Obesity due to prohormone convertase I deficiency: genes and variants
Obesity due to prohormone convertase I deficiency is linked to 1 analyzed protein (PCSK1). 6 DNA variants are known to cause it; 27 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 Obesity due to prohormone convertase I deficiency
PCSK1: Neuroendocrine convertase 1
It activates numerous peptide hormones and neuropeptides by cleaving their precursor proteins in endocrine and neuroendocrine secretory granules. Biallelic loss-of-function variants can cause severe early-onset obesity, endocrine abnormalities, and malabsorptive diarrhea.
6 disease-causing and 27 uncertain variants in PCSK1 are linked to Obesity due to prohormone convertase I deficiency.
Where Obesity due to prohormone convertase I deficiency variants cluster
- PCSK1 P/Homo B (positions 460–597): 3 of 6 disease-causing changes, 2.7× more than its size predicts.
Known disease-causing variants in Obesity due to prohormone convertase I deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PCSK1 R438Q | 438 | Peptidase S8 | Disease-causing (★) |
| PCSK1 L535F | 535 | P/Homo B | Disease-causing (★) |
| PCSK1 L449P | 449 | Peptidase S8 | Disease-causing (★) |
| PCSK1 P563R | 563 | P/Homo B | Disease-causing (★) |
| PCSK1 S307L | 307 | Peptidase S8 | Disease-causing |
| PCSK1 G483R | 483 | P/Homo B | Disease-causing |
Diseases related to Obesity due to prohormone convertase I deficiency
- BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20, also linked to PCSK1
- Obesity due to melanocortin 4 receptor deficiency, also linked to PCSK1
Frequently asked questions
Which genes are linked to Obesity due to prohormone convertase I deficiency?
In CATVariant, Obesity due to prohormone convertase I deficiency is linked to 1 analyzed protein: PCSK1 (Neuroendocrine convertase 1).
How many genetic variants are linked to Obesity due to prohormone convertase I deficiency?
43 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 27 are of uncertain significance or have conflicting reports.
Which uncertain variants in Obesity due to prohormone convertase I deficiency 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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