RBCC Red Blood Cell Collection

APRT [Confidence: low (only semi-automatic identification from reviews)]
Adenine phosphoribosyltransferase; APRT; 2.4.2.7
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P07741
ID APT_HUMAN Reviewed; 180 AA.
AC P07741; G5E9J2; Q3KP55; Q68DF9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Adenine phosphoribosyltransferase;
DE Short=APRT;
DE EC=2.4.2.7;
GN Name=APRT;
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 [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=3684585; DOI=10.1093/nar/15.21.9086;
RA Hidaka Y., Tarle S.A., Toole T.E.O., Kelley W.N., Palella T.D.;
RT "Nucleotide sequence of the human APRT gene.";
RL Nucleic Acids Res. 15:9086-9086(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3554238; DOI=10.1073/pnas.84.10.3349;
RA Broderick T.P., Schaff D.A., Bertino A.M., Dush M.K., Tischfield J.A.,
RA Stambrook P.J.;
RT "Comparative anatomy of the human APRT gene and enzyme: nucleotide
RT sequence divergence and conservation of a nonrandom CpG dinucleotide
RT arrangement.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:3349-3353(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterine endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-121.
RG NIEHS SNPs program;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Astrocytoma;
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 [8]
RP PROTEIN SEQUENCE OF 2-180.
RX PubMed=3531209;
RA Wilson J.M., O'Toole T.E., Argos P., Shewach D.S., Daddona P.E.,
RA Kelley W.N.;
RT "Human adenine phosphoribosyltransferase. Complete amino acid sequence
RT of the erythrocyte enzyme.";
RL J. Biol. Chem. 261:13677-13683(1986).
RN [9]
RP PROTEIN SEQUENCE OF 2-12, AND ACETYLATION AT ALA-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, 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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-4; SER-15; TYR-60; SER-66 AND THR-135, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, 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 [15]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=15196008; DOI=10.1021/bi0360758;
RA Silva M., Silva C.H., Iulek J., Thiemann O.H.;
RT "Three-dimensional structure of human adenine
RT phosphoribosyltransferase and its relation to DHA-urolithiasis.";
RL Biochemistry 43:7663-7671(2004).
RN [16]
RP VARIANT APRTD VAL-65.
RX PubMed=1746557;
RA Chen J., Sahota A., Laxdal T., Scrine M., Bowman S., Cui C.,
RA Stambrook P.J., Tischfield J.A.;
RT "Identification of a single missense mutation in the adenine
RT phosphoribosyltransferase (APRT) gene from five Icelandic patients and
RT a British patient.";
RL Am. J. Hum. Genet. 49:1306-1311(1991).
RN [17]
RP VARIANT APRTD PRO-110.
RX PubMed=7915931; DOI=10.1093/hmg/3.5.817;
RA Sahota A., Chen J., Boyadjiev S.A., Gault M.H., Tischfield J.A.;
RT "Missense mutation in the adenine phosphoribosyltransferase gene
RT causing 2,8-dihydroxyadenine urolithiasis.";
RL Hum. Mol. Genet. 3:817-818(1994).
RN [18]
RP VARIANT APRTD THR-136.
RX PubMed=3680503; DOI=10.1172/JCI113219;
RA Hidaka Y., Palella T.D., O'Toole T.E., Tarle S.A., Kelley W.N.;
RT "Human adenine phosphoribosyltransferase. Identification of allelic
RT mutations at the nucleotide level as a cause of complete deficiency of
RT the enzyme.";
RL J. Clin. Invest. 80:1409-1415(1987).
RN [19]
RP VARIANTS APRTD THR-136 AND PHE-173 DEL.
RX PubMed=3343350; DOI=10.1172/JCI113408;
RA Hidaka Y., Tarle S.A., Fujimori S., Kamatani N., Kelley W.N.;
RT "Human adenine phosphoribosyltransferase deficiency. Demonstration of
RT a single mutant allele common to the Japanese.";
RL J. Clin. Invest. 81:945-950(1988).
RN [20]
RP VARIANT APRTD THR-136.
RX PubMed=1353080; DOI=10.1172/JCI115825;
RA Kamatani N., Hakoda M., Otsuka S., Yoshikawa H., Kashiwazaki S.;
RT "Only three mutations account for almost all defective alleles causing
RT adenine phosphoribosyltransferase deficiency in Japanese patients.";
RL J. Clin. Invest. 90:130-135(1992).
RN [21]
RP VARIANTS APRTD PHE-150 AND ARG-153.
RX PubMed=11243733; DOI=10.1006/mgme.2000.3142;
RA Deng L., Yang M., Fruend S., Wessel T., De Abreu R.A.,
RA Tischfield J.A., Sahota A.;
RT "2,8-Dihydroxyadenine urolithiasis in a patient with considerable
RT residual adenine phosphoribosyltransferase activity in cell extracts
RT but with mutations in both copies of APRT.";
RL Mol. Genet. Metab. 72:260-264(2001).
RN [22]
RP VARIANTS APRTD MET-84 AND ASP-133.
RX PubMed=15571218; DOI=10.1081/NCN-200027393;
RA Taniguchi A., Tsuchida S., Kuno S., Mita M., Machida T., Ioritani N.,
RA Terai C., Yamanaka H., Kamatani N.;
RT "Identification of two novel mutations in adenine
RT phosphoribosyltransferase gene in patients with 2,8-dihydroxyadenine
RT urolithiasis.";
RL Nucleosides Nucleotides Nucleic Acids 23:1141-1145(2004).
RN [23]
RP VARIANTS APRTD PRO-33 AND THR-136.
RX PubMed=21635362; DOI=10.1111/j.1651-2227.2011.02371.x;
RA Nozue H., Kamoda T., Saitoh H., Ichikawa K., Taniguchi A.;
RT "A Japanese boy with adenine phosphoribosyltransferase (APRT)
RT deficiency caused by compound heterozygosity including a novel
RT missense mutation in APRT gene.";
RL Acta Paediatr. 100:E285-E288(2011).
CC -!- FUNCTION: Catalyzes a salvage reaction resulting in the formation
CC of AMP, that is energically less costly than de novo synthesis.
CC -!- CATALYTIC ACTIVITY: AMP + diphosphate = adenine + 5-phospho-alpha-
CC D-ribose 1-diphosphate.
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via salvage pathway;
CC AMP from adenine: step 1/1.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P07741-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P07741-2; Sequence=VSP_045705;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Adenine phosphoribosyltransferase deficiency (APRTD)
CC [MIM:614723]: An enzymatic deficiency that can lead to
CC urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine
CC (DHA) urinary stones. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the purine/pyrimidine
CC phosphoribosyltransferase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/APRT";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/aprt/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Adenine
CC phosphoribosyltransferase entry;
CC URL="http://en.wikipedia.org/wiki/Adenine_phosphoribosyltransferase";
CC -----------------------------------------------------------------------
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DR EMBL; Y00486; CAA68543.1; -; Genomic_DNA.
DR EMBL; M16446; AAA51769.1; -; Genomic_DNA.
DR EMBL; CR749423; CAH18261.1; -; mRNA.
DR EMBL; AY306126; AAP45051.1; -; Genomic_DNA.
DR EMBL; AC092384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471184; EAW66761.1; -; Genomic_DNA.
DR EMBL; BC107151; AAI07152.1; -; mRNA.
DR EMBL; BM550173; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; S06232; RTHUA.
DR RefSeq; NP_000476.1; NM_000485.2.
DR RefSeq; NP_001025189.1; NM_001030018.1.
DR UniGene; Hs.28914; -.
DR PDB; 1OPU; Model; -; A=1-180.
DR PDB; 1ORE; X-ray; 2.10 A; A=1-180.
DR PDB; 1ZN7; X-ray; 1.83 A; A/B=1-180.
DR PDB; 1ZN8; X-ray; 1.76 A; A/B=1-180.
DR PDB; 1ZN9; X-ray; 2.05 A; A/B=1-180.
DR PDBsum; 1OPU; -.
DR PDBsum; 1ORE; -.
DR PDBsum; 1ZN7; -.
DR PDBsum; 1ZN8; -.
DR PDBsum; 1ZN9; -.
DR ProteinModelPortal; P07741; -.
DR SMR; P07741; 2-180.
DR IntAct; P07741; 2.
DR MINT; MINT-4999823; -.
DR STRING; 9606.ENSP00000367615; -.
DR DrugBank; DB00173; Adenine.
DR DrugBank; DB00131; Adenosine monophosphate.
DR PhosphoSite; P07741; -.
DR DMDM; 114074; -.
DR SWISS-2DPAGE; P07741; -.
DR PaxDb; P07741; -.
DR PRIDE; P07741; -.
DR Ensembl; ENST00000378364; ENSP00000367615; ENSG00000198931.
DR Ensembl; ENST00000426324; ENSP00000397007; ENSG00000198931.
DR GeneID; 353; -.
DR KEGG; hsa:353; -.
DR UCSC; uc002flw.3; human.
DR CTD; 353; -.
DR GeneCards; GC16M088875; -.
DR HGNC; HGNC:626; APRT.
DR HPA; HPA026681; -.
DR MIM; 102600; gene.
DR MIM; 614723; phenotype.
DR neXtProt; NX_P07741; -.
DR Orphanet; 976; Adenine phosphoribosyltransferase deficiency.
DR PharmGKB; PA24914; -.
DR eggNOG; COG0503; -.
DR HOGENOM; HOG000036776; -.
DR HOVERGEN; HBG003144; -.
DR InParanoid; P07741; -.
DR KO; K00759; -.
DR OMA; YGLEYGK; -.
DR OrthoDB; EOG7FFMT9; -.
DR PhylomeDB; P07741; -.
DR BRENDA; 2.4.2.7; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P07741; -.
DR UniPathway; UPA00588; UER00646.
DR EvolutionaryTrace; P07741; -.
DR GeneWiki; Adenine_phosphoribosyltransferase; -.
DR GenomeRNAi; 353; -.
DR NextBio; 1453; -.
DR PRO; PR:P07741; -.
DR ArrayExpress; P07741; -.
DR Bgee; P07741; -.
DR CleanEx; HS_APRT; -.
DR Genevestigator; P07741; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0002055; F:adenine binding; IEA:Ensembl.
DR GO; GO:0003999; F:adenine phosphoribosyltransferase activity; TAS:Reactome.
DR GO; GO:0016208; F:AMP binding; IDA:MGI.
DR GO; GO:0006168; P:adenine salvage; IEA:Ensembl.
DR GO; GO:0044209; P:AMP salvage; IEA:UniProtKB-UniPathway.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0007625; P:grooming behavior; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0006144; P:purine nucleobase metabolic process; TAS:Reactome.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR GO; GO:0043101; P:purine-containing compound salvage; TAS:Reactome.
DR InterPro; IPR005764; Ade_phspho_trans.
DR InterPro; IPR000836; PRibTrfase_dom.
DR Pfam; PF00156; Pribosyltran; 1.
DR TIGRFAMs; TIGR01090; apt; 1.
DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation;
KW Glycosyltransferase; Phosphoprotein; Polymorphism; Purine salvage;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 180 Adenine phosphoribosyltransferase.
FT /FTId=PRO_0000149504.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 4 4 Phosphoserine.
FT MOD_RES 15 15 Phosphoserine.
FT MOD_RES 60 60 Phosphotyrosine.
FT MOD_RES 66 66 Phosphoserine.
FT MOD_RES 114 114 N6-acetyllysine.
FT MOD_RES 135 135 Phosphothreonine.
FT VAR_SEQ 134 180 GTMNAACELLGRLQAEVLECVSLVELTSLKGREKLAPVPFF
FT SLLQYE -> V (in isoform 2).
FT /FTId=VSP_045705.
FT VARIANT 33 33 L -> P (in APRTD).
FT /FTId=VAR_069049.
FT VARIANT 65 65 D -> V (in APRTD; Icelandic type).
FT /FTId=VAR_006747.
FT VARIANT 84 84 V -> M (in APRTD; dbSNP:rs200392753).
FT /FTId=VAR_069050.
FT VARIANT 110 110 L -> P (in APRTD; Newfoundland type).
FT /FTId=VAR_006748.
FT VARIANT 121 121 Q -> R (in dbSNP:rs8191494).
FT /FTId=VAR_019055.
FT VARIANT 133 133 G -> D (in APRTD).
FT /FTId=VAR_069051.
FT VARIANT 136 136 M -> T (in APRTD; Japanese type; allele
FT APRT*J; most common mutation;
FT dbSNP:rs28999113).
FT /FTId=VAR_006749.
FT VARIANT 150 150 V -> F (in APRTD).
FT /FTId=VAR_022608.
FT VARIANT 153 153 C -> R (in APRTD).
FT /FTId=VAR_022609.
FT VARIANT 173 173 Missing (in APRTD).
FT /FTId=VAR_037575.
FT HELIX 4 10
FT STRAND 14 17
FT STRAND 19 21
FT STRAND 25 28
FT HELIX 30 34
FT HELIX 36 54
FT STRAND 60 64
FT TURN 65 67
FT HELIX 68 79
FT STRAND 82 88
FT STRAND 94 103
FT STRAND 106 113
FT STRAND 122 133
FT HELIX 134 145
FT STRAND 149 159
FT HELIX 160 162
FT HELIX 164 168
FT STRAND 173 179
SQ SEQUENCE 180 AA; 19608 MW; CDC7703337A6E453 CRC64;
MADSELQLVE QRIRSFPDFP TPGVVFRDIS PVLKDPASFR AAIGLLARHL KATHGGRIDY
IAGLDSRGFL FGPSLAQELG LGCVLIRKRG KLPGPTLWAS YSLEYGKAEL EIQKDALEPG
QRVVVVDDLL ATGGTMNAAC ELLGRLQAEV LECVSLVELT SLKGREKLAP VPFFSLLQYE
//

MIM 102600
*RECORD*
*FIELD* NO
102600
*FIELD* TI
*102600 ADENINE PHOSPHORIBOSYLTRANSFERASE; APRT
*FIELD* TX

DESCRIPTION

The APRT gene encodes adenine phosphoribosyltransferase (EC 2.4.2.7), an
read moreenzyme that catalyzes the formation of AMP from adenine and
phosphoribosylpyrophosphate. APRT acts as a salvage enzyme for the
recycling of adenine into nucleic acids (summary by Broderick et al.,
1987).

CLONING

Wilson et al. (1986) determined the amino acid sequence of the APRT
protein. The enzyme has 179 residues with a calculated molecular weight
of 19.5 kD.

Broderick et al. (1987) determined the nucleotide sequence of the human
APRT gene. The APRT gene encodes a 180-amino acid protein (Tischfield
and Ruddle, 1974). Comparative analysis by Broderick et al. (1987)
showed that the amino acid sequence is highly conserved: the human
protein was 82% and 90% identical to the mouse and hamster sequences,
respectively. The gene is constitutively expressed and subject to
little, if any, regulation.

Hidaka et al. (1987) prepared a complete sequence of the APRT gene and
found a number of discrepancies from the sequence reported by Broderick
et al. (1987), all occurring within noncoding regions.

GENE STRUCTURE

Broderick et al. (1987) determined that the APRT gene is about 2.6 kb
long and contains 5 exons. The promoter region of the human APRT gene,
like that of several other housekeeping genes, lacks the 'TATA' and
'CCAAT' boxes but contains 5 GC boxes that are potential binding sites
for the Sp1 transcription factor. Broderick et al. (1987) found that CpG
dinucleotides in the APRT gene in species as widely separated in
evolution as man, mouse, hamster, and E. coli were conserved at a
frequency higher than expected on the basis of randomness considering
the G+C content of the gene. This suggested some importance of this
sequence to the function of the gene. Although the intron 1 sequences of
mouse and man had no apparent homology, both had retained a very high
CpG content.

MAPPING

By cell hybridization studies, Tischfield and Ruddle (1974) concluded
that the APRT locus is on chromosome 16. Marimo and Giannelli (1975)
confirmed this assignment by demonstrating a 1.69-fold increase in
enzyme level in trisomy 16 cells. The same cells showed no difference in
the levels of HGPRT (308000), G6PD (305900) or adenosine kinase (102750)
from controls.

Barg et al. (1982) assigned APRT to chromosome 16pter-q12. Lavinha et
al. (1984) assigned APRT and DIA4 (125860) to 16q12-q22 by study of
rearranged chromosomes 16 in somatic cell hybrids. For APRT,
Ferguson-Smith and Cox (1984) found a smallest region of overlap (SRO)
of 16q22.2-q22.3.

Fratini et al. (1986) mapped the APRT locus with respect to the HP
(140100) locus and the fragile site at 16q23.2 (FRA16D). A subclone of
the APRT gene and a cDNA clone of HP were used for molecular
hybridization to DNA from mouse-human hybrid cell lines containing
specific chromosome 16 translocations. The APRT subclone was used for in
situ hybridization to chromosomes expressing FRA16D. APRT was found to
be distal to HP and FRA16D and was localized at 16q24, making the gene
order cen--FRA16B--HP--FRA16D--APRT--qter.

MOLECULAR GENETICS

Mutant forms of adenine phosphoribosyltransferase resulting in enzyme
deficiency (APRTD; 614723) were described by Kelley et al. (1968) and by
Henderson et al. (1969), who found the inheritance to be autosomal. A
heat-stable enzyme allele had a frequency of about 15% and the
heat-labile enzyme allele a frequency of about 85%. Kelley et al. (1968)
found apparent heterozygosity in 4 persons in 3 generations of a family.
However, the level of enzyme activity ranged from 21 to 37%, not 50%.

In a lymphoblastoid cell line from a Caucasian patient in Belgium with
complete APRT deficiency (614723), Hidaka et al. (1987) identified
compound heterozygosity for 2 mutations in the APRT gene (102600.0001
and 102600.0002). Gathof et al. (1991) identified homozygosity for an
APRT mutation (102600.0002) in identical twin brothers born to
nonconsanguineous German parents with APRT deficiency. In 5 patients
from Iceland with complete APRT deficiency, Chen et al. (1990)
identified a homozygous mutation in the APRT gene (D65V; 102600.0004).

In Japanese, partial deficiency of APRT leads to 2,8-dihydroxyadenine
urolithiasis (type II), whereas all Caucasian patients with 2,8-DHA
urolithiasis have been completely deficient (type I). Fujimori et al.
(1985) found that partially purified enzyme from Japanese families has a
reduced affinity for phosphoribosylpyrophosphate (PRPP), as well as
increased resistance to heat and reduced sensitivity to the stabilizing
effect of PRPP. They referred to this common Japanese mutant allele as
APRT*J. In Japanese patients with APRT deficiency, Hidaka et al. (1988)
identified the molecular basis for the APRT*J allele: an M136T
(102600.0003) substitution in the putative PRPP-binding site. The mutant
enzyme showed abnormal kinetics and activity that was less than 10.3% of
normal. By a specific cleavage method using cyanogen bromide (BrCN) to
identify the M136T allele, Kamatani et al. (1989) found that 79% of all
Japanese patients with APRT deficiency and more than half of the world's
patients have this particular mutation.

Hakoda et al. (1990) made the interesting observation that 2-step
mutations leading to homozygous deficiencies at the somatic cell level,
as proposed by the Knudson hypothesis of carcinogenesis in
retinoblastoma (180200) and some other human tumors, occur at other
autosomal loci. They cloned and enumerated somatic T cells with
mutations at the APRT locus by taking advantage of the presence of
heterozygous APRT deficiency and an effective selection procedure for
homozygosity. They cultured peripheral blood mononuclear cells with
2,6-diaminopurine, an APRT-dependent cytotoxin, to search for in vivo
mutational cells. In all 4 heterozygotes studied, homozygously deficient
T cells were found, at an average frequency of 1.3 x 10(-4). Among 310
normal persons, Hakoda et al. (1990) identified only 1 homozygous
APRT-deficient clone, with a calculated frequency of 5.0 x 10(-9).
Homozygous cells were found at rather high frequencies in 15 putative
heterozygotes, as reported by Hakoda et al. (1991). Analysis of genomic
DNA in 82 resistant clones from 2 of the heterozygotes showed that 64
(78%) had lost the germinally intact alleles. This approach may prove
useful for identifying heterozygotes for other enzyme deficiencies.

CYTOGENETICS

Wang et al. (1999) described a Czech patient with Morquio syndrome
(253000) who also had deficiency of APRT leading to 2,8-dihydroxyadenine
urolithiasis. They pointed out that both GALNS (612222) and APRT are
located on 16q24.3, suggesting that the patient had a deletion involving
both genes. PCR amplification of genomic DNA indicated that a novel
junction was created by the fusion of sequences distal to GALNS exon 2
and proximal to APRT exon 3, and that the size of the deleted region was
approximately 100 kb. The deletion breakpoints were localized within
GALNS intron 2 and APRT intron 2. Several other genes, including CYBA
(608508), which is deleted or mutated in an autosomal form of chronic
granulomatous disease (233690), are located in the 16q24.3 region.
However, PCR amplification showed that the CYBA gene was present in the
proband. Fukuda et al. (1996) described a Japanese patient with a
submicroscopic deletion involving GALNS and APRT in one chromosome and a
point mutation (R386C; 253000.0003) in the other GALNS allele. Wang et
al. (1999) concluded that these findings indicated that APRT is located
telomeric to GALNS, that GALNS and APRT are transcribed in the same
orientation (centromeric to telomeric), and that combined APRT/GALNS
deficiency may be more common than hitherto realized.

ANIMAL MODEL

Engle et al. (1996) used targeted homologous recombination in embryonic
stem cells to produce mice that lack APRT. Mice homozygous for a null
Aprt allele excreted adenine and DHA crystals in their urine. Renal
histopathology showed extensive tubular dilation, inflammation,
necrosis, and fibrosis that varied in severity between different mouse
backgrounds.

*FIELD* AV
.0001
APRT DEFICIENCY
APRT, 3-BP DEL, 2179TTC

In a lymphoblastoid cell line from a Caucasian patient in Belgium with
complete APRT deficiency (614723), Hidaka et al. (1987) identified
compound heterozygosity for 2 mutations in the APRT gene: a 3-bp
deletion (2179delTTC) in exon 4, resulting in the deletion of codon
phe173, and a 1-bp insertion (1834insT) immediately adjacent to the
splice site at the 5-prime end of intron 4 (102600.0002). This insertion
led to aberrant splicing, the absence of exon 4, frameshift, and
premature termination at amino acid 110. The enzyme activity was less
than 1% of normal and the enzyme protein was immunologically
undetectable.

.0002
APRT DEFICIENCY
APRT, 1-BP INS, 1834T

See 102600.0001 and Hidaka et al. (1987).

In identical twin brothers born to nonconsanguineous German parents with
APRT deficiency (614723), Gathof et al. (1991) identified a homozygous
1-bp insertion in the splice donor site of intron 4 of the APRT gene
(the numbering system used by Gathof et al. (1991) indicated that the
insertion was between bases 1831 and 1832 or 1832 and 1833). The
insertion resulted in aberrant splicing. They quoted finding of the same
mutation in 2 other Caucasian patients living in the U.S., and as one of
2 alleles in a Belgian patient with compound heterozygous APRT mutations
(Hidaka et al., 1987).

Menardi et al. (1997) demonstrated homozygosity for this common T
insertion at the exon 4/intron 4 junction, resulting in the lack of exon
4 in the APRT mRNA. This common splice site mutation had always been
found in association with a TaqI RFLP, leading to the proposal that this
splice site mutation originated from a single event (Chen et al., 1993).
However, Menardi et al. (1997) found a patient with this mutation who
was negative for the TaqI RFLP. The position of this T insertion
suggested it was a hotspot for mutational events (Chen et al., 1993).

.0003
APRT DEFICIENCY, JAPANESE TYPE
APRT, MET136THR

This mutation has been designated APRT*J.

In Japanese patients with APRT deficiency (614723), Hidaka et al. (1988)
identified a 2069T-C transition in exon 5 of the APRT gene, resulting in
a met136-to-thr (M136T) substitution in the putative PRPP-binding site.
The mutant enzyme showed abnormal kinetics and activity that was less
than 10.3% of normal.

By a specific cleavage method using cyanogen bromide (BrCN) to identify
the M136T allele, Kamatani et al. (1989) found that 79% of all Japanese
patients with APRT deficiency and more than half of the world's patients
have this particular mutation.

Kamatani et al. (1990) found that 24 of 39 Japanese patients with
2,8-dihydroxyadenine urolithiasis had only APRT*J alleles. They found
that normal alleles occur in 4 major haplotypes, whereas all APRT*J
alleles occurred in only 2. They interpreted this as meaning that all
APRT*J alleles had a single origin and that this mutant sequence has
been maintained for a long time, as reflected in the frequency of the
recombinant alleles.

Sahota et al. (1991) described DHA-lithiasis in a Japanese patient with
APRT deficiency who was heterozygous for the M136T mutation. Enzyme
studies showed decreased overall activity, with decreased affinity for
PRPP. Lithiasis had previously only been observed in homozygotes. The
polyamine pathway is thought to be the major source of endogenous
adenine in man. Whether increased polyamine synthesis could lead to
increased adenine production and predispose to DHA-lithiasis in an APRT
heterozygote, remained to be determined.

Among 141 defective APRT alleles from 72 different Japanese families,
Kamatani et al. (1992) found the met136-to-thr mutation in 96 (68%).
Thirty (21%) and 10 (7%) alleles had the TGG-to-TGA nonsense mutation at
codon 98 (102600.0005) and duplication of a 4-bp sequence in exon 3
(102600.0006), respectively.

Kamatani et al. (1996) noted that the APRT*J mutation is distributed
nearly uniformly on the 4 main islands of Japan and Okinawa, suggesting
a very early origin. Among 955 random Japanese blood samples, 7 (0.73%)
were heterozygous for the APRT*J mutation. None of 231 Taiwanese samples
contained heterozygotes for this mutation, whereas 2 (0.53%) of 356
Korean samples were heterozygous. Since the APRT*J mutation was found in
Koreans and Okinawans who shared ancestors only before the Yayoi era
(3rd century B.C. to 3rd century A.D.), the origin of the APRT*J
mutation predates 300 B.C.

.0004
APRT DEFICIENCY
APRT, ASP65VAL

In 5 patients from Iceland with complete APRT deficiency (614723), Chen
et al. (1990) identified a homozygous 1350A-T transversion in exon 3 of
the APRT gene, resulting in an asp65-to-val (D65V) substitution. Common
ancestry could only be identified for 2 of the cases.

.0005
APRT DEFICIENCY
APRT, TRP98TER

In 4 unrelated Japanese individuals with complete APRT deficiency
(614723), Mimori et al. (1991) identified a 1453G-A transition in the
APRT gene, resulting in a trp98-to-ter (Y98X) substitution.

.0006
APRT DEFICIENCY
APRT, 4-BP DUP, EX3

Among 141 defective APRT alleles from 72 different Japanese families
with APRT deficiency (614723), Kamatani et al. (1992) found that 10 (7%)
had duplication of a CCGA sequence in exon 3. The duplication resulted
in an APRT*Q0 (null) allele. Two other alleles, APRT*J (102600.0003) and
trp98-to-ter (Y98X; 102600.0005), accounted for 68% and 21% mutant
alleles, respectively. The different alleles with the same mutation had
the same haplotype, except for APRT*J. Evidence for a crossover or a
gene conversion event within the APRT gene was observed in an APRT*J
mutant allele.

.0007
APRT DEFICIENCY
APRT, LEU110PRO

In 2 sisters from Newfoundland with APRT deficiency (614723), Sahota et
al. (1994) identified a homozygous mutation in the APRT gene, resulting
in a leu110-to-pro (L110P) substitution. One of the sisters exhibited
2,8-dihydroxyadenine urolithiasis, whereas the other was disease-free.

.0008
APRT DEFICIENCY
APRT, 254-BP DEL AND 8-BP INS

In a Caucasian patient with complete APRT deficiency (614723), Menardi
et al. (1997) found compound heterozygosity for 2 mutations in the APRT
gene: a common T insertion at the IVS4 splice donor site (102600.0002)
and a novel complex mutation involving simultaneous deletion/insertion
and repair events. The second mutation involved a deletion of 254 bp and
an insertion of 8 bp exactly at the site of the deletion. Downstream of
the mutations, Menardi et al. (1997) found a 14-bp sequence of inverse
complementary to this insertion and 6 flanking nucleotides. A more
detailed analysis of the region where the deletion had occurred revealed
several informative sequence features suitable to explain how the
mutation took place.

.0009
APRT DEFICIENCY
APRT, TER-SER

In a Japanese man with APRT deficiency (614723), Taniguchi et al. (1998)
found that the physiologic stop codon of the gene, TGA, was replaced by
TCA. This base substitution generated a new HinfI restriction site, and,
using PCR and subsequent digestion by this enzyme, they could confirm
that the patient was homozygous for the base substitution. The amount of
mRNA in transformed B cells was approximately one-quarter of that in
control subjects, and no APRT proteins were detected. In eukaryotes,
unlike prokaryotes, no rescue systems for defective polypeptide
termination caused by a missing stop codon have been found. Therefore,
the outcome of the defect in this patient was unclear from present
knowledge about termination of polypeptide synthesis. The stop codon was
changed to a serine codon and the reading frame was extended to the
poly(A) addition site. The poly(A) signal AGTAAA is located 213
nucleotides downstream of the physiologic stop codon, but there are no
stop codons between them (Broderick et al., 1987). The patient developed
pseudoarthrosis after a traumatic broken arm, and was found to have
increased serum creatinine and 2,8-dihydroxyadenine crystals in his
urine. Imaging showed a small right kidney.

*FIELD* SA
Doppler et al. (1981); Johnson et al. (1977); Kamatani et al. (1987);
Kamatani et al. (1987); Lester et al. (1980); Nesterova et al. (1987);
Sahota et al. (2001); Simon and Taylor (1983); Takeuchi et al. (1985)
*FIELD* RF
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Cell Genet. 32: 252-253, 1982.

2. Broderick, T. P.; Schaff, D. A.; Bertino, A. M.; Dush, M. K.; Tischfield,
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1987.

3. Chen, J.; Sahota, A.; Laxdal, T.; Stambrook, P. J.; Tischfield,
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mice develop 2,8-dihydroxyadenine nephrolithiasis. Proc. Nat. Acad.
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7. Ferguson-Smith, M. A.; Cox, D. R.: Report of the committee on
the genetic constitution of chromosomes 13, 14, 15, 16 and 17. Cytogenet.
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8. Fratini, A.; Simmers, R. N.; Callen, D. F.; Hyland, V. J.; Tischfield,
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human adenine phosphoribosyltransferase gene (APRT) distal to the
haptoglobin (HP) and fra(16)(q23) (FRA16D) loci. Cytogenet. Cell
Genet. 43: 10-13, 1986.

9. Fujimori, S.; Akaoka, I.; Sakamoto, K.; Yamanaka, H.; Nishioka,
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from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis
associated with partial enzyme deficiencies. Hum. Genet. 71: 171-176,
1985.

10. Fukuda, S.; Tomatsu, S.; Masuno, M.; Ogawa, T.; Yamagishi, A.;
Rezvi, G. M. M.; Sukegawa, K.; Shimozawa, N.; Suzuki, Y.; Kondo, N.;
Imaizumi, K.; Kuroki, Y.; Okabe, T.; Orii, T.: Mucopolysaccharidosis
IVA: submicroscopic deletion of 16q24.3 and a novel R386C mutation
of N-acetylgalactosamine-6-sulfate sulfatase gene in a classical Morquio
disease. Hum. Mutat. 7: 123-134, 1996.

11. Gathof, B. S.; Sahota, A.; Gresser, U.; Chen, J.; Stambrook, P.
J.; Tischfield, J. A.; Zollner, N.: Identification of a splice mutation
at the adenine phosphoribosyltransferase locus in a German family. Klin.
Wschr. 69: 1152-1155, 1991.

12. Hakoda, M.; Nishioka, K.; Kamatani, N.: Homozygous deficiency
at autosomal locus APRT in human somatic cells in vivo induced by
two different mechanisms. Cancer Res. 50: 1738-1741, 1990.

13. Hakoda, M.; Yamanaka, H.; Kamatani, N.; Kamatani, N.: Diagnosis
of heterozygous states for adenine phosphoribosyltransferase deficiency
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to screening of heterozygotes. Am. J. Hum. Genet. 48: 552-562, 1991.

14. Henderson, J. F.; Kelley, W. N.; Rosenbloom, F. M.; Seegmiller,
J. E.: Inheritance of purine phosphoribosyltransferases in man. Am.
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15. Hidaka, Y.; Palella, T. D.; O'Toole, T. E.; Tarle, S. A.; Kelley,
W. N.: Human adenine phosphoribosyltransferase: identification of
allelic mutations at the nucleotide level as a cause of complete deficiency
of the enzyme. J. Clin. Invest. 80: 1409-1415, 1987.

16. Hidaka, Y.; Tarle, S. A.; Fujimori, S.; Kamatani, N.; Kelley,
W. N.; Palella, T. D.: Human adenine phosphoribosyltransferase deficiency:
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Clin. Invest. 81: 945-950, 1988.

17. Hidaka, Y.; Tarle, S. A.; O'Toole, T. E.; Kelley, W. N.; Palella,
T. D.: Nucleotide sequence of the human APRT gene. Nucleic Acids
Res. 15: 9086, 1987.

18. Johnson, L. A.; Gordon, R. B.; Emmerson, B. T.: Adenine phosphoribosyltransferase:
a simple spectrophotometric assay and the incidence of mutation in
the normal population. Biochem. Genet. 15: 265-272, 1977.

19. Kamatani, N.; Hakoda, M.; Otsuka, S.; Yoshikawa, H.; Kashiwazaki,
S.: Only three mutations account for almost all defective alleles
causing adenine phosphoribosyltransferase deficiency in Japanese patients. J.
Clin. Invest. 90: 130-135, 1992.

20. Kamatani, N.; Kuroshima, S.; Hakoda, M.; Palella, T. D.; Hidaka,
Y.: Crossovers within a short DNA sequence indicate a long evolutionary
history of the APRT*J mutation. Hum. Genet. 85: 600-604, 1990.

21. Kamatani, N.; Kuroshima, S.; Terai, C.; Hidaka, Y.; Palella, T.
D.; Nishioka, K.: Detection of an amino acid substitution in the
mutant enzyme for a special type of adenine phosphoribosyltransferase
(APRT) deficiency by sequence-specific protein cleavage. Am. J. Hum.
Genet. 45: 325-331, 1989.

22. Kamatani, N.; Kuroshima, S.; Terai, C.; Kawai, K.; Mikanagi, K.;
Nishioka, K.: Selection of human cells having two different types
of mutations in individual cells (genetic/artificial mutants): application
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deficiency. Hum. Genet. 76: 148-152, 1987.

23. Kamatani, N.; Terai, C.; Kim, S. Y.; Chen, C.-L.; Yamanaka, H.;
Hakoda, M.; Totokawa, S.; Kashiwazaki, S.: The origin of the most
common mutation of adenine phosphoribosyltransferase among Japanese
goes back to a prehistoric era. Hum. Genet. 98: 596-600, 1996.

24. Kamatani, N.; Terai, C.; Kuroshima, S.; Nishioka, K.; Mikanagi,
K.: Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase
deficiencies. Hum. Genet. 75: 163-168, 1987.

25. Kelley, W. N.; Levy, R. I.; Rosenbloom, F. M.; Henderson, J. F.;
Seegmiller, J. E.: Adenine phosphoribosyltransferase deficiency:
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2281-2289, 1968.

26. Lavinha, J.; Morrison, N.; Glasgow, L.; Ferguson-Smith, M. A.
: Further evidence for the regional localization of human APRT and
DIA4 on chromosome 16. (Abstract) Cytogenet. Cell Genet. 37: 517
only, 1984.

27. Lester, S. C.; LeVan, S. K.; Steglich, C.; DeMars, R.: Expression
of human genes of adenine phosphoribosyltransferase and hypoxanthine-guanine
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with purified human DNA. Somat. Cell Genet. 6: 241-259, 1980.

28. Marimo, B.; Giannelli, F.: Gene dosage effect in human trisomy
16. Nature 256: 204-206, 1975.

29. Menardi, C.; Schneider, R.; Neuschmid-Kaspar, F.; Klocker, H.;
Hirsch-Kauffmann, M.; Auer, B.; Schweiger, M.: Human APRT deficiency:
indication for multiple origins of the most common Caucasian mutation
and detection of a novel type of mutation involving intrastrand-templated
repair. Hum. Mutat. 10: 251-255, 1997.

30. Mimori, A.; Hidaka, Y.; Wu, V. C.; Tarle, S. A.; Kamatani, N.;
Kelley, W. N.; Pallela, T. D.: A mutant allele common to the type
I adenine phosphoribosyltransferase deficiency in Japanese subjects. Am.
J. Hum. Genet. 48: 103-107, 1991.

31. Nesterova, T. B.; Borodin, P. M.; Zakian, S. M.; Serov, O. L.
: Assignment of the gene for adenine phosphoribosyltransferase on
the genetic map of mouse chromosome 8. Biochem. Genet. 25: 563-568,
1987.

32. Sahota, A.; Chen, J.; Behzadian, M. A.; Ravindra, R.; Takeuchi,
H.; Stambrook, P. J.; Tischfield, J. A.: 2,8-Dihydroxyadenine lithiasis
in a Japanese patient heterozygous at the adenine phosphoribosyltransferase
locus. Am. J. Hum. Genet. 48: 983-989, 1991.

33. Sahota, A.; Chen, J.; Boyadijev, S. A.; Gault, M. H.; Tischfield,
J. A.: Missense mutation in the adenine phosphoribosyltransferase
gene causing 2,8-dihydroxyadenine urolithiasis. Hum. Molec. Genet. 3:
817-818, 1994.

34. Sahota, A. S.; Tischfield, J. A.; Kamatani, N.; Simmonds, H. A.
: Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine
lithiasis.:In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle,
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Vol. II. New York: McGraw-Hill (8th ed.): 2001. Pp. 2571-2583.

35. Simon, A. E.; Taylor, M. W.: High-frequency mutation at the adenine
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36. Takeuchi, F.; Matsuta, K.; Miyamoto, T.; Enomoto, S.; Fujimori,
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1985.

37. Taniguchi, A.; Hakoda, M.; Yamanaka, H.; Terai, C.; Hikiji, K.;
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mutation abolishing the original stop codon of the human adenine phosphoribosyltransferase
(APRT) gene leads to complete loss of the enzyme protein. Hum. Genet. 102:
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38. Tischfield, J. A.; Ruddle, F. H.: Assignment of the gene for
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somatic cell hybridization. Proc. Nat. Acad. Sci. 71: 45-49, 1974.

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J. A.; Sahota, A.: Combined adenine phosphoribosyltransferase and
N-acetylgalactosamine-6-sulfate sulfatase deficiency. Molec. Genet.
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40. Wilson, J. M.; O'Toole, T. E.; Argos, P.; Shewach, D. S.; Daddona,
P. E.; Kelley, W. N.: Human adenine phosphoribosyltransferase: complete
amino acid sequence of the erythrocyte enzyme. J. Biol. Chem. 261:
13677-13683, 1986.

*FIELD* CN
Cassandra L. Kniffin - updated: 9/19/2012
Victor A. McKusick - updated: 1/6/2000
Victor A. McKusick - updated: 4/25/1998
Victor A. McKusick - updated: 4/1/1998
Victor A. McKusick - updated: 10/10/1997

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
carol: 09/18/2013
carol: 9/20/2012
ckniffin: 9/19/2012
carol: 4/22/2011
wwang: 12/28/2009
carol: 3/24/2009
carol: 3/23/2009
ckniffin: 9/24/2008
carol: 8/27/2008
alopez: 2/3/2006
terry: 5/17/2005
carol: 3/17/2004
ckniffin: 3/12/2004
cwells: 11/10/2003
mcapotos: 11/30/2000
terry: 10/6/2000
mgross: 1/11/2000
terry: 1/6/2000
terry: 4/29/1999
carol: 11/10/1998
alopez: 5/14/1998
carol: 5/2/1998
terry: 4/25/1998
alopez: 4/1/1998
terry: 3/23/1998
terry: 3/20/1998
jenny: 10/17/1997
terry: 10/10/1997
alopez: 6/3/1997
alopez: 5/13/1997
terry: 5/6/1997
carol: 7/6/1996
mark: 6/24/1996
terry: 6/12/1996
carol: 5/18/1996
mark: 1/17/1996
pfoster: 11/29/1994
mimadm: 4/14/1994
warfield: 4/6/1994
carol: 7/9/1993
carol: 2/17/1993
carol: 10/28/1992

MIM 614723
*RECORD*
*FIELD* NO
614723
*FIELD* TI
#614723 ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY; APRTD
;;APRT DEFICIENCY;;
UROLITHIASIS, 2,8-@DIHYDROXYADENINE;;
read moreUROLITHIASIS, DHA;;
NEPHROLITHIASIS, DHA
*FIELD* TX
A number sign (#) is used with this entry because adenine
phosphoribosyltransferase deficiency (APRTD) is caused by homozygous or
compound heterozygous mutation in the gene encoding adenine
phosphoribosyltransferase (APRT; 102600) on chromosome 16q24.

DESCRIPTION

APRT deficiency is an autosomal recessive metabolic disorder that can
lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA)
in the kidney, which results in crystalluria and the formation of
urinary stones. Clinical features include renal colic, hematuria,
urinary tract infection, dysuria, and, in some cases, renal failure. The
age at onset can range from 5 months to late adulthood; however, as many
as 50% of APRT-deficient individuals may be asymptomatic (summary by
Sahota et al., 2001).

Two types of APRT deficiency have been described based on the level of
residual enzyme activity in in vitro studies of erythrocytes. Type I
deficiency is characterized by complete enzyme deficiency in intact
cells and in cell lysates, whereas type II deficiency is characterized
by complete enzyme deficiency in intact cells, but only a partial
deficiency in cell lysates. Type II alleles show reduced affinity for
phosphoribosyl pyrophosphate (PRPP) compared to wildtype. In both types,
APRT activity is not functional in vivo. Type II deficiency is most
common among Japanese. Heterozygotes of either type do not appear to
have any clinical or biochemical abnormalities (summary by Sahota et
al., 2001).

CLINICAL FEATURES

Mutant forms of adenine phosphoribosyltransferase were described by
Kelley et al. (1968) and by Henderson et al. (1969) who found the
inheritance to be autosomal. The heat-stable enzyme allele has a
frequency of about 15% and the heat-labile enzyme allele a frequency of
about 85%. Kelley et al. (1968) found apparent heterozygosity in 4
persons in 3 generations of a family. However, the level of enzyme
activity in heterozygotes ranged from 21 to 37%, not 50%.

Fox et al. (1973) described a family with partial deficiency of red cell
APRT, consistent with a heterozygous state, although enzyme activity was
less than 50%. The partial deficiency of erythrocyte APRT was not
associated with any detectable abnormality in purine metabolism. The
proband had a normal concentration of PRPP and ATP in erythrocytes, a
normal availability of purine nucleotides, a normal rate of purine
biosynthesis de novo, a normal excretion of uric acid, and a normal
response to adenine administration. Although the proband had both
hyperuricemia and reduced erythrocyte APRT activity, these 2 traits
segregated independently in the family.

Delbarre et al. (1974) found deficiency of APRT in persons with gout but
recognized that purine overproduction was not necessarily caused by the
APRT deficiency.

Emmerson et al. (1975) described a family with autosomal inheritance of
APRT deficiency. The proband was a 24-year-old woman who had suffered
from recurrent gouty arthritis since the age of 11 years. She also
demonstrated considerable, although asymptomatic, renal impairment with
a creatinine clearance of one-third normal. Eleven other asymptomatic
members of the family also demonstrated a similar reduction in APRT
activity in erythrocyte lysates. The partially purified APRT enzyme in
the proband showed no difference in Michaelis constants, heat stability,
or electrophoresis.

Debray et al. (1976) observed a child with urolithiasis and complete
deficiency of APRT. Both parents had partial deficiency.

Van Acker et al. (1977) described brothers with complete deficiency of
APRT. They were detected because one of them had from birth excreted
gravel consisting of stones of 2,8-dihydroxyadenine in urine. Neither
showed hyperuricemia or gout. Treatment with allopurinol and a low
purine diet stopped stone formation. The authors concluded that
homozygotes can be detected by raised urinary adenine levels and absence
of detectable red cell APRT.

Barratt et al. (1979) reported a child, born of consanguineous Arab
parents, who had 2,8-dihydroxyadenine stones resulting from a complete
lack of APRT.

Gault et al. (1981) described 2,8-dihydroxyadenine urolithiasis in a
white woman who lived in Newfoundland and first developed symptoms of
urolithiasis at the age of 42. The authors noted that the use of
infrared or x-ray diffraction analysis of calculi positive for uric acid
with standard wet chemical tests can make the diagnosis. Affected adults
may first present with renal failure. Renal biopsy shows changes similar
to those of uric acid nephropathy.

Kishi et al. (1984) found only 10 reported cases of complete deficiency
of APRT, beginning with the case of Cartier et al. (1974). Kishi et al.
(1984) reported 3 cases in 2 families. Although APRT deficiency occurred
in mononuclear cells and polymorphonuclear leukocytes as well as in red
cells, no abnormality of immunologic or phagocytic function was
detected. The sole clinical manifestation was urinary calculi composed
of 2,8-DHA.

Manyak et al. (1987) found DHA-urolithiasis in a 50-year-old white woman
who was homozygous for APRT deficiency.

Glicklich et al. (1988) reported the second case of homozygous APRT
deficiency from the United States. The disorder was recognized 23 years
after the patient, a black woman from Bermuda, had her initial episode
of renal colic, and after 2,8-dihydroxyadenine stones had recurred after
renal transplant.

- APRT Deficiency in Japanese

Kamatani et al. (1987) examined samples from 19 Japanese families with
DHA-urolithiasis. In 15 (79%) of the 19 families, the patients had only
partial APRT deficiency, which contrasted with complete deficiency
reported in all non-Japanese patients. All Japanese patients with
DHA-urolithiasis were homozygotes regardless of whether the deficiency
was complete or partial. However, family studies revealed 4 asymptomatic
homozygous family members. The segregation pattern was consistent with
an autosomal recessive mode of inheritance. Kamatani et al. (1987)
estimated that about 1% of the Japanese population are carriers.

BIOCHEMICAL FEATURES

Rappaport and DeMars (1973) identified clones of cells resistant to
2,6-diaminopurine (DAP) in skin fibroblast cultures derived from 13 of
21 normal humans. In some of the mutant cultures adenine
phosphoribosyltransferase was normal. Two mutants from unrelated boys
had little or no detectable APRT activity, and resistance to DAP
resulted from reduced ability to convert DAP to its toxic ribonucleotide
via APRT. The authors reasoned that mutant-yielding cultures were
heterozygous to begin with, and suggested that DAP resistance has a
heterozygote frequency as high as 0.2. This contrasted with the very low
frequency of electrophoretic variants of APRT. There may be other
mechanisms for DAP-resistance: for example, azaguanine resistance is
determined by mutation at the X-linked HPRT locus.

DIAGNOSIS

Maddocks and Al-Safi (1988) used identification of adenine in the urine
by thin-layer chromatography to diagnose APRT deficiency.

Simmonds et al. (1992) pointed out that patients who are mistakenly
diagnosed as having uric acid lithiasis will be treated successfully
with allopurinol despite the incorrect diagnosis. This may be
responsible for underdiagnosis of the disorder. Families carrying the
mutant APRT gene need to be aware of it since acute renal failure may be
the presenting symptom and this may be reversible, though some patients
progress to chronic renal failure requiring dialysis and
transplantation. Maddocks (1992) described a simple test for
distinguishing uric acid calculi from 2,8-DHA calculi. Ward and Addison
(1992) indicated that even visual examination can distinguish the two:
2,8-DHA stones are reddish-brown when wet and grayish when dry; they are
also very soft and friable. Stones composed mainly of uric acid are very
rare in children.

Laxdal and Jonasson (1988) found 2 children and 2 adults in 4 unrelated
families with 2,8-dihydroxyadenine crystalluria. They suggested that the
presence of round, brownish urine crystals, even without radiolucent
kidney stones, should alert the physician to the diagnosis. Thirteen
heterozygotes were identified by study of the families.

Laxdal (1992) pointed out that Iceland contributed 8 of the 62
APRT-deficient type I homozygotes. The 8 cases were from 8 different
families. Although remote ancestral connections were identified, all 8
cases were detected by the finding of typical round reddish-brown
crystals in the urine on light microscopy. The importance of alert
laboratory technicians in making the diagnosis was emphasized.

Terai et al. (1995) detected homozygous APRT deficiency by the finding
of 2,8-dihydroxyadenine-like spherical crystals in the urinary sediment.
The molecular diagnosis was established using PCR-SSCP with the
demonstration of the APRT*J allele (102600.0003).

INHERITANCE

APRT deficiency is usually inherited in an autosomal recessive pattern
(Kamatani et al., 1987).

Ishidate et al. (1991) reported father and daughter with
DHA-urolithiasis. The father and his wife were first cousins; thus, this
was an example of pseudodominance.

MOLECULAR GENETICS

In a lymphoblastoid cell line from a Caucasian patient in Belgium with
complete APRT deficiency, Hidaka et al. (1987) identified compound
heterozygosity for 2 mutations in the APRT gene (102600.0001 and
102600.0002). Gathof et al. (1991) identified homozygosity for an APRT
mutation (102600.0002) in identical twin brothers born to
nonconsanguineous German parents with APRT deficiency.

In 5 patients from Iceland with complete APRT deficiency, Chen et al.
(1990) identified a homozygous mutation in the APRT gene (D65V;
102600.0004).

In Japanese, partial deficiency of APRT leads to 2,8-dihydroxyadenine
urolithiasis (type II), whereas all Caucasian patients with 2,8-DHA
urolithiasis have been completely deficient (type I). Fujimori et al.
(1985) found that partially purified enzyme from Japanese families has a
reduced affinity for phosphoribosylpyrophosphate (PRPP), as well as
increased resistance to heat and reduced sensitivity to the stabilizing
effect of PRPP. They referred to this common Japanese mutant allele as
APRT*J. In Japanese patients with APRT deficiency, Hidaka et al. (1988)
identified the molecular basis for the APRT*J allele: an M136T
(102600.0003) substitution in the putative PRPP-binding site. The mutant
enzyme showed abnormal kinetics and activity that was less than 10.3% of
normal. By a specific cleavage method using cyanogen bromide (BrCN) to
identify the M136T allele, Kamatani et al. (1989) found that 79% of all
Japanese patients with APRT deficiency and more than half of the world's
patients have this particular mutation.

Kamatani et al. (1990) reported a 2-year-old Japanese boy with DHA
urolithiasis due to compound heterozygosity for a null APRT allele
(APRT*Q0) and the APRT*J allele.

In 2 sisters from Newfoundland with APRT deficiency, Sahota et al.
(1994) identified a homozygous mutation in the APRT gene (L110P;
102600.0007). One of the sisters exhibited 2,8-dihydroxyadenine
urolithiasis, whereas the other was disease-free.

POPULATION GENETICS

Kamatani et al. (1992) stated that about 70 Japanese families with
homozygous APRT deficiency have been reported, whereas the number of
reported non-Japanese families is about 36. The estimated gene frequency
among Japanese is about 1.2%. Kamatani et al. (1992) found that most
APRT-deficient Japanese patients carry 1 of 3 mutant alleles. Among 141
defective APRT alleles from 72 different Japanese families, 96 (68%)
carried the M136T mutation (102600.0003). Thirty (21%) and 10 (7%)
alleles had the TGG-to-TGA nonsense mutation at codon 98 (102600.0005)
and duplication of a 4-bp sequence in exon 3 (102600.0006),
respectively.

*FIELD* SA
Doppler et al. (1981); Fox et al. (1977); Hakoda et al. (1991); Hirsch-Kauffmann
and Doppler (1981); Kamatani et al. (1987); Menardi et al. (1997);
Mimori et al. (1991); Sahota et al. (1991); Simmonds (1979); Takeuchi
et al. (1985); Taniguchi et al. (1998); Wang et al. (1999)
*FIELD* RF
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Rose, G. A.; Arkell, D. G.; Williams, D. I.: Complete deficiency
of adenine phosphoribosyltransferase: a third case presenting as renal
stones in a young child. Arch. Dis. Child. 54: 25-31, 1979.

2. Cartier, P.; Hamet, M.; Hamburger, J.: Une nouvelle maladie metabolique:
le deficit complet en adenine phosphoribosyltransferase avec lithiase
de 2,8-dihydroxyadenine. C. R. Seances Acad. Sci. 279: 883-886,
1974.

3. Chen, J.; Sahota, A.; Laxdal, T.; Stambrook, P. J.; Tischfield,
J. A.: Demonstration of a common mutation at the adenine phosphoribosyltransferase
(APRT) locus in the Icelandic population. (Abstract) Am. J. Hum.
Genet. 47 (suppl.): A152 only, 1990.

4. Debray, H.; Cartier, P.; Temstet, A.; Cendron, J.: Child's urinary
lithiasis revealing a complete deficit in adenine phosphoribosyl transferase. Pediat.
Res. 10: 762-766, 1976.

5. Delbarre, F.; Aucher, C.; Amor, B.; de Gery, A.; Cartier, P.; Hamet,
M.: Gout with adenine phosphoribosyltransferase deficiency. Biomedicine 21:
82-85, 1974.

6. Doppler, W.; Hirsch-Kauffmann, M.; Schabel, F.; Schweiger, M.:
Characterization of the biochemical basis of a complete deficiency
of the adenine phosphoribosyl transferase (APRT). Hum. Genet. 57:
404-410, 1981.

7. Emmerson, B. T.; Gordon, R. B.; Thompson, L.: Adenine phosphoribosyltransferase
deficiency: its inheritance and occurrence in a female with gout and
renal disease. Aust. New Zeal. J. Med. 5: 440-446, 1975.

8. Fox, I. H.; Lacroix, S.; Planet, G.; Moore, M.: Partial deficiency
of adenine phosphoribosyltransferase in man. Medicine 56: 515-526,
1977.

9. Fox, I. H.; Meade, J. C.; Kelley, W. N.: Adenine phosphoribosyltransferase
deficiency in man: report of a second family. Am. J. Med. 55: 614-619,
1973.

10. Fujimori, S.; Akaoka, I.; Sakamoto, K.; Yamanaka, H.; Nishioka,
K.; Kamatani, N.: Common characteristics of mutant adenine phosphoribosyltransferases
from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis
associated with partial enzyme deficiencies. Hum. Genet. 71: 171-176,
1985.

11. Gathof, B. S.; Sahota, A.; Gresser, U.; Chen, J.; Stambrook, P.
J.; Tischfield, J. A.; Zollner, N.: Identification of a splice mutation
at the adenine phosphoribosyltransferase locus in a German family. Klin.
Wschr. 69: 1152-1155, 1991.

12. Gault, M. H.; Simmonds, H. A.; Snedden, W.; Dow, D.; Churchill,
D. N.; Penney, H.: Urolithiasis due to 2,8-dihydroxyadenine in an
adult. New Eng. J. Med. 305: 1570-1572, 1981.

13. Glicklich, D.; Gruber, H. E.; Matas, A. J.; Tellis, V. A.; Karwa,
G.; Finley, K.; Salem, C.; Soberman, R.; Seegmiller, J. E.: 2,8-Dihydroxyadenine
urolithiasis: report of a case first diagnosed after renal transplant. Quart.
J. Med. (N.S.) 69: 785-793, 1988.

14. Hakoda, M.; Yamanaka, H.; Kamatani, N.; Kamatani, N.: Diagnosis
of heterozygous states for adenine phosphoribosyltransferase deficiency
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to screening of heterozygotes. Am. J. Hum. Genet. 48: 552-562, 1991.

15. Henderson, J. F.; Kelley, W. N.; Rosenbloom, F. M.; Seegmiller,
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J. Hum. Genet. 21: 61-70, 1969.

16. Hidaka, Y.; Palella, T. D.; O'Toole, T. E.; Tarle, S. A.; Kelley,
W. N.: Human adenine phosphoribosyltransferase: identification of
allelic mutations at the nucleotide level as a cause of complete deficiency
of the enzyme. J. Clin. Invest. 80: 1409-1415, 1987.

17. Hidaka, Y.; Tarle, S. A.; Fujimori, S.; Kamatani, N.; Kelley,
W. N.; Palella, T. D.: Human adenine phosphoribosyltransferase deficiency:
demonstration of a single mutant allele common to the Japanese. J.
Clin. Invest. 81: 945-950, 1988.

18. Hirsch-Kauffmann, M.; Doppler, W.: Biochemical studies on a patient
with complete APRT-deficiency. (Abstract) Sixth Int. Cong. Hum. Genet.,
Jerusalem 96 only, 1981.

19. Ishidate, T.; Igarashi, S.; Kamatani, N.: Pseudodominant transmission
of an autosomal recessive disease, adenine phosphoribosyltransferase
deficiency. J. Pediat. 118: 90-91, 1991.

20. Kamatani, N.; Hakoda, M.; Otsuka, S.; Yoshikawa, H.; Kashiwazaki,
S.: Only three mutations account for almost all defective alleles
causing adenine phosphoribosyltransferase deficiency in Japanese patients. J.
Clin. Invest. 90: 130-135, 1992.

21. Kamatani, N.; Kuroshima, S.; Terai, C.; Hidaka, Y.; Palella, T.
D.; Nishioka, K.: Detection of an amino acid substitution in the
mutant enzyme for a special type of adenine phosphoribosyltransferase
(APRT) deficiency by sequence-specific protein cleavage. Am. J. Hum.
Genet. 45: 325-331, 1989.

22. Kamatani, N.; Kuroshima, S.; Terai, C.; Kawai, K.; Mikanagi, K.;
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of mutations in individual cells (genetic/artificial mutants): application
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deficiency. Hum. Genet. 76: 148-152, 1987.

23. Kamatani, N.; Kuroshima, S.; Yamanaka, H.; Nakashe, S.; Take,
H.; Hakoda, M.: Identification of a compound heterozygote for adenine
phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine
urolithiasis. Hum. Genet. 85: 500-504, 1990.

24. Kamatani, N.; Terai, C.; Kuroshima, S.; Nishioka, K.; Mikanagi,
K.: Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase
deficiencies. Hum. Genet. 75: 163-168, 1987.

25. Kelley, W. N.; Levy, R. I.; Rosenbloom, F. M.; Henderson, J. F.;
Seegmiller, J. E.: Adenine phosphoribosyltransferase deficiency:
a previously undescribed genetic defect in man. J. Clin. Invest. 47:
2281-2289, 1968.

26. Kishi, T.; Kidani, K.; Komazawa, Y.; Sakura, N.; Matsuura, R.;
Kobayashi, M.; Tanabe, A.; Hyodo, S.; Kittaka, E.; Sakano, T.; Tanaka,
Y.; Kobayashi, Y.; Nakamoto, T.; Nakatsu, H.; Moriyama, H.; Hayashi,
M.; Nihira, H.; Usui, T.: Complete deficiency of adenine phosphoribosyltransferase:
a report of three cases and immunologic and phagocytic investigations. Pediat.
Res. 18: 30-34, 1984.

27. Laxdal, T.: 2,8-Dihydroxyadenine crystalluria vs urolithiasis.
(Letter) Lancet 340: 184 only, 1992.

28. Laxdal, T.; Jonasson, T. A.: Adenine phosphoribosyltransferase
deficiency in Iceland. Acta Med. Scand. 224: 621-626, 1988.

29. Maddocks, J. L.: 2,8-Dihydroxyadenine urolithiasis. (Letter) Lancet 339:
1296 only, 1992.

30. Maddocks, J. L.; Al-Safi, S. A.: Adenine phosphoribosyltransferase
deficiency: a simple diagnostic test. Clin. Sci. 75: 217-220, 1988.

31. Manyak, M. J.; Frensilli, F. J.; Miller, H. C.: 2,8-Dihydroxyadenine
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312-314, 1987.

32. Menardi, C.; Schneider, R.; Neuschmid-Kaspar, F.; Klocker, H.;
Hirsch-Kauffmann, M.; Auer, B.; Schweiger, M.: Human APRT deficiency:
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33. Mimori, A.; Hidaka, Y.; Wu, V. C.; Tarle, S. A.; Kamatani, N.;
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J. Hum. Genet. 48: 103-107, 1991.

34. Rappaport, H.; DeMars, R.: Diaminopurine-resistant mutants of
cultured, diploid human fibroblasts. Genetics 75: 335-345, 1973.

35. Sahota, A.; Chen, J.; Behzadian, M. A.; Ravindra, R.; Takeuchi,
H.; Stambrook, P. J.; Tischfield, J. A.: 2,8-Dihydroxyadenine lithiasis
in a Japanese patient heterozygous at the adenine phosphoribosyltransferase
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36. Sahota, A.; Chen, J.; Boyadijev, S. A.; Gault, M. H.; Tischfield,
J. A.: Missense mutation in the adenine phosphoribosyltransferase
gene causing 2,8-dihydroxyadenine urolithiasis. Hum. Molec. Genet. 3:
817-818, 1994.

37. Sahota, A. S.; Tischfield, J. A.; Kamatani, N.; Simmonds, H. A.
: Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine
lithiasis.:In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle,
D. (eds.): The Metabolic and Molecular Bases of Inherited Disease.
Vol. II. New York: McGraw-Hill (8th ed.): 2001. Pp. 2571-2583.

38. Simmonds, H. A.: 2,8-Dihydroxyadeninuria--or when is a uric acid
stone not a uric acid stone? Clin. Nephrol. 12: 195-197, 1979.

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diagnosis of partial adenine phosphoribosyltransferase deficiencies
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1985.

41. Taniguchi, A.; Hakoda, M.; Yamanaka, H.; Terai, C.; Hikiji, K.;
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(Letter) Lancet 339: 1296, 1992.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GENITOURINARY:
[Kidneys];
Renal failure;
[Ureters];
Urolithiasis

LABORATORY ABNORMALITIES:
APRT deficiency measured in erythrocyte lysate;
2,8-dihydroxyadenine (DHA) urinary stones;
Round, yellow-brown DHA urine crystals

MISCELLANEOUS:
Type I patients have undetectable APRT activity and are homozygous
or compound heterozygous for null alleles;
Type II patients are usually Japanese and have significant APRT activity
(10-25%);
Approximately 85% of type II patients are homozygous for a missense
mutation M136T (102600.0003)

MOLECULAR BASIS:
Caused by mutation in the adenine phosphoribosyltransferase gene (APRT,
102600.0001)

*FIELD* CN
Ada Hamosh - reviewed: 5/15/2000
Kelly A. Przylepa - revised: 2/18/2000

*FIELD* ED
joanna: 09/21/2012
ckniffin: 9/19/2012
joanna: 5/15/2000
kayiaros: 2/25/2000
kayiaros: 2/18/2000

*FIELD* CN
Victor A. McKusick - updated: 1/6/2000
Victor A. McKusick - updated: 4/25/1998

*FIELD* CD
Cassandra L. Kniffin: 7/17/2012

*FIELD* ED
carol: 09/20/2012
ckniffin: 9/19/2012