SPINK5
Serine Peptidase Inhibitor, Kazal Type 5
Gene Information Card
| Symbol | SPINK5 |
|---|---|
| Full Name | Serine Peptidase Inhibitor, Kazal Type 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q32 |
| NCBI Gene ID | 11005 ncbi.nlm.nih.gov/gene/11005 |
| Ensembl ID | ENSG00000133710 |
| UniProt ID | Q9NQ38 |
| OMIM ID | 605010 |
| HGNC ID | 11246 |
| Aliases | LEKTI, VSH, NETS, NS, FLJ45721 |
Description
The SPINK5 gene encodes the serine protease inhibitor LEKTI (Lympho-Epithelial Kazal-Type-related Inhibitor), which is crucial for regulating proteolytic activity in the skin and other epithelia. Loss-of-function mutations cause Netherton syndrome, characterized by ichthyosis, hair abnormalities, and atopic diathesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Netherton syndrome | Loss-of-function mutations in SPINK5 lead to unopposed serine protease activity (e.g., KLK5, KLK7), disrupting skin barrier integrity and causing desquamation and inflammation. | ClinVar, OMIM |
| Atopic dermatitis | SPINK5 polymorphisms (e.g., Glu420Lys) are associated with increased risk of atopic dermatitis due to impaired protease inhibition. | NCBI Gene, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 15.2 | Medium |
| Esophagus | 12.8 | Medium |
| Lung | 6.5 | Low |
| Thymus | 5.1 | Low |
| Prostate | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 18.5 | High expression |
| A549 (lung) | 7.2 | Moderate expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.153delT | Frameshift | Rare | Loss of function; associated with Netherton syndrome |
| c.247C>T (p.Gln83*) | Nonsense | Rare | Premature stop; loss of function |
| c.1258A>G (p.Glu420Lys) | Missense | Common (polymorphism) | Reduced inhibitory activity; risk factor for atopic dermatitis |
Mutation functional classification
Loss of Function (LOF)
Most SPINK5 mutations in Netherton syndrome are loss-of-function (nonsense, frameshift, splice-site), leading to absent or truncated LEKTI.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase inhibitor activity | • extracellular region |
| • negative regulation of proteolysis | • skin development |
| • cornification |
Pathways
• Kallikrein-kinin system
• Proteolysis in skin barrier formation
Protein Summary
LEKTI is a multidomain serine protease inhibitor expressed in stratified epithelia. It inhibits trypsin-like serine proteases (e.g., KLK5, KLK7, KLK14) to regulate desquamation and prevent premature degradation of corneodesmosomes. Deficiency leads to Netherton syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPINK5 Knockout HEK293 Cell Line | EDJ-KQ7240 | Human | 11005 | Details Get a Quote |
| SPINK5 Knockout HeLa Cell Line | EDJ-KQ32222 | Human | 11005 | Details Get a Quote |
| SPINK5 Knockout A-549 Cell Line | EDJ-KQ64035 | Human | 11005 | Details Get a Quote |
| SPINK5 Knockout HCT 116 Cell Line | EDJ-KQ72485 | Human | 11005 | Details Get a Quote |
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