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Pathway Description
Porphyria Variegata (PV)
Homo sapiens
Disease Pathway
Created: 2022-11-10
Last Updated: 2023-10-25
Porphyria variegata (PV) is a rare inborn error of metabolism (IEM) which arises from a defective gene called PPOX. PPOX is responsible for protoporphyrinogen oxidase. A defect in this enzyme results in the build up of several compounds, including porphobilinogen, 5-aminolevulinic acid, and in feces and urine, porphyrin and coproporphyrin. Of the wide range of symptoms which present themselves in affected individuals, some include abdominal pain, vomiting, and diarrhea. As well as seizures, hallucinations and skin sensitivity to light. Indeed, the skin sensitivity can be so extreme that skin pigmentation changes, scarring and blistering and even hair growth can ensue on exposed areas.
References
Porphyria Variegata (PV) References
Brenner DA, Bloomer JR: The enzymatic defect in variegate prophyria. Studies with human cultured skin fibroblasts. N Engl J Med. 1980 Apr 3;302(14):765-9. doi: 10.1056/NEJM198004033021401.
Pubmed: 7354807
Coakley J, Hawkins R, Crinis N, McManus J, Blake D, Nordmann Y, Sloan L, Connelly J: An unusual case of variegate porphyria with possible homozygous inheritance. Aust N Z J Med. 1990 Aug;20(4):587-9. doi: 10.1111/j.1445-5994.1990.tb01320.x.
Pubmed: 2222353
Deybach JC, Puy H, Robreau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y: Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria. Hum Mol Genet. 1996 Mar;5(3):407-10. doi: 10.1093/hmg/5.3.407.
Pubmed: 8852667
Norris PG, Elder GH, Hawk JL: Homozygous variegate porphyria: a case report. Br J Dermatol. 1990 Feb;122(2):253-7. doi: 10.1111/j.1365-2133.1990.tb08272.x.
Pubmed: 2317449
von und zu Fraunberg M, Timonen K, Mustajoki P, Kauppinen R: Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients. Eur J Hum Genet. 2002 Oct;10(10):649-57. doi: 10.1038/sj.ejhg.5200860.
Pubmed: 12357337
Hofmann C, Schmidt D, Braun-Falco O: [Porphyria variegata (author's transl)]. MMW Munch Med Wochenschr. 1975 Dec 12;117(50):1969-74.
Pubmed: 814414
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Bishop DF: Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes. Nucleic Acids Res. 1990 Dec 11;18(23):7187-8. doi: 10.1093/nar/18.23.7187.
Pubmed: 2263504
Bawden MJ, Borthwick IA, Healy HM, Morris CP, May BK, Elliott WH: Sequence of human 5-aminolevulinate synthase cDNA. Nucleic Acids Res. 1987 Oct 26;15(20):8563. doi: 10.1093/nar/15.20.8563.
Pubmed: 3671094
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Pubmed: 15489334
Zhao Y, Wang L, Shen HB, Wang ZX, Wei QY, Chen F: Association between delta-aminolevulinic acid dehydratase (ALAD) polymorphism and blood lead levels: a meta-regression analysis. J Toxicol Environ Health A. 2007 Dec;70(23):1986-94. doi: 10.1080/15287390701550946.
Pubmed: 17966070
Wetmur JG, Kaya AH, Plewinska M, Desnick RJ: Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am J Hum Genet. 1991 Oct;49(4):757-63.
Pubmed: 1716854
Wetmur JG, Bishop DF, Cantelmo C, Desnick RJ: Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7703-7. doi: 10.1073/pnas.83.20.7703.
Pubmed: 3463993
Raich N, Romeo PH, Dubart A, Beaupain D, Cohen-Solal M, Goossens M: Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase. Nucleic Acids Res. 1986 Aug 11;14(15):5955-68. doi: 10.1093/nar/14.15.5955.
Pubmed: 2875434
Grandchamp B, De Verneuil H, Beaumont C, Chretien S, Walter O, Nordmann Y: Tissue-specific expression of porphobilinogen deaminase. Two isoenzymes from a single gene. Eur J Biochem. 1987 Jan 2;162(1):105-10. doi: 10.1111/j.1432-1033.1987.tb10548.x.
Pubmed: 3816774
Yoo HW, Warner CA, Chen CH, Desnick RJ: Hydroxymethylbilane synthase: complete genomic sequence and amplifiable polymorphisms in the human gene. Genomics. 1993 Jan;15(1):21-9. doi: 10.1006/geno.1993.1005.
Pubmed: 7916736
Tsai SF, Bishop DF, Desnick RJ: Human uroporphyrinogen III synthase: molecular cloning, nucleotide sequence, and expression of a full-length cDNA. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7049-53. doi: 10.1073/pnas.85.19.7049.
Pubmed: 3174619
Aizencang G, Solis C, Bishop DF, Warner C, Desnick RJ: Human uroporphyrinogen-III synthase: genomic organization, alternative promoters, and erythroid-specific expression. Genomics. 2000 Dec 1;70(2):223-31. doi: 10.1006/geno.2000.6373.
Pubmed: 11112350
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Moran-Jimenez MJ, Ged C, Romana M, Enriquez De Salamanca R, Taieb A, Topi G, D'Alessandro L, de Verneuil H: Uroporphyrinogen decarboxylase: complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria. Am J Hum Genet. 1996 Apr;58(4):712-21.
Pubmed: 8644733
Romeo PH, Raich N, Dubart A, Beaupain D, Pryor M, Kushner J, Cohen-Solal M, Goossens M: Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA. J Biol Chem. 1986 Jul 25;261(21):9825-31.
Pubmed: 3015909
Delfau-Larue MH, Martasek P, Grandchamp B: Coproporphyrinogen oxidase: gene organization and description of a mutation leading to exon 6 skipping. Hum Mol Genet. 1994 Aug;3(8):1325-30. doi: 10.1093/hmg/3.8.1325.
Pubmed: 7987309
Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J: A human mitochondrial ferritin encoded by an intronless gene. J Biol Chem. 2001 Jul 6;276(27):24437-40. doi: 10.1074/jbc.C100141200. Epub 2001 Apr 25.
Pubmed: 11323407
Langlois d'Estaintot B, Santambrogio P, Granier T, Gallois B, Chevalier JM, Precigoux G, Levi S, Arosio P: Crystal structure and biochemical properties of the human mitochondrial ferritin and its mutant Ser144Ala. J Mol Biol. 2004 Jul 2;340(2):277-93. doi: 10.1016/j.jmb.2004.04.036.
Pubmed: 15201052
Nakahashi Y, Taketani S, Okuda M, Inoue K, Tokunaga R: Molecular cloning and sequence analysis of cDNA encoding human ferrochelatase. Biochem Biophys Res Commun. 1990 Dec 14;173(2):748-55. doi: 10.1016/s0006-291x(05)80099-3.
Pubmed: 2260980
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