RBCC Red Blood Cell Collection

UROD [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Uroporphyrinogen decarboxylase; UPD; URO-D; 4.1.1.37
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00301489
IPI00301489 Uroporphyrinogen decarboxylase Uroporphyrinogen III = coproporphyrinogen + 4 CO2 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight

UniProt P06132
ID DCUP_HUMAN Reviewed; 367 AA.
AC P06132; A8K762; Q16863; Q16883; Q53YB8; Q53ZP6; Q6IB28; Q9BUZ0;
read moreDT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 22-JAN-2014, entry version 166.
DE RecName: Full=Uroporphyrinogen decarboxylase;
DE Short=UPD;
DE Short=URO-D;
DE EC=4.1.1.37;
GN Name=UROD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-21; 37-65;
RP 101-123; 175-251; 259-322; 325-344 AND 346-367.
RX PubMed=3015909;
RA Romeo P.-H., Raich N., Dubart A., Beaupain D., Pryor M., Kushner J.P.,
RA Cohen-Solal M., Goossens M.;
RT "Molecular cloning and nucleotide sequence of a complete human
RT uroporphyrinogen decarboxylase cDNA.";
RL J. Biol. Chem. 261:9825-9831(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HEP LEU-62; LEU-77;
RP GLU-281 AND CYS-311.
RX PubMed=8644733;
RA Moran-Jimenez M.J., Ged C., Romana M., de Salamanca R.E., Taieb A.,
RA Topi G., D'Alessandro L., de Verneuil H.;
RT "Uroporphyrinogen decarboxylase: complete human gene sequence and
RT molecular study of three families with hepatoerythropoietic
RT porphyria.";
RL Am. J. Hum. Genet. 58:712-721(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Mendez M.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-77.
RA Martinez di Montemuros F., Fiorelli G., Cappellini M.D.;
RT "Uroporphyrinogen decarboxylase (UROD) cDNA sequence from Italian
RT population.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-77.
RA Martinez di Montemuros F., Cappellini M.D.;
RT "Molecular characterization of UROD gene in Italian patients with
RT familial porphyria cutanea tarda (f-PCT).";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-303.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-303.
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-7.
RX PubMed=3658695; DOI=10.1093/nar/15.18.7343;
RA Romana M., Dubart A., Beaupain D., Chabret C., Goossens M.,
RA Romeo P.-H.;
RT "Structure of the gene for human uroporphyrinogen decarboxylase.";
RL Nucleic Acids Res. 15:7343-7356(1987).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-258, AND INVOLVEMENT IN FPCT.
RX PubMed=2243121; DOI=10.1172/JCI114856;
RA Garey J.R., Harrison L.M., Franklin K.F., Metcalf K.M., Radisky E.S.,
RA Kushner J.P.;
RT "Uroporphyrinogen decarboxylase: a splice site mutation causes the
RT deletion of exon 6 in multiple families with porphyria cutanea
RT tarda.";
RL J. Clin. Invest. 86:1416-1422(1990).
RN [15]
RP CRYSTALLIZATION, MASS SPECTROMETRY, AND SUBUNIT.
RX PubMed=9194196;
RA Phillips J.D., Whitby F.G., Kushner J.P., Hill C.P.;
RT "Characterization and crystallization of human uroporphyrinogen
RT decarboxylase.";
RL Protein Sci. 6:1343-1346(1997).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND SUBUNIT.
RX PubMed=9564029; DOI=10.1093/emboj/17.9.2463;
RA Whitby F.G., Phillips J.D., Kushner J.P., Hill C.P.;
RT "Crystal structure of human uroporphyrinogen decarboxylase.";
RL EMBO J. 17:2463-2471(1998).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANTS FPCT ASP-156;
RP LEU-232 AND THR-260, VARIANTS FPCT GLU-25; SER-80; GLN-134; ASP-156;
RP ARG-165; LYS-167; PRO-193; LEU-232; GLN-253 AND THR-260, AND
RP CHARACTERIZATION OF VARIANTS FPCT GLU-25; SER-80; GLN-134; ASP-156;
RP ARG-165; LYS-167; PRO-193; LEU-232; GLN-253 AND THR-260.
RX PubMed=11719352; DOI=10.1182/blood.V98.12.3179;
RA Phillips J.D., Parker T.L., Schubert H.L., Whitby F.G., Hill C.P.,
RA Kushner J.P.;
RT "Functional consequences of naturally occurring mutations in human
RT uroporphyrinogen decarboxylase.";
RL Blood 98:3179-3185(2001).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF WILD-TYPE AND MUTANTS
RP ASN-86; GLU-86; GLY-86 AND PHE-164 IN COMPLEX WITH SUBSTRATE ANALOGS,
RP MUTAGENESIS OF ASP-86 AND TYR-164, AND REACTION MECHANISM.
RX PubMed=14633982; DOI=10.1093/emboj/cdg606;
RA Phillips J.D., Whitby F.G., Kushner J.P., Hill C.P.;
RT "Structural basis for tetrapyrrole coordination by uroporphyrinogen
RT decarboxylase.";
RL EMBO J. 22:6225-6233(2003).
RN [22]
RP VARIANT HEP GLU-281.
RX PubMed=3775362; DOI=10.1126/science.3775362;
RA de Verneuil H., Grandchamp B., Beaumont C., Picat C., Nordmann Y.;
RT "Uroporphyrinogen decarboxylase structural mutant (Gly-281-->Glu) in a
RT case of porphyria.";
RL Science 234:732-734(1986).
RN [23]
RP VARIANT FPCT VAL-281.
RX PubMed=2920211;
RA Garey J.R., Hansen J.L., Harrison L.M., Kennedy J.B., Kushner J.P.;
RT "A point mutation in the coding region of uroporphyrinogen
RT decarboxylase associated with familial porphyria cutanea tarda.";
RL Blood 73:892-895(1989).
RN [24]
RP VARIANT HEP LYS-167.
RX PubMed=1905636; DOI=10.1111/j.1365-2362.1991.tb01814.x;
RA Romana M., Grandchamp B., Dubart A., Amselem S., Chabret C.,
RA Nordmann Y., Goossens M., Romeo P.-H.;
RT "Identification of a new mutation responsible for hepatoerythropoietic
RT porphyria.";
RL Eur. J. Clin. Invest. 21:225-229(1991).
RN [25]
RP VARIANT HEP GLY-292.
RX PubMed=1634232;
RA de Verneuil H., Bourgeois F., de Rooij F.W.M., Siersema P.D.,
RA Wilson J.H.P., Grandchamp B., Nordmann Y.;
RT "Characterization of a new mutation (R292G) and a deletion at the
RT human uroporphyrinogen decarboxylase locus in two patients with
RT hepatoerythropoietic porphyria.";
RL Hum. Genet. 89:548-552(1992).
RN [26]
RP VARIANTS HEP GLN-134 AND PRO-220.
RX PubMed=8176248; DOI=10.1111/1523-1747.ep12374134;
RA Meguro K., Fujita H., Ishida N., Akagi R., Kurihara T.,
RA Galbraith R.A., Kappas A., Zabriskie J.B., Toback A.C., Harber L.C.,
RA Sassa S.;
RT "Molecular defects of uroporphyrinogen decarboxylase in a patient with
RT mild hepatoerythropoietic porphyria.";
RL J. Invest. Dermatol. 102:681-685(1994).
RN [27]
RP VARIANT FPCT/HEP GLU-281.
RX PubMed=7706766; DOI=10.1111/1523-1747.ep12605953;
RA Roberts A.G., Elder G.H., de Salamanca R.E., Herrero C., Lecha M.,
RA Mascaro J.M.;
RT "A mutation 'G281E' of the human uroporphyrinogen decarboxylase gene
RT causes both hepatoerythropoietic porphyria and overt familial
RT porphyria cutanea tarda: biochemical and genetic studies on Spanish
RT patients.";
RL J. Invest. Dermatol. 104:500-502(1995).
RN [28]
RP VARIANT HEP GLY-80, AND VARIANTS FPCT GLN-253; ARG-318 AND THR-334.
RX PubMed=8896428;
RA McManus J.F., Begley C.G., Sassa S., Ratnaike S.;
RT "Five new mutations in the uroporphyrinogen decarboxylase gene
RT identified in families with cutaneous porphyria.";
RL Blood 88:3589-3600(1996).
RN [29]
RP VARIANTS FPCT ARG-165; PHE-195; LYS-304 AND HIS-332.
RX PubMed=9792863; DOI=10.1086/302119;
RA Mendez M., Sorkin L., Rossetti M.V., Astrin K.H., Batlle A.M.C.,
RA Parera V.E., Aizencang G.I., Desnick R.J.;
RT "Familial porphyria cutanea tarda: characterization of seven novel
RT uroporphyrinogen decarboxylase mutations and frequency of common
RT hemochromatosis alleles.";
RL Am. J. Hum. Genet. 63:1363-1375(1998).
RN [30]
RP VARIANT FPCT GLN-134.
RX PubMed=10338097;
RX DOI=10.1002/(SICI)1098-1004(1999)13:5<412::AID-HUMU11>3.3.CO;2-K;
RA McManus J.F., Begley C.G., Sassa S., Ratnaike S.;
RT "Three new mutations in the uroporphyrinogen decarboxylase gene in
RT familial porphyria cutanea tarda.";
RL Hum. Mutat. 13:412-412(1999).
RN [31]
RP VARIANTS FPCT LEU-229 AND THR-324.
RX PubMed=10477430;
RX DOI=10.1002/(SICI)1098-1004(1999)14:3<222::AID-HUMU5>3.0.CO;2-V;
RA Christiansen L., Ged C., Hombrados I., Broens-Poulsen J.,
RA Fontanellas A., de Verneuil H., Hoerder M., Petersen N.E.;
RT "Screening for mutations in the uroporphyrinogen decarboxylase gene
RT using denaturing gradient gel electrophoresis. Identification and
RT characterization of six novel mutations associated with familial
RT PCT.";
RL Hum. Mutat. 14:222-232(1999).
RN [32]
RP VARIANTS FPCT SER-80; GLN-134; PRO-144; GLN-216; LYS-218; VAL-281;
RP ARG-282; SER-303 AND ARG-318, AND CHARACTERIZATION OF VARIANTS FPCT
RP PRO-144 AND LYS-218.
RX PubMed=11069625; DOI=10.1046/j.1523-1747.2000.00148.x;
RA Brady J.J., Jackson H.A., Roberts A.G., Morgan R.R., Whatley S.D.,
RA Rowlands G.L., Darby C., Shudell E., Watson R., Paiker J.,
RA Worwood M.W., Elder G.H.;
RT "Co-inheritance of mutations in the uroporphyrinogen decarboxylase and
RT hemochromatosis genes accelerates the onset of porphyria cutanea
RT tarda.";
RL J. Invest. Dermatol. 115:868-874(2000).
RN [33]
RP VARIANTS FPCT GLN-142; GLN-161; PHE-219 AND SER-235.
RX PubMed=11295834; DOI=10.1002/humu.35;
RA Cappellini M.D., Martinez Di Montemuros F., Tavazzi D., Fargion S.,
RA Pizzuti A., Comino A., Cainelli T., Fiorelli G.;
RT "Seven novel point mutations in the uroporphyrinogen decarboxylase
RT (UROD) gene in patients with familial porphyria cutanea tarda (f-
RT PCT).";
RL Hum. Mutat. 17:350-350(2001).
RN [34]
RP VARIANT HEP LEU-46, AND CHARACTERIZATION OF VARIANT HEP LEU-46.
RX PubMed=12071824; DOI=10.1001/archderm.138.7.957;
RA Ged C., Ozalla D., Herrero C., Lecha M., Mendez M., de Verneuil H.,
RA Mascaro J.M.;
RT "Description of a new mutation in hepatoerythropoietic porphyria and
RT prenatal exclusion of a homozygous fetus.";
RL Arch. Dermatol. 138:957-960(2002).
RN [35]
RP VARIANT HEP LEU-46.
RX PubMed=15491440; DOI=10.1111/j.1365-2133.2004.06101.x;
RA Armstrong D.K.B., Sharpe P.C., Chambers C.R., Whatley S.D.,
RA Roberts A.G., Elder G.H.;
RT "Hepatoerythropoietic porphyria: a missense mutation in the UROD gene
RT is associated with mild disease and an unusual porphyrin excretion
RT pattern.";
RL Br. J. Dermatol. 151:920-923(2004).
RN [36]
RP VARIANT HEP ARG-168, AND CHARACTERIZATION OF VARIANT HEP ARG-168.
RX PubMed=17240319; DOI=10.1016/j.trsl.2006.08.006;
RA Phillips J.D., Whitby F.G., Stadtmueller B.M., Edwards C.Q.,
RA Hill C.P., Kushner J.P.;
RT "Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing
RT hepatoerythropoietic porphyria (HEP).";
RL Transl. Res. 149:85-91(2007).
RN [37]
RP VARIANT HEP ASP-170, AND CHARACTERIZATION OF VARIANT HEP ASP-170.
RX PubMed=21668429; DOI=10.1111/j.1365-2133.2011.10453.x;
RA To-Figueras J., Phillips J., Gonzalez-Lopez J.M., Badenas C.,
RA Madrigal I., Gonzalez-Romaris E.M., Ramos C., Aguirre J.M.,
RA Herrero C.;
RT "Hepatoerythropoietic porphyria due to a novel mutation in the
RT uroporphyrinogen decarboxylase gene.";
RL Br. J. Dermatol. 165:499-505(2011).
CC -!- FUNCTION: Catalyzes the decarboxylation of four acetate groups of
CC uroporphyrinogen-III to yield coproporphyrinogen-III.
CC -!- CATALYTIC ACTIVITY: Uroporphyrinogen III = coproporphyrinogen + 4
CC CO(2).
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-
CC IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate:
CC step 4/4.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- DISEASE: Familial porphyria cutanea tarda (FPCT) [MIM:176100]: A
CC form of porphyria. Porphyrias are inherited defects in the
CC biosynthesis of heme, resulting in the accumulation and increased
CC excretion of porphyrins or porphyrin precursors. They are
CC classified as erythropoietic or hepatic, depending on whether the
CC enzyme deficiency occurs in red blood cells or in the liver.
CC Familial porphyria cutanea tarda is an autosomal dominant disorder
CC characterized by light-sensitive dermatitis, with onset in later
CC life. It is associated with the excretion of large amounts of
CC uroporphyrin in the urine. Iron overload is often present in
CC association with varying degrees of liver damage. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hepatoerythropoietic porphyria (HEP) [MIM:176100]: A form
CC of porphyria. Porphyrias are inherited defects in the biosynthesis
CC of heme, resulting in the accumulation and increased excretion of
CC porphyrins or porphyrin precursors. They are classified as
CC erythropoietic or hepatic, depending on whether the enzyme
CC deficiency occurs in red blood cells or in the liver. HEP is a
CC cutaneous porphyria that presents in infancy. It is characterized
CC biochemically by excessive excretion of acetate-substituted
CC porphyrins and accumulation of protoporphyrin in erythrocytes.
CC Uroporphyrinogen decarboxylase levels are very low in erythrocytes
CC and cultured skin fibroblasts. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the uroporphyrinogen decarboxylase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/UROD";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Uroporphyrinogen III
CC decarboxylase entry;
CC URL="http://en.wikipedia.org/wiki/Uroporphyrinogen_III_decarboxylase";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M14016; AAA61258.1; -; mRNA.
DR EMBL; X89267; CAA61540.1; -; Genomic_DNA.
DR EMBL; AF047383; AAC03563.1; -; Genomic_DNA.
DR EMBL; AF104421; AAD04571.1; -; mRNA.
DR EMBL; AF104422; AAD04572.1; -; mRNA.
DR EMBL; AF104423; AAD04573.1; -; mRNA.
DR EMBL; AF104424; AAD04574.1; -; mRNA.
DR EMBL; AF104425; AAD04575.1; -; mRNA.
DR EMBL; AF104426; AAD04576.1; -; mRNA.
DR EMBL; AF104427; AAD04577.1; -; mRNA.
DR EMBL; AF104428; AAD04578.1; -; mRNA.
DR EMBL; AF104429; AAD04579.1; -; mRNA.
DR EMBL; AF104430; AAD04580.1; -; mRNA.
DR EMBL; AF104431; AAD04581.1; -; mRNA.
DR EMBL; AF104432; AAD04582.1; -; mRNA.
DR EMBL; AF104433; AAD04583.1; -; mRNA.
DR EMBL; AF104434; AAD04584.1; -; mRNA.
DR EMBL; AF104435; AAD04585.1; -; mRNA.
DR EMBL; AF104436; AAD04586.1; -; mRNA.
DR EMBL; AF104437; AAD04587.1; -; mRNA.
DR EMBL; AF104438; AAD04588.1; -; mRNA.
DR EMBL; AF104439; AAD04589.1; -; mRNA.
DR EMBL; AF104440; AAD04590.1; -; mRNA.
DR EMBL; AY292986; AAP44118.1; -; Genomic_DNA.
DR EMBL; BT006737; AAP35383.1; -; mRNA.
DR EMBL; CR456976; CAG33257.1; -; mRNA.
DR EMBL; CR542057; CAG46854.1; -; mRNA.
DR EMBL; AK291877; BAF84566.1; -; mRNA.
DR EMBL; AL359473; CAI16440.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07007.1; -; Genomic_DNA.
DR EMBL; BC001778; AAH01778.1; -; mRNA.
DR EMBL; U30787; AAC50482.1; -; Genomic_DNA.
DR EMBL; M60891; AAB59456.1; -; Genomic_DNA.
DR PIR; A24411; A24411.
DR PIR; G02786; G02786.
DR RefSeq; NP_000365.3; NM_000374.4.
DR UniGene; Hs.78601; -.
DR PDB; 1JPH; X-ray; 2.10 A; A=1-367.
DR PDB; 1JPI; X-ray; 2.30 A; A=1-367.
DR PDB; 1JPK; X-ray; 2.20 A; A=1-367.
DR PDB; 1R3Q; X-ray; 1.70 A; A=1-367.
DR PDB; 1R3R; X-ray; 1.85 A; A=1-367.
DR PDB; 1R3S; X-ray; 1.65 A; A=1-367.
DR PDB; 1R3T; X-ray; 1.70 A; A=1-367.
DR PDB; 1R3V; X-ray; 1.90 A; A=1-367.
DR PDB; 1R3W; X-ray; 1.70 A; A=1-367.
DR PDB; 1R3Y; X-ray; 1.75 A; A=1-367.
DR PDB; 1URO; X-ray; 1.80 A; A=1-367.
DR PDB; 2Q6Z; X-ray; 2.00 A; A=11-366.
DR PDB; 2Q71; X-ray; 1.90 A; A=11-366.
DR PDB; 3GVQ; X-ray; 2.10 A; A=1-367.
DR PDB; 3GVR; X-ray; 2.20 A; A=1-367.
DR PDB; 3GVV; X-ray; 2.80 A; A=1-367.
DR PDB; 3GVW; X-ray; 2.80 A; A=1-367.
DR PDB; 3GW0; X-ray; 2.00 A; A=1-367.
DR PDB; 3GW3; X-ray; 1.70 A; A=1-367.
DR PDBsum; 1JPH; -.
DR PDBsum; 1JPI; -.
DR PDBsum; 1JPK; -.
DR PDBsum; 1R3Q; -.
DR PDBsum; 1R3R; -.
DR PDBsum; 1R3S; -.
DR PDBsum; 1R3T; -.
DR PDBsum; 1R3V; -.
DR PDBsum; 1R3W; -.
DR PDBsum; 1R3Y; -.
DR PDBsum; 1URO; -.
DR PDBsum; 2Q6Z; -.
DR PDBsum; 2Q71; -.
DR PDBsum; 3GVQ; -.
DR PDBsum; 3GVR; -.
DR PDBsum; 3GVV; -.
DR PDBsum; 3GVW; -.
DR PDBsum; 3GW0; -.
DR PDBsum; 3GW3; -.
DR DisProt; DP00308; -.
DR ProteinModelPortal; P06132; -.
DR SMR; P06132; 10-366.
DR IntAct; P06132; 6.
DR MINT; MINT-3005024; -.
DR STRING; 9606.ENSP00000246337; -.
DR ChEMBL; CHEMBL1681619; -.
DR PhosphoSite; P06132; -.
DR DMDM; 2507533; -.
DR OGP; P06132; -.
DR PaxDb; P06132; -.
DR PeptideAtlas; P06132; -.
DR PRIDE; P06132; -.
DR DNASU; 7389; -.
DR Ensembl; ENST00000246337; ENSP00000246337; ENSG00000126088.
DR GeneID; 7389; -.
DR KEGG; hsa:7389; -.
DR UCSC; uc001cna.2; human.
DR CTD; 7389; -.
DR GeneCards; GC01P045477; -.
DR HGNC; HGNC:12591; UROD.
DR HPA; HPA027468; -.
DR HPA; HPA028668; -.
DR MIM; 176100; phenotype.
DR MIM; 613521; gene.
DR neXtProt; NX_P06132; -.
DR Orphanet; 95159; Hepatoerythropoietic porphyria.
DR Orphanet; 101330; Porphyria cutanea tarda.
DR PharmGKB; PA37221; -.
DR eggNOG; COG0407; -.
DR HOVERGEN; HBG000229; -.
DR InParanoid; P06132; -.
DR KO; K01599; -.
DR OMA; TLATYMI; -.
DR PhylomeDB; P06132; -.
DR BioCyc; MetaCyc:HS04993-MONOMER; -.
DR BRENDA; 4.1.1.37; 2681.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00251; UER00321.
DR ChiTaRS; UROD; human.
DR EvolutionaryTrace; P06132; -.
DR GeneWiki; Uroporphyrinogen_III_decarboxylase; -.
DR GenomeRNAi; 7389; -.
DR NextBio; 28930; -.
DR PRO; PR:P06132; -.
DR ArrayExpress; P06132; -.
DR Bgee; P06132; -.
DR CleanEx; HS_UROD; -.
DR Genevestigator; P06132; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0004853; F:uroporphyrinogen decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0006783; P:heme biosynthetic process; IC:UniProtKB.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR006361; Uroporphyrinogen_deCO2ase_HemE.
DR InterPro; IPR000257; Uroporphyrinogen_deCOase.
DR PANTHER; PTHR21091:SF2; PTHR21091:SF2; 1.
DR Pfam; PF01208; URO-D; 1.
DR TIGRFAMs; TIGR01464; hemE; 1.
DR PROSITE; PS00906; UROD_1; 1.
DR PROSITE; PS00907; UROD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Decarboxylase; Direct protein sequencing; Disease mutation;
KW Heme biosynthesis; Lyase; Porphyrin biosynthesis; Reference proteome.
FT CHAIN 1 367 Uroporphyrinogen decarboxylase.
FT /FTId=PRO_0000187569.
FT REGION 37 41 Substrate binding.
FT BINDING 55 55 Substrate.
FT BINDING 85 85 Substrate.
FT BINDING 86 86 Substrate.
FT BINDING 164 164 Substrate.
FT BINDING 219 219 Substrate.
FT BINDING 339 339 Substrate.
FT SITE 86 86 Transition state stabilizer.
FT MOD_RES 1 1 N-acetylmethionine.
FT VARIANT 15 15 K -> E (in dbSNP:rs11541959).
FT /FTId=VAR_060683.
FT VARIANT 25 25 G -> E (in FPCT; insoluble protein).
FT /FTId=VAR_022567.
FT VARIANT 46 46 F -> L (in HEP; mild phenotype; strong
FT decrease of activity).
FT /FTId=VAR_022568.
FT VARIANT 62 62 P -> L (in HEP).
FT /FTId=VAR_009103.
FT VARIANT 77 77 P -> L (in dbSNP:rs1131147).
FT /FTId=VAR_067457.
FT VARIANT 80 80 A -> G (in HEP).
FT /FTId=VAR_007910.
FT VARIANT 80 80 A -> S (in FPCT; decrease of activity).
FT /FTId=VAR_022569.
FT VARIANT 106 106 P -> L (in dbSNP:rs11541962).
FT /FTId=VAR_060684.
FT VARIANT 113 113 R -> T (in dbSNP:rs11541963).
FT /FTId=VAR_060685.
FT VARIANT 134 134 V -> Q (in FPCT and HEP; requires 2
FT nucleotide substitutions; nearly normal
FT activity).
FT /FTId=VAR_009104.
FT VARIANT 142 142 R -> Q (in FPCT).
FT /FTId=VAR_010985.
FT VARIANT 144 144 R -> P (in FPCT; decrease of activity).
FT /FTId=VAR_022570.
FT VARIANT 156 156 G -> D (in FPCT; decrease of activity).
FT /FTId=VAR_022571.
FT VARIANT 161 161 L -> Q (in FPCT).
FT /FTId=VAR_010986.
FT VARIANT 165 165 M -> R (in FPCT; activity < 2%).
FT /FTId=VAR_007911.
FT VARIANT 167 167 E -> K (in HEP and FPCT; nearly normal
FT activity).
FT /FTId=VAR_007714.
FT VARIANT 168 168 G -> R (in HEP; relative activity of 65%
FT of wild-type towards uroporphyrinogen
FT III).
FT /FTId=VAR_065558.
FT VARIANT 170 170 G -> D (in HEP; relative activity of 17%
FT and 60% of wild-type towards
FT uroporphyrinogen I and III respectively).
FT /FTId=VAR_065559.
FT VARIANT 193 193 R -> P (in FPCT; insoluble protein).
FT /FTId=VAR_022572.
FT VARIANT 195 195 L -> F (in FPCT).
FT /FTId=VAR_007912.
FT VARIANT 216 216 L -> Q (in FPCT).
FT /FTId=VAR_022573.
FT VARIANT 218 218 E -> K (in FPCT; significant decrease of
FT activity).
FT /FTId=VAR_022574.
FT VARIANT 219 219 S -> F (in FPCT).
FT /FTId=VAR_010987.
FT VARIANT 220 220 H -> P (in HEP; mild form).
FT /FTId=VAR_009105.
FT VARIANT 229 229 F -> L (in FPCT).
FT /FTId=VAR_009106.
FT VARIANT 232 232 F -> L (in FPCT; decrease of activity).
FT /FTId=VAR_022575.
FT VARIANT 235 235 P -> S (in FPCT).
FT /FTId=VAR_010988.
FT VARIANT 253 253 L -> Q (in FPCT; decrease of activity;
FT dbSNP:rs36033115).
FT /FTId=VAR_007913.
FT VARIANT 260 260 I -> T (in FPCT; decrease of activity).
FT /FTId=VAR_022576.
FT VARIANT 281 281 G -> E (in FPTC and HEP).
FT /FTId=VAR_007715.
FT VARIANT 281 281 G -> V (in FPCT).
FT /FTId=VAR_007716.
FT VARIANT 282 282 L -> R (in FPCT).
FT /FTId=VAR_022577.
FT VARIANT 292 292 R -> G (in HEP).
FT /FTId=VAR_007717.
FT VARIANT 303 303 G -> S (in FPCT).
FT /FTId=VAR_022578.
FT VARIANT 303 303 G -> V (in dbSNP:rs17849533).
FT /FTId=VAR_060686.
FT VARIANT 304 304 N -> K (in FPCT).
FT /FTId=VAR_007914.
FT VARIANT 311 311 Y -> C (in HEP).
FT /FTId=VAR_009107.
FT VARIANT 318 318 G -> R (in FPCT; dbSNP:rs116233118).
FT /FTId=VAR_007915.
FT VARIANT 324 324 M -> T (in FPCT).
FT /FTId=VAR_009108.
FT VARIANT 332 332 R -> H (in FPCT).
FT /FTId=VAR_007916.
FT VARIANT 334 334 I -> T (in FPCT).
FT /FTId=VAR_007917.
FT MUTAGEN 86 86 D->E: 5-10% of wild-type activity.
FT MUTAGEN 86 86 D->G: Very low activity. Binds substrate
FT with similar geometry as wild-type.
FT MUTAGEN 86 86 D->N: No activity. Unable to bind
FT substrate.
FT MUTAGEN 164 164 Y->F: 25-30% of wild-type activity.
FT CONFLICT 103 103 G -> S (in Ref. 1; AAA61258 and 14;
FT AAB59456).
FT CONFLICT 120 120 R -> A (in Ref. 1; AAA61258 and 14;
FT AAB59456).
FT CONFLICT 212 214 Missing (in Ref. 14; AAB59456).
FT HELIX 18 24
FT STRAND 38 40
FT HELIX 44 51
FT HELIX 55 59
FT HELIX 62 75
FT HELIX 89 93
FT STRAND 99 101
FT TURN 102 104
FT STRAND 105 107
FT HELIX 115 120
FT HELIX 124 126
FT HELIX 127 130
FT HELIX 132 145
FT STRAND 151 156
FT HELIX 158 167
FT HELIX 175 183
FT HELIX 185 208
FT STRAND 212 218
FT HELIX 221 223
FT HELIX 226 232
FT HELIX 234 250
FT STRAND 258 262
FT HELIX 266 268
FT HELIX 269 272
FT TURN 273 276
FT STRAND 278 281
FT HELIX 288 295
FT STRAND 297 305
FT HELIX 307 311
FT HELIX 314 328
FT STRAND 330 339
FT HELIX 347 365
SQ SEQUENCE 367 AA; 40787 MW; 840510B36CFC3856 CRC64;
MEANGLGPQG FPELKNDTFL RAAWGEETDY TPVWCMRQAG RYLPEFRETR AAQDFFSTCR
SPEACCELTL QPLRRFPLDA AIIFSDILVV PQALGMEVTM VPGKGPSFPE PLREEQDLER
LRDPEVVASE LGYVFQAITL TRQRLAGRVP LIGFAGAPWT LMTYMVEGGG SSTMAQAKRW
LYQRPQASHQ LLRILTDALV PYLVGQVVAG AQALQLFESH AGHLGPQLFN KFALPYIRDV
AKQVKARLRE AGLAPVPMII FAKDGHFALE ELAQAGYEVV GLDWTVAPKK ARECVGKTVT
LQGNLDPCAL YASEEEIGQL VKQMLDDFGP HRYIANLGHG LYPDMDPEHV GAFVDAVHKH
SRLLRQN
//

MIM 176100
*RECORD*
*FIELD* NO
176100
*FIELD* TI
#176100 PORPHYRIA CUTANEA TARDA
;;PCT;;
PORPHYRIA CUTANEA TARDA, TYPE II;;
PCT, TYPE II;;
read morePCT, 'FAMILIAL' TYPE;;
PORPHYRIA, HEPATOCUTANEOUS TYPE;;
UROPORPHYRINOGEN DECARBOXYLASE DEFICIENCY;;
UROD DEFICIENCY
PORPHYRIA, HEPATOERYTHROPOIETIC, INCLUDED; HEP, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because porphyria cutanea
tarda type II, or familial PCT, is caused by heterozygous mutation in
the gene encoding uroporphyrinogen decarboxylase (UROD; 613521).
Hepatoerythropoietic porphyria (HEP) is caused by homozygous or compound
heterozygous mutation in the UROD gene.

DESCRIPTION

Porphyria cutanea tarda (PCT) is characterized by light-sensitive
dermatitis and the excretion of large amounts of uroporphyrin in urine
(Elder et al., 1980).

De Verneuil et al. (1978) and others classified porphyria cutanea tarda,
the most common type of porphyria, into 2 types: type I (176090), or
'sporadic' type, associated with approximately 50% level of
uroporphyrinogen decarboxylase (UROD) in liver (Elder et al., 1978;
Felsher et al., 1982), and type II, or 'familial' type, characterized by
50% deficient activity of the same enzyme in many tissues (Kushner et
al., 1976; Elder et al., 1980).

PCT type II is an autosomal dominant disorder with low penetrance and
constitutes about 20% of cases of PCT. Recognized exacerbating factors
of PCT include iron overload, excessive use of alcohol, exposure to
polyhalogenated aromatic chemicals, exposure to estrogens, chronic viral
hepatitis C, HIV infections, and mutation in the HFE gene (613609) that
are responsible for hereditary hemochromatosis (235200) (review by
Lambrecht et al., 2007).

CLINICAL FEATURES

Onset of light-sensitive dermatitis in later adult life, associated with
the excretion of large amounts of uroporphyrin in urine, characterizes
porphyria cutanea tarda, which was so named by Waldenstrom (1937). On
areas of skin exposed to sunlight, especially the face, ears, and backs
of the hands, chronic ulcerating lesions commence as blisters, and the
skin may also be mechanically fragile (Grossman et al., 1979).
Hyperpigmentation and hypertrichosis also occur. Acute neuropathic
episodes do not occur in this form of porphyria. Onset is often
associated with alcoholism, and occasionally with exposure to other
agents, such as estrogens. Iron overload is frequently present, and may
be associated, coincidentally or causally, with varying degrees of liver
damage or fibrosis; liver histology may be characteristic (Cortes et
al., 1980). On biopsy, liver parenchyma cells are also loaded with
porphyrins and fluoresce bright red in ultraviolet light. The skin
lesions are distinctly related to circulating porphyrins (Holti et al.,
1958).

Malina and Lim (1988) described a 29-year-old woman who first presented
with blisters and erosions on the dorsum of the fingers and hands
bilaterally 3 weeks after delivery of her second child. The diagnosis of
PCT was established enzymatically and by porphyrin studies. Reduced red
cell UROD activity was found also in the newborn child and in the
patient's mother.

Classic congenital erythropoietic porphyria (263700) is due to
deficiency of uroporphyrinogen III cosynthase. Kushner et al. (1982)
described a remarkable 51-year-old man with congenital erythropoietic
porphyria (Gunther disease), first manifested in infancy with eventual
development of mutilating skin photosensitivity. The morphologic
features of dyserythropoietic bone marrow cells, studied by light and
electron microscopy, were identical to those found in congenital
dyserythropoietic anemia type I (224120); such had been described before
in Gunther disease. A red-orange nuclear fluorescence is not seen in
type I dyserythropoietic anemia. The patient of Kushner et al. (1982)
showed massive porphyrinuria, but the pattern of porphyrin excretion was
atypical for classic Gunther disease: hepta-carboxyl (7-COOH) porphyrin
was the major urine porphyrin, much uroporphyrin was present, and both
were predominantly of the isomer III type. Erythrocyte uroporphyrinogen
III cosynthase activity was normal, but uroporphyrinogen decarboxylase
activity was 50% of normal. Two sons showed equally subnormal
uroporphyrinogen decarboxylase activity. It was the opinion of the
authors that their 51-year-old patient had 2 genetic
diseases--uroporphyrinogen decarboxylase deficiency (a heterozygous
state) and type I congenital dyserythropoietic anemia (a presumably
homozygous state). With coexisting hepatic siderosis, heterozygous
uroporphyrinogen decarboxylase deficiency leads to porphyria cutanea
tarda. Homozygosity for a deficiency gene leads to hepatoerythropoietic
porphyria. Thus, Gunther disease can have more than one cause. Two other
reported patients with clinically typical congenital erythropoietic
porphyria, but with a pattern of urinary porphyrin excretion similar to
porphyria cutanea tarda, were referenced by Kushner et al. (1982).

- Hepatoerythropoietic Porphyria

Hepatoerythropoietic porphyria (HEP) is a severe, autosomal recessive
form of cutaneous porphyria that presents in infancy and is
characterized biochemically by excessive excretion of
acetate-substituted porphyrins and accumulation of protoporphyrin in
erythrocytes (Hofstad et al., 1973; Simon et al., 1977; Czarnecki,
1980). As in porphyria cutanea tarda, uroporphyrinogen decarboxylase is
deficient. However, the enzyme level is very low (7-8%) in erythrocytes
and cultured skin fibroblasts, leading Elder et al. (1981) to propose
that HEP is the homozygous state for porphyria cutanea tarda.

De Verneuil et al. (1984) brought to 9 the number of known cases of HEP
and confirmed that these patients are homozygous for mutations in the
same gene that causes PCT. The patients of de Verneuil et al. (1984)
were twin daughters of a Tunisian couple related as second cousins. Both
parents, although asymptomatic, showed intermediate levels of enzymatic
and immunoreactive URO decarboxylase. The twins were CRM-negative, in
contrast to previously reported homozygous patients.

Toback et al. (1987) described a man with relatively mild
hepatoerythropoietic porphyria and concluded that the man was a
homozygote since both of his parents and his 3 children, all of whom
were asymptomatic, showed moderate deficiency of UROD. They concluded
that the relative mildness of the clinical symptoms in the proband was
probably related to the level of residual enzyme activity and that the
genetic defect in UROD in this disorder can be heterogeneous.

Fujimoto and Brazil (1992) reported a 23-year-old woman thought to
represent the 18th instance of HEP reported worldwide. She had
photosensitive skin of early onset, hypertrichosis, and severe
scleroderma-like lesions of the hands.

- PCT 'Phenocopy'

A syndrome similar to PCT, a 'phenocopy,' is caused by toxic exposure to
certain organic chemicals such as hexachlorobenzene, as in the epidemic
caused by contaminated seed wheat in Turkey (Cam and Nigogosyan, 1963;
Dean, 1972) and by occupational exposure to chlorinated hydrocarbons
(Bleiberg et al., 1964).

PATHOGENESIS

Felsher et al. (1982) concluded that reduced hepatic uroporphyrinogen
decarboxylase activity is a specific and intrinsic hepatic defect in
PCT, but modulation of uroporphyrinogen synthesis by extrinsic factors
is required for full biochemical expression of the disease.

BIOCHEMICAL FEATURES

Reduced liver and red cell uroporphyrinogen decarboxylase activity has
been reported in familial (Kushner et al., 1976; Lehr and Doss, 1981)
and sporadic cases of porphyria cutanea tarda (Elder et al., 1978;
Felsher et al., 1978). Impaired activity of this enzyme step in heme
synthesis in liver could possibly explain resulting 'overflow' of
uroporphyrin. Hepatic uroporphyrinogen decarboxylase activity was
reduced to approximately 50% of normal levels in 17 cases of porphyria
cutanea tarda and reduced levels persisted after hepatic iron overload
was relieved by phlebotomy (Felsher et al., 1982). Elder et al. (1978)
found normal levels of enzyme in red cells and fibroblasts. In assays of
UROD activity in red cells, de Verneuil et al. (1978) found 50% levels
of uroporphyrinogen decarboxylase in persons with familial porphyria
cutanea, but normal enzyme levels in sporadic cases.

In hemolysates from 7 unrelated patients with familial PCT, Elder et al.
(1983) found that immunoreactive uroporphyrinogen decarboxylase was
decreased (average 51% of normal) to the same extent as catalytic
activity (average 56% of normal), whereas in 6 sporadic cases both
measurements were normal. The failure to find evidence of CRM+ mutations
among the familial cases suggested to Elder et al. (1983) that a simple
immunoelectrophoretic method can be used for routine diagnosis.

Using a UROD cDNA probe in Northern blot analysis, Hansen et al. (1988)
found no difference in the levels of UROD mRNA between affected
individuals and their normal relatives.

INHERITANCE

Most cases of PCT are sporadic and are more common in men than women,
but familial cases have been described frequently, and apparent
autosomal dominant segregation of the disorder has been reported (Holti
et al., 1958; Ziprkowski et al., 1966; Topi and Gandalfo, 1977;
Benedetto et al., 1978).

Although it is unusual for an enzyme deficiency to produce symptoms in
the heterozygous state, i.e., in single gene dose, this is also the
pattern in other types of genetic porphyrias (e.g., 121300, 176000,
176200, 177000). It seems likely that a reduced level of activity of
uroporphyrinogen decarboxylase may segregate as an autosomal dominant
trait, but that additional environmental factors are required for
manifestation of the disorder; iron overload may have a direct metabolic
role (Kushner et al., 1972; Kushner, 1982).

Blekkenhorst et al. (1979) suggested that 2 forms of PCT exist: a rare
familial form and a relatively common idiosyncratic form occurring
sporadically as an unusual accompaniment of common hepatic disorders
such as alcohol-associated liver disease.

Hepatoerythropoietic porphyria (HEP) is an autosomal recessive trait (de
Verneuil et al., 1984).

POPULATION GENETICS

The incidence of PCT varies from approximately 1 in 25,000 in the United
States to approximately 1 in 5,000 in the Czech Republic and Slovakia
(review by Lambrecht et al., 2007).

PCT is common in the Bantu races in South Africa in association with
iron overload (Barnes, 1955).

CLINICAL MANAGEMENT

Treatment is directed first to reducing iron overload by regular
phlebotomy, as in the management of hemochromatosis (Epstein and
Redeker, 1968; Ramsay et al., 1974; Grossman et al., 1979). Porphyrin
excretion diminishes, and in many patients skin lesions disappear. When
this is ineffective or when a more rapid effect is desired, oral
chloroquine therapy usually induces rapid remission (Taljaard et al.,
1972; Kowertz, 1973). It may also cause a transient increase in
porphyrin excretion, sometimes associated with evidence of acute liver
damage (Vogler et al., 1970). Remission is sustained while chloroquine
is continued in regular low doses.

Several cases of porphyria cutanea tarda have been described in patients
on maintenance hemodialysis for chronic renal failure (e.g.,
Poh-Fitzpatrick et al., 1978). The cause is thought to be insufficient
removal of porphyrins through the hemodialysis membrane which leads to
markedly increased levels of plasma porphyrins with resulting severe and
mutilating skin lesions. The treatment of the disorder is very difficult
because chloroquine is ineffective and the anemia that accompanies
chronic renal failure contraindicates venesection therapy. Praga et al.
(1987) found that deferoxamine was effective therapy in a patient in
whom there was evidence of iron overload due to multiple blood
transfusions.

MOLECULAR GENETICS

Using hybridization probes for the UROD gene in the study of genomic DNA
from patients with familial PCT, Hansen et al. (1988) could not identify
any major deletions, rearrangements, or restriction fragment length
polymorphisms.

In the UROD cDNA from a patient with familial PCT, Garey et al. (1989)
demonstrated a gly-to-val substitution at amino acid position 281
(G281V; 613521.0001). The mutation was not detected in affected persons
from 7 other PCT pedigrees with an autosomal dominant pattern. They
showed that the UROD protein in the patient with the identified mutation
had a greatly shortened half-life, both in vitro and in vivo (assuming,
as these workers did, that one can call the findings in cultured
lymphocytes an 'in vivo' observation). Hepatoerythropoietic porphyria
results from a different nucleotide substitution in the same codon
(G281E; 613521.0002). The UROD protein resulting from the G281E mutation
also has a decreased half-life, but not so severely decreased as in the
case of the G281V mutation. Garey et al. (1989) suggested that the
former mutation may be so severe in the homozygous state that it is
lethal to the embryo; PCT can result in the heterozygote for the first
mutation, but only the homozygote for the milder mutation expresses
itself (as HEP). Garey et al. (1989) pointed out that familial PCT is
relatively common, but only 16 cases of HEP have been described to date.

Using a cDNA clone for the UROD gene, de Verneuil et al. (1986) studied
DNA from 2 homozygous patients, offspring of consanguineous parents, who
suffered from HEP. They could detect neither deletions nor
rearrangements in the UROD gene. Synthesis, processing, and cell-free
translation of the specific transcripts appeared to be normal. The
half-life of the abnormal protein was 12 times shorter than that of the
normal enzyme. Thus, rapid degradation in vivo is the probable basis of
the enzyme deficiency. Study of homozygous patients avoided the
difficulties of studying the enzyme defect in the heterozygous PCT where
both normal and abnormal protein is present. The authors suggested that
use of oligonucleotide probes complementary to the normal and mutant
sequences could allow them to determine if the mutation in familial PCT
is the same as that in HEP; in other words, whether HEP is indeed the
homozygous state of PCT.

In a Spanish family, Moran-Jimenez et al. (1996) found homozygosity for
the G281E (613521.0001) mutation as the cause of HEP. A paternal uncle
of the proband developed clinically overt porphyria cutanea tarda as an
adult and proved to be heterozygous for the G281E mutation.

Mendez et al. (1998) sequenced the entire UROD gene, and developed a
long-range PCR method to amplify the entire gene for mutation analysis.
Four missense mutations (M165R, 613521.0009; L195F, 613521.0010; N304K,
613521.0011; and R332H, 613521.0012), a microinsertion, a deletion, and
a novel exonic splicing defect were identified. Expression of the L195F,
N304K, and R332H polypeptides revealed significant residual activity,
whereas RT-PCR and sequencing demonstrated that the E314E (613521.0008)
lesion caused abnormal splicing and exon 9 skipping. Screening of 9
familial PCT probands revealed that 4 (44%) were heterozygous or
homozygous for the common hemochromatosis mutations, which suggested
that iron overload may predispose to clinical expression. However, there
was no clear correlation between the severity of familial PCT and the
UROD and/or hemochromatosis genotypes. Presymptomatic molecular
diagnosis should now be possible, permitting counseling to enable family
members to avoid disease-precipitating factors.

- Role of Mutations in the HFE Gene

An association between PCT and HLA-linked hereditary hemochromatosis
(HFE; 235200) was suggested by Kushner et al. (1985), but disputed by
Beaumont et al. (1986). Santos et al. (1997) assessed the role of HFE
(613609) mutations in PCT by an allelic-association study between PCT
and the mutations identified in hemochromatosis. They studied 15
unselected, unrelated patients with PCT being treated with regular
phlebotomy. The controls were 23 anonymous blood donors and 71 patients
with hereditary hemochromatosis. The cys282-to-tyr mutation (C282Y;
613609.0001) was found in 83% of 142 hereditary hemochromatosis
chromosomes, 47% of 30 PCT chromosomes, and 9% of 46 normal blood donor
chromosomes. Santos et al. (1997) concluded that the hemochromatosis
gene contributes to the pathogenesis of PCT. They suggested that all
first-degree relatives of patients with PCT should be screened for
hereditary hemochromatosis. PCT can be viewed as having a digenic basis.

Ivanova et al. (1999) found the C282Y mutation of the HFE gene in only 1
of 48 PCT patients (2.1%). This individual was heterozygous for the
mutation. The mutation was found in none of 100 healthy Bulgarian
subjects. This indicates a very low frequency of the C282Y mutation in
Bulgaria. A similarly low frequency of HFE mutations was found in
Japanese cases of PCT and in Japanese patients generally, leading
Furuyama et al. (1999) to suggest that abnormal iron metabolism
associated with PCT in Japanese patients occurs by a mechanism unrelated
to HFE gene mutations.

Brady et al. (2000) investigated the relationship between age of onset
of skin lesions and mutations (C282Y, 613609.0001; H63D, 613609.0002) in
the hemochromatosis gene in 19 familial and 65 sporadic porphyria
cutanea tarda patients. Familial porphyria cutanea tarda was identified
by mutation analysis of the uroporphyrinogen decarboxylase gene. Five
previously described and 8 novel mutations were identified. Homozygosity
for the C282Y hemochromatosis mutation was associated with an earlier
onset of skin lesions in both familial and sporadic porphyria cutanea
tarda, the effect being more marked in familial porphyria cutanea tarda
where anticipation was demonstrated in family studies. Analysis of the
frequencies of hemochromatosis genotypes in each type of porphyria
cutanea tarda indicated that C282Y homozygosity is an important
susceptibility factor in both types but suggested that heterozygosity
for this mutation has much less effect on the development of the
disease.

Dereure et al. (2001) evaluated 36 consecutive patients with either
sporadic or familial PCT for the presence of the 3 main mutations of the
HFE gene and identification of the transferrin receptor alleles. Seven
patients (19%) showed heterozygous C282Y (613609.0001) mutation, but no
C282Y homozygote was present; 5 patients (14%) carried homozygous H63D
(613609.0002) mutation, while 8 (22%) were heterozygous for this
mutation. One patient was heterozygous for the S65C (613609.0003)
mutation (3%). Iron parameters demonstrated overload in all patients,
without a clear difference between patients with and without deleterious
mutations of the HFE gene. Infection by hepatitis C virus was documented
in 20 patients (56%), and was significantly less frequent in patients
with deleterious HFE mutations. The profile of transferrin receptor
alleles in PCT patients did not show significant variation compared with
the general population. Dereure et al. (2001) concluded that there is a
high frequency of HFE mutations in patients with PCT and that HFE gene
abnormalities might play a significant part in the PCT pathomechanism,
probably through iron overload; by contrast, transferrin receptor
polymorphisms do not appear to play a significant part in iron overload
in PCT.

Stolzel et al. (2003) retrospectively analyzed 62 German PCT patients
exclusively treated with low-dose chloroquine to determine whether HFE
mutations C282Y (613609.0001) and H63D (613609.0002) influenced the
clinical response, urinary porphyrin excretion, liver enzyme activities,
and serum iron markers. Chloroquine therapy was accompanied by clinical
remission and reduced urinary porphyrin excretion in the 24 patients
(39%) with HFE wildtype as well as in 35 HFE heterozygous patients with
PCT (56%). Decreases of serum iron markers following chloroquine therapy
were limited to patients with PCT and HFE wildtype. All 3 patients
homozygous for the C282Y mutation (5%) had high serum iron, ferritin,
and transferrin saturation and failed to respond to chloroquine
treatment. Stolzel et al. (2003) concluded that the therapeutic response
to chloroquine was not compromised by C282Y heterozygosity and compound
heterozygosity of HFE mutations. However, because HFE C282Y homozygotes
did not respond to chloroquine and a decrease in serum iron
concentration was limited to patients with PCT and HFE wildtype,
phlebotomy should be first-line therapy in patients with PCT and HFE
mutations.

- Role of Mutations in the CYP12A Gene

Individuals with PCT are believed to be genetically predisposed to
development of clinically overt disease through mutations and
polymorphisms in particular genes in response to precipitating factors.
Christiansen et al. (2000) examined a group of Danish patients with PCT
for the presence of a C/A polymorphism in intron 1 of CYP1A2 (124060).
The results demonstrated that the frequency of the highly inducible A/A
genotype is increased in both familial and sporadic PCT. This suggested
that inheritance of this genotype is a susceptibility factor for PCT.

ANIMAL MODEL

The zebrafish mutant 'yquem' shows a photosensitive porphyria syndrome.
Wang et al. (1998) showed that the porphyric phenotype is due to an
inherited homozygous mutation in the UROD gene. Thus, the zebrafish
mutant represented the first genetically 'accurate' model of
hepatoerythropoietic porphyria; Wang et al. (1998) suggested that the
model would be useful for studying the pathogenesis of UROD deficiency
and evaluating gene therapy vectors. Wang et al. (1998) rescued the
mutant phenotype by transient and germline expression of the wildtype
allele.

Most heterozygotes for UROD mutations do not express a porphyric
phenotype unless hepatic siderosis is present. Mutations in the
hemochromatosis gene are frequently found when the porphyric phenotype
is expressed in the heterozygote. Phillips et al. (2001) used homologous
recombination to disrupt 1 allele of the murine Urod gene. Urod +/- mice
had half-wildtype UROD protein and enzymatic activity in all tissues but
did not accumulate hepatic porphyrins, indicating that half-normal UROD
activity is not rate limiting. When Urod +/- mice were injected with
iron-dextran and given drinking water containing delta-aminolevulinic
acid (ALA) for 21 days, hepatic porphyrins accumulated, and hepatic UROD
activity was reduced to 20% of weight. Phillips et al. (2001) also bred
mice homozygous for the HFE gene disruption (Hfe -/-) to Urod +/- mice,
generating mice with the heterozygous Urod genotype and the homozygous
null Hfe genotype. These animals developed a porphyric phenotype by 14
weeks of age without ALA supplementation, and UROD activity was reduced
to 14% of weight. These data indicated that iron overload alone is
sufficient to reduce UROD activity to rate-limiting levels in
heterozygous Urod mice. Thus these mice serve as an excellent model of
familial PCT and afford the opportunity to define the mechanism by which
iron influences UROD activity.

*FIELD* SA
Day et al. (1982); Hansen et al. (1988); Romana et al. (1991); Romeo
(1977)
*FIELD* RF
1. Barnes, H. D.: Porphyria in the Bantu races on the Witwatersrand. S.
Afr. Med. J. 29: 781-784, 1955.

2. Beaumont, C.; Nordmann, Y.; Fauchet, R.: HLA-linked hemochromatosis
and sporadic porphyria cutanea tarda. (Letter) Gastroenterology 90:
800 only, 1986.

3. Benedetto, A. V.; Kushner, J. P.; Taylor, J. S.: Porphyria cutanea
tarda in three generations of a single family. New Eng. J. Med. 298:
358-361, 1978.

4. Bleiberg, J.; Wallen, M.; Brodkin, R.; Applebaum, I.: Industrially
acquired porphyria. Arch. Derm. 89: 793-797, 1964.

5. Blekkenhorst, G. H.; Day, R. S.; Eales, L.: Two forms of porphyria
cutanea tarda? (Letter) New Eng. J. Med. 300: 93, 1979.

6. Brady, J. J.; Jackson, H. A.; Roberts, A. G.; Morgan, R. R.; Whatley,
S. D.; Rowlands, G. L.; Darby, C.; Shudell, E.; Watson, R.; Paiker,
J.; Worwood, M. W.; Elder, G. H.: Co-inheritance of mutations in
the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates
the onset of porphyria cutanea tarda. J. Invest. Derm. 115: 868-874,
2000.

7. Cam, C.; Nigogosyan, G.: Acquired toxic porphyria cutanea tarda
due to hexachlorobenzene. JAMA 183: 88-91, 1963.

8. Christiansen, L.; Bygum, A.; Jensen, A.; Thomsen, K.; Brandrup,
F.; Horder, M.; Petersen, N. E.: Association between CYP1A2 polymorphism
and susceptibility to porphyria cutanea tarda. Hum. Genet. 107:
612-614, 2000.

9. Cortes, J. M.; Oliva, H.; Paradinas, F. J.; Hernandez-Guio, C.
: The pathology of the liver in porphyria cutanea tarda. Histopathology 4:
471-485, 1980.

10. Czarnecki, D. B.: Hepatoerythropoietic porphyria. Arch. Derm. 116:
307-311, 1980.

11. Day, R. S.; Eales, L.; Meissner, D.: Coexistent variegate porphyria
and porphyria cutanea tarda. New Eng. J. Med. 307: 36-41, 1982.

12. Dean, G.: The Porphyrias. A Story of Inheritance and Environment.
Philadelphia: J. B. Lippincott (pub.) (2nd ed.): 1972.

13. Dereure, O.; Aguilar-Martinez, P.; Bessis, D.; Perney, P.; Vallat,
C.; Guillot, B.; Blanc, F.; Guilhou, J.-J.: HFE mutations and transferrin
receptor polymorphism analysis in porphyria cutanea tarda: a prospective
study of 36 cases from southern France. Brit. J. Derm. 144: 533-539,
2001.

14. de Verneuil, H.; Aitken, G.; Nordmann, Y.: Familial and sporadic
porphyria cutanea: two different diseases. Hum. Genet. 44: 145-151,
1978.

15. de Verneuil, H.; Beaumont, C.; Deybach, J.-C.; Nordmann, Y.; Sfar,
Z.; Kastally, R.: Enzymatic and immunological studies of uroporphyrinogen
decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic
porphyria. Am. J. Hum. Genet. 36: 613-622, 1984.

16. de Verneuil, H.; Grandchamp, B.; Beaumont, C.; Picat, C.; Nordmann,
Y.: Uroporphyrinogen decarboxylase structural mutant (gly-281-to-glu)
in a case of porphyria. Science 234: 732-734, 1986.

17. Elder, G. H.; Lee, G. B.; Tovey, J. A.: Decreased activity of
hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea
tarda. New Eng. J. Med. 299: 274-278, 1978.

18. Elder, G. H.; Sheppard, D. M.; de Salamanca, R. E.; Olmos, A.
: Identification of two types of porphyria cutanea tarda by measurement
of erythrocyte uroporphyrinogen decarboxylase. Clin. Sci. 58: 477-484,
1980.

19. Elder, G. H.; Sheppard, D. M.; Tovey, J. A.; Urquhart, A. J.:
Immunoreactive uroporphyrinogen decarboxylase in porphyria cutanea
tarda. Lancet 321: 1301-1304, 1983. Note: Originally Volume I.

20. Elder, G. H.; Smith, S. G.; Herrero, C.; Mascaro, J. M.; Lecha,
M.; Muniesa, A. M.; Czarnecki, D. B.; Brenan, J.; Poulos, V.; de Salamanca,
R. E.: Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase
defect or homozygous porphyria cutanea tarda? Lancet 317: 916-919,
1981. Note: Originally Volume I.

21. Epstein, J. H.; Redeker, A. G.: Porphyria cutanea tarda: a study
of the effect of phlebotomy. New Eng. J. Med. 279: 1301-1304, 1968.

22. Felsher, B. F.; Carpio, N. M.; Engleking, D. W.; Nunn, A. T.:
Decreased hepatic uroporphyrinogen decarboxylase activity in porphyria
cutanea tarda. New Eng. J. Med. 306: 766-769, 1982.

23. Felsher, B. F.; Norris, M. E.; Shih, J. C.: Red-cell uroporphyrinogen
decarboxylase activity in porphyria cutanea tarda and in other forms
of porphyria. New Eng. J. Med. 299: 1095-1098, 1978.

24. Fujimoto, A.; Brazil, J. L.: Hepatoerythropoietic porphyria in
a woman with short stature and deformed hands. Am. J. Med. Genet. 44:
496-499, 1992.

25. Furuyama, K.; Kondo, M.; Hirata, K.; Fujita, H.; Sassa, S.: Extremely
rare association of HFE mutations with porphyria cutanea tarda in
Japanese patients. (Letter) Hepatology 30: 1532-1533, 1999.

26. Garey, J. R.; Hansen, J. L.; Harrison, L. M.; Kennedy, J. B.;
Kushner, J. P.: A point mutation in the coding region of uroporphyrinogen
decarboxylase associated with familial porphyria cutanea tarda. Blood 73:
892-895, 1989.

27. Grossman, M. E.; Bickers, D. R.; Poh-Fitzpatrick, M. B.; Delco,
V. A.; Harber, L. C.: Porphyria cutanea tarda: clinical features
and laboratory findings in 40 patients. Am. J. Med. 67: 277-286,
1979.

28. Hansen, J. L.; O'Connell, P. O.; Romana, M.; Romeo, P.-H.; Kushner,
J. P.: Familial porphyria cutanea tarda: hybridization analysis of
the uroporphyrinogen decarboxylase locus. Hum. Hered. 38: 283-286,
1988.

29. Hansen, J. L.; Pryor, M. A.; Kennedy, J. B.; Kushner, J. P.:
Steady-state levels of uroporphyrinogen decarboxylase mRNA in lymphoblastoid
cell lines from patients with familial porphyria cutanea tarda and
their relatives. Am. J. Hum. Genet. 42: 847-853, 1988.

30. Hofstad, F.; Seip, M.; Eriksen, L.: Congenital erythropoietic
porphyria with a hitherto undescribed porphyrin pattern. Acta Paediat.
Scand. 62: 380-384, 1973.

31. Holti, G.; Rimington, C.; Tate, B. C.; Thomas, G.: An investigation
of 'porphyria cutanea tarda'. Quart. J. Med. 27: 1-19, 1958.

32. Ivanova, A.; von Ahsen, N.; Adjarov, D.; Krastev, Z.; Oellerich,
M.; Wieland, E.: C282Y and H63D mutations in the HFE gene are not
associated with porphyria cutanea tarda in Bulgaria. (Letter) Hepatology 30:
1531-1532, 1999.

33. Kowertz, M. J.: The therapeutic effect of chloroquine. JAMA 223:
515-519, 1973.

34. Kushner, J. P.: The enzymatic defect in porphyria cutanea tarda.
(Editorial) New Eng. J. Med. 306: 799-800, 1982.

35. Kushner, J. P.; Barbuto, A. J.; Lee, G. R.: An inherited enzymatic
defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase
activity. J. Clin. Invest. 58: 1089-1097, 1976.

36. Kushner, J. P.; Edwards, C. Q.; Dadone, M. M.; Skolnick, M. H.
: Heterozygosity for HLA-linked hemochromatosis as a likely cause
of the hepatic siderosis associated with sporadic porphyria cutanea
tarda. Gastroenterology 88: 1232-1238, 1985.

37. Kushner, J. P.; Lee, G. R.; Nacht, S.: The role of iron in the
pathogenesis of porphyria cutanea tarda: an in vitro model. J. Clin.
Invest. 51: 3044-3051, 1972.

38. Kushner, J. P.; Pimstone, N. R.; Kjeldsberg, C. R.; Pryor, M.
A.; Huntley, A.: Congenital erythropoietic porphyria, diminished
activity of uroporphyrinogen decarboxylase and dyserythropoiesis. Blood 59:
725-737, 1982.

39. Lambrecht, R. W.; Thapar, M.; Bonkovsky, H. L.: Genetic aspects
of porphyria cutanea tarda. Semin. Liver Dis. 27: 99-108, 2007.

40. Lehr, P. A.; Doss, M.: Chronishe hepatische porphyrie mit Uroporphyrinogen-Decarboxylase-Defekt
in vier Generationen. Dtsch. Med. Wschr. 106: 241-245, 1981.

41. Malina, L.; Lim, C. K.: Manifestation of familial porphyria cutanea
tarda after childbirth. Brit. J. Derm. 118: 243-245, 1988.

42. Mendez, M.; Sorkin, L.; Rossetti, M. V.; Astrin, K. H.; Batlle,
A. M. del C.; Parera, V. E.; Aizencang, G.; Desnick, R. J.: Familial
porphyria cutanea tarda: characterization of seven novel uroporphyrinogen
decarboxylase mutations and frequency of common hemochromatosis alleles. Am.
J. Hum. Genet. 63: 1363-1375, 1998.

43. Moran-Jimenez, M. J.; 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. 58:
712-721, 1996.

44. Phillips, J. D.; Jackson, L. K.; Bunting, M.; Franklin, M. R.;
Thomas, K. R.; Levy, J. E.; Andrews, N. C.; Kushner, J. P.: A mouse
model of familial porphyria cutanea tarda. Proc. Nat. Acad. Sci. 98:
259-264, 2001.

45. Poh-Fitzpatrick, M. B.; Bellet, N.; DeLeo, V. A.; Grossman, M.
E.; Bickers, D. R.: Porphyria cutanea tarda in two patients treated
with hemodialysis for chronic renal failure. New Eng. J. Med. 299:
292-294, 1978.

46. Praga, M.; de Salamanca, R. E.; Andres, A.; Nieto, J.; Oliet,
A.; Perpina, J.; Morales, J. M.: Treatment of hemodialysis-related
porphyria cutanea tarda with deferoxamine. (Letter) New Eng. J. Med. 316:
547-548, 1987.

47. Ramsay, C. A.; Magnus, I. A.; Turnbull, A.; Baker, H.: The treatment
of porphyria cutanea tarda by venesection. Quart. J. Med. 43: 1-24,
1974.

48. Romana, M.; Grandchamp, B.; Dubart, A.; Amselem, S.; Chabret,
C.; Nordmann, Y.; Goossens, M.; Romeo, P.-H.: Identification of a
new mutation responsible for hepatoerythropoietic porphyria. Europ.
J. Clin. Invest. 21: 225-229, 1991.

49. Romeo, G.: Enzymatic defects of hereditary porphyrias. Hum.
Genet. 39: 261-276, 1977.

50. Santos, M.; Clevers, H. C.; Marx, J. J. M.: Mutations of the
hereditary hemochromatosis candidate gene HLA-H in porphyria cutanea
tarda. (Letter) New Eng. J. Med. 336: 1327-1328, 1997.

51. Simon, N.; Berko, G.; Schneider, I.: Hepato-erythropoietic porphyria
presenting as scleroderma and acrosclerosis in a sibling pair. Brit.
J. Derm. 96: 663-668, 1977.

52. Stolzel, U.; Kostler, E.; Schuppan, D.; Richter, M.; Wollina,
U.; Doss, M. O.; Wittekind, C.; Tannapfel, A.: Hemochromatosis (HFE)
gene mutations and response to chloroquine in porphyria cutanea tarda. Arch.
Derm. 139: 309-313, 2003.

53. Taljaard, J. F.; Shanley, B. C.; Stewart-Wynne, E.; Deppe, W.
M.; Joubert, S. M.: Studies on low dose chloroquine therapy and the
action of chloroquine in symptomatic porphyria. Brit. J. Derm. 87:
261-269, 1972.

54. Toback, A. C.; Sassa, S.; Poh-Fitzpatrick, M. B.; Schechter, J.;
Zaider, E.; Harber, L. C.; Kappas, A.: Hepatoerythropoietic porphyria:
clinical, biochemical, and enzymatic studies in a three-generation
family lineage. New Eng. J. Med. 316: 645-650, 1987.

55. Topi, G.; Gandalfo, L. D.: Inheritance of porphyria cutanea tarda:
analysis of 14 cases in 5 families. Brit. J. Derm. 97: 617-627,
1977.

56. Vogler, W. R.; Galambos, J. T.; Olansky, S.: Biochemical effects
of chloroquine therapy in porphyria cutanea tarda. Am. J. Med. 49:
316-321, 1970.

57. Waldenstrom, J.: Studien ueber Porphyrie. Acta Med. Scand. 82
(suppl.): 1-254, 1937.

58. Wang, H.; Long, Q.; Marty, S. D.; Sassa, S.; Lin, S.: A zebrafish
model for hepatoerythropoietic porphyria. Nature Genet. 20: 239-243,
1998.

59. Ziprkowski, L.; Krakowski, A.; Crispin, M.; Szeinberg, A.: Porphyria
cutanea tarda hereditaria. Isr. J. Med. Sci. 2: 338-343, 1966.

*FIELD* CS
INHERITANCE:
Autosomal dominant

ABDOMEN:
[Liver];
Hepatic hemosiderosis;
Hepatic cirrhosis;
Liver biopsy shows red autofluorescence and needle-like cytoplasmic
inclusion bodies

SKIN, NAILS, HAIR:
[Skin];
Photosensitivity;
Blisters in sun-exposed areas;
Mechanically fragile skin;
Hyperpigmentation in sun-exposed areas;
Pseudoscleroderma;
[Nails];
Fingernail onycholysis;
[Hair];
Facial hypertrichosis;
Alopecia

NEOPLASIA:
Increased incidence of hepatocellular carcinoma

LABORATORY ABNORMALITIES:
Reduced liver and red cell uroporphyrinogen decarboxylase (URO decarboxylase)

MISCELLANEOUS:
Most common form of porphyria;
Three types of PCT: Type I (176090) sporadic, presents in adults:
Types II and III (176100) familial, presents in childhood;
Sporadic or acquired PCT precipitated by alcohol, estrogens, iron,
and polychlorinated cyclic hydrocarbons;
More common in men than women;
Hepatoerythropoietic porphyria (HEP, 176100.0005) is a severe infantile
form due to homozygous PCT

MOLECULAR BASIS:
Caused by mutation in the uroporphyrinogen decarboxylase gene (UROD,
176100.0001)

*FIELD* CN
Ada Hamosh - reviewed: 1/5/2001
Kelly A. Przylepa - revised: 2/28/2000

*FIELD* CD
John F. Jackson: 6/15/1995

*FIELD* ED
joanna: 07/23/2013
joanna: 12/2/2008
joanna: 1/5/2001
kayiaros: 2/28/2000

*FIELD* CN
Marla J. F. O'Neill - updated: 11/16/2005
Gary A. Bellus - updated: 4/10/2003
Gary A. Bellus - updated: 4/9/2002
Gary A. Bellus - updated: 4/10/2001
Victor A. McKusick - updated: 2/2/2001
Victor A. McKusick - updated: 12/18/2000
Victor A. McKusick - updated: 1/31/2000
Wilson H. Y. Lo - updated: 7/14/1999
Victor A. McKusick - updated: 12/7/1998
Victor A. McKusick - updated: 10/23/1998
Victor A. McKusick - updated: 6/5/1997

*FIELD* CD
Victor A. McKusick: 6/2/1986

*FIELD* ED
carol: 01/26/2012
joanna: 1/26/2012
terry: 12/7/2010
carol: 10/21/2010
carol: 8/10/2010
terry: 8/9/2010
carol: 8/9/2010
carol: 8/6/2010
terry: 4/30/2010
terry: 6/3/2009
carol: 4/16/2009
terry: 2/6/2009
ckniffin: 1/5/2006
wwang: 11/18/2005
terry: 11/16/2005
joanna: 11/2/2005
carol: 3/17/2004
alopez: 4/10/2003
alopez: 4/9/2002
cwells: 4/13/2001
cwells: 4/10/2001
mcapotos: 2/9/2001
mcapotos: 2/6/2001
terry: 2/2/2001
mcapotos: 1/11/2001
mcapotos: 1/5/2001
terry: 12/18/2000
mcapotos: 2/8/2000
mcapotos: 2/4/2000
terry: 1/31/2000
carol: 7/16/1999
kayiaros: 7/14/1999
terry: 5/11/1999
carol: 12/14/1998
terry: 12/7/1998
alopez: 10/26/1998
carol: 10/23/1998
jenny: 7/9/1997
mark: 6/14/1997
alopez: 6/11/1997
terry: 6/5/1997
mark: 4/24/1996
terry: 4/19/1996
mark: 6/13/1995
carol: 11/17/1994
pfoster: 11/16/1994
davew: 7/26/1994
terry: 5/3/1994
warfield: 3/4/1994

MIM 613521
*RECORD*
*FIELD* NO
613521
*FIELD* TI
*613521 UROPORPHYRINOGEN DECARBOXYLASE; UROD
*FIELD* TX

DESCRIPTION

Uroporphyrinogen decarboxylase (UROD; EC 4.1.1.37) is a cytosolic enzyme
read moreinvolved in the biosynthesis of heme. It catalyzes the sequential
removal of 4 of the carboxymethyl side chains of uroporphyrinogen to
yield coproporphyrinogen. Sassa et al. (1983) purified UROD to
homogeneity. A single enzyme is involved in the 4 successive
decarboxylations.

CLONING

Romeo et al. (1986) cloned and sequenced a full-length cDNA coding for
human UROD. The deduced 367-amino acid protein has a molecular mass of
40.8 kD. Northern blot analysis demonstrated the presence of a single
size species of mRNA in erythroid and nonerythroid tissues and in
several cultured cell lines. The level of UROD mRNA was markedly
increased in tissues and cell lines of erythroid origin.

GENE STRUCTURE

Romana et al. (1987) demonstrated that the UROD gene has 10 exons spread
over 3 kb.

MAPPING

De Verneuil et al. (1984) assigned the locus for uroporphyrinogen
decarboxylase to chromosome 1 by somatic cell hybridization and specific
enzyme assay. This was the fourth enzyme of the heme biosynthetic
pathway to be mapped; the other 3 are CPOX (612732) on 9, PBGD (609806)
on 11, and ALAD (125270) on 9. Mattei et al. (1985) used a cDNA clone to
localize UROD to 1p34 by in situ hybridization. McLellan et al. (1985)
arrived at a different location, 1pter-1p21, by somatic cell
hybridization using cell lines with rearranged chromosomes. Using a cDNA
probe in both somatic cell and in situ hybridization, Dubart et al.
(1986) confirmed the assignment to 1p34.

Bahary et al. (1991) assigned the homologous Urod gene to chromosome 4
of the mouse.

MOLECULAR GENETICS

- Porphyria Cutanea Tarda

In the UROD cDNA from a patient with familial porphyria cutanea tarda
(PCT; 176100), Garey et al. (1989) demonstrated a heterozygous
gly281-to-val substitution (G281V; 613521.0001). The mutation was not
detected in affected persons from 7 other PCT pedigrees with an
autosomal dominant pattern.

- Hepatoerythropoietic Porphyria

In a Tunisian family with hepatoerythropoietic porphyria (HEP; see
176100), de Verneuil et al. (1988) identified homozygosity for a G281E
mutation (613521.0002) in the UROD gene product.

*FIELD* AV
.0001
PORPHYRIA CUTANEA TARDA
UROD, GLY281VAL

In a patient with familial porphyria cutanea tarda (PCT; 176100), Garey
et al. (1989) identified heterozygosity for a gly281-to-val (G281V)
mutation in UROD cDNA.

.0002
PORPHYRIA, HEPATOERYTHROPOIETIC
PORPHYRIA CUTANEA TARDA, INCLUDED
UROD, GLY281GLU

De Verneuil et al. (1986) cloned and sequenced cDNA for the mutated gene
in 1 of their 2 homozygous HEP patients (see 176100) and found that the
glycine residue at position 281 was replaced by glutamic acid (G281E).
This single amino acid change led to a protein that was rapidly degraded
in the presence of cell lysate. Using a synthetic oligonucleotide probe
to screen for the presence of the G281E mutation, de Verneuil et al.
(1988) demonstrated the mutation in HEP-affected members of 2 unrelated
families from Spain, but found that it was absent in 2 other HEP
patients from Italy and Portugal. Moreover, the mutation was not
detected in 13 unrelated cases of familial porphyria cutanea tarda.

Garey et al. (1989) demonstrated this substitution in homozygous state
in a case of HEP.

In a study of 5 Spanish families with hepatoerythropoietic porphyria and
9 unrelated Spanish patients with familial porphyria cutanea tarda,
Roberts et al. (1995) found homozygosity for the G281E mutation in 4
patients with HEP and compound heterozygosity for this mutation in the
fifth. The calculated carrier frequency for G281E in Spain was 1 in
1,800. None of the 9 familial porphyria cutanea tarda patients carried
the G281E mutation. However, one G281E heterozygote in a family with
hepatoerythropoietic porphyria had overt porphyria cutanea tarda. These
findings suggested that the G281E mutation is functionally less severe
than erythrocyte measurements indicate, that its clinical penetrance is
very low in heterozygotes, and that, for this particular mutation,
hepatoerythropoietic porphyria is the homozygous form of familial
porphyria cutanea tarda. The results also indicated that HEP in Spain is
genetically homogeneous, since 9 of the 10 UROD-deficient chromosomes
carried the G281E mutation. In contrast, studies in most of the 14
families reported from outside Spain were likely to have different
mutations. The parents of only 1 of the Spanish cases were
consanguineous, and the other families came from widely different
regions of Spain and did not appear to be related. The mutation probably
entered Spain in the distant past and had become widely distributed. The
G281E mutation was originally described in a Tunisian family (de
Verneuil et al., 1988).

In a Spanish family, Moran-Jimenez et al. (1996) found homozygosity for
the G281E mutation as the cause of HEP. A paternal uncle of the proband
developed clinically overt porphyria cutanea tarda as an adult and
proved to be heterozygous for the G281E mutation.

.0003
PORPHYRIA CUTANEA TARDA
UROD, IVS6DS, G-C, +1

In affected members of 5 of 22 unrelated families segregating PCT
(176100), Garey et al. (1990) found a heterozygous splice site mutation
in the UROD gene (IVS6+1G-C). The mutation resulted in the deletion of
exon 6. The intron/exon junctions on either side of exon 6 fall between
codons; thus, the resulting protein is shorter than the normal protein,
missing only the amino acids coded by exon 6. The shortened protein
lacked catalytic activity, was rapidly degraded when exposed to human
lymphocyte lysates, and was not detectable by Western blot analysis in
lymphocyte lysates derived from affected persons.

.0004
PORPHYRIA, HEPATOERYTHROPOIETIC
UROD, GLU167LYS

Romana et al. (1991) demonstrated that a patient with
hepatoerythropoietic porphyria (176100) was homozygous for a GAG-to-AAG
mutation in the UROD gene that changed glutamic acid-167 to lysine
(E167K).

.0005
PORPHYRIA, HEPATOERYTHROPOIETIC
UROD, ARG292GLY

In 2 Dutch sisters with HEP (see 176100), de Verneuil et al. (1992)
demonstrated compound heterozygosity for a deletion inherited from the
father and an R292G mutation inherited from the mother.

.0006
PORPHYRIA, HEPATOERYTHROPOIETIC
UROD, PRO62LEU

In affected members of a Portuguese family segregating
hepatoerythropoietic porphyria (see 176100), Moran-Jimenez et al. (1996)
demonstrated homozygosity for a pro61-to-leu (P62L) substitution in
UROD. Mutant cDNA corresponding to the P62L change was created by
site-directed mutagenesis. The recombinant protein proved to have
subnormal enzyme activity.

.0007
PORPHYRIA, HEPATOERYTHROPOIETIC
UROD, TYR311CYS

In an Italian family, Moran-Jimenez et al. (1996) identified a
tyr311-to-cys (Y311C) substitution in homoallelic state in the UROD gene
as the cause of HEP (see 176100). Mutant cDNA corresponding to the Y311C
change was created by site-directed mutagenesis. The recombinant protein
proved to have subnormal enzyme activity and was thermolabile.

.0008
PORPHYRIA CUTANEA TARDA
UROD, GLU314GLU

In their family 1 with porphyria cutanea tarda (176100), Mendez et al.
(1998) found that the proband had a heterozygous G-to-A transition in
the last base of exon 9 of the UROD gene causing a GAG (glu) to GAA
(glu) change at codon 314; the amino acid sequence was not altered.
However, the splicing of intron 9 was defective; the entire 67-bp exon 9
was deleted and exon 8 was joined directly to exon 10.

.0009
PORPHYRIA CUTANEA TARDA
UROD, MET165ARG

In a patient of Italian ancestry with porphyria cutanea tarda (176100),
Mendez et al. (1998) identified a heterozygous met165-to-arg
substitution in the UROD gene product.

.0010
PORPHYRIA CUTANEA TARDA
UROD, LEU195PHE

In a patient of Spanish ancestry with porphyria cutanea tarda (176100),
Mendez et al. (1998) identified a heterozygous leu195-to-phe (L195F)
substitution in the UROD gene product.

.0011
PORPHYRIA CUTANEA TARDA
UROD, ASN304LYS

In a patient of Spanish ancestry with porphyria cutanea tarda (176100),
Mendez et al. (1998) identified a heterozygous asn304-to-lys (N304K)
substitution in the UROD gene product.

.0012
PORPHYRIA CUTANEA TARDA
UROD, ARG332HIS

In a patient of Portuguese ancestry with porphyria cutanea tarda
(176100), Mendez et al. (1998) identified a heterozygous arg332-to-his
(R332H) substitution in the UROD gene product.

.0013
PORPHYRIA CUTANEA TARDA
UROD, 10-BP DEL, NT5

In a Spanish patient with porphyria cutanea tarda (176100), Badenas et
al. (2009) identified a 10-bp deletion in exon 1 of the UROD gene
(5del10).

.0014
PORPHYRIA CUTANEA TARDA
UROD, GLN116TER

In a Spanish patient with porphyria cutanea tarda (176100), Badenas et
al. (2009) identified a 346C-T transition in exon 5 of the UROD gene,
resulting in a gln116-to-ter (Q116X) substitution.

*FIELD* SA
de Verneuil et al. (1986); Garey et al. (1988)
*FIELD* RF
1. Badenas, C.; To-Fibueras, J.; Phillips, J. D.; Warby, C. A.; Munoz,
C.; Herrero, C.: Identification and characterization of novel uroporphyrinogen
decarboxylase gene mutations in a large series of porphyria cutanea
tarda patients and relatives. Clin. Genet. 75: 346-353, 2009.

2. Bahary, N.; Zorich, G.; Pachter, J. E.; Leibel, R. L.; Friedman,
J. M.: Molecular genetic linkage maps of mouse chromosomes 4 and
6. Genomics 11: 33-47, 1991.

3. de Verneuil, H.; Bourgeois, F.; de Rooij, F.; Siersema, P. D.;
Wilson, J. H. P.; Grandchamp, B.; Nordmann, Y.: Characterization
of a new mutation (R292G) and a deletion at the human uroporphyrinogen
decarboxylase locus in two patients with hepatoerythropoietic porphyria. Hum.
Genet. 89: 548-552, 1992.

4. de Verneuil, H.; Grandchamp, B.; Beaumont, C.; Picat, C.; Nordmann,
Y.: Uroporphyrinogen decarboxylase structural mutant (gly281-to-glu)
in a case of porphyria. Science 234: 732-734, 1986.

5. de Verneuil, H.; Grandchamp, B.; Foubert, C.; Weil, D.; Van Cong,
N.; Gross, M.-S.; Sassa, S.; Nordmann, Y.: Assignment of the gene
for uroporphyrinogen decarboxylase to human chromosome 1 by somatic
cell hybridization and specific enzyme immunoassay. Hum. Genet. 66:
202-205, 1984.

6. de Verneuil, H.; Grandchamp, B.; Romeo, P. H.; Raich, N.; Beaumont,
C.; Goossens, M.; Nicolas, H.; Nordmann, Y.: Molecular analysis of
uroporphyrinogen decarboxylase deficiency in a family with two cases
of hepatoerythropoietic porphyria. J. Clin. Invest. 77: 431-435,
1986.

7. de Verneuil, H.; Hansen, J.; Picat, C.; Grandchamp, B.; Kushner,
J.; Roberts, A.; Elder, G.; Nordmann, Y.: Prevalence of the 281 (gly-to-glu)
mutation in hepatoerythropoietic porphyria and porphyria cutanea tarda. Hum.
Genet. 78: 101-102, 1988.

8. Dubart, A.; Mattei, M. G.; Raich, N.; Beaupain, D.; Romeo, P. H.;
Mattei, J. F.; Goossens, M.: Assignment of human uroporphyrinogen
decarboxylase (URO-D) to the p34 band of chromosome 1. Hum. Genet. 73:
277-279, 1986.

9. Garey, J. R.; Hansen, J. L.; Harrison, L. M.; Kennedy, J. B.; Kushner,
J. P.: A point mutation in the coding region of uroporphyrinogen
decarboxylase associated with familial porphyria cutanea tarda. Blood 73:
892-895, 1989.

10. Garey, J. R.; Hansen, J. L.; Kushner, J. P.: The molecular basis
of familial porphyria cutanea tarda (F-PCT). (Abstract) Clin. Res. 36:
612A, 1988.

11. Garey, J. R.; Harrison, L. M.; Franklin, K. F.; Metcalf, K. M.;
Radisky, E. S.; Kushner, J. P.: Uroporphyrinogen decarboxylase: a
splice site mutation causes the deletion of exon 6 in multiple families
with porphyria cutanea tarda. J. Clin. Invest. 86: 1416-1422, 1990.

12. Mattei, M. G.; Dubart, A.; Beaupain, D.; Goossens, M.; Mattei,
J. F.: Localization of the uroporphyrinogen decarboxylase gene to
1p34 band, by in situ hybridization. (Abstract) Cytogenet. Cell Genet. 40:
692, 1985.

13. McLellan, T.; Pryor, M. A.; Kushner, J. P.; Eddy, R. L.; Shows,
T. B.: Assignment of uroporphyrinogen decarboxylase (UROD) to the
pter-p21 region of human chromosome 1. Cytogenet. Cell Genet. 39:
224-227, 1985.

14. Mendez, M.; Sorkin, L.; Rossetti, M. V.; Astrin, K. H.; Batlle,
A. M. del C.; Parera, V. E.; Aizencang, G.; Desnick, R. J.: Familial
porphyria cutanea tarda: characterization of seven novel uroporphyrinogen
decarboxylase mutations and frequency of common hemochromatosis alleles. Am.
J. Hum. Genet. 63: 1363-1375, 1998.

15. Moran-Jimenez, M. J.; 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. 58: 712-721, 1996.

16. Roberts, A. G.; Elder, G. H.; De Salamanca, R. E.; Herrero, C.;
Lecha, M.; Mascaro, J. M.: A mutation (G281E) of the human uroporphyrinogen
decarboxylase gene causes both hepatoerythropoietic porphyria and
overt familial porphyria cutanea tarda: biochemical and genetic studies
on Spanish patients. J. Invest. Derm. 104: 500-502, 1995.

17. Romana, M.; Dubart, A.; Beaupain, D.; Chabret, C.; Goossens, M.;
Romeo, P.-H.: Structure of the gene for human uroporphyrinogen decarboxylase. Nucleic
Acids Res. 15: 7343-7356, 1987.

18. Romana, M.; Grandchamp, B.; Dubart, A.; Amselem, S.; Chabret,
C.; Nordmann, Y.; Goossens, M.; Romeo, P.-H.: Identification of a
new mutation responsible for hepatoerythropoietic porphyria. Europ.
J. Clin. Invest. 21: 225-229, 1991.

19. Romeo, P.-H.; 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. 261: 9825-9831, 1986.

20. Sassa, S.; de Verneuil, H.; Anderson, K. E.; Kappas, A.: Purification
and properties of human erythrocyte uroporphyrinogen decarboxylase:
immunological demonstration of the enzyme defect in porphyria cutanea
tarda. Trans. Assoc. Am. Phys. 96: 65-75, 1983.

*FIELD* CN
Jumana Al-Aama - updated: 9/11/2013

*FIELD* CD
Carol A. Bocchini: 8/6/2010

*FIELD* ED
carol: 09/11/2013
carol: 9/11/2013
carol: 8/21/2013
carol: 8/6/2010