HGNC Approved Gene Symbol: CAT
Cytogenetic location: 11p13 Genomic coordinates (GRCh38) : 11:34,438,934-34,472,060 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11p13 | Acatalasemia | 614097 | 3 |
Catalase (EC 1.11.1.6) catalyzes the decomposition of hydrogen peroxide to oxygen and water. Mammalian catalase of approximately 240 kD occurs as a complex of 4 identical subunits, each of which contains 526 amino acid residues (summary by Ogata, 1991; Ogata et al., 2008).
Bell et al. (1986) gave the cDNA sequence for human kidney catalase. The coding region had 1,581 basepairs.
Quan et al. (1986) found that the CAT gene is 34 kb long and split into 13 exons.
Wieacker et al. (1980) assigned a gene for catalase to 11p by study of man-mouse cell hybrid clones. In the hybrid cells, detection of human catalase was precluded by the complexity of the electrophoretic patterns resulting from interference by a catalase-modifying enzyme activity. Therefore, a specific antihuman antibody was used in conjunction with electrophoresis. In mouse, catalase is not syntenic to the beta-globin cluster or to LDH-A.
Niikawa et al. (1982) confirmed the close linkage of catalase to the gene of the WAGR complex (see 194070) by demonstrating low levels of catalase activity in the erythrocytes of 2 unrelated patients with the WAGR syndrome and small deletions in 11p. From the study of dosage in 2 unrelated patients with an interstitial deletion involving 11p13, Narahara et al. (1984) concluded that both the catalase locus and the WAGR locus are situated in the chromosome segment 11p1306-p1305, with catalase distal to WAGR.
By classic linkage studies using RFLPs of the several genes as markers, Kittur et al. (1985) derived the following sequence of loci: cen--CAT--16 cM--CALC--8 cM--PTH--pter, with the interval between CAT and PTH estimated at 26 cM.
Junien et al. (1980) investigated catalase gene dosage effects in a case of 11p13 deletion, a case of trisomy of all of 11p except 11p13, and a case of trisomy 11p13. The results were consistent with assignment of the catalase locus to 11p13 and its linkage with the WAGR complex (194070). Assay of catalase activity should be useful in identifying those cases of presumed new mutation aniridia that have a risk of Wilms tumor or gonadoblastoma, even in the absence of visible chromosomal deletion. In karyotypically normal patients with aniridia, Wilms tumor, or the combination of the 2, Ferrell and Riccardi (1981) found normal catalase levels.
Several rare electrophoretic variants of red cell catalase were identified by Baur (1963). Nance et al. (1968) also described electrophoretic variants.
Kenney et al. (2005) found that keratoconus (see 148300) corneas exhibited a 2.20-fold increase in catalase mRNA and 1.8-fold increase in enzyme activity. They concluded that elevated levels of cathepsins V/L2, B (116810), and G (116830) in keratoconus corneas could stimulate hydrogen peroxide production which, in turn, could upregulate catalase, an antioxidant enzyme. These and other findings supported the hypothesis that keratoconus corneas undergo oxidative stress and tissue degradation.
Shibata et al. (1967) found that an immunologically reactive but enzymatically inactive protein about one-sixth the size of active catalase is present in red cells of patients with acatalasemia (614097).
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
Acatalasemia
In Japanese patients with acatalasemia (614097), Wen et al. (1990) identified a homozygous splice site mutation in the CAT gene (115500.0001).
Goth and Eaton (2000) reported an increased frequency of diabetes in catalase-deficient (hypo/acatalasemic) Hungarian patients as compared with unaffected first-degree relatives and the general Hungarian population. The authors speculated that quantitative deficiency of catalase might predispose to cumulative oxidant damage of pancreatic beta-cells and resulting diabetes.
Aniridia
Boyd et al. (1986) described a catalase RFLP with 2 different enzymes and used these polymorphisms to exclude deletion of the catalase gene in patients with sporadic aniridia, including one who was known to have a deletion and another suspected of having a deletion.
Mannens et al. (1987) found deletion of the catalase locus in 6 of 9 patients with aniridia (AN2; 106210). One of these catalase-deficient aniridia patients had a normal karyotype. No catalase deletion could be demonstrated in 7 Wilms tumors.
Hypertension
Jiang et al. (2001) found an association between essential hypertension defined as elevation of systolic blood pressure and a single-nucleotide polymorphism (SNP) located 844 bp upstream of the start codon of the CAT gene. The TT phenotype was associated with higher blood pressure than the CC phenotype and CT was intermediate.
In the acatalasemic mouse, Shaffer and Preston (1990) demonstrated that a CAG (glutamine)-to-CAT (histidine) transversion in the third position of codon 11 was responsible for the deficiency.
To determine the role of reactive oxygen species in mammalian longevity, Schriner et al. (2005) generated transgenic mice that overexpressed human catalase localized to the peroxisome, the nucleus, or mitochondria. Median and maximum life spans were maximally increased (average of 5 months and 5.5 months, respectively) in the mitochondrial catalase-expressing animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, peroxide production and peroxide-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. Schriner et al. (2005) concluded that their results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.
By sequencing the CAT gene for all exons, exon/intron junctions, and 5-prime and 3-prime flanking regions in a case of the Japanese type of acatalasemia (614097), Wen et al. (1990) concluded that the genetic disorder resulted from a splicing mutation, namely, a G-to-A substitution at the fifth position of intron 4. In studies using chimeric genes constructed from the normal or mutant CAT gene and a part of the alpha-globin gene, Wen et al. (1990) showed that when the mutant gene construct was introduced into COS-7 cells, abnormal splicing occurred. The same splice site mutation was found in the genomic DNA of another unrelated acatalasemic person. Kishimoto et al. (1992) found the same mutation in 2 other unrelated Japanese patients and suggested that only a single mutated allele had spread in the Japanese population.
In a Japanese individual with acatalasemia (614097), Hirono et al. (1995) identified a homozygous 1-bp deletion (358T) in exon 4 of the CAT gene, causing a frameshift and a premature termination codon. The truncated peptide chain consisted of 133 amino acid residues.
In a Hungarian patient with acatalasemia (614097), Goth et al. (2000) identified a 138GA insertion in exon 2 of the CAT gene, increasing the GA repeat number from 4 to 5. The insertion caused a frameshift and a premature termination codon. The truncated protein lacks the essential amino acid (histidine 74) in the active center.
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Baur, E. W. Catalase abnormality in a Caucasian family in the United States. Science 140: 816-817, 1963. [PubMed: 13967025] [Full Text: https://doi.org/10.1126/science.140.3568.816]
Bell, G. I., Najarian, R. C., Mullenbach, G. T., Hallewell, R. A. cDNA sequence coding for human kidney catalase. Nucleic Acids Res. 14: 5561-5562, 1986. [PubMed: 3755526]
Boyd, P., van Heyningen, V., Seawright, A., Fekete, G., Hastie, N. Use of catalase polymorphisms in the study of sporadic aniridia. Hum. Genet. 73: 171-174, 1986. [PubMed: 3013756] [Full Text: https://doi.org/10.1007/BF00291609]
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Ferrell, R. E., Riccardi, V. M. Catalase levels in patients with aniridia and-or Wilms' tumor: utility and limitations. Cytogenet. Cell Genet. 31: 120-123, 1981. [PubMed: 6273073] [Full Text: https://doi.org/10.1159/000131636]
Goth, L., Eaton, J. W. Hereditary catalase deficiencies and increased risk of diabetes. Lancet 356: 1820-1821, 2000. [PubMed: 11117918] [Full Text: https://doi.org/10.1016/S0140-6736(00)03238-4]
Goth, L., Shemirani, A., Kalmar, T. A novel catalase mutation (a GA insertion) causes the Hungarian type of acatalasemia. Blood Cells Molec. Dis. 26: 151-154, 2000. [PubMed: 11001624] [Full Text: https://doi.org/10.1006/bcmd.2000.0288]
Hirono, A., Sasaya-Hamada, F., Kanno, H., Fujii, H., Yoshida, T., Miwa, S. A novel human catalase mutation (358T-del) causing Japanese-type acatalasemia. Blood Cells Molec. Dis. 21: 232-234, 1995. [PubMed: 8673475] [Full Text: https://doi.org/10.1006/bcmd.1995.0026]
Jiang, Z., Akey, J. M., Shi, J., Xiong, M., Wang, Y., Shen, Y., Xu, X., Chen, H., Wu, H., Xiao, J., Lu, D., Huang, W., Jin, L. A polymorphism in the promoter region of catalase is associated with blood pressure levels. Hum. Genet. 109: 95-98, 2001. [PubMed: 11479740] [Full Text: https://doi.org/10.1007/s004390100553]
Junien, C., Turleau, C., de Grouchy, J., Said, R., Rethore, M.-O., Tenconi, R., Dufier, J. L. Regional assignment of catalase (CAT) gene to band 11p13: association with the aniridia-Wilms' tumor-gonadoblastoma (WAGR) complex. Ann. Genet. 23: 165-168, 1980. [PubMed: 6252821]
Kenney, M. C., Chwa, M., Atilano, S. R., Tran, A., Carballo, M., Saghizadeh, M., Vasiliou, V., Adachi, W., Brown, D. J. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays an role in this disorder. Invest. Ophthal. Vis. Sci. 46: 823-832, 2005. [PubMed: 15728537] [Full Text: https://doi.org/10.1167/iovs.04-0549]
Kidd, J. R., Castiglione, C. M., Pakstis, A. J., Kidd, K. K. The anonymous RFLP locus D11S16 is tightly linked to catalase on 11p. Cytogenet. Cell Genet. 45: 63-64, 1987. [PubMed: 2885154] [Full Text: https://doi.org/10.1159/000132428]
Kishimoto, Y., Murakami, Y., Hayashi, K., Takahara, S., Sugimura, T., Sekiya, T. Detection of a common mutation of the catalase gene in Japanese acatalasemic patients. Hum. Genet. 88: 487-490, 1992. [PubMed: 1551654] [Full Text: https://doi.org/10.1007/BF00219333]
Kittur, S. D., Hoppener, J. W. M., Antonarakis, S. E., Daniels, J. D. J., Meyers, D. A., Maestri, N. E., Jansen, M., Korneluk, R. G., Nelkin, B. D., Kazazian, H. H., Jr. Linkage map of the short arm of human chromosome 11: location of the genes for catalase calcitonin, and insulin-like growth factor II. Proc. Nat. Acad. Sci. 82: 5064-5067, 1985. [PubMed: 2991908] [Full Text: https://doi.org/10.1073/pnas.82.15.5064]
Mannens, M., Slater, R. M., Heyting, C., Bliek, J., Hoovers, J., Bleeker-Wagemakers, E. M., Voute, P. A., Coad, N., Frants, R. R., Pearson, P. L. Chromosome 11, Wilms' tumour and associated congenital diseases. (Abstract) Cytogenet. Cell Genet. 46: 655 only, 1987.
Nance, W. E., Empson, J. E., Bennett, T. W., Larson, L. Haptoglobin and catalase loci in man: possible genetic linkage. Science 160: 1230-1231, 1968. [PubMed: 5648259] [Full Text: https://doi.org/10.1126/science.160.3833.1230]
Narahara, K., Kikkawa, K., Kimira, S., Kimoto, H., Ogata, M., Kasai, R., Hamawaki, M., Matsuoka, K. Regional mapping of catalase and Wilms tumor--aniridia, genitourinary abnormalities, and mental retardation triad loci to the chromosome segment 11p1305-p1306. Hum. Genet. 66: 181-185, 1984. [PubMed: 6325323] [Full Text: https://doi.org/10.1007/BF00286597]
Niikawa, N., Fukushima, Y., Taniguchi, N., Iizuka, S., Kajii, T. Chromosome abnormalities involving 11p13 and low erythrocyte catalase activity. Hum. Genet. 60: 373-375, 1982. [PubMed: 7106775] [Full Text: https://doi.org/10.1007/BF00569223]
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Quan, F., Korneluk, R. G., MacLeod, H. L., Tsui, L. C., Gravel, R. A. An RFLP associated with the human catalase gene. Nucleic Acids Res. 13: 8288 only, 1985. [PubMed: 2933636] [Full Text: https://doi.org/10.1093/nar/13.22.8288]
Quan, F., Korneluk, R. G., Tropak, M. B., Gravel, R. A. Isolation and characterization of the human catalase gene. Nucleic Acids Res. 14: 5321-5335, 1986. [PubMed: 3755525] [Full Text: https://doi.org/10.1093/nar/14.13.5321]
Roychoudhury, A. K., Nei, M. Human Polymorphic Genes: World Distribution. New York: Oxford Univ. Press (pub.) 1988.
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., Wallace, D. C., Rabinovitch, P. S. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308: 1909-1911, 2005. [PubMed: 15879174] [Full Text: https://doi.org/10.1126/science.1106653]
Schroeder, W. T., Saunders, G. F. Localization of the human catalase and apolipoprotein A-I genes to chromosome 11. Cytogenet. Cell Genet. 44: 231-233, 1987. [PubMed: 3107917] [Full Text: https://doi.org/10.1159/000132377]
Shaffer, J. B., Preston, K. E. Molecular analysis of an acatalasemic mouse mutant. Biochem. Biophys. Res. Commun. 173: 1043-1050, 1990. [PubMed: 2268310] [Full Text: https://doi.org/10.1016/s0006-291x(05)80891-5]
Shibata, Y., Higashi, T., Hirai, H., Hamilton, H. B. Immunochemical studies on catalase. II. An anticatalase reacting component in normal hypocatalasic, and acatalasic human erythrocytes. Arch. Biochem. 118: 200-209, 1967.
Wen, J. K., Osumi, T., Hashimoto, T., Ogata, M. Molecular analysis of human acatalasemia: identification of a splicing mutation. J. Molec. Biol. 211: 383-393, 1990. [PubMed: 2308162] [Full Text: https://doi.org/10.1016/0022-2836(90)90359-T]
Wieacker, P., Mueller, C. R., Mayerova, A., Grzeschik, K. H., Ropers, H. H. Assignment of the gene coding for human catalase to the short arm of chromosome 11. Ann. Genet. 23: 73-77, 1980. [PubMed: 6967289]