MBTPS2
Chr XXLRmembrane bound transcription factor peptidase, site 2
Also known as: BRESEK, IFAP, KFSD, KFSDX, OI19, OLMSX, S2P
This intramembrane zinc metalloprotease cleaves sterol regulatory element-binding proteins (SREBPs) and ATF6 to activate transcription factors essential for cholesterol homeostasis and ER stress response. X-linked recessive mutations cause IFAP syndrome (ichthyosis follicularis with atrichia and photophobia), keratosis follicularis spinulosa decalvans, osteogenesis imperfecta type XIX, and possibly Olmsted syndrome through loss of function. The pathogenic mechanism involves impaired cholesterol homeostasis and defective ER stress response due to reduced protease activity.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MBTPS2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools