MBTPS2 Gene

Name	membrane-bound transcription factor peptidase, site 2
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMBTPS2 encodes the membrane‐bound transcription factor protease, site‐2 (S2P), a zinc metalloprotease that catalyzes regulated intramembrane proteolysis necessary for activating key transcription factors involved in both the unfolded protein response and cholesterol homeostasis. In its normal function, MBTPS2 cleaves ER‐anchored substrates—such as ATF6 and sterol regulatory element–binding proteins—after an initial site‐1 proteolysis step, thereby releasing soluble transcription factor domains that translocate to the nucleus to regulate stress and metabolic gene expression. This proteolytic processing is executed in the Golgi apparatus and is essential to enable cells to adapt to changes in lipid levels and ER stress conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in MBTPS2 disrupt its protease activity and are associated with a spectrum of X‐linked disorders. Missense and splicing mutations that impair MBTPS2 function lead to aberrant processing of regulators—including ATF6, OASIS, and SREBP—resulting in dysregulated cholesterol metabolism, a compromised ER stress response, defective osteoblast differentiation, and diminished collagen production observed in conditions such as ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome, keratosis follicularis spinulosa decalvans (KFSD), and osteogenesis imperfecta. Moreover, altered MBTPS2 activity has been implicated in affecting regulatory regions of TRPV3, suggesting that the impaired proteolytic activation of multiple substrates contributes to overlapping clinical features among these disorders. The severity of the clinical phenotype appears to correlate with the extent of the protease dysfunction across different mutations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kyungho Lee, Witoon Tirasophon, Xiaohua Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.964702"}], "href": "https://doi.org/10.1101/gad.964702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11850408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11850408"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jingshi Shen, Ron Prywes "}, {"type": "b", "children": [{"type": "t", "text": "Dependence of site-2 protease cleavage of ATF6 on prior site-1 protease digestion is determined by the size of the luminal domain of ATF6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408466200"}], "href": "https://doi.org/10.1074/jbc.M408466200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15299016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15299016"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Robert B Rawson "}, {"type": "b", "children": [{"type": "t", "text": "The site-2 protease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamem.2013.03.031"}], "href": "https://doi.org/10.1016/j.bbamem.2013.03.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23571157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23571157"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Frank Oeffner, Gayle Fischer, Rudolf Happle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.03.014"}], "href": "https://doi.org/10.1016/j.ajhg.2009.03.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19361614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19361614"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Andrew Ming, Rudolf Happle, Karl-Heinz Grzeschik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome due to mutation of the gene MBTPS2 in a large Australian kindred."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Dermatol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1525-1470.2009.00946.x"}], "href": "https://doi.org/10.1111/j.1525-1470.2009.00946.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19689518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19689518"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Emmelien Aten, Lisa C Brasz, Dorothea Bornholdt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21335"}], "href": "https://doi.org/10.1002/humu.21335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20672378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20672378"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Li Tang, Jianying Liang, Wenzhang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mutation in MBTPS2 causes a broad phenotypic spectrum of ichthyosis follicularis, atrichia, and photophobia syndrome in a large Chinese family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Acad Dermatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaad.2010.02.045"}], "href": "https://doi.org/10.1016/j.jaad.2010.02.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21315478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21315478"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Frank Oeffner, Francisco Martinez, Julie Schaffer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intronic mutations affecting splicing of MBTPS2 cause ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0625.2010.01238.x"}], "href": "https://doi.org/10.1111/j.1600-0625.2010.01238.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21426410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21426410"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "K Fong, E K Wedgeworth, J E Lai-Cheong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MBTPS2 mutation in a British pedigree with keratosis follicularis spinulosa decalvans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Dermatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2230.2011.04288.x"}], "href": "https://doi.org/10.1111/j.1365-2230.2011.04288.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22816986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22816986"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dorothea Bornholdt, T Prescott Atkinson, Bakar Bouadjar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotype-phenotype correlations emerging from the identification of missense mutations in MBTPS2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22275"}], "href": "https://doi.org/10.1002/humu.22275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23316014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23316014"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Uschi Lindert, Wayne A Cabral, Surasawadee Ausavarat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11920"}], "href": "https://doi.org/10.1038/ncomms11920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27380894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27380894"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Georges Nemer, Rémi Safi, Firas Kreidieh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Understanding the phenotypic similarities between IFAP and Olmsted syndrome from a molecular perspective: the interaction of MBTPS2 and TRPV3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Dermatol Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00403-017-1762-z"}], "href": "https://doi.org/10.1007/s00403-017-1762-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28717930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28717930"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Natarin Caengprasath, Thanakorn Theerapanon, Thantrira Porntaveetus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-021-02779-5"}], "href": "https://doi.org/10.1186/s12967-021-02779-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33743732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33743732"}]}]}]}
Synonyms	OLMSX, OI19, IFAP, S2P, BRESEK
Proteins	MBTP2_HUMAN
NCBI Gene ID	51360
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MBTPS2 has 6,690 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for MBTPS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MBTPS2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MBTPS2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MBTPS2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of MBTPS2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MBTPS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of MBTPS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MBTPS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MBTPS2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MBTPS2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MBTPS2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MBTPS2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of MBTPS2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MBTPS2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of MBTPS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MBTPS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MBTPS2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MBTPS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MBTPS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of MBTPS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with MBTPS2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MBTPS2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MBTPS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MBTPS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MBTPS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MBTPS2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing MBTPS2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MBTPS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with MBTPS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MBTPS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MBTPS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MBTPS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MBTPS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving MBTPS2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving MBTPS2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MBTPS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with MBTPS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with MBTPS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MBTPS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MBTPS2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MBTPS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MBTPS2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.