Netherton syndrome: genes and variants
Netherton syndrome is linked to 1 analyzed protein (SPINK5). 1 DNA variants are known to cause it; 119 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Netherton syndrome
SPINK5: Serine protease inhibitor Kazal-type 5
Its processed inhibitory domains restrain epidermal serine proteases and protect the skin barrier from excessive proteolysis and inflammation. Biallelic loss-of-function variants cause Netherton syndrome with ichthyosis, hair-shaft defects, severe atopy, and infection risk.
1 disease-causing and 119 uncertain variants in SPINK5 are linked to Netherton syndrome.
Known disease-causing variants in Netherton syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SPINK5 T808I | 808 | Kazal-like 12 | Disease-causing (★★) |
Diseases related to Netherton syndrome
- Ichthyosis linearis circumflexa, also linked to SPINK5
Frequently asked questions
Which genes are linked to Netherton syndrome?
In CATVariant, Netherton syndrome is linked to 1 analyzed protein: SPINK5 (Serine protease inhibitor Kazal-type 5).
How many genetic variants are linked to Netherton syndrome?
150 variants: 1 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 119 are of uncertain significance or have conflicting reports.
Which uncertain variants in Netherton syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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