MBTPS2

Chr X

membrane bound transcription factor peptidase, site 2

Also known as: BRESEK, IFAP, KFSD, KFSDX, OI19, OLMSX, S2P

NCBI Gene: 51360 ENSG00000012174 UniProt: O43462

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.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.[provided by RefSeq, Aug 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIFAP syndrome 1, with or without Bresheck syndrome

UniProtOlmsted syndrome, X-linked

UniProtKeratosis follicularis spinulosa decalvans X-linked

UniProtOsteogenesis imperfecta 19

Clinical highlights

Gene-disease validity (ClinGen)

IFAP syndrome 1, with or without BRESHECK syndrome · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)