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External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



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Rhomboid family member 2 is a protein that in humans is encoded by the RHBDF2 gene.[1][2] The alternative name iRhom2 has been proposed, in order to clarify that it is a catalytically inactive member of the rhomboid family of intramembrane serine proteases.[3][4]

The RHBDF2 gene is located on the long arm of chromosome 17 (17q25.1) on the Crick (minus) strand. It is 30.534 kilobases in length and encodes a protein of 856 amino acids with a predicted molecular weight of 96.686 kiloDaltons.

The RHBDF2 protein plays an important role in the secretion of tumor necrosis factor alpha,[5][6][7] and has also been implicated in familial esophageal cancer.[8]

It is involved in the regulation of the secretion of several ligands of the epidermal growth factor receptor.[9]


  1. Puente XS, Sánchez LM, Overall CM, López-Otín C (Jul 2003). "Human and mouse proteases: a comparative genomic approach". Nature Reviews Genetics. 4 (7): 544–58. doi:10.1038/nrg1111. PMID 12838346.
  2. "Entrez Gene: RHBDF2 rhomboid 5 homolog 2 (Drosophila)".
  3. Lemberg MK, Freeman M (Nov 2007). "Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases". Genome Research. 17 (11): 1634–46. doi:10.1101/gr.6425307. PMC 2045146. PMID 17938163.
  4. Zettl M, Adrain C, Strisovsky K, Lastun V, Freeman M (Apr 2011). "Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling". Cell. 145 (1): 79–91. doi:10.1016/j.cell.2011.02.047. PMC 3149277. PMID 21439629.
  5. Siggs OM, Xiao N, Wang Y, Shi H, Tomisato W, Li X, Xia Y, Beutler B (Jun 2012). "iRhom2 is required for the secretion of mouse TNFα". Blood. 119 (24): 5769–71. doi:10.1182/blood-2012-03-417949. PMC 3382936. PMID 22550345.
  6. Adrain C, Zettl M, Christova Y, Taylor N, Freeman M (Jan 2012). "Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE". Science. 335 (6065): 225–8. doi:10.1126/science.1214400. PMC 3272371. PMID 22246777.
  7. McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW (Jan 2012). "iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS". Science. 335 (6065): 229–32. doi:10.1126/science.1214448. PMC 4250273. PMID 22246778.
  8. Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, Carroll R, Plagnol V, McRonald FE, Stevens HP, Spurr NK, Bishop DT, Ellis A, Jankowski J, Field JK, Leigh IM, South AP, Kelsell DP (Feb 2012). "RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome". American Journal of Human Genetics. 90 (2): 340–6. doi:10.1016/j.ajhg.2011.12.008. PMC 3276661. PMID 22265016.
  9. Siggs OM, Grieve A, Xu H, Bambrough P, Christova Y, Freeman M (November 2014). "Genetic interaction implicates iRhom2 in the regulation of EGF receptor signalling in mice". Biol Open. 3 (12): 1151–7. doi:10.1242/bio.201410116. PMC 4265752. PMID 25395669.

Further reading