RBCC Red Blood Cell Collection

SLC37A4 (G6PT, G6PT1) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glucose-6-phosphate translocase (Glucose-5-phosphate transporter; Solute carrier family 37 member 4; Transformation-related gene 19 protein; TRG-19)

Comments
Isoform O43826-2 was detected.

UniProt O43826
ID G6PT1_HUMAN Reviewed; 429 AA.
AC O43826; O96016; Q5J7V4; Q9UI19; Q9UNS4;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1998, sequence version 1.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Glucose-6-phosphate translocase;
DE AltName: Full=Glucose-5-phosphate transporter;
DE AltName: Full=Solute carrier family 37 member 4;
DE AltName: Full=Transformation-related gene 19 protein;
DE Short=TRG-19;
GN Name=SLC37A4; Synonyms=G6PT, G6PT1; ORFNames=PRO0685, TRG19;
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] (ISOFORM 1), AND VARIANT GSD1B CYS-339.
RC TISSUE=Urinary bladder;
RX PubMed=9428641; DOI=10.1016/S0014-5793(97)01463-4;
RA Gerin I., Veiga-Da-Cunha M., Achouri Y., Collet J.-F.,
RA van Schaftingen E.;
RT "Sequence of a putative glucose 6-phosphate translocase, mutated in
RT glycogen storage disease type Ib.";
RL FEBS Lett. 419:235-238(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT GSD1B
RP ARG-118.
RX PubMed=9856496; DOI=10.1007/s004390050856;
RA Ihara K., Kuromaru R., Hara T.;
RT "Genomic structure of the human glucose 6-phosphate translocase gene
RT and novel mutations in the gene of a Japanese patient with glycogen
RT storage disease type Ib.";
RL Hum. Genet. 103:493-496(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, VARIANT GSD1B HIS-28, AND
RP CHARACTERIZATION OF VARIANT HIS-28.
RC TISSUE=Liver;
RX PubMed=10026167; DOI=10.1074/jbc.274.9.5532;
RA Hiraiwa H., Pan C.-J., Lin B., Moses S.W., Chou J.Y.;
RT "Inactivation of the glucose 6-phosphate transporter causes glycogen
RT storage disease type 1b.";
RL J. Biol. Chem. 274:5532-5536(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Ouyang S., Luo L., Wei H., Zhou G.,
RA Zhang Y., Liu M., He F.;
RT "Functional prediction of the coding sequences of 9 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Li Y., van de Werve G.;
RT "Four different transcripts of putative glucose-6-phosphate
RT translocase in human leukocytes.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=10023055; DOI=10.1016/S0378-1119(98)00614-3;
RA Gerin I., Veiga-Da-Cunha M., Noel G., Van Schaftingen E.;
RT "Structure of the gene mutated in glycogen storage disease type Ib.";
RL Gene 227:189-195(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10323254; DOI=10.1007/s004390050948;
RA Janecke A.R., Bosshard N.U., Mayatepek E., Schulze A., Gitzelmann R.,
RA Burchell A., Bartram C.R., Janssen B.;
RT "Molecular diagnosis of type 1c glycogen storage disease.";
RL Hum. Genet. 104:275-277(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human transformation gene.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Eye, and Lung;
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 [11]
RP REVIEW ON GSD1B VARIANTS, AND VARIANTS GSD1B HIS-28; PRO-85; ASN-278;
RP ASP-339 AND ASP-373.
RX PubMed=11949931;
RA Chou J.Y., Matern D., Mansfield B.C., Chen Y.-T.;
RT "Type I glycogen storage diseases: disorders of the glucose-6-
RT phosphatase complex.";
RL Curr. Mol. Med. 2:121-143(2002).
RN [12]
RP VARIANTS GSD1B ASP-20; CYS-28; ARG-55; ARG-68; ASP-88 AND ARG-150, AND
RP VARIANT ILE-198.
RX PubMed=9758626; DOI=10.1086/302068;
RA Veiga-da-Cunha M., Gerin I., Chen Y.-T., de Barsy T., de Lonlay P.,
RA Dionisi-Vici C., Fenske C.D., Lee P.J., Leonard J.V., Maire I.,
RA McConkie-Rosell A., Schweitzer S., Vikkula M., Van Schaftingen E.;
RT "A gene on chromosome 11q23 coding for a putative glucose-6-phosphate
RT translocase is mutated in glycogen-storage disease types Ib and Ic.";
RL Am. J. Hum. Genet. 63:976-983(1998).
RN [13]
RP VARIANT GSD1B HIS-300.
RX PubMed=9781688; DOI=10.1016/S0014-5793(98)01129-6;
RA Marcolongo P., Barone V., Priori G., Pirola B., Giglio S.,
RA Biasucci G., Zammarchi E., Parenti G., Burchell A., Benedetti A.,
RA Sorrentino V.;
RT "Structure and mutation analysis of the glycogen storage disease type
RT 1b gene.";
RL FEBS Lett. 436:247-250(1998).
RN [14]
RP ERRATUM.
RA Marcolongo P., Barone V., Priori G., Giglio S., Benedetti A.,
RA Sorrentino V.;
RL FEBS Lett. 445:451-451(1999).
RN [15]
RP VARIANTS GSD1B ARG-50; ARG-176; ARG-183 AND CYS-300, AND VARIANTS
RP GSD1C PRO-133 AND SER-376.
RX PubMed=10482962; DOI=10.1038/sj.ejhg.5200366;
RA Veiga-da-Cunha M., Gerin I., Chen Y.-T., Lee P.J., Leonard J.V.,
RA Maire I., Wendel U., Vikkula M., Van Schaftingen E.;
RT "The putative glucose 6-phosphate translocase gene is mutated in
RT essentially all cases of glycogen storage disease type I non-a.";
RL Eur. J. Hum. Genet. 7:717-723(1999).
RN [16]
RP VARIANT GSD1B THR-367.
RX PubMed=10518030; DOI=10.1016/S0014-5793(99)01248-X;
RA Galli L., Orrico A., Marcolongo P., Fulceri R., Burchell A., Melis D.,
RA Parini R., Gatti R., Lam C.-W., Benedetti A., Sorrentino V.;
RT "Mutations in the glucose-6-phosphate transporter (G6PT) gene in
RT patients with glycogen storage diseases type 1b and 1c.";
RL FEBS Lett. 459:255-258(1999).
RN [17]
RP VARIANT GSD1B ARG-118.
RX PubMed=9675154; DOI=10.1006/bbrc.1998.8985;
RA Kure S., Suzuki Y., Matsubara Y., Sakamoto O., Shintaku H.,
RA Isshiki G., Hoshida C., Izumi I., Sakura N., Narisawa K.;
RT "Molecular analysis of glycogen storage disease type Ib:
RT identification of a prevalent mutation among Japanese patients and
RT assignment of a putative glucose-6-phosphate translocase gene to
RT chromosome 11.";
RL Biochem. Biophys. Res. Commun. 248:426-431(1998).
RN [18]
RP VARIANTS GSD1B ARG-118 AND VAL-235 DEL.
RX PubMed=10482875;
RX DOI=10.1002/(SICI)1096-8628(19990917)86:3<253::AID-AJMG11>3.0.CO;2-7;
RA Hou D.-C., Kure S., Suzuki Y., Hasegawa Y., Hara Y., Inoue T.,
RA Kida Y., Matsubara Y., Narisawa K.;
RT "Glycogen storage disease type Ib: structural and mutational analysis
RT of the microsomal glucose-6-phosphate transporter gene.";
RL Am. J. Med. Genet. 86:253-257(1999).
RN [19]
RP VARIANT GSD1B GLU-149.
RA Lam C.-W., Tong S.-F., Lam Y.-Y., Chan B.-Y., Ma C.-H., Lim P.-L.;
RT "Identification of a novel missense mutation (G149E) in the glucose-6-
RT phosphate translocase gene in a Chinese family with glycogen storage
RT disease 1b.";
RL Hum. Mutat. 13:507-507(1999).
RN [20]
RP VARIANT GSD1B ARG-54.
RX PubMed=11071391; DOI=10.1007/s004390000371;
RA Janecke A.R., Lindner M., Erdel M., Mayatepek E., Moeslinger D.,
RA Podskarbi T., Fresser F., Stoeckler-Ipsiroglu S., Hoffmann G.F.,
RA Utermann G.;
RT "Mutation analysis in glycogen storage disease type 1 non-a.";
RL Hum. Genet. 107:285-289(2000).
RN [21]
RP VARIANT GSD1B LEU-191.
RX PubMed=10874322;
RX DOI=10.1002/1098-1004(200007)16:1<94::AID-HUMU26>3.0.CO;2-Q;
RA Lam C.-W., Chan K.-Y., Tong S.-F., Chan B.Y., Chan Y.-T., Chan Y.-W.;
RT "A novel missense mutation (P191L) in the glucose-6-phosphate
RT translocase gene identified in a Chinese family with glycogen storage
RT disease 1b.";
RL Hum. Mutat. 16:94-94(2000).
RN [22]
RP VARIANTS GSD1B LYS-27; LEU-153 AND PRO-301.
RX PubMed=10923042;
RX DOI=10.1002/1098-1004(200008)16:2<177::AID-HUMU13>3.0.CO;2-8;
RA Santer R., Rischewski J., Block G., Kinner M., Wendel U., Schaub J.,
RA Schneppenheim R.;
RT "Molecular analysis in glycogen storage disease 1 non-A: DHPLC
RT detection of the highly prevalent exon 8 mutations of the G6PT1 gene
RT in German patients.";
RL Hum. Mutat. 16:177-177(2000).
RN [23]
RP VARIANT GSD1B ASP-339.
RX PubMed=10931421; DOI=10.1067/mpd.2000.107472;
RA Kure S., Hou D.-C., Suzuki Y., Yamagishi A., Hiratsuka M., Fukuda T.,
RA Sugie H., Kondo N., Matsubara Y., Narisawa K.;
RT "Glycogen storage disease type Ib without neutropenia.";
RL J. Pediatr. 137:253-256(2000).
RN [24]
RP VARIANT GSD1B HIS-24.
RX PubMed=12409273; DOI=10.1016/S1096-7192(02)00110-5;
RA Yuen Y.-P., Cheng W.-F., Tong S.-F., Chan Y.-T., Chan Y.-W.,
RA Lam C.-W.;
RT "Novel missense mutation (Y24H) in the G6PT1 gene causing glycogen
RT storage disease type 1b.";
RL Mol. Genet. Metab. 77:249-251(2002).
RN [25]
RP VARIANT GSD1B PRO-229.
RX PubMed=15669677; DOI=10.1023/B:BOLI.0000042987.43395.c6;
RA Trioche P., Petit F., Francoual J., Gajdos V., Capel L., Poues C.,
RA Labrune P.;
RT "Allelic heterogeneity of glycogen storage disease type Ib in French
RT patients: a study of 11 cases.";
RL J. Inherit. Metab. Dis. 27:621-623(2004).
RN [26]
RP VARIANT GSD1B ARG-118.
RX PubMed=15059622; DOI=10.1016/j.ymgme.2003.12.004;
RA Kojima K., Kure S., Kamada F., Hao K., Ichinohe A., Sato K., Aoki Y.,
RA Yoichi S., Kubota M., Horikawa R., Utsumi A., Miura M., Ogawa S.,
RA Kanazawa M., Kohno Y., Inokuchi M., Hasegawa T., Narisawa K.,
RA Matsubara Y.;
RT "Genetic testing of glycogen storage disease type Ib in Japan: five
RT novel G6PT1 mutations and a rapid detection method for a prevalent
RT mutation W118R.";
RL Mol. Genet. Metab. 81:343-346(2004).
RN [27]
RP VARIANT GSD1B VAL-148.
RX PubMed=15953877; DOI=10.3346/jkms.2005.20.3.499;
RA Han S.H., Ki C.S., Lee J.E., Hong Y.J., Son B.K., Lee K.H., Choe Y.H.,
RA Lee S.Y., Kim J.W.;
RT "A novel mutation (A148V) in the glucose 6-phosphate translocase
RT (SLC37A4) gene in a Korean patient with glycogen storage disease type
RT 1b.";
RL J. Korean Med. Sci. 20:499-501(2005).
RN [28]
RP VARIANT GSD1B ARG-246.
RX PubMed=19579760; DOI=10.1016/S1875-9572(09)60048-6;
RA Hsiao H.J., Chang H.H., Hwu W.L., Lam C.W., Lee N.C., Chien Y.H.;
RT "Glycogen storage disease type Ib: the first case in Taiwan.";
RL Pediatr. Neonatol. 50:125-128(2009).
RN [29]
RP VARIANT GSD1B GLU-50.
RX PubMed=21629566;
RA Dissanayake V.H., Jayasinghe J.D., Thilakaratne V., Jayasekara R.W.;
RT "A novel mutation in SLC37A4 gene in a Sri Lankan boy with glycogen
RT storage disease type Ib associated with very early onset
RT neutropenia.";
RL J. Mol. Genet. Med. 5:262-263(2011).
CC -!- FUNCTION: Transports glucose-6-phosphate from the cytoplasm to the
CC lumen of the endoplasmic reticulum. Forms with glucose-6-
CC phosphatase the complex responsible for glucose production through
CC glycogenolysis and gluconeogenesis. Hence, it plays a central role
CC in homeostatic regulation of blood glucose levels.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43826-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43826-2; Sequence=VSP_006171;
CC -!- TISSUE SPECIFICITY: Mostly expressed in liver and kidney.
CC -!- DISEASE: Glycogen storage disease 1B (GSD1B) [MIM:232220]: A
CC metabolic disorder characterized by impairment of terminal steps
CC of glycogenolysis and gluconeogenesis. Patients manifest a wide
CC range of clinical symptoms and biochemical abnormalities,
CC including hypoglycemia, severe hepatomegaly due to excessive
CC accumulation of glycogen, kidney enlargement, growth retardation,
CC lactic acidemia, hyperlipidemia, and hyperuricemia. Glycogen
CC storage disease type 1B patients also present a tendency towards
CC infections associated with neutropenia, relapsing aphthous
CC gingivostomatitis, and inflammatory bowel disease. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Glycogen storage disease 1C (GSD1C) [MIM:232240]: A
CC metabolic disorder characterized by impairment of terminal steps
CC of glycogenolysis and gluconeogenesis. Patients manifest a wide
CC range of clinical symptoms and biochemical abnormalities,
CC including hypoglycemia, severe hepatomegaly due to excessive
CC accumulation of glycogen, kidney enlargement, growth retardation,
CC lactic acidemia, hyperlipidemia, and hyperuricemia. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Glycogen storage disease 1D (GSD1D) [MIM:232240]: A
CC metabolic disorder characterized by impairment of terminal steps
CC of glycogenolysis and gluconeogenesis. Patients manifest a wide
CC range of clinical symptoms and biochemical abnormalities,
CC including hypoglycemia, severe hepatomegaly due to excessive
CC accumulation of glycogen, kidney enlargement, growth retardation,
CC lactic acidemia, hyperlipidemia, and hyperuricemia. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF16691.1; Type=Frameshift; Positions=128;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC37A4";
CC -!- WEB RESOURCE: Name=Mendelian genes solute carrier family 37
CC (glucose-6-phosphate transporter), member 4 (SLC37A4); Note=Leiden
CC Open Variation Database (LOVD);
CC URL="http://www.lovd.nl/SLC37A4";
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DR EMBL; Y15409; CAA75608.1; -; mRNA.
DR EMBL; AF078163; AAC72916.1; -; Genomic_DNA.
DR EMBL; AF097831; AAD19898.1; -; Genomic_DNA.
DR EMBL; AF111852; AAF16691.1; ALT_FRAME; mRNA.
DR EMBL; AF110819; AAF37735.1; -; mRNA.
DR EMBL; AF110820; AAF37736.1; -; mRNA.
DR EMBL; Y17864; CAA76898.1; -; Genomic_DNA.
DR EMBL; AF116864; AAD13111.1; -; Genomic_DNA.
DR EMBL; AF116862; AAD13111.1; JOINED; Genomic_DNA.
DR EMBL; AF116863; AAD13111.1; JOINED; Genomic_DNA.
DR EMBL; AY423732; AAS00495.1; -; mRNA.
DR EMBL; CH471065; EAW67432.1; -; Genomic_DNA.
DR EMBL; BC002400; AAH02400.1; -; mRNA.
DR EMBL; BC003589; AAH03589.1; -; mRNA.
DR EMBL; BC014663; AAH14663.1; -; mRNA.
DR EMBL; BC015650; AAH15650.1; -; mRNA.
DR EMBL; BC064563; AAH64563.1; -; mRNA.
DR RefSeq; NP_001157749.1; NM_001164277.1.
DR RefSeq; NP_001157750.1; NM_001164278.1.
DR RefSeq; NP_001157751.1; NM_001164279.1.
DR RefSeq; NP_001157752.1; NM_001164280.1.
DR RefSeq; NP_001458.1; NM_001467.5.
DR RefSeq; XP_005277769.1; XM_005277712.1.
DR RefSeq; XP_005277770.1; XM_005277713.1.
DR UniGene; Hs.719203; -.
DR ProteinModelPortal; O43826; -.
DR SMR; O43826; 6-381.
DR IntAct; O43826; 1.
DR STRING; 9606.ENSP00000339048; -.
DR TCDB; 2.A.1.4.5; the major facilitator superfamily (mfs).
DR PhosphoSite; O43826; -.
DR PaxDb; O43826; -.
DR PRIDE; O43826; -.
DR DNASU; 2542; -.
DR Ensembl; ENST00000572996; ENSP00000458712; ENSG00000262676.
DR Ensembl; ENST00000577093; ENSP00000461344; ENSG00000262676.
DR Ensembl; ENST00000590663; ENSP00000464769; ENSG00000262676.
DR GeneID; 2542; -.
DR KEGG; hsa:2542; -.
DR UCSC; uc001pus.2; human.
DR CTD; 2542; -.
DR GeneCards; GC11M118894; -.
DR HGNC; HGNC:4061; SLC37A4.
DR MIM; 232220; phenotype.
DR MIM; 232240; phenotype.
DR MIM; 602671; gene.
DR neXtProt; NX_O43826; -.
DR Orphanet; 79259; Glycogen storage disease due to glucose-6-phosphatase deficiency type b.
DR PharmGKB; PA28472; -.
DR eggNOG; COG2271; -.
DR HOGENOM; HOG000274730; -.
DR HOVERGEN; HBG051682; -.
DR KO; K08171; -.
DR OMA; PINVLFT; -.
DR OrthoDB; EOG70CR7M; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; SLC37A4; -.
DR GenomeRNAi; 2542; -.
DR NextBio; 10031; -.
DR PRO; PR:O43826; -.
DR CleanEx; HS_SLC37A4; -.
DR Genevestigator; O43826; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral to endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; NAS:UniProtKB.
DR GO; GO:0015152; F:glucose-6-phosphate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IDA:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; NAS:UniProtKB.
DR GO; GO:0015758; P:glucose transport; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR016196; MFS_dom_general_subst_transpt.
DR InterPro; IPR021159; Sugar-P_transporter_CS.
DR InterPro; IPR000849; Sugar_P_transporter.
DR Pfam; PF07690; MFS_1; 1.
DR PIRSF; PIRSF002808; Hexose_phosphate_transp; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00881; 2A0104; 1.
DR PROSITE; PS00942; GLPT; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disease mutation;
KW Endoplasmic reticulum; Glycogen storage disease; Membrane;
KW Reference proteome; Sugar transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 429 Glucose-6-phosphate translocase.
FT /FTId=PRO_0000199891.
FT TRANSMEM 84 104 Helical; (Potential).
FT TRANSMEM 105 125 Helical; (Potential).
FT TRANSMEM 139 159 Helical; (Potential).
FT TRANSMEM 167 187 Helical; (Potential).
FT TRANSMEM 219 239 Helical; (Potential).
FT TRANSMEM 260 280 Helical; (Potential).
FT TRANSMEM 302 322 Helical; (Potential).
FT TRANSMEM 329 349 Helical; (Potential).
FT TRANSMEM 368 388 Helical; (Potential).
FT TRANSMEM 394 414 Helical; (Potential).
FT VAR_SEQ 328 328 K -> KDVAFWTLALHPLAELTGFTEHE (in isoform
FT 2).
FT /FTId=VSP_006171.
FT VARIANT 20 20 G -> D (in GSD1B; dbSNP:rs193302881).
FT /FTId=VAR_025581.
FT VARIANT 24 24 Y -> H (in GSD1B; dbSNP:rs193302887).
FT /FTId=VAR_025582.
FT VARIANT 27 27 N -> K (in GSD1B; dbSNP:rs193302889).
FT /FTId=VAR_025583.
FT VARIANT 28 28 R -> C (in GSD1B; dbSNP:rs193302882).
FT /FTId=VAR_025584.
FT VARIANT 28 28 R -> H (in GSD1B; inactive glucose-6-
FT phosphate transport; dbSNP:rs121908978).
FT /FTId=VAR_016840.
FT VARIANT 50 50 G -> E (in GSD1B; dbSNP:rs193302877).
FT /FTId=VAR_066394.
FT VARIANT 50 50 G -> R (in GSD1B; dbSNP:rs193302894).
FT /FTId=VAR_025585.
FT VARIANT 54 54 S -> R (in GSD1B; dbSNP:rs193302898).
FT /FTId=VAR_025586.
FT VARIANT 55 55 S -> R (in GSD1B; dbSNP:rs193302884).
FT /FTId=VAR_025587.
FT VARIANT 68 68 G -> R (in GSD1B; dbSNP:rs193302885).
FT /FTId=VAR_025588.
FT VARIANT 85 85 L -> P (in GSD1B; dbSNP:rs193302899).
FT /FTId=VAR_025589.
FT VARIANT 88 88 G -> D (in GSD1B; dbSNP:rs193302886).
FT /FTId=VAR_025590.
FT VARIANT 118 118 W -> R (in GSD1B; dbSNP:rs80356489).
FT /FTId=VAR_007850.
FT VARIANT 133 133 Q -> P (in GSD1C; dbSNP:rs193302896).
FT /FTId=VAR_025591.
FT VARIANT 148 148 A -> V (in GSD1B; dbSNP:rs193302879).
FT /FTId=VAR_066395.
FT VARIANT 149 149 G -> E (in GSD1B; dbSNP:rs193302892).
FT /FTId=VAR_003184.
FT VARIANT 150 150 G -> R (in GSD1B; dbSNP:rs193302883).
FT /FTId=VAR_025592.
FT VARIANT 153 153 P -> L (in GSD1B; dbSNP:rs193302890).
FT /FTId=VAR_025593.
FT VARIANT 176 176 C -> R (in GSD1B; dbSNP:rs193302895).
FT /FTId=VAR_025594.
FT VARIANT 183 183 C -> R (in GSD1B; dbSNP:rs193302893).
FT /FTId=VAR_025595.
FT VARIANT 191 191 P -> L (in GSD1B; dbSNP:rs193302888).
FT /FTId=VAR_032113.
FT VARIANT 198 198 N -> I (in dbSNP:rs34203644).
FT /FTId=VAR_025596.
FT VARIANT 229 229 L -> P (in GSD1B; dbSNP:rs193302902).
FT /FTId=VAR_025597.
FT VARIANT 235 235 Missing (in GSD1B).
FT /FTId=VAR_012356.
FT VARIANT 246 246 W -> R (in GSD1B; dbSNP:rs193302878).
FT /FTId=VAR_066396.
FT VARIANT 278 278 I -> N (in GSD1B; dbSNP:rs193302900).
FT /FTId=VAR_025598.
FT VARIANT 300 300 R -> C (in GSD1B; dbSNP:rs193302880).
FT /FTId=VAR_066397.
FT VARIANT 300 300 R -> H (in GSD1B; dbSNP:rs193302903).
FT /FTId=VAR_025599.
FT VARIANT 301 301 H -> P (in GSD1B; dbSNP:rs193302891).
FT /FTId=VAR_025600.
FT VARIANT 339 339 G -> C (in GSD1B; dbSNP:rs80356490).
FT /FTId=VAR_003185.
FT VARIANT 339 339 G -> D (in GSD1B; dbSNP:rs121908980).
FT /FTId=VAR_025601.
FT VARIANT 367 367 A -> T (in GSD1B; dbSNP:rs80356492).
FT /FTId=VAR_025602.
FT VARIANT 373 373 A -> D (in GSD1B; dbSNP:rs193302901).
FT /FTId=VAR_025603.
FT VARIANT 376 376 G -> S (in GSD1C; dbSNP:rs193302897).
FT /FTId=VAR_025604.
FT CONFLICT 109 109 L -> F (in Ref. 3; AAD19898).
SQ SEQUENCE 429 AA; 46360 MW; C0399332FE72694B CRC64;
MAAQGYGYYR TVIFSAMFGG YSLYYFNRKT FSFVMPSLVE EIPLDKDDLG FITSSQSAAY
AISKFVSGVL SDQMSARWLF SSGLLLVGLV NIFFAWSSTV PVFAALWFLN GLAQGLGWPP
CGKVLRKWFE PSQFGTWWAI LSTSMNLAGG LGPILATILA QSYSWRSTLA LSGALCVVVS
FLCLLLIHNE PADVGLRNLD PMPSEGKKGS LKEESTLQEL LLSPYLWVLS TGYLVVFGVK
TCCTDWGQFF LIQEKGQSAL VGSSYMSALE VGGLVGSIAA GYLSDRAMAK AGLSNYGNPR
HGLLLFMMAG MTVSMYLFRV TVTSDSPKLW ILVLGAVFGF SSYGPIALFG VIANESAPPN
LCGTSHAIVG LMANVGGFLA GLPFSTIAKH YSWSTAFWVA EVICAASTAA FFLLRNIRTK
MGRVSKKAE
//

MIM 232220
*RECORD*
*FIELD* NO
232220
*FIELD* TI
#232220 GLYCOGEN STORAGE DISEASE Ib
;;GSD1B;;
GLUCOSE-6-PHOSPHATE TRANSPORT DEFECT
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that type
Ib glycogen storage disease can result from mutation in the
glucose-6-phosphate transporter gene (602671).

Senior and Loridan (1968) proposed the existence of a second type of von
Gierke disease in which, although glucose-6-phosphatase (G6PC; 613742)
activity is present on in vitro assay, glucose is not liberated from
glucose-6-phosphate in vivo. They referred to this as 'functional
deficiency of G6P.' They pointed out that some mutants in Neurospora
show impaired enzyme function in the intact fungus despite normal
activity in homogenates.

Arion et al. (1975) concluded that G6Pase activity requires 2 components
of the microsomal membrane: (1) a glucose-6-phosphate specific transport
system that shuttles G6P from the cytoplasm to the lumen of the
endoplasmic reticulum (a G6P translocase), and (2) an enzyme,
glucose-6-phosphate phosphohydrolase, bound to the luminal surface of
the membrane.

Narisawa et al. (1978) described a patient who appeared to have a defect
in the transport system. In liver without detergent, enzyme activity was
very low but normal activity was obtained by addition of detergent.
Kuzuya et al. (1983) reported a 25-year-old patient. Protuberant abdomen
and diarrhea were noted at age 1 or 2 years, and short stature and
hepatomegaly at age 4 years. At age 18, yellowish-red spots appeared on
her legs and hypertension was detected. At age 20, she was 138 cm tall.
Eruptive xanthoma and hyperlipidemia were present. Liver scintography
suggested the presence of adenomas.

Recurrent infections and neutropenia have been recognized as distinctive
features of GSD Ib. Corbeel et al. (1983) provided a 6-year follow-up on
the hematologic effects of termino-lateral portacaval anastomosis.
Granulocyte counts returned to normal and recurrent infections ceased
after the shunt. Platelet dysfunction, evident before surgery, was also
corrected. Marked hypochromic anemia, probably caused by sequestration
of iron in the spleen and resistant to therapy, was a persistent feature
in this patient. The mechanism of the granulocyte defect in this
disorder was discussed. Roe et al. (1986) observed Crohn disease in 2
unrelated boys with GSD Ib. Their neutrophils showed severe chronic
neutropenia and markedly deficient chemotactic response, whereas the
leukocytes were normal in 4 patients with GSD Ia (232200). Thus, chronic
inflammatory bowel disease (IBD; see 266600) appears to be an integral
part of GSD Ib and the abnormality of leukocytes is probably involved in
the pathogenesis of the IBD. Oral lesions and perianal abscesses are
common in this disorder (Ambruso et al., 1985). Ueno et al. (1986) found
that neutrophils were defective in both motility and respiratory burst,
whereas monocytes showed a defect only in respiratory burst. Bashan et
al. (1988) showed that the rate of 2-deoxyglucose transport into GSD Ib
polymorphonuclear leukocytes was 30% of that into cells of normal
controls. Transport was normal in GSD Ib lymphocytes and in GSD Ia
polymorphonuclear leukocytes and lymphocytes. The striking limitation of
glucose transport across the cell membrane of polymorphonuclear
leukocytes probably accounts for the impairment of leukocyte function
that is characteristic of GSD Ib but not GSD Ia. Schroten et al. (1991)
used granulocyte colony-stimulating factor (CSF3; 138970) to treat
successfully the neutropenia in 2 patients with GSD Ib associated with
recurrent bacterial infections. Roe et al. (1992) administered
granulocyte-macrophage colony stimulating factor (CSF2; 138960) to the 2
adolescent boys whom they had reported in 1986 (Roe et al., 1986). They
observed a prompt increase in neutrophil counts to normal, complete
relief from abdominal symptoms, and an increase in appetite, energy, and
weight, and a feeling of well being. There was radiologic evidence of
bowel healing and a decrease in the erythrocyte sedimentation rate. Both
patients remained free of oral and anal lesions over a period of 10 and
12 months of treatment. One patient was switched to G-CSF (CSF3) because
of a presumed allergic reaction to GM-CSF. In a multicenter study in the
United States and Canada, Talente et al. (1994) identified 5 patients
with GSD type Ib who were 18 years of age or older. Severe recurrent
bacterial infections and gingivitis were present. One patient, a
22-year-old college student, was described in detail. She had severe
recurrent stomatitis, recurrent otitis media and externa, perianal and
perirectal abscesses, and, at the age of 12 years, 2 brain abscesses due
to Staphylococcus aureus. At 18 years of age, she was as tall as an
8-year-old and had not undergone any pubertal changes.

In a patient with GSD Ib, Heyne and Henke-Wolter (1989) found a change
in the oligosaccharide side chains of the alpha-1-antitrypsin (107400)
glycoprotein suggesting effects of the limited availability of glucose
or glucose derivatives for the synthesis of N-glycosidic glycoproteins.
Kikuchi et al. (1990) found secondary amyloidosis in a 12-year-old girl
with GSD Ib.

In 14 children (aged 4 to 16 years) with GSD Ia and GSD Ib, Lee et al.
(1996) found that the use of uncooked cornstarch loads resulted in
satisfactory glycemia lasting only a median of 4.25 hours (range 2.5 to
6).

In studies of 5 patients with GSD Ib, Kuijpers et al. (2003) found
neutrophils in the circulation that showed signs of apoptosis with
increased caspase activity, condensed nuclei, and perinuclear clustering
of mitochondria to which the proapoptotic BCL2 member BAX (600040) had
translocated already. Granulocyte colony-stimulating factor (GCSF;
138970) added to in vitro cultures did not rescue the GSD Ib neutrophils
from apoptosis as occurred with GCSF-treated control neutrophils.
Moreover, the 2 GSD Ib patients on GCSF treatment did not show
significantly lower levels of apoptotic neutrophils in the bloodstream.
Kuijpers et al. (2003) studied neutrophils from children with infections
(active pneumonia or septicemia) or with other neutropenic syndromes
(Shwachman-Diamond syndrome; 260400), but to date had not observed
circulating apoptotic neutrophils in these patients.

Annabi et al. (1998) reported linkage of the GSD Ib locus to genetic
markers spanning a 3-cM region on 11q23. The region is located between
D11S939 centromerically and D11S4129 telomerically and includes the
IL10R (146933), ATP1G1 (601814), and ALL1 (159555) genes. The authors
studied 8 consanguineous families and 1 nonconsanguineous family of
various ethnic origins. The assignment to chromosome 11 was confirmed by
Kure et al. (1998), who showed that the translocase gene that is mutated
in this disorder maps to chromosome 11 by study of somatic cell hybrids.

In 2 female patients with GSD Ib, Gerin et al. (1997) found 2 point
mutations in the glucose-6-phosphate translocase gene (602671.0001 and
602671.0002). Kure et al. (1998) identified 3 additional mutations, one
of which, W118R (602671.0003), may be unusually frequent among Japanese
patients with GSD Ib.

Kure et al. (2000) proposed that GSD Ib without neutropenia could be due
to glucose-6-phosphate translocase mutations with residual transporter
activity based on finding biallelic mutations with normal liver
microsomal GTPase activity in 2 Japanese patients; see 602671.0015 and
602671.0016.

Chou and Mansfield (1999) reviewed the molecular genetics of type I
glycogen storage diseases.

*FIELD* SA
Buchino et al. (1983); Heyne et al. (1984); Kamoun (1980); Narisawa
et al. (1986); Sann et al. (1980); Schaub et al. (1981); Schaub and
Heyne (1983); Seger et al. (1984)
*FIELD* RF
1. Ambruso, D. R.; McCabe, E. R. B.; Anderson, D.; Beaudet, A.; Ballas,
L. M.; Brandt, I. K.; Brown, B.; Coleman, R.; Dunger, D. B.; Falletta,
J. M.; Friedman, H. S.; Haymond, M. W.; Keating, J. P.; Kinney, T.
R.; Leonard, J. V.; Mahoney, D. H., Jr.; Matalon, R.; Roe, T. F.;
Simmons, P.; Slonim, A. E.: Infectious and bleeding complications
in patients with glycogenosis Ib. Am. J. Dis. Child. 139: 691-697,
1985.

2. Annabi, B.; Hiraiwa, H.; Mansfield, B. C.; Lei, K.-J.; Ubagai,
T.; Polymeropoulos, M. H.; Moses, S. W.; Parvari, R.; Hershkovitz,
E.; Mandel, H.; Fryman, M.; Chou, J. Y.: The gene for glycogen-storage
disease type 1b maps to chromosome 11q23. Am. J. Hum. Genet. 62:
400-405, 1998.

3. Arion, W. J.; Wallin, B. K.; Lange, A. J.; Ballas, L. M.: On the
involvement of a glucose-6-phosphate transport system in the function
of microsomal glucose-6-phosphate. Molec. Cell. Biochem. 6: 75-83,
1975.

4. Bashan, N.; Hagai, Y.; Potashnik, R.; Moses, S. W.: Impaired carbohydrate
metabolism of polymorphonuclear leukocytes in glycogen storage disease
Ib. J. Clin. Invest. 81: 1317-1322, 1988.

5. Buchino, J. J.; Brown, B. I.; Volk, D. M.: Glycogen storage disease
type Ib. Arch. Path. Lab. Med. 107: 283-285, 1983.

6. Chou, J.Y.; Mansfield, B.C.: Molecular genetics of type 1 glycogen
storage diseases. Trends Endocr. Metab. 10: 104-113, 1999.

7. Corbeel, L.; Boogaerts, M.; Van den Berghe, G.; Everaerts, M. C.;
Marchal, G.; Eeckels, R.: Haematological findings in type Ib glycogen
storage disease before and after portacaval shunt. Europ. J. Pediat. 140:
273-275, 1983.

8. Gerin, I.; Veiga-da-Cunha, M.; Achouri, Y.; Collet, J.-F.; Van
Schaftingen, E.: Sequence of a putative glucose 6-phosphate translocase,
mutated in glycogen storage disease type Ib. FEBS Lett. 419: 235-238,
1997.

9. Heyne, K.; Henke-Wolter, J.: Glycogen storage disease Ib: modification
of alpha-1-antitrypsin glycoprotein microheterogeneity. Europ. J.
Pediat. 148: 341-343, 1989.

10. Heyne, K.; Hosenfeld, D.; Grote, W.; Schaub, J.: Glycogen storage
disease type Ib: familial bleeding tendency. Europ. J. Pediat. 143:
7-9, 1984.

11. Kamoun, P. P.: Is type 1b glycogenosis related to an anomeric
preference for glucose-6-phosphate uptake by hepatic microsomes? Med.
Hypotheses 6: 1135-1139, 1980.

12. Kikuchi, M.; Haginoya, K.; Miyabayashi, S.; Igarashi, Y.; Narisawa,
K.; Tada, K.: Secondary amyloidosis in glycogen storage disease type
Ib. Europ. J. Pediat. 149: 344-345, 1990.

13. Kuijpers, T. W.; Maianski, N. A.; Tool, A. T. J.; Smit, P. A.;
Rake, J. P.; Roos, D.; Visser, G.: Apoptotic neutrophils in the circulation
of patients with glycogen storage disease type 1b (GSD1b). Blood 101:
5021-5024, 2003.

14. Kure, S.; Hou, D.-C.; Suzuki, Y.; Yamagishi, A.; Hiratsuka, M.;
Fukuda, T.; Sugie, H.; Kondo, N.; Matsubara, Y.; Narisawa, K.: Glycogen
storage disease type Ib without neutropenia. J. Pediat. 137: 253-256,
2000.

15. Kure, S.; Suzuki, Y.; Matsubara, Y.; Sakamoto, O.; Shintaku, H.;
Isshiki, G.; Hoshida, C.; Izumi, I.; Sakura, N.; Narisawa, K.: Molecular
analysis of glycogen storage disease type Ib: identification of a
prevalent mutation among Japanese patients and assignment of a putative
glucose-6-phosphate translocase gene to chromosome 11. Biochem. Biophys.
Res. Commun. 248: 426-431, 1998.

16. Kuzuya, T.; Matsuda, A.; Yoshida, S.; Narisawa, K.; Tada, K.;
Saito, T.; Matsushita, M.: An adult case of type Ib glycogen-storage
disease: enzymatic and histochemical studies. New Eng. J. Med. 308:
566-569, 1983.

17. Lee, P. J.; Dixon, M. A.; Leonard, J. V.: Uncooked cornstarch--efficacy
in type I glycogenosis. Arch. Dis. Child. 74: 546-547, 1996.

18. Narisawa, K.; Igarashi, Y.; Otomo, H.; Tada, K.: A new variant
of glycogen storage disease type I probably due to a defect in the
glucose-6-phosphate transport system. Biochem. Biophys. Res. Commun. 83:
1360-1364, 1978.

19. Narisawa, K.; Ishizawa, S.; Okumura, H.; Tada, K.; Kuzuya, T.
: Neutrophil metabolic dysfunction in genetically heterogeneous patients
with glycogen storage disease type 1b. J. Inherit. Metab. Dis. 9:
297-300, 1986.

20. Roe, T. F.; Coates, T. D.; Thomas, D. W.; Miller, J. H.; Gilsanz,
V.: Treatment of chronic inflammatory bowel disease in glycogen storage
disease type Ib with colony-stimulating factors. New Eng. J. Med. 326:
1666-1669, 1992.

21. Roe, T. F.; Thomas, D. W.; Gilsanz, V.; Isaacs, H., Jr.; Atkinson,
J. B.: Inflammatory bowel disease in glycogen storage disease type
Ib. J. Pediat. 109: 55-59, 1986.

22. Sann, L.; Mathieu, M.; Bourgeous, J.; Bienvenu, J.; Bethenod,
M.: In vivo evidence for defective activity of glucose-6-phosphatase
in type I B glycogenosis. J. Pediat. 96: 691-694, 1980.

23. Schaub, J.; Bartholome, K.; Feist, D.; Schmidt, H.: Glycogenosis
type Ib: further evidence for a membrane disease. (Letter) Europ.
J. Pediat. 135: 325 only, 1981.

24. Schaub, J.; Heyne, K.: Glycogen storage disease type Ib. Europ.
J. Pediat. 140: 283-288, 1983.

25. Schroten, H.; Roesler, J.; Breidenbach, T.; Wendel, U.; Elsner,
J.; Schweitzer, S.; Zeidler, C.; Burdach, S.; Lohmann-Matthes, M.-L.;
Wahn, V.; Welte, K.: Granulocyte and granulocyte-macrophage colony-stimulating
factors for treatment of neutropenia in glycogen storage disease type
Ib. J. Pediat. 119: 748-754, 1991.

26. Seger, R.; Steinmann, B.; Tiefenauer, L.; Matsunaga, T.; Gitzelmann,
R.: Glycogenosis Ib: neutrophil microbicidal defects due to impaired
hexose monophosphate shunt. Pediat. Res. 18: 297-299, 1984.

27. Senior, B.; Loridan, L.: Functional differentiation of glycogenoses
of the liver with respect to the use of glycerol. New Eng. J. Med. 279:
965-970, 1968.

28. Talente, G. M.; Coleman, R. A.; Alter, C.; Baker, L.; Brown, B.
I.; Cannon, R. A.; Chen, Y.-T.; Crigler, J. F., Jr.; Ferreira, P.;
Haworth, J. C.; Herman, G. E.; Issenman, R. M.; Keating, J. P.; Linde,
R.; Roe, T. F.; Senior, B.; Wolfsdorf, J. I.: Glycogen storage disease
in adults. Ann. Intern. Med. 120: 218-226, 1994.

29. Ueno, N.; Tomita, M.; Ariga, T.; Ohkawa, M.; Nagano, S.; Takahashi,
Y.; Arashima, S.; Matsumoto, S.: Impaired monocyte function in glycogen
storage disease type Ib. Europ. J. Pediat. 145: 312-314, 1986.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Height];
Short stature;
[Other];
Delayed puberty

HEAD AND NECK:
[Face];
'Doll-like' facies;
[Eyes];
Lipemia retinalis;
[Mouth];
Oral ulcers

CARDIOVASCULAR:
[Vascular];
Hypertension

ABDOMEN:
[External features];
Protuberant abdomen;
[Liver];
Hepatomegaly;
Liveradenomas;
Hepatocellular carcinoma;
[Pancreas];
Pancreatitis;
[Gastrointestinal];
Chronic inflammatory bowel disease (IBD);
Intestinal mucosal ulceration

GENITOURINARY:
[Kidneys];
Reduced creatinine clearance;
Focal segmental glomerulosclerosis;
Renal stones;
Renal enlargement

SKELETAL:
Osteoporosis;
Gouty arthritis

SKIN, NAILS, HAIR:
[Skin];
Xanthoma

HEMATOLOGY:
Neutropenia;
Abnormal leukocyte function

LABORATORY ABNORMALITIES:
T1 transport protein (Glucose-6-phosphate translocase) defect;
Hyperlipidemia;
Hyperuricemia;
Lactic acidosis;
Hypoglycemia;
Proteinuria;
Liver transaminases normal to slightly increased

MISCELLANEOUS:
Recurrent bacterial infections

MOLECULAR BASIS:
Caused by mutation in the glucose-6-phosphate transporter 1 gene (G6PT1,
602671.0001)

*FIELD* CN
Kelly A. Przylepa - revised: 9/20/2000

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

*FIELD* ED
joanna: 12/05/2008
joanna: 3/18/2002
kayiaros: 9/20/2000

*FIELD* CN
Natalie E. Krasikov - updated: 3/4/2004
Victor A. McKusick - updated: 9/8/2003
John A. Phillips, III - updated: 9/29/2000
Victor A. McKusick - updated: 9/2/1998
Victor A. McKusick - updated: 3/27/1998
Cynthia K. Ewing - updated: 5/8/1997

*FIELD* CD
Victor A. McKusick: 6/3/1986

*FIELD* ED
carol: 02/15/2011
carol: 10/29/2008
carol: 3/18/2004
terry: 3/4/2004
carol: 3/1/2004
cwells: 9/9/2003
terry: 9/8/2003
cwells: 9/3/2003
terry: 9/2/2003
mgross: 10/3/2000
terry: 9/29/2000
terry: 6/11/1999
carol: 9/8/1998
alopez: 9/2/1998
alopez: 6/1/1998
psherman: 3/27/1998
terry: 3/26/1998
mark: 5/8/1997
davew: 6/2/1994
carol: 5/31/1994
mimadm: 2/19/1994
carol: 7/15/1993
carol: 7/1/1992
carol: 6/30/1992

MIM 232240
*RECORD*
*FIELD* NO
232240
*FIELD* TI
#232240 GLYCOGEN STORAGE DISEASE Ic
;;GSD1C
GLYCOGEN STORAGE DISEASE Id, INCLUDED; GSD1D, INCLUDED
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that this
form of glycogen storage disease is caused by mutations in the
glucose-6-phosphate translocase gene (G6PT1; 602671), which is also the
site of the defect in glycogen storage disease Ib (232220).

Nordlie et al. (1983) reported studies of liver tissue from an
11-year-old girl with classic clinical features of type I glycogenosis.
As in type Ib, glucose-6-phosphatase activity was lacking except in
detergent-disrupted microsomes. Findings that differed from those of
type Ib were interpreted on the basis of the multicomponent G6Pase
system proposed by Arion et al. (1980). Defects in both T1, the
translocase specific for G6P (deficient in type Ib), and T2, the
putative translocase specific for Pi, PPi, and carbamyl-P, were thought
to be involved. Burchell et al. (1987) described a second case of GSD
type Ic in a 52-year-old man who had had no hypoglycemic symptoms.
Glucose tolerance test showed impaired carbohydrate tolerance and
glycosuria. These authors thought that only translocase T2 was
defective. T1 is responsible for transport of glucose-6-phosphate into
the endoplasmic reticulum, and T3 is responsible for transport of
glucose out of the endoplasmic reticulum. Translocase T2 is concerned
with transport of pyrophosphate into, and phosphate out of, the
endoplasmic reticulum. The inability to transport phosphate means that,
although glucose-6-phosphate can be taken into the lumen of the
endoplasmic reticulum and hydrolyzed to glucose and phosphate, the
phosphate cannot be removed from the lumen. Phosphate is an inhibitor of
glucose-6-phosphatase activity. It is not surprising that there are
multiple forms of type I GSD inasmuch as at least 5 different
polypeptides are required for normal glucose-6-phosphatase activity in
vivo (reviewed by Burchell, 1990). There are 3 transport proteins,
termed T1, T2, and T3, which allow the substrates and products
glucose-6-phosphate, phosphate (and pyrophosphate), and glucose to cross
the endoplasmic reticulum membrane. Defects in the 3 transport proteins
are referred to as types Ib, Ic, and Id glycogen storage disease,
respectively. Burchell and Gibb (1991) reported experience with assays
of 5 cases of GSD type Ib and 7 cases of GSD type Ic.

Visser et al. (1998) described a patient with GSD type Ic who suffered
from neutropenia and neutrophil dysfunction as in GSD type Ib.
Hypoglycemia had been noted in the neonatal period. At 3 months of age,
hepatomegaly was noted combined with fasting intolerance, hyperlactic
acidemia, and neutropenia. She suffered from recurrent infections of the
upper respiratory tract and gastrointestinal tract from severe
stomatitis. Recurrent neutropenia and disturbed neutrophil function were
identified; furthermore, inflammatory bowel disease was confirmed by
bowel radiography and bowel biopsy. At the age of 6 months, because of
12 infections in 6 months and continuous admission to hospital from the
age of 4 months, treatment with granulocyte colony-stimulating factor
(GCSF; 138970) was started. Thereafter the patient improved remarkably.
Infection rate decreased dramatically and colonoscopy with bowel
biopsies was normal. Studies of fresh liver tissues in this patient
showed decreased enzyme activity in untreated homogenate, and higher
activity in disruptive preparations, indicating a defect in 1 of the
transporters, GSD Ib or GSD Ic. Further classification by investigation
of the pyrophosphate phosphohydrolase showed that enzyme activity in the
patient was decreased compared to controls, in untreated homogenates as
well as in treated homogenates. This was considered compatible only with
GSD Ic.

Gerin et al. (1997) cloned a cDNA encoding a putative
glucose-6-phosphate translocase and found it to be mutated in 2 patients
with GSD type Ib. GSD type Ib was mapped to 11q23 by Annabi et al.
(1998) and GSD type Ic was mapped to 11q23-q24.2 by Fenske et al.
(1998). Veiga-da-Cunha et al. (1998) showed that the gene encoding the
putative translocase also maps to this region and demonstrated that the
gene was mutated in 26 patients from a total of 22 families who had been
diagnosed as either GSD type Ib or GSD type Ic.

Lin et al. (1999) studied the original patient with GSD Ic reported by
Nordlie et al. (1983) and demonstrated that her G6PT gene was intact,
suggesting that mutations in some other gene must be responsible. The
GSD Ic disorder had been defined based on detailed kinetic analysis of
the patient's G6Pase system. The index patient manifested neither
neutropenia nor neutrophil/monocyte dysfunction, characteristic of GSD
Ib. The GSD Ic patients identified by Veiga-da-Cunha et al. (1998) and
Janecke et al. (1999) had been diagnosed solely on the basis of
increased latency in hepatic microsomal inorganic pyrophosphatase
activity, despite the fact that 3 patients also manifested neutropenia.
The apparent discrepancy suggested to Lin et al. (1999) that GSD Ic
cannot accurately be diagnosed by simply measuring inorganic
pyrophosphatase activity in patients' hepatic microsomes. In fact,
Nordlie et al. (1983) had shown that using G6P as a substrate, phosphate
did not accumulate within the endoplasmic reticulum lumen of the
original GSD Ic patient, suggesting pyrophosphate/phosphate transport
comprises at least 2 proteins.

*FIELD* SA
Nordlie and Sukalski (1986)
*FIELD* RF
1. Annabi, B.; Hiraiwa, H.; Mansfield, B. C.; Lei, K.-J.; Ubagai,
T.; Polymeropoulos, M. H.; Moses, S. W.; Parvari, R.; Hershkovitz,
E.; Mandel, H.; Fryman, M.; Chou, J. Y.: The gene for glycogen-storage
disease type 1b maps to chromosome 11q23. Am. J. Hum. Genet. 62:
400-405, 1998.

2. Arion, W. J.; Lange, A. J.; Walls, H. E.; Ballas, L. M.: Evidence
for the participation of independent translocases for phosphate and
glucose-6-phosphate in the microsomal glucose-6-phosphate system. J.
Biol. Chem. 255: 10396-10406, 1980.

3. Burchell, A.: Molecular pathology of glucose-6-phosphatase. FASEB
J. 4: 2978-2988, 1990.

4. Burchell, A.; Gibb, L.: Diagnosis of type 1B and 1C glycogen storage
disease. J. Inherit. Metab. Dis. 14: 305-307, 1991.

5. Burchell, A.; Jung, R. T.; Lang, C. C.; Bennet, W.; Shepherd, A.
N.: Diagnosis of type 1a and type 1c glycogen storage diseases in
adults. Lancet 329: 1059-1062, 1987. Note: Originally Volume I.

6. Fenske, C. D.; Jeffery, S.; Weber, J. L.; Houlston, R. S.; Leonard,
J. V.; Lee, P. J.: Localisation of the gene for glycogen storage
disease type 1c by homozygosity mapping to 11q. J. Med. Genet. 35:
269-272, 1998.

7. Gerin, I.; Veiga-da-Cunha, M.; Achouri, Y.; Collet, J.-F.; Van
Schaftingen, E.: Sequence of a putative glucose 6-phosphate translocase,
mutated in glycogen storage disease type Ib. FEBS Lett. 419: 235-238,
1997.

8. Janecke, A. R.; Bosshard, N. U.; Mayatepek, E.; Schulze, A.; Gitzelmann,
R.; Burchell, A.; Bartram, C. R.; Janssen, B.: Molecular diagnosis
of type 1c glycogen storage disease. Hum. Genet. 104: 275-277, 1999.

9. Lin, B.; Hiraiwa, H.; Pan, C.-J.; Nordlie, R. C.; Chou, J. Y.:
Type-1c glycogen storage disease is not caused by mutations in the
glucose-6-phosphate transporter gene. Hum. Genet. 105: 515-517,
1999.

10. Nordlie, R. C.; Sukalski, K. A.: Multiple forms of type I glycogen
storage disease: underlying mechanisms. Trends Biochem. Sci. 11:
61-65, 1986.

11. Nordlie, R. C.; Sukalski, K. A.; Munoz, J. M.; Baldwin, J. J.
: Type Ic, a novel glycogenosis: underlying mechanism. J. Biol. Chem. 258:
9739-9744, 1983.

12. Veiga-da-Cunha, M.; Gerin, I.; Chen, Y.-T.; de Barsy, T.; de Lonlay,
P.; Dionisi-Vici, C.; Fenske, C. D.; Lee, P. J.; Leonard, J. V.; Maire,
I.; McConkie-Rosell, A.; Schweitzer, S.; Vikkula, M.; Van Schaftingen,
E.: A gene on chromosome 11q23 coding for a putative glucose-6-phosphate
translocase is mutated in glycogen-storage disease types Ib and Ic. Am.
J. Hum. Genet. 63: 976-983, 1998.

13. Visser, G.; Herwig, J.; Rake, J. P.; Niezen-Koning, K. E.; Verhoeven,
A. J.; Smit, G. P. A.: Neutropenia and neutrophil dysfunction in
glycogen storage disease type 1c. J. Inherit. Metab. Dis. 21: 227-231,
1998.

*FIELD* CS

Endo:
Hypoglycemia;
Hypertension

GU:
Proteinuria;
Hematuria;
Reduced creatinine clearance;
Renal insufficiency;
Focal segmental glomerulosclerosis

Growth:
Growth lag;
Delalyed puberty

GI:
Liver adenomas;
Hepatocellular carcinoma;
Hepatoblastoma;
Hepatomegaly;
Chronic pancreatitis

Skin:
Xanthoma;
Spider angioma;
Gouty tophi

Joints:
Gouty arthritis

Heme:
No leukocyte dysfunction

Pulmonary:
Pulmonary hypertension

Lab:
T2 transport protein (Phosphate-pyrophosphate translocase) defect;
Lipidemia;
Hyperuricemia;
Hyperlacticacidemia;
Ketonemia;
Metabolic acidosis

Inheritance:
Autosomal recessive

*FIELD* CN
Victor A. McKusick - updated: 12/6/1999
Victor A. McKusick - updated: 10/22/1998
Victor A. McKusick - updated: 9/8/1998

*FIELD* CD
Victor A. McKusick: 6/3/1986

*FIELD* ED
terry: 03/04/2009
carol: 4/17/2007
terry: 4/6/2005
terry: 2/28/2000
mgross: 12/10/1999
terry: 12/6/1999
alopez: 11/12/1999
mgross: 9/9/1999
dkim: 11/13/1998
carol: 10/26/1998
terry: 10/22/1998
carol: 9/15/1998
terry: 9/8/1998
mimadm: 2/19/1994
supermim: 3/16/1992
carol: 10/15/1991
carol: 10/7/1991
carol: 9/13/1991
supermim: 3/20/1990

MIM 602671
*RECORD*
*FIELD* NO
602671
*FIELD* TI
*602671 SOLUTE CARRIER FAMILY 37 (GLUCOSE-6-PHOSPHATE TRANSPORTER), MEMBER
4; SLC37A4
read more;;GLUCOSE-6-PHOSPHATE TRANSPORTER 1; G6PT1;;
GLUCOSE-6-PHOSPHATE TRANSLOCASE;;
G6P TRANSLOCASE
*FIELD* TX

DESCRIPTION

G6PT1 regulates the rate-limiting step of glucose-6-phosphate (G6P)
transport through the endoplasmic reticulum (ER) membrane. It also
functions in ATP-mediated calcium sequestration in the ER lumen and as a
G6P receptor/sensor (Belkaid et al., 2006).

CLONING

Gerin et al. (1997) isolated a cDNA from a human bladder tumor cDNA
library. The cDNA predicted a 429-amino acid protein with a calculated
molecular mass of 46 kD. The protein contains a putative signal for
retention in the endoplasmic reticulum. Its nearest homolog was the
bacterial gene UhpC, an E. coli glucose-6-phosphate receptor. Northern
blot analysis revealed a 2.0-kb mRNA in human liver. The authors
concluded that this gene is likely to be a human glucose-6-phosphate
translocase.

Using Northern blot analysis, Gerin et al. (1999) detected a G6PT1
transcript of about 2.4 kb in liver and kidney, with weaker expression
in leukocytes. They identified a G6PT1 splice variant containing exon 7
in fetal brain EST libraries. Exon 7 introduces 22 amino acids into the
luminal loop between transmembrane helices 9 and 10. PCR analysis did
not detect the exon 7-containing variant in liver, kidney, or leukocyte
mRNA. PCR analysis of mouse tissues revealed exon 7-containing
transcripts in brain and heart, but not in liver, kidney, lung, or
spleen. In mouse, exon 7 encodes 20 amino acids.

Ihara et al. (2000) investigated the quantitative expression of the
G6PT1 gene and its splice variants in human tissues. The G6PT1 gene was
strongly expressed in liver, kidney, and hematopoietic progenitor cells.
RT-PCR amplification of G6PT1 cDNA revealed tissue-specific expression
of several splice variants. The exon 7-containing brain isoform was also
identified in heart and skeletal muscle.

GENE STRUCTURE

Ihara et al. (1998) determined that the G6P translocase gene spans
approximately 5 kb and contains 8 exons. Marcolongo et al. (1998)
determined that the G6PT1 gene contains 9 exons and spans about 4 kb.
Hou et al. (1999) found that the G6PT1 gene spans 4.5 kb and that all
exon/intron boundaries adhere to the canonical ag/gt rule. Gerin et al.
(1999) and Hiraiwa et al. (1999) determined that the G6PT1 gene contains
9 exons, and Hiraiwa et al. (1999) determined that the G6PT gene spans
5.3 kb.

Gerin et al. (1999) identified an upstream TATA box and 2 main
transcriptional start sites at about -100 and -200 nt with respect to
the initiator ATG. They also found 3 Alu sequences at about -3400,
-2800, and -1800 nt with respect to the initiator ATG.

MAPPING

Kure et al. (1998) mapped the G6PT1 gene to chromosome 11 by study of a
DNA panel of human/hamster hybrid cells. Veiga-da-Cunha et al. (1998)
used radiation hybrid analysis to map the G6PT1 gene to chromosome
11q23. By fluorescence in situ hybridization, Ihara et al. (1998)
refined the localization of the G6PT1 gene to chromosome 11q23.3.

GENE FUNCTION

Lin et al. (2000) showed that the exon 7-containing G6PT splice variant,
which they designated vG6PT, was active in microsomal G6P transport.
They raised the possibility that mutations in exon 7 of the G6PT gene,
which would not perturb glucose homeostasis, might have other
deleterious effects.

Using small interfering RNA, Belkaid et al. (2006) found that silencing
G6PT induced necrosis and late apoptosis in brain tumor-derived U87
glioma cells. The anticancer drug curcumin, which regulates key enzymes
involved in carbohydrate metabolism, inhibited G6PT expression by more
than 90% and triggered U87 cell death. Overexpression of G6PT rescued
cells from curcumin-induced cell death.

MOLECULAR GENETICS

In 4 unrelated Japanese families with glycogen storage disease (GSD) Ib
(232220), Kure et al. (1998) identified 3 novel mutations in the G6PT1
gene; the W118R mutation (602671.0003) accounted for 4 of 8 mutant
alleles, suggesting that it is particularly prevalent among Japanese
patients. Ihara et al. (1998) also reported 2 novel mutations in a
Japanese patient.

In 2 patients with glycogen storage disease Ib, Gerin et al. (1997)
found 2 mutations in the putative glucose-6-phosphate translocase. One
patient was homozygous for a gly339-to-cys substitution (602671.0001).
The other patient was a compound heterozygote for the gly339-to-cys
mutation and a glu355-to-ter (602671.0002) mutation. Both patients
showed typical clinical and laboratory findings of GSD Ib, including
neutropenia. Neither mutation was present in 4 normal controls.

Veiga-da-Cunha et al. (1998) showed that mutations in the G6PT1 gene
account for GSD types Ib and Ic (232240). Using SSCP analysis and
sequencing, they screened this gene for mutations in genomic DNA from 22
families with GSD types Ib and Ic. Of 20 mutations found, 11 resulted in
truncated proteins that were probably nonfunctional. Most other
mutations resulted in substitutions of conserved or semiconserved
residues. The 2 most common mutations, gly339 to cys and 1211-1212delCT
(602671.0006), together accounted for approximately 40% of the disease
alleles. The fact that the same mutations were found in GSD types Ib and
Ic could indicate either that Pi and glucose-6-phosphate are transported
in microsomes by the same transporter or that the biochemical assays
used to differentiate Pi and glucose-6-phosphate transport defects are
not reliable.

In 12 of the 22 families investigated by Veiga-da-Cunha et al. (1998),
patients were homozygous for the identified mutation of the G6PT1 gene.
In 4 of these families the parents were consanguineous. In 7 of the 10
families in which the patients showed compound heterozygosity, the
availability of parental DNA enabled them to show that the 2 mutations
were on different chromosomes.

Hiraiwa et al. (1999) identified mutations in the G6PT gene that
segregated with GSD Ib. They functionally characterized the recombinant
G6PT and demonstrated that mutations found in GSD Ib patients disrupt
G6P transport. Hiraiwa et al. (1999) stated that this was the first
definition of a molecular basis for functional deficiency in GSD Ib and
raised the possibility that defective G6PT contributes to neutropenia
and neutrophil/monocyte dysfunctions characteristic of GSD Ib patients.

Hou et al. (1999) studied 5 Japanese patients with GSD type Ib. Two
novel homozygous mutations were identified in 2 families: a 3-bp
deletion (V235del) in exon 2 in a consanguineous family and a splicing
mutation (IVS7DS+1G-T) in intron 7 in a nonconsanguineous family. Two
patients were homozygotes for W118R. A fifth patient was a compound
heterozygote for W118R and IVS1DS+1G-A. Including their previous study
(Kure et al., 1998), this group found a total of 10 W118R alleles in 9
Japanese patients.

Veiga-da-Cunha et al. (1999) analyzed 23 additional families diagnosed
as having GSD I non-a (i.e., GSD Ib, Ic, Id). The 9 exons of the G6PT1
gene were amplified by PCR and mutations sought both by SSCP and
heteroduplex analysis. Except for one family in which only 1 mutation
was found, all patients had 2 allelic mutations in the gene encoding the
putative translocase. The mutations were new in 16 and they all were
predicted to result in nonfunctional proteins. All investigated patients
had some degree of neutropenia or neutrophil dysfunction, and the
clinical phenotype of 4 new patients who had been diagnosed as GSD Ic
and the one diagnosed as GSD Id was no different from that of the GSD Ib
patients. Since these patients, and the 4 type Ic patients from 2
families previously studied, shared several mutations with GSD Ib
patients, Veiga-da-Cunha et al. (1999) concluded that their basic defect
is in the putative translocase and that they should be reclassified as
GSD Ib. Isolated defects in microsomal Pi transporter or in microsomal
glucose transporter must be very rare or have phenotypes that are not
recognized as GSD I, so that in practice there are only 2 subtypes of
GSD I (Ia and Ib).

Galli et al. (1999) reported on the analysis by SSCP and/or DNA
sequencing of the exons of the G6PT gene in 14 patients diagnosed as
affected with either the GSD Ib or GSD Ic subtype. Mutations in the G6PT
gene were found in all patients. Four of the mutations were novel. The
results confirmed that the Ib and Ic forms are due to mutations in the
same gene. Galli et al. (1999) also showed that the same kind of
mutation may or may not be associated with evident clinical
complications such as neutrophil impairment. There was no correlation
between the type and position of the mutation and the severity of the
disease, including the presence of neutropenia.

Janecke et al. (2000) studied 13 patients with glycogen storage disease
type I non-A. Analysis of the G6PT gene revealed mutations on both
chromosomes in each case, 4 of which were novel.

Chen et al. (2000) demonstrated that 15 missense mutations and a codon
deletion mutation abolished microsomal G6P uptake activity and that 2
splicing mutations caused exon skipping in the G6PT gene in patients
with glycogen storage disease Ib. Mutation analysis elucidated the
structural requirements for stability and transport activity of the G6PT
protein.

Using an assay based on an adenoviral vector-mediated expression system,
Chen et al. (2002) functionally characterized all 30 codon mutations
found in GSD Ib patients. Twenty of the naturally occurring mutations
completely abolished microsomal G6P uptake activity, whereas the other
10 mutations (including 5 previously characterized) partially
inactivated the transporter. The authors also demonstrated that 5 of the
mutations, including val235del (602671.0010), G339C (602671.0001), and
G339D (602671.0015), also compromised G6PT stability. The N-terminal
domain of G6PT was required for optimal G6P uptake activity. Degradation
of both wildtype and mutant G6PT was inhibited by the proteasome
inhibitor lactacystin, demonstrating that G6PT is a substrate for
proteasome-mediated degradation.

ANIMAL MODEL

Hiraiwa et al. (2001) investigated whether there is a molecular link
between HNF1-alpha (HNF1A; 142410) deficiency and function of the G6Pase
system. Transactivation studies revealed that HNF1A is required for
transcription of the G6PT gene. Hepatic G6PT mRNA levels and microsomal
G6P transport activity are also markedly reduced in Hnf1a -/- mice as
compared with Hnf1a +/+ and Hnf1a +/- littermates. On the other hand,
hepatic G6Pase mRNA expression and activity are upregulated in Hnf1a -/-
mice, consistent with observations that G6Pase expression is increased
in diabetic animals. Taken together, these results strongly suggest that
metabolic abnormalities in Hnf1a-null mice are caused in part by G6PT
deficiency and by perturbations of the G6Pase system.

Chen et al. (2003) generated a G6pt-knockout (G6pt -/-) mouse that
mimicked all known defects of human GSD Ib. Neutropenia was caused
directly by the loss of G6PT activity; chemotaxis and calcium flux,
induced by the chemokines KC (MGSA; see 155730) and macrophage
inflammatory protein-2 (139110), were defective in G6pt -/- neutrophils;
local production of these chemokines and the resultant neutrophil
trafficking in vivo were depressed in G6pt -/- ascites during an
inflammatory response. The bone and spleen of G6pt -/- mice were
developmentally delayed and accompanied by marked hypocellularity of the
bone marrow, elevation of myeloid progenitor cell frequencies in both
organs, and a corresponding dramatic increase in granulocyte
colony-stimulating factor (138970) levels in both GSD Ib mice and
humans. The authors concluded that G6PT is not only a G6P transport
protein, but is also an important immunomodulatory protein with a role
in myeloid complications in GSD Ib.

*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, GLY339CYS

In a 22-year-old female patient with type Ib glycogen storage disease
(232220), Gerin et al. (1997) demonstrated homozygosity for a
gly339-to-cys (G339C) substitution in the glucose 6-phosphate
transporter.

.0002
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, GLU355TER

Gerin et al. (1997) found that a 10-year-old female patient with type Ib
glycogen storage disease (232220) was a compound heterozygote for the
G339C substitution (602671.0001) and a glu-355-to-ter (E355X) mutation.

.0003
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, TRP118ARG

In 4 unrelated Japanese families with glycogen storage disease Ib
(232220), Kure et al. (1998) found that a W118R missense mutation in the
G6PT1 gene accounted for 4 of 8 mutant alleles. This same group (Hou et
al., 1999) reported that they found a total of 10 W118R alleles in 9
Japanese patients, suggesting that this is an unusually prevalent
mutation in Japan.

.0004
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, 4-BP DEL, 2-BP INS, NT1094

In a Japanese patient with glycogen storage disease Ib (232220), Kure et
al. (1998) found homozygosity for a deletion/insertion mutation of the
G6PT1 gene. GCTG at nucleotides 1094-1097 were deleted and replaced by
TC.

.0005
GLYCOGEN STORAGE DISEASE Ib
GLYCOGEN STORAGE DISEASE Ic, INCLUDED
SLC37A4, 170-BP DEL, NT148

In a Japanese patient with glycogen storage disease (GSD) Ib (232220),
Kure et al. (1998) found compound heterozygosity for the W118R mutation
(602671.0003) and a G-to-A substitution within a consensus splicing
donor site, which resulted in deletion of 170 bp (nucleotides 148-317)
and involved the initiation methionine codon.

In a German patient with GSD Ic (232240), Janecke et al. (1999)
identified the same mutation in homozygous state. Genomic sequencing
revealed a homozygous 317+1G-T substitution within a consensus splicing
donor site.

.0006
GLYCOGEN STORAGE DISEASE Ib
GLYCOGEN STORAGE DISEASE Ic, INCLUDED
SLC37A4, 2-BP DEL, 1211CT

In 2 families, Veiga-da-Cunha et al. (1998) found that patients with
glycogen storage disease (GSD) Ib (232220) were homozygous for a 2-bp
deletion (1211-1212delCT) in the G6PT1 gene, resulting in a change in
reading frame after ala347.

This common frameshift mutation was reported by Veiga-da-Cunha et al.
(1998) to be present in 8 GSD Ib patients. In a Turkish patient with GSD
Ic (232240), Janecke et al. (1999) identified the same mutation. Thus,
GSD Ib and Ic result from the same mutation of the same gene.

.0007
GLYCOGEN STORAGE DISEASE Ic
SLC37A4, IVS8, 4-BP DEL

In a Pakistani family in which Fenske et al. (1998) mapped the glycogen
storage disease Ic (232240) locus to 11q23-q24.2, Veiga-da-Cunha et al.
(1998) demonstrated a splice site mutation at the exon 8/intron 8
junction in homozygous state in affected individuals.

.0008
GLYCOGEN STORAGE DISEASE Ic
SLC37A4, TRP96TER

In a female patient with glycogen storage disease (GSD) Ic (232240),
Veiga-da-Cunha et al. (1998) demonstrated compound heterozygosity for a
trp96-to-ter (W96X) nonsense mutation and insertion of a 4-amino acid
repeat after met311 (602671.0009) of the G6PT1 gene. They found the
latter mutation in compound heterozygous state in a patient diagnosed as
GSD Ib (232220).

.0009
GLYCOGEN STORAGE DISEASE Ib
GLYCOGEN STORAGE DISEASE Ic, INCLUDED
SLC37A4, 12-BP INS, NT1103

In 2 unrelated patients, 1 with glycogen storage disease (GSD) Ib
(232220) and 1 with GSD Ic (232240), Veiga-da-Cunha et al. (1998)
observed compound heterozygosity for a 12-nucleotide insertion resulting
in a 4-amino acid repeat inserted after met311. In the patient with GSD
Ic, the mutation was combined with the missense mutation trp96 to ter
(602671.0008); in the patient with GSD Ib, the mutation was combined
with a deletion causing a shift of reading frame after ala347. That
mutation due to deletion of nucleotides CT (1211-1212) (602671.0006) was
found in homozygous state in 2 families with GSD Ib.

.0010
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, VAL235DEL

In a consanguineous family with GSD Ib (232220), Hou et al. (1999)
identified a 3-bp deletion (val235del) in exon 2 of the G6PT1 gene.

.0011
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, IVS7, G-T, +1

In a nonconsanguineous family with GSD Ib (232220), Hou et al. (1999)
identified a G-to-T change at position +1 of IVS7 of the G6PT1 gene.

.0012
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, IVS1, G-A, +1

Hou et al. (1999) determined that a patient with GSD Ib (232220) was a
compound heterozygote for the W118R mutation (602671.0003) and a G-to-A
change at position +1 in intron 1 of the G6PT1 gene.

.0013
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, ARG28HIS

In 2 of 9 families with GSD Ib (232220), Hiraiwa et al. (1999)
identified a G-to-A transition at nucleotide 252 of the G6PT1 gene,
resulting in an arg28-to-his mutation. They demonstrated that this
mutation resulted in inactive G6P transport.

.0014
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, ARG415TER

In patients with classic GSD type Ib (232220), Veiga-da-Cunha et al.
(1999) reported a T-to-C transition at nucleotide 415 in exon 8 of the
G6PT1 gene, resulting in an arg415-to-ter substitution.

.0015
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, GLY339ASP

In a 25-year-old patient with glycogen storage disease type Ib based on
enzymatic analysis but no evidence of neutropenia or recurrent
infections, Kure et al. (2000) identified an arg415-to-ter mutation
(606671.0014), which has been reported in patients with neutropenia, in
compound heterozygosity with a gly339-to-asp mutation due to a G-to-A
transition at nucleotide 1185 in exon 7 of the G6PT1 gene.

.0016
GLYCOGEN STORAGE DISEASE Ib
SLC37A4, 794G-A

In a 9-year-old patient with glycogen storage type Ib (232220) but no
evidence of neutropenia or recurrent infections, Kure et al. (2000)
identified homozygosity for a G-to-A transition at nucleotide 794 of the
G6PT1 gene, which is the last nucleotide of exon 3, resulting in
skipping of exon 3 in a proportion of amplified cDNA. Kure et al. (2000)
suggested that the residual full-length allele spared the patient from
the neutropenia and its complications.

*FIELD* RF
1. Belkaid, A.; Copland, I. B.; Massillon, D.; Annabi, B.: Silencing
of the human microsomal glucose-6-phosphate translocase induces glioma
cell death: potential new anticancer target for curcumin. FEBS Lett. 580:
3746-3752, 2006.

2. Chen, L.-Y.; Lin, B.; Pan, C.-J.; Hiraiwa, H.; Chou, J. Y.: Structural
requirements for the stability and microsomal transport activity of
the human glucose 6-phosphate transporter. J. Biol. Chem. 275: 34280-34286,
2000.

3. Chen, L.-Y.; Pan, C.-J.; Shieh, J.-J.; Chou, J. Y.: Structure-function
analysis of the glucose-6-phosphate transporter deficient in glycogen
storage disease type Ib. Hum. Molec. Genet. 11: 3199-3207, 2002.

4. Chen, L.-Y.; Shieh, J.-J.; Lin, B.; Pan, C.-J.; Gao, J.-L.; Murphy,
P. M.; Roe, T. F.; Moses, S.; Ward, J. M.; Lee, E. J.; Westphal, H.;
Mansfield, B. C.; Chou, J. Y.: Impaired glucose homeostasis, neutrophil
trafficking and function in mice lacking the glucose-6-phosphate transporter. Hum.
Molec. Genet. 12: 2547-2558, 2003.

5. Fenske, C. D.; Jeffery, S.; Weber, J. L.; Houlston, R. S.; Leonard,
J. V.; Lee, P.: Localisation of the gene for glycogen storage disease
type Ic by homozygosity mapping to 11q. J. Med. Genet. 35: 269-272,
1998.

6. Galli, L.; Orrico, A.; Marcolongo, P.; Fulceri, R.; Burchell, A.;
Melis, D.; Parini, R.; Gatti, R.; Lam, C.-W.; Benedetti, A.; Sorrentino,
V.: Mutations in the glucose-6-phosphate transporter (G6PT) gene
in patients with glycogen storage diseases type 1b and 1c. FEBS Lett. 459:
255-258, 1999.

7. Gerin, I.; Veiga-da-Cunha, M.; Achouri, Y.; Collet, J.-F.; Van
Schaftingen, E.: Sequence of a putative glucose 6-phosphate translocase,
mutated in glycogen storage disease type Ib. FEBS Lett. 419: 235-238,
1997.

8. Gerin, I.; Veiga-da-Cunha, M.; Noel, G.; Van Schaftingen, E.:
Structure of the gene mutated in glycogen storage disease type Ib. Gene 227:
189-195, 1999.

9. Hiraiwa, H.; Pan, C.-J.; Lin, B.; Akiyama, T. E.; Gonzalez, F.
J.; Chou, J. Y.: A molecular link between the common phenotypes of
type 1 glycogen storage disease and HNF1-alpha-null mice. J. Biol.
Chem. 276: 7963-7967, 2001.

10. Hiraiwa, H.; Pan, C.-J.; Lin, B.; Moses, S. W.; Chou, J. Y.:
Inactivation of the glucose 6-phosphate transporter causes glycogen
storage disease type 1b. J. Biol. Chem. 274: 5532-5536, 1999.

11. Hou, D.-C.; Kure, S.; Suzuki, Y.; Hasegawa, Y.; Hara, Y.; Inoue,
T.; Kida, Y.; Matsubara, Y.; Narisawa, K.: Glycogen storage disease
type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate
transporter gene. Am. J. Med. Genet. 86: 253-257, 1999.

12. Ihara, K.; Kuromaru, R.; Hara, T.: Genomic structure of the human
glucose 6-phosphate translocase gene and novel mutations in the gene
of a Japanese patient with glycogen storage disease type Ib. Hum.
Genet. 103: 493-496, 1998.

13. Ihara, K.; Nomura, A.; Hikino, S.; Takada, H.; Hara, T.: Quantitative
analysis of glucose-6-phosphate translocase gene expression in various
human tissues and haematopoietic progenitor cells. J. Inherit. Metab.
Dis. 23: 583-592, 2000.

14. Ihara, K.; Takabayashi, A.; Terasaki, K.; Hara, T.: Assignment
of glucose 6-phosphate translocase (G6PT1) to human chromosome band
11q23.3 by in situ hybridization. Cytogenet. Cell Genet. 83: 50-51,
1998.

15. Janecke, A. R.; Bosshard, N. U.; Mayatepek, E.; Schulze, A.; Gitzelmann,
R.; Burchell, A.; Bartram, C. R.; Janssen, B.: Molecular diagnosis
of type 1c glycogen storage disease. Hum. Genet. 104: 275-277, 1999.

16. Janecke, A. R.; Lindner, M.; Erdel, M.; Mayatepek, E.; Moslinger,
D.; Podskarbi, T.; Fresser, F.; Stockler-Ipsiroglu, S.; Hoffmann,
G. F.; Utermann, G.: Mutation analysis in glycogen storage disease
type 1 non-a. Hum. Genet. 107: 285-289, 2000.

17. Kure, S.; Hou, D.-C.; Suzuki, Y.; Yamagishi, A.; Hiratsuka, M.;
Fukuda, T.; Sugie, H.; Kondo, N.; Matsubara, Y.; Narisawa, K.: Glycogen
storage disease type Ib without neutropenia. J. Pediat. 137: 253-256,
2000.

18. Kure, S.; Suzuki, Y.; Matsubara, Y.; Sakamoto, O.; Shintaku, H.;
Isshiki, G.; Hoshida, C.; Izumi, I.; Sakura, N.; Narisawa, K.: Molecular
analysis of glycogen storage disease type Ib: identification of a
prevalent mutation among Japanese patients and assignment of a putative
glucose-6-phosphate translocase gene to chromosome 11. Biochem. Biophys.
Res. Commun. 248: 426-431, 1998.

19. Lin, B.; Pan, C.-J.; Chou, J. Y.: Human variant glucose-6-phosphate
transporter is active in microsomal transport. Hum. Genet. 107:
526-529, 2000.

20. Marcolongo, P.; Barone, V.; Priori, G.; Pirola, B.; Giglio, S.;
Biasucci, G.; Zammarchi, E.; Parenti, G.; Burchell, A.; Benedetti,
A.; Sorrentino, V.: Structure and mutation analysis of the glycogen
storage disease type 1b gene. FEBS Lett. 436: 247-250, 1998. Note:
Erratum: FEBS Lett. 445: 451 only, 1999.

21. Veiga-da-Cunha, M.; Gerin, I.; Chen, Y.-T.; de Barsy, T.; de Lonlay,
P.; Dionisi-Vici, C.; Fenske, C. D.; Lee, P. J.; Leonard, J. V.; Maire,
I.; McConkie-Rosell, A.; Schweitzer, S.; Vikkula, M.; Van Schaftingen,
E.: A gene on chromosome 11q23 coding for a putative glucose-6-phosphate
translocase is mutated in glycogen-storage disease types Ib and Ic. Am.
J. Hum. Genet. 63: 976-983, 1998.

22. Veiga-da-Cunha, M.; Gerin, I.; Chen, Y.-T.; Lee, P. J.; Leonard,
J. V.; Maire, I.; Wendel, U.; Vikkula, M.; Van Schaftingen, E.: The
putative glucose 6-phosphate translocase gene is mutated in essentially
all cases of glycogen storage disease type I non-a. Europ. J. Hum.
Genet. 7: 717-723, 1999.

*FIELD* CN
Patricia A. Hartz - updated: 2/13/2009
George E. Tiller - updated: 9/12/2005
George E. Tiller - updated: 9/2/2004
Ada Hamosh - updated: 3/4/2004
Victor A. McKusick - updated: 2/5/2002
Ada Hamosh - updated: 4/20/2001
Victor A. McKusick - updated: 12/19/2000
Ada Hamosh - updated: 10/31/2000
Victor A. McKusick - updated: 10/3/2000
Victor A. McKusick - updated: 1/19/2000
Victor A. McKusick - updated: 11/8/1999
Victor A. McKusick - updated: 10/21/1999
Victor A. McKusick - updated: 4/26/1999
Carol A. Bocchini - updated: 4/5/1999
Ada Hamosh - updated: 3/10/1999
Victor A. McKusick - updated: 10/22/1998
Victor A. McKusick - updated: 9/2/1998

*FIELD* CD
Jennifer P. Macke: 5/30/1998

*FIELD* ED
terry: 11/29/2012
carol: 5/8/2009
mgross: 2/17/2009
terry: 2/13/2009
alopez: 10/20/2005
terry: 9/12/2005
carol: 9/3/2004
terry: 9/2/2004
carol: 3/4/2004
terry: 3/4/2004
mgross: 2/19/2002
terry: 2/5/2002
alopez: 4/30/2001
terry: 4/20/2001
mcapotos: 1/4/2001
mcapotos: 1/3/2001
terry: 12/19/2000
mgross: 11/2/2000
terry: 10/31/2000
mcapotos: 10/12/2000
mcapotos: 10/9/2000
terry: 10/3/2000
mcapotos: 1/28/2000
mcapotos: 1/24/2000
terry: 1/19/2000
alopez: 11/12/1999
terry: 11/8/1999
carol: 10/25/1999
terry: 10/21/1999
mgross: 5/7/1999
mgross: 4/29/1999
terry: 4/26/1999
mgross: 4/7/1999
carol: 4/5/1999
alopez: 3/11/1999
alopez: 3/10/1999
carol: 10/26/1998
terry: 10/22/1998
carol: 9/8/1998
alopez: 9/2/1998
alopez: 8/3/1998
alopez: 7/17/1998
alopez: 6/1/1998