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Gene Review

CIC  -  capicua transcriptional repressor

Homo sapiens

Synonyms: KIAA0306, Protein capicua homolog
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Disease relevance of CIC


Psychiatry related information on CIC


High impact information on CIC

  • In contrast to most known ion channels, which have single pores, a chloride channel belonging to the CIC family (Torpedo CIC-0) has functional features that suggest that it has a unique 'double-barrelled' architecture in which each of two subunits forms an independent pore [7].
  • Although the CIC channels expressed in Xenopus oocytes have been characterized, their channel properties are still poorly understood [8].
  • Indeed, CIC-DUX4 directly binds the ERM promoter by recognizing a novel target sequence and significantly up-regulates its expression [3].
  • Sequence analysis of 780 bp of ORF from the clones suggests that the identified gene, termed hCIC-K2, encodes a new member of the CIC family of voltage-gated chloride channels [9].
  • Using a specific antibody raised against a 15-amino acid peptide from the CIC sequence, we concluded that CIC and P25 are identical entities, and hence that P25 belongs to the MIP family [10].

Chemical compound and disease context of CIC


Biological context of CIC

  • Alternative splicing of ClC-6 (a member of the CIC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific [15].
  • A new cold-regulated (COR) gene, msa CIC, was isolated by differential screening of a cDNA library from cold-acclimated crowns of alfalfa (Medicago sativa L. cv. Apica) [16].
  • The DNA sequence analysis of a full-length cDNA clone revealed that msa CIC encodes for a putative protein (MSACIC) of 166 amino acids with distinct proline-rich and hydrophobic domains [16].
  • The concentration of CIC and the light dose that correspond to ca 50% level of phototoxicity induce predominantly an apoptotic-type of cell death, whereas the conditions providing 100% level of phototoxicity induced necrosis [17].
  • No significant relationship among erythrocyte CR1 molecules, erythrocyte surface-associated immunoglobulins, CIC, and HLA phenotype was observed in any patient group [18].

Anatomical context of CIC


Associations of CIC with chemical compounds

  • Although PEG precipitates were enriched for high molecular weight IgA and IgG (presumably bound within CIC), significant amounts of IgM, unbound IgG and C3 were also present [22].
  • Compounds of more recent research are MERCK 3535 (aminopropionic acid ethylester), p-menthane-3,8 diol, CIC 4 (a lacton) and the piperidine derivatives AI3-37220 and Bayrepel (Icaridin) [23].
  • In addition, the CIC cholesterol level diagnoses extracoronary atherosclerosis with high accuracy [14].
  • Even though vitamin A supplementation in malnourished children did not significantly alter the duration of diarrhea, a beneficial effect was observed in children who had CIC state 3 and above in association with malnutrition (p = 0.025) [24].
  • The determination of CIC is carried out by means of precipitation with 3.5% PEG and a posterior determination of C4 of the precipitates as well as optical density [25].

Other interactions of CIC

  • This study clarifies the function of CIC and its role in tumorigenesis, as well as the importance of the PEA3 subclass of ETS family proteins in the development of EFTs arising through mechanisms different from those involving EWS-ETS chimeras [3].
  • In a parallel study increased CIC and anti-IgG Ab levels were found in most of the 81 patients with seropositive or seronegative rheumatoid arthritis [26].
  • The levels of L-CR1 transcription correlated negatively with the levels of CIC and anti dsDNA antibodies and positively with serum C3 levels [27].
  • The influence of therapeutic regimens on elevated CIC level in the CSF was insignificant [28].
  • Obstructive complications were defined as increased PVR (greater than 100 cc), or the need for CIC, prolonged Foley catheter drainage or urethrolysis [29].

Analytical, diagnostic and therapeutic context of CIC

  • RT-PCR and in situ hybridization verified the expression of CIC in tumor cells, although the level of expression varied between different medulloblastoma subtypes [1].
  • CIC have played a major role in cancer-associated immunosuppression [19].
  • In these patients, there was a good correlation between the level of IgM-RF and the amount of IgE detected in the CIC by the RIA method (r = 0.87) whereas the RF-interference free ELISA method showed no correlation between these two parameters (r = 0.06) [30].
  • Analysis of sera by HPLC revealed that both monomeric and higher molecular forms of IgA antibodies were present, the latter being coincident with the peak of IgA CIC [31].
  • The incidence of Epstein-Barr virus (EBV) viraemia and lymphoproliferative disease (LPD) was studied in a consecutive cohort of 128 paediatric patients undergoing stem cell transplantation (SCT) with reduced-intensity conditioning (RIC; n = 65) or conventional-intensity conditioning (CIC; n = 68) [32].


  1. CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas. Lee, C.J., Chan, W.I., Scotting, P.J. J. Neurooncol. (2005) [Pubmed]
  2. Clonality analysis of synchronous lesions of cervical carcinoma based on X chromosome inactivation polymorphism, human papillomavirus type 16 genome mutations, and loss of heterozygosity. Hu, X., Pang, T., Asplund, A., Pontén, J., Nistér, M. J. Exp. Med. (2002) [Pubmed]
  3. Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation. Kawamura-Saito, M., Yamazaki, Y., Kaneko, K., Kawaguchi, N., Kanda, H., Mukai, H., Gotoh, T., Motoi, T., Fukayama, M., Aburatani, H., Takizawa, T., Nakamura, T. Hum. Mol. Genet. (2006) [Pubmed]
  4. IgG-containing and IgE-containing circulating immune complexes in patients with asthma and rhinitis. Stevens, W.J., Bridts, C.H. J. Allergy Clin. Immunol. (1984) [Pubmed]
  5. A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer. Jefford, M., Michael, M., Rosenthal, M.A., Davis, I.D., Green, M., McClure, B., Smith, J., Waite, B., Zalcberg, J. Investigational new drugs. (2004) [Pubmed]
  6. Changing views about personality disorders: Comment about the prospective studies CIC, CLPS, and MSAD. Pukrop, R., Krischer, M. J. Personal. Disord. (2005) [Pubmed]
  7. Pore stoichiometry of a voltage-gated chloride channel. Fahlke, C., Rhodes, T.H., Desai, R.R., George, A.L. Nature (1998) [Pubmed]
  8. Stable and functional expression of the CIC-3 chloride channel in somatic cell lines. Kawasaki, M., Suzuki, M., Uchida, S., Sasaki, S., Marumo, F. Neuron (1995) [Pubmed]
  9. Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent's disease (an X-linked hereditary nephrolithiasis). Fisher, S.E., Black, G.C., Lloyd, S.E., Hatchwell, E., Wrong, O., Thakker, R.V., Craig, I.W. Hum. Mol. Genet. (1994) [Pubmed]
  10. Structural analysis of a MIP family protein from the digestive tract of Cicadella viridis. Beuron, F., Le Cahérec, F., Guillam, M.T., Cavalier, A., Garret, A., Tassan, J.P., Delamarche, C., Schultz, P., Mallouh, V., Rolland, J.P. J. Biol. Chem. (1995) [Pubmed]
  11. CBS domains in CIC chloride channels implicated in myotonia and nephrolithiasis (kidney stones). Ponting, C.P. J. Mol. Med. (1997) [Pubmed]
  12. A pilot study of chronomodulated infusional 5-fluorouracil chemoradiation for pancreatic cancer. Penberthy, D.R., Rich, T.A., Shelton, C.H., Adams, R., Minasi, J.S., Jones, R.S. Ann. Oncol. (2001) [Pubmed]
  13. Predictive value of serum anti-C1q antibody levels in experimental autoimmune myasthenia gravis. Tüzün, E., Saini, S.S., Ghosh, S., Rowin, J., Meriggioli, M.N., Christadoss, P. Neuromuscul. Disord. (2006) [Pubmed]
  14. Lipoprotein immune complexes as markers of atherosclerosis. Orekhov, A.N., Kalenich, O.S., Tertov, V.V., Novikov, I.D. International journal of tissue reactions. (1991) [Pubmed]
  15. Alternative splicing of ClC-6 (a member of the CIC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific. Eggermont, J., Buyse, G., Voets, T., Tytgat, J., De Smedt, H., Droogmans, G., Nilius, B. Biochem. J. (1997) [Pubmed]
  16. A cold-induced gene from Medicago sativa encodes a bimodular protein similar to developmentally regulated proteins. Castonguay, Y., Laberge, S., Nadeau, P., Vézina, L.P. Plant Mol. Biol. (1994) [Pubmed]
  17. Near-infrared photosensitizer based on a cycloimide derivative of chlorin p6: 13,15-N-(3'-hydroxypropyl)cycloimide chlorin p6. Feofanov, A., Grichine, A., Karmakova, T., Pljutinskaya, A., Lebedeva, V., Filyasova, A., Yakubovskaya, R., Mironov, A., Egret-Charlier, M., Vigny, P. Photochem. Photobiol. (2002) [Pubmed]
  18. Complement receptor (CR1) and IgG or IgA on erythrocytes and in circulating immune complexes in patients with glomerulonephritis. Coppo, R., Amore, A., Roccatello, D., Amoroso, A., Maffei, S., Quattrocchio, G., Molino, A., Gianoglio, B., Piccoli, G. Nephrol. Dial. Transplant. (1989) [Pubmed]
  19. Protein A immunotherapy in the treatment of cancer: an update. Messerschmidt, G.L., Henry, D.H., Snyder, H.W., Bertram, J., Mittelman, A., Ainsworth, S., Fiore, J., Viola, M.V., Louie, J., Ambinder, E. Semin. Hematol. (1989) [Pubmed]
  20. Circulating immune complexes containing rubella antigens in late-onset rubella syndrome. Tardieu, M., Grospierre, B., Durandy, A., GAriscelli, C. J. Pediatr. (1980) [Pubmed]
  21. IgA containing circulating immune complexes and IgA anti-single stranded DNA antibodies in patients with obstructive jaundice. Ohshio, G., Furukawa, F., Sekita, K., Manabe, T., Tobe, T., Hamashima, Y. Clin. Exp. Immunol. (1985) [Pubmed]
  22. Polyethylene glycol precipitates of serum contain a large proportion of uncomplexed immunoglobulins and C3. Crowley-Nowick, P.A., Campbell, E., Schrohenloher, R.E., Mestecky, J., Mestecky, J., Jackson, S. Immunol. Invest. (1996) [Pubmed]
  23. Use of repellents as prophylactic agents. Nentwig, G. Parasitol. Res. (2003) [Pubmed]
  24. A randomized controlled trial of vitamin A supplementation in acute diarrhea. Dewan, V., Patwari, A.K., Jain, M., Dewan, N. Indian pediatrics. (1995) [Pubmed]
  25. Circulating immune complexes in pollinosis and chronic bronchopathies. Effect of immunotherapy. Muñoz, D., Sanz, M.L., Tabar, A., Oehling, A., Fernández de Corres, L. Allergologia et immunopathologia. (1983) [Pubmed]
  26. Failure to find C1q-binding material and anti-IgG antibodies in ankylosing spondylitis. Duquesnoy, B., Santoro, F., Wattre, P., Delcambre, B. Ann. Rheum. Dis. (1980) [Pubmed]
  27. Association of leukocyte CR1 gene transcription with the disease severity and renal involvement in systemic lupus erythematosus. Verma, J., Arora, V., Marwaha, V., Kumar, A., Das, N. Lupus (2005) [Pubmed]
  28. Effect of immunosuppressive therapy on humoral immune response in multiple sclerosis. Wajgt, A., Górny, M., Szczechowski, L., Grzybowski, G., Ochudło, S. Acta medica Polona. (1989) [Pubmed]
  29. Transobturator versus transabdominal mid urethral slings: a multi-institutional comparison of obstructive voiding complications. Morey, A.F., Medendorp, A.R., Noller, M.W., Mora, R.V., Shandera, K.C., Foley, J.P., Rivera, L.R., Reyna, J.A., Terry, P.J. J. Urol. (2006) [Pubmed]
  30. Role of IgM-rheumatoid factor interference in the determination of total serum IgE and IgE-containing circulating immune complexes. De Clerck, L.S., Gigase, P.L., Bridts, C.H., Stevens, W.J. Clin. Exp. Immunol. (1988) [Pubmed]
  31. Food antigens, IgA-immune complexes and IgA mesangial nephropathy. Fornasieri, A., Sinico, R.A., Maldifassi, P., Paterna, L., Benuzzi, S., Colasanti, G., D'Amico, G. Nephrol. Dial. Transplant. (1988) [Pubmed]
  32. Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning. Cohen, J., Gandhi, M., Naik, P., Cubitt, D., Rao, K., Thaker, U., Davies, E.G., Gaspar, H.B., Amrolia, P.J., Veys, P. Br. J. Haematol. (2005) [Pubmed]
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