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Gene Review

NOS1AP  -  nitric oxide synthase 1 (neuronal) adaptor...

Homo sapiens

Synonyms: 6330408P19Rik, C-terminal PDZ ligand of neuronal nitric oxide synthase protein, CAPON, Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein, KIAA0464, ...
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Disease relevance of NOS1AP

  • Two melanoma cell lines (M1Dor and M3Da) previously reported to secrete proMMP-2 in a direct relationship with their tumorigenic potential into nude mice were used (F. Capon et al., 1999, Clin. Exp. Metastasis 17, 463-469) [1].

Psychiatry related information on NOS1AP


High impact information on NOS1AP

  • It binds to neuronal nitric oxide synthase (nNOS) via the adaptor protein CAPON, eliciting S-nitrosylation and activation of Dexras1 [3].
  • Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22 [4].
  • Consistent with several recently identified candidate genes for schizophrenia, CAPON is involved in signal transduction in the NMDA receptor system, highlighting the potential importance of this pathway in the etiology of schizophrenia [4].
  • Therefore, we carried out further fine mapping between the RGS4 and CAPON genes [5].
  • RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia [5].

Biological context of NOS1AP

  • The present finding weakens the evidence that mutations or variation in the CAPON gene are causing genetic susceptibility to schizophrenia in European populations [6].
  • A second Chinese study found a base pair polymorphism at the CAPON gene also associated with schizophrenia [6].
  • Recently, some genetic variants within CAPON have been reported as exhibiting significant linkage disequilibrium to schizophrenia in Canadian familial-schizophrenia pedigrees [7].
  • We examined nine single nucleotide polymorphisms (SNPs), which span an approximately 236-kb region of CAPON, in 664 schizophrenia cases and 941 controls in the Chinese Han population [7].
  • Comparison of this value to that estimated for the hydrolysis of beta-chitobiosyl fluoride by HEWL (1200s(-1)M(-1)) [Ballardie, F. W.; Capon, B.; Cuthbert, M. W.; Dearie, W. M. Bioorg. Chem.1977, 6, 483-509] revealed a 126-fold rate decrease upon substitution of a fluorine group for the 2-acetamido group of beta-chitobiosyl fluoride [8].

Other interactions of NOS1AP

  • Our findings indicate that CAPON gene may be a candidate susceptibility gene for schizophrenia in Chinese Han population, and also provide further support for the potential importance of NMDAR-mediated glutamatergic transmission in the etiology of schizophrenia [7].
  • This antibody-like molecule, termed an immunoadhesin, was produced in an effort to combine the binding specificity of CD4 with several potentially desirable properties of IgG molecules [Capon et al. (1989) Nature 337, 525-531] [9].


  1. Cumulative influence of matrix metalloproteinase-1 and -2 in the migration of melanoma cells within three-dimensional type I collagen lattices. Ntayi, C., Lorimier, S., Berthier-Vergnes, O., Hornebeck, W., Bernard, P. Exp. Cell Res. (2001) [Pubmed]
  2. Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder. Xu, B., Wratten, N., Charych, E.I., Buyske, S., Firestein, B.L., Brzustowicz, L.M. PLoS Med. (2005) [Pubmed]
  3. NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Cheah, J.H., Kim, S.F., Hester, L.D., Clancy, K.W., Patterson, S.E., Papadopoulos, V., Snyder, S.H. Neuron (2006) [Pubmed]
  4. Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22. Brzustowicz, L.M., Simone, J., Mohseni, P., Hayter, J.E., Hodgkinson, K.A., Chow, E.W., Bassett, A.S. Am. J. Hum. Genet. (2004) [Pubmed]
  5. Fine Mapping by Genetic Association Implicates the Chromosome 1q23.3 Gene UHMK1, Encoding a Serine/Threonine Protein Kinase, as a Novel Schizophrenia Susceptibility Gene. Puri, V., McQuillin, A., Choudhury, K., Datta, S., Pimm, J., Thirumalai, S., Krasucki, R., Lawrence, J., Quested, D., Bass, N., Moorey, H., Morgan, J., Punukollu, B., Kandasami, G., Curtis, D., Gurling, H. Biol. Psychiatry (2007) [Pubmed]
  6. Failure to confirm allelic association between markers at the CAPON gene locus and schizophrenia in a British sample. Puri, V., McQuillin, A., Thirumalai, S., Lawrence, J., Krasucki, R., Choudhury, K., Datta, S., Kerwin, S., Quested, D., Bass, N., Pimm, J., Lamb, G., Moorey, H., Kandasami, G., Badacsonyi, A., Kelly, K., Morgan, J., Punukollu, B., Nadeem, H., Curtis, D., Gurling, H.M. Biol. Psychiatry (2006) [Pubmed]
  7. Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population. Zheng, Y., Li, H., Qin, W., Chen, W., Duan, Y., Xiao, Y., Li, C., Zhang, J., Li, X., Feng, G., He, L. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  8. The chemical synthesis of 2-deoxy-2-fluorodisaccharide probes of the hen egg white lysozyme mechanism. Vocadlo, D.J., Withers, S.G. Carbohydr. Res. (2005) [Pubmed]
  9. Structural characterization of a recombinant CD4-IgG hybrid molecule. Harris, R.J., Wagner, K.L., Spellman, M.W. Eur. J. Biochem. (1990) [Pubmed]
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