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Gene Review

INVS  -  inversin

Homo sapiens

Synonyms: INV, Inversin, Inversion of embryo turning homolog, NPH2, NPHP2, ...
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Disease relevance of INVS


High impact information on INVS

  • Three loci are associated with the juvenile, infantile and adolescent forms, on chromosomes 2q13 (NPHP1; refs 5,6), 9q22 (NPHP2; ref. 7) and 3q21 (NPHP3; ref. 8), respectively [5].
  • When analyzed individually, there was no difference (p = NS) in death (INV, 6.9%; CON, 7.4%) or recurrent infarction (INV, 9.4%; CON, 9.8%) between the two groups [3].
  • Activation of hINV promoter activity by the green tea polyphenol, (-)-epigellocathecin-3-gallate, is also inhibited by apigenin, suggesting that the two chemopreventive agents can produce opposing actions in keratinocytes [6].
  • Apigenin suppresses the 12-O-tetradeconylphorbol-13-acetate-dependent increase in AP1 factor expression and binding to the hINV promoter and the increase in hINV promoter activity [6].
  • The physiological importance of this phosphorylation event was confirmed by showing that the PKCdelta phosphorylation-defective mutant, PKCdelta-Y311F, is less able to increase hINV promoter activity [6].

Chemical compound and disease context of INVS

  • An antibody (C'-B5R) raised to a 15-amino-acid peptide from the translated B5R ORF reacted with a 42-kDa protein (gp42) found in vaccinia virus-infected cells and cesium chloride-banded EEV but not INV [7].
  • Using a reverse genetic approach, we have demonstrated that the product of the B5R open reading frame (ORF), which has homology with members of the family of complement control proteins, is a membrane glycoprotein present in the extracellular enveloped (EEV) form of vaccinia virus but absent from the intracellular naked (INV) form [7].

Biological context of INVS

  • In contrast to the mouse, the affected individuals have no biliary anomalies, and the absence of mutation in a series of seven cases with lateralization defect and biliary anomalies demonstrates that INV is not frequently involved in such a phenotype in humans [2].
  • Our studies indicate that calcium increases hINV promoter activity and endogenous hINV gene expression [8].
  • We now show that EGCG activation of this pathway results in increased CCAAT/enhancer-binding protein (C/EBPalpha and C/EBPbeta) factor level and increased complex formation at the hINV promoter C/EBP DNA binding site [9].
  • The calcium-dependent regulatory response is mediated by an AP1 transcription factor-binding site located within the hINV promoter distal regulatory region that is also required for PKCdelta-dependent regulation; moreover, both calcium and PKCdelta produce similar, but not identical, changes in AP1 factor expression [8].
  • In the teleost fish Xiphophorus two versions of the Xmrk gene exist, an oncogene (ONC) and a proto-oncogene (INV) [10].

Anatomical context of INVS

  • Fluorescently labeled INV and EEV from both the IHD-J and WR strains of vaccinia virus fused with HeLa cells at neutral pH, suggesting that fusion occurs with the plasma membrane during virus entry [11].
  • Based on clinicopathological observations of 91 female patients with breast cancer in Miyagi Prefecture, TNM stage, histologic type, grade of infiltrative growth tendency (INV), vessel involvement, lymph node metastasis, nuclear grade and sinus histiocytosis were assessed in relation to prognosis [12].

Associations of INVS with chemical compounds

  • In the present study, we examine the effect of PKCdelta and PKCalpha on calcium-dependent keratinocyte differentiation as measured by effects on involucrin (hINV) gene expression [8].
  • Curcumin also inhibits the EGCG-dependent increase in endogenous hINV levels [9].
  • Protein kinase C and tyrosine kinase inhibitors inhibit both the TPA-dependent mRNA increase and the TPA-dependent increase in hINV promoter activity [13].
  • The fastest migrating peptide (68 kDa) comigrates with a peptide that is released after CNBr cleavage of bacterially produced-recombinant hINV [14].

Other interactions of INVS

  • CONCLUSIONS: This is the first report of the presence of RP in a patient with NPHP type 2 and INVS mutations [1].

Analytical, diagnostic and therapeutic context of INVS

  • Cardiac catheterization and PTCA were performed more often in INV (98.0% and 61.2%, respectively) compared with CON (45.2% and 20.5%, respectively) patients [3].
  • RESULTS: Of the clinicopathological features, only histological portal involvement or intrahepatic metastasis, or both (INV), was significantly correlated to the disease-free survival rates (DFS; P < 0.05) [15].
  • Total body bone mineral (TBBM) was measured using a dual-energy X-ray absorptiometry (DXA) (Hologic INV., Waltham, U.S.A.). Similarly, regional and total body soft tissue (lean and fat tissue) were measured using the DXA system [16].
  • AIM: The aim of this study was to evaluate a modified version of the INV for use with ambulatory surgery patients [17].


  1. Retinitis pigmentosa and renal failure in a patient with mutations in INVS. O'Toole, J.F., Otto, E.A., Frishberg, Y., Hildebrandt, F. Nephrol. Dial. Transplant. (2006) [Pubmed]
  2. Identification, genomic organization, chromosomal mapping and mutation analysis of the human INV gene, the ortholog of a murine gene implicated in left-right axis development and biliary atresia. Schön, P., Tsuchiya, K., Lenoir, D., Mochizuki, T., Guichard, C., Takai, S., Maiti, A.K., Nihei, H., Weil, J., Yokoyama, T., Bouvagnet, P. Hum. Genet. (2002) [Pubmed]
  3. One-year results of the Thrombolysis in Myocardial Infarction investigation (TIMI) Phase II Trial. Williams, D.O., Braunwald, E., Knatterud, G., Babb, J., Bresnahan, J., Greenberg, M.A., Raizner, A., Wasserman, A., Robertson, T., Ross, R. Circulation (1992) [Pubmed]
  4. Acceleration of G(1) cooperates with core binding factor beta-smooth muscle myosin heavy chain to induce acute leukemia in mice. Yang, Y., Wang, W., Cleaves, R., Zahurak, M., Cheng, L., Civin, C.I., Friedman, A.D. Cancer Res. (2002) [Pubmed]
  5. The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Mollet, G., Salomon, R., Gribouval, O., Silbermann, F., Bacq, D., Landthaler, G., Milford, D., Nayir, A., Rizzoni, G., Antignac, C., Saunier, S. Nat. Genet. (2002) [Pubmed]
  6. Apigenin Inhibition of Involucrin Gene Expression Is Associated with a Specific Reduction in Phosphorylation of Protein Kinase C{delta} Tyr311. Balasubramanian, S., Zhu, L., Eckert, R.L. J. Biol. Chem. (2006) [Pubmed]
  7. Characterization of a vaccinia virus-encoded 42-kilodalton class I membrane glycoprotein component of the extracellular virus envelope. Isaacs, S.N., Wolffe, E.J., Payne, L.G., Moss, B. J. Virol. (1992) [Pubmed]
  8. Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta. Deucher, A., Efimova, T., Eckert, R.L. J. Biol. Chem. (2002) [Pubmed]
  9. Green tea polyphenol and curcumin inversely regulate human involucrin promoter activity via opposing effects on CCAAT/enhancer-binding protein function. Balasubramanian, S., Eckert, R.L. J. Biol. Chem. (2004) [Pubmed]
  10. Activation of the Xmrk proto-oncogene of Xiphophorus by overexpression and mutational alterations. Dimitrijevic, N., Winkler, C., Wellbrock, C., Gómez, A., Duschl, J., Altschmied, J., Schartl, M. Oncogene (1998) [Pubmed]
  11. Fusion of intra- and extracellular forms of vaccinia virus with the cell membrane. Doms, R.W., Blumenthal, R., Moss, B. J. Virol. (1990) [Pubmed]
  12. Significant prognostic factors in breast cancer of Japanese women: special reference to nuclear grade and sinus histiocytosis. Sato, E., Kumagai, N., Abe, R. Tohoku J. Exp. Med. (1976) [Pubmed]
  13. Regulation of human involucrin promoter activity by a protein kinase C, Ras, MEKK1, MEK3, p38/RK, AP1 signal transduction pathway. Efimova, T., LaCelle, P., Welter, J.F., Eckert, R.L. J. Biol. Chem. (1998) [Pubmed]
  14. Involucrin is a covalently crosslinked constituent of highly purified epidermal corneocytes: evidence for a common pattern of involucrin crosslinking in vivo and in vitro. Robinson, N.A., LaCelle, P.T., Eckert, R.L. J. Invest. Dermatol. (1996) [Pubmed]
  15. Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma. Itoh, T., Hayashi, Y., Kanamaru, T., Morita, Y., Suzuki, S., Wang, W., Zhou, L., Rui, J.A., Yamamoto, M., Kuroda, Y., Itoh, H. J. Gastroenterol. Hepatol. (2000) [Pubmed]
  16. Body composition measurements using DXA and other techniques in tamoxifen-treated patients. Ali, P.A., al-Ghorabie, F.H., Evans, C.J., el-Sharkawi, A.M., Hancock, D.A. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. (1998) [Pubmed]
  17. Evaluation of the Rhodes Index of Nausea and Vomiting for ambulatory surgery patients. Fetzer, S.J., Hand, M.C., Bouchard, P.A., Smith, H., Jenkins, M.B. Journal of advanced nursing. (2004) [Pubmed]
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