S	0.968
20:45253604:C:G	C72S	0.965
20:45253605:A:T	C72S	0.965
20:45253019:C:G	C126S	0.964
20:45253020:A:T	C126S	0.964
20:45253073:T:A	D108V	0.964
20:45253031:C:G	C122S	0.960
20:45253032:A:T	C122S	0.960
20:45253631:C:G	C63S	0.960
20:45253632:A:T	C63S	0.960
20:45253131:A:G	C89R	0.954
20:45253043:C:G	C118S	0.953
20:45253044:A:T	C118S	0.953
20:45253082:C:A	C105F	0.953

dbSNP variants (sampled 300 via entrez): RS1000709789 (20:45253809 A>G), RS1000771927 (20:45254350 G>A,C,T), RS1000774576 (20:45255283 G>A,C), RS1000884073 (20:45252035 A>G), RS1001081338 (20:45254109 G>A), RS1002233121 (20:45252613 A>G), RS1002452626 (20:45254370 G>C), RS1002809335 (20:45251944 G>A), RS1003188356 (20:45255897 A>C,G), RS1003283168 (20:45256154 T>C), RS1004190165 (20:45255174 G>C), RS1004590105 (20:45253418 G>A,C), RS1004625560 (20:45254909 C>T), RS1005015136 (20:45254746 G>A), RS1005762019 (20:45256454 T>C)

Disease associations

OMIM: gene MIM:107285 | disease phenotypes: MIM:166760, MIM:125853

GenCC curated gene-disease

Disease	Classification	Inheritance
otitis media	Limited	Autosomal dominant

Mondo (3): otitis media, susceptibility to (MONDO:0008162), type 2 diabetes mellitus (MONDO:0005148), otitis media (MONDO:0005441)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_2658	Blood protein levels	2.000000e-07
GCST008103_143	Bipolar disorder	3.000000e-06
GCST010396_169	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06
GCST010725_40	Malaria	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D010033	Otitis Media	C09.218.705.663

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression	5
Tobacco Smoke Pollution	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Fluticasone	increases expression, increases reaction, affects cotreatment	2
Salmeterol Xinafoate	affects cotreatment, increases expression, increases reaction	2
Zoledronic Acid	increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Aspirin	decreases expression, increases expression	2
Cisplatin	decreases expression, affects response to substance	2
Silicon Dioxide	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	increases expression, decreases methylation	2
Cyclosporine	decreases expression	2
hempseed oil	decreases secretion, affects cotreatment	1
oxybutynin	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pirprofen	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
nimesulide	increases expression	1
hydroxyhydroquinone	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
chloroquine diphosphate	increases expression	1
perfluorodecanoic acid	decreases expression	1
esmolol	increases expression	1
epigallocatechin gallate	decreases reaction, decreases secretion, increases expression	1
nefazodone	increases expression	1
bromfenac	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2GG	Abcam HeLa SLPI KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00189462	PHASE4	COMPLETED	A Pilot Study to Evaluate the Efficacy of Montelukast in the Treatment of Acute Otitis Media (AOM) in Children
NCT00393159	PHASE4	UNKNOWN	The Influence of The Ear Popper on Serous Otitis Media and on the Accompanying Conductive Hearing Loss in Children
NCT00419380	PHASE4	COMPLETED	Treatment of Clogged Tympanostomy Tubes: An Off-Label Use of Dornase Alfa (Pulmozyme®)
NCT00539149	PHASE4	COMPLETED	Long-term Antibiotics for Treatment and Prevention of Otitis Media in Aborignal Children
NCT00956748	PHASE4	WITHDRAWN	N-Acetylcysteine as an Adjunct for Refractory Chronic Suppurative Otitis Media
NCT01174849	PHASE4	COMPLETED	Pneumococcal Vaccines Early and in Combination
NCT01244126	PHASE4	COMPLETED	Postoperative Effects of Intranasal Fentanyl, IV and IM Morphine in Children Undergoing Myringotomy
NCT01735084	PHASE4	COMPLETED	Using Pneumococcal Vaccines in Combination for Maximum Protection From Ear and Lung Infections in First 3 Years of Life
NCT02653742	PHASE4	UNKNOWN	Ketorolac Sublingual vs. Fentanyl Intranasal in Pain Control for Bilateral Myringotomy and Tubes (BMT) Placement in Children
NCT03655665	PHASE4	RECRUITING	Does Topical Otic Drop Use at Time of Tympanostomy Tube Surgery Improve Outcomes When no Middle Ear Effusion is Present
NCT04600752	PHASE4	COMPLETED	Study to Evaluate the Safety and Clinical Efficacy of Augmentin® Extra Strength-600 in Children With Acute Otitis Media in India
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes