SPINK5

Chr 5AR

serine peptidase inhibitor Kazal type 5

Also known as: LEKTI, LETKI, NETS, NS, VAKTI

NCBI Gene: 11005 ENSG00000133710 UniProt: Q9NQ38 OMIM: 605010

The protein is a serine protease inhibitor that regulates skin barrier function by inhibiting proteases involved in desquamation and defense, particularly KLK5, KLK7, KLK14, and CASP14. Mutations cause Netherton syndrome, an autosomal recessive disorder characterized by severe ichthyosis, hair shaft abnormalities, and atopic manifestations that typically present in the neonatal period. The gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from OMIM, UniProt

This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Netherton syndromeMIM #256500

Clinical highlights

Gene-disease validity (ClinGen)

Netherton syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.93

LOEUF

LOF

Mechanism· G2P

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GeneReview available — SPINK5