RBCC Red Blood Cell Collection

PFKM (PFKX) [Confidence: high (present in two of the MS resources)]
6-phosphofructokinase, muscle type; 2.7.1.11 (Phosphofructo-1-kinase isozyme A; PFK-A; Phosphofructokinase-M; Phosphofructokinase 1; Phosphohexokinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00181260
IPI00181260 Splice isoform 1 of P08237 6-phosphofructokinase, muscle type Splice isoform 1 of P08237 6-phosphofructokinase, muscle type membrane n/a n/a 1 n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 glycolisis, cytoplasmic n/a found at its expected molecular weight found at molecular weight

UniProt P08237
ID K6PF_HUMAN Reviewed; 780 AA.
AC P08237; J3KNX3; Q16814; Q16815; Q6ZTT1;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 160.
DE RecName: Full=6-phosphofructokinase, muscle type;
DE EC=2.7.1.11;
DE AltName: Full=Phosphofructo-1-kinase isozyme A;
DE Short=PFK-A;
DE Short=Phosphofructokinase-M;
DE AltName: Full=Phosphofructokinase 1;
DE AltName: Full=Phosphohexokinase;
GN Name=PFKM; Synonyms=PFKX;
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=Muscle;
RX PubMed=1833270; DOI=10.1016/0378-1119(91)90262-A;
RA Yamasaki T., Nakajima H., Kono N., Hotta K., Yamada K., Imai E.,
RA Kuwajima M., Noguchi T., Tanaka T., Tarui S.;
RT "Structure of the entire human muscle phosphofructokinase-encoding
RT gene: a two-promoter system.";
RL Gene 104:277-282(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=2526045; DOI=10.1016/0378-1119(89)90372-7;
RA Sharma P.M., Reddy G.R., Vora S., Babior B.M., McLachlan A.;
RT "Cloning and expression of a human muscle phosphofructokinase cDNA.";
RL Gene 77:177-183(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=2822475; DOI=10.1016/0014-5793(87)80519-7;
RA Nakajima H., Noguchi T., Yamasaki T., Kono N., Tanaka T., Tarui S.;
RT "Cloning of human muscle phosphofructokinase cDNA.";
RL FEBS Lett. 223:113-116(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Muscle;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 272-681 (ISOFORM 2).
RC TISSUE=Muscle;
RX PubMed=2140567;
RA Sharma P.M., Reddy G.R., Babior B.M., McLachlan A.;
RT "Alternative splicing of the transcript encoding the human muscle
RT isoenzyme of phosphofructokinase.";
RL J. Biol. Chem. 265:9006-9010(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
RC TISSUE=Muscle;
RX PubMed=2526044; DOI=10.1016/0378-1119(89)90019-X;
RA Valdez B.C., Chen Z., Sosa M.G., Younathan E.S., Chang S.H.;
RT "Human 6-phosphofructo-1-kinase gene has an additional intron upstream
RT of start codon.";
RL Gene 76:167-169(1989).
RN [9]
RP REVIEW ON GSD7 VARIANTS.
RX PubMed=7550225; DOI=10.1002/humu.1380060102;
RA Raben N., Sherman J.B.;
RT "Mutations in muscle phosphofructokinase gene.";
RL Hum. Mutat. 6:1-6(1995).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
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 [12]
RP VARIANTS GSD7 PRO-39 AND ALA-543.
RX PubMed=7513946;
RA Tsujino S., Servidei S., Tonin P., Shanske S., Azan G., DiMauro S.;
RT "Identification of three novel mutations in non-Ashkenazi Italian
RT patients with muscle phosphofructokinase deficiency.";
RL Am. J. Hum. Genet. 54:812-819(1994).
RN [13]
RP VARIANTS GSD7 GLN-100; ASP-209 AND HIS-696.
RX PubMed=7825568;
RA Raben N., Exelbert R., Spiegel R., Sherman J.B., Plotz P.,
RA Heinisch J.J.;
RT "Functional expression of human mutant phosphofructokinase in yeast:
RT genetic defects in French Canadian and Swiss patients with
RT phosphofructokinase deficiency.";
RL Am. J. Hum. Genet. 56:131-141(1995).
RN [14]
RP VARIANT GSD7 CYS-686.
RX PubMed=8889589;
RX DOI=10.1002/(SICI)1098-1004(1996)8:3<273::AID-HUMU13>3.3.CO;2-4;
RA Hamaguchi T., Nakajima H., Noguchi T., Nakagawa C., Kuwajima M.,
RA Kono N., Tarui S., Matsuzawa Y.;
RT "Novel missense mutation (W686C) of the phosphofructokinase-M gene in
RT a Japanese patient with a mild form of glycogenosis VII.";
RL Hum. Mutat. 8:273-275(1996).
CC -!- FUNCTION: Catalyzes the third step of glycolysis, the
CC phosphorylation of fructose-6-phosphate (F6P) by ATP to generate
CC fructose-1,6-bisphosphate (FBP) and ADP.
CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D-
CC fructose 1,6-bisphosphate.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Allosteric enzyme activated by ADP, AMP, or
CC fructose bisphosphate and inhibited by ATP or citrate.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 3/4.
CC -!- SUBUNIT: Tetramer. Muscle is M4, liver is L4, and red cell is M3L,
CC M2L2, or ML3.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-514788, EBI-514788;
CC P17858:PFKL; NbExp=6; IntAct=EBI-514788, EBI-487243;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P08237-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08237-2; Sequence=VSP_004667;
CC Name=3;
CC IsoId=P08237-3; Sequence=VSP_046125;
CC Note=No experimental confirmation available. Ref.4 (BAC86498)
CC sequence is in conflict in position: 2:H->L;
CC -!- PTM: GlcNAcylation decreases enzyme activity (By similarity).
CC -!- DISEASE: Glycogen storage disease 7 (GSD7) [MIM:232800]: A
CC metabolic disorder characterized by exercise intolerance with
CC associated nausea and vomiting, muscle cramping, exertional
CC myopathy and compensated hemolysis. Short bursts of intense
CC activity are particularly difficult. Severe muscle cramps and
CC myoglobinuria develop after vigorous exercise. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of
CC subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet)
CC isoenzymes.
CC -!- SIMILARITY: Belongs to the phosphofructokinase family. Two domains
CC subfamily.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PFKM";
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DR EMBL; M59741; AAA82938.1; -; Genomic_DNA.
DR EMBL; M59720; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59721; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59722; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59723; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59724; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59725; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59726; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59727; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59728; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59729; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59730; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59731; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59732; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59733; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59734; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59735; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59736; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59737; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59738; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59739; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59740; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M26066; AAA60068.1; -; mRNA.
DR EMBL; Y00698; CAA68692.1; -; mRNA.
DR EMBL; AK126229; BAC86498.1; -; mRNA.
DR EMBL; AC004801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000534; AAH00534.1; -; mRNA.
DR EMBL; BC012799; AAH12799.1; -; mRNA.
DR EMBL; BC013298; AAH13298.1; -; mRNA.
DR EMBL; BC021203; AAH21203.1; -; mRNA.
DR EMBL; J05533; AAA79220.1; -; mRNA.
DR EMBL; M24925; AAA36436.1; -; Genomic_DNA.
DR PIR; A91605; KIHUFM.
DR RefSeq; NP_000280.1; NM_000289.5.
DR RefSeq; NP_001160158.1; NM_001166686.1.
DR RefSeq; NP_001160159.1; NM_001166687.1.
DR RefSeq; NP_001160160.1; NM_001166688.1.
DR RefSeq; XP_005269034.1; XM_005268977.1.
DR RefSeq; XP_005269035.1; XM_005268978.1.
DR RefSeq; XP_005269036.1; XM_005268979.1.
DR UniGene; Hs.75160; -.
DR ProteinModelPortal; P08237; -.
DR SMR; P08237; 9-756.
DR IntAct; P08237; 7.
DR MINT; MINT-5005297; -.
DR STRING; 9606.ENSP00000352842; -.
DR BindingDB; P08237; -.
DR ChEMBL; CHEMBL3291; -.
DR PhosphoSite; P08237; -.
DR DMDM; 125126; -.
DR UCD-2DPAGE; P08237; -.
DR PaxDb; P08237; -.
DR PRIDE; P08237; -.
DR DNASU; 5213; -.
DR Ensembl; ENST00000312352; ENSP00000309438; ENSG00000152556.
DR Ensembl; ENST00000340802; ENSP00000345771; ENSG00000152556.
DR Ensembl; ENST00000359794; ENSP00000352842; ENSG00000152556.
DR Ensembl; ENST00000395233; ENSP00000378656; ENSG00000152556.
DR Ensembl; ENST00000547587; ENSP00000449426; ENSG00000152556.
DR Ensembl; ENST00000551804; ENSP00000448177; ENSG00000152556.
DR GeneID; 5213; -.
DR KEGG; hsa:5213; -.
DR UCSC; uc001rra.2; human.
DR CTD; 5213; -.
DR GeneCards; GC12P048501; -.
DR HGNC; HGNC:8877; PFKM.
DR HPA; HPA002117; -.
DR MIM; 232800; phenotype.
DR MIM; 610681; gene.
DR neXtProt; NX_P08237; -.
DR Orphanet; 371; Glycogen storage disease due to muscle phosphofructokinase deficiency.
DR PharmGKB; PA33216; -.
DR eggNOG; COG0205; -.
DR HOGENOM; HOG000200154; -.
DR HOVERGEN; HBG000976; -.
DR InParanoid; P08237; -.
DR KO; K00850; -.
DR OMA; VYHMASK; -.
DR OrthoDB; EOG7ZSHV5; -.
DR PhylomeDB; P08237; -.
DR BioCyc; MetaCyc:HS07832-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P08237; -.
DR UniPathway; UPA00109; UER00182.
DR ChiTaRS; PFKM; human.
DR GeneWiki; PFKM; -.
DR GenomeRNAi; 5213; -.
DR NextBio; 20164; -.
DR PMAP-CutDB; P08237; -.
DR PRO; PR:P08237; -.
DR ArrayExpress; P08237; -.
DR Bgee; P08237; -.
DR CleanEx; HS_PFKM; -.
DR Genevestigator; P08237; -.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0006096; P:glycolysis; IMP:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:BHF-UCL.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0051259; P:protein oligomerization; IDA:BHF-UCL.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR009161; 6-phosphofructokinase_euk.
DR InterPro; IPR022953; Phosphofructokinase.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR Pfam; PF00365; PFK; 2.
DR PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 2.
DR TIGRFAMs; TIGR02478; 6PF1K_euk; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding;
KW Complete proteome; Disease mutation; Glycogen storage disease;
KW Glycolysis; Glycoprotein; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 780 6-phosphofructokinase, muscle type.
FT /FTId=PRO_0000112016.
FT NP_BIND 35 39 ATP (By similarity).
FT NP_BIND 193 197 ATP (By similarity).
FT NP_BIND 210 226 ATP (By similarity).
FT ACT_SITE 166 166 Proton acceptor (By similarity).
FT METAL 224 224 Magnesium; via carbonyl oxygen (By
FT similarity).
FT BINDING 201 201 Substrate (By similarity).
FT BINDING 292 292 Substrate (By similarity).
FT BINDING 298 298 Substrate (By similarity).
FT BINDING 301 301 Substrate (By similarity).
FT MOD_RES 2 2 N-acetylthreonine (By similarity).
FT MOD_RES 667 667 Phosphoserine.
FT MOD_RES 775 775 Phosphoserine (By similarity).
FT CARBOHYD 530 530 O-linked (GlcNAc) (By similarity).
FT VAR_SEQ 1 1 M -> MHKDEFHLKFFMCVIQSRQLVRTPQRTAGEASTSSM
FT LIPKPPPKTDILKSLDTMDDPDTVGSIPVFKTEWIM (in
FT isoform 3).
FT /FTId=VSP_046125.
FT VAR_SEQ 282 312 Missing (in isoform 2).
FT /FTId=VSP_004667.
FT VARIANT 39 39 R -> L (in GSD7; Ashkenazi).
FT /FTId=VAR_006063.
FT VARIANT 39 39 R -> P (in GSD7; Italian).
FT /FTId=VAR_006064.
FT VARIANT 100 100 R -> Q (in GSD7; Swiss; dbSNP:rs2228500).
FT /FTId=VAR_006065.
FT VARIANT 209 209 G -> D (in GSD7; French Canadian).
FT /FTId=VAR_006066.
FT VARIANT 543 543 D -> A (in GSD7; Italian).
FT /FTId=VAR_006067.
FT VARIANT 686 686 W -> C (in GSD7; Japanese).
FT /FTId=VAR_006068.
FT VARIANT 696 696 R -> H (in GSD7; Swiss;
FT dbSNP:rs41291971).
FT /FTId=VAR_006069.
FT CONFLICT 670 670 P -> S (in Ref. 4; BAC86498).
SQ SEQUENCE 780 AA; 85183 MW; 769A2C01F97D1122 CRC64;
MTHEEHHAAK TLGIGKAIAV LTSGGDAQGM NAAVRAVVRV GIFTGARVFF VHEGYQGLVD
GGDHIKEATW ESVSMMLQLG GTVIGSARCK DFREREGRLR AAYNLVKRGI TNLCVIGGDG
SLTGADTFRS EWSDLLSDLQ KAGKITDEEA TKSSYLNIVG LVGSIDNDFC GTDMTIGTDS
ALHRIMEIVD AITTTAQSHQ RTFVLEVMGR HCGYLALVTS LSCGADWVFI PECPPDDDWE
EHLCRRLSET RTRGSRLNII IVAEGAIDKN GKPITSEDIK NLVVKRLGYD TRVTVLGHVQ
RGGTPSAFDR ILGSRMGVEA VMALLEGTPD TPACVVSLSG NQAVRLPLME CVQVTKDVTK
AMDEKKFDEA LKLRGRSFMN NWEVYKLLAH VRPPVSKSGS HTVAVMNVGA PAAGMNAAVR
STVRIGLIQG NRVLVVHDGF EGLAKGQIEE AGWSYVGGWT GQGGSKLGTK RTLPKKSFEQ
ISANITKFNI QGLVIIGGFE AYTGGLELME GRKQFDELCI PFVVIPATVS NNVPGSDFSV
GADTALNTIC TTCDRIKQSA AGTKRRVFII ETMGGYCGYL ATMAGLAAGA DAAYIFEEPF
TIRDLQANVE HLVQKMKTTV KRGLVLRNEK CNENYTTDFI FNLYSEEGKG IFDSRKNVLG
HMQQGGSPTP FDRNFATKMG AKAMNWMSGK IKESYRNGRI FANTPDSGCV LGMRKRALVF
QPVAELKDQT DFEHRIPKEQ WWLKLRPILK ILAKYEIDLD TSDHAHLEHI TRKRSGEAAV
//

MIM 232800
*RECORD*
*FIELD* NO
232800
*FIELD* TI
#232800 GLYCOGEN STORAGE DISEASE VII
;;GSD VII; GSD7;;
MUSCLE PHOSPHOFRUCTOKINASE DEFICIENCY;;
read morePFKM DEFICIENCY;;
TARUI DISEASE
*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease VII is caused by mutation in the gene encoding muscle
phosphofructokinase (PFKM; 610681).

DESCRIPTION

Glycogen storage disease VII is an autosomal recessive metabolic
disorder characterized clinically by exercise intolerance, muscle
cramping, exertional myopathy, and compensated hemolysis. Myoglobinuria
may also occur. The deficiency of the muscle isoform of PFK results in a
total and partial loss of muscle and red cell PFK activity,
respectively. Raben and Sherman (1995) noted that not all patients with
GSD VII seek medical care because in some cases it is a relatively mild
disorder.

CLINICAL FEATURES

Tarui et al. (1965) first described this disorder in 3 affected Japanese
sibs, a 20-year-old female and 23- and 27-year-old males. The parents
were first cousins. The affected sibs complained of easy fatigability
and inability to keep pace with other persons. Physical examination
revealed marked weakness and stiffness in muscle groups subjected to
vigorous or prolonged exertion. Venous lactate failed to rise with the
ischemic exercise test; 1 sib had myoglobinuria following the test. PFK
activity was entirely absent in muscle and about half normal in
erythrocytes.

Layzer et al. (1967) reported an 18-year-old male with muscle PFK
deficiency and red cell hemolysis. The erythrocytes of both unaffected
parents showed partial enzyme activity. Layzer et al. (1967) suggested
that red cell PFK is composed of 2 types of subunits, 1 of which is the
sole subunit present in muscle PFK. The authors concluded that the
genetic defect likely involves a subunit common to both the muscle and
the red cell enzyme, and furthermore postulated autosomal recessive
inheritance.

Satoyoshi and Kowa (1967) described myopathy in 2 affected brothers.
Family history revealed that myopathy was also present in a sister,
their mother, and a son of 1 sister. Onset was about age 35 years with
delayed muscle pain and stiffness on exertion, but absence of
contracture or weakness on ischemic exercise. Phosphofructokinase
activity was about 40% of normal in skeletal muscle. Oral ingestion of
fructose relieved the symptoms. Satoyoshi and Kowa (1967) suggested the
possible role of an inhibitor in the disease process. Waterbury and
Frenkel (1972) found an intermediate level (60% of normal) of the PFK
enzyme in the red cells of a physician with chronic compensated
hemolysis and in his mother and grandmother who lacked evidence of
hemolysis. The proband had 9% reticulocytes. PFK of the proband showed
markedly increased lability on in vitro studies. The absence of muscle
disease was atypical of the usual phenotype associated with type VII
glycogen storage disease.

Vora et al. (1980) studied a patient with the rare Tarui disease, in
which myopathy and hemolysis are associated with PFK deficiency. The
proband was a 31-year-old man who suffered from muscular weakness and
myoglobinuria on exertion. He showed mild erythrocytosis despite
laboratory evidence of hemolysis. His red cell PFK was exclusively of
the L (liver) type (PFKL; 171860). Decreased production of 2,3-DPG was
held responsible for the paradoxic erythrocytosis.

Tani et al. (1983) studied 2 unrelated Japanese kindreds with PFKM
deficiency associated with congenital nonspherocytic hemolytic anemia
and mild myopathy. Both probands had jaundice, gallstones, and slight to
moderate exercise intolerance. Both also had decreased red cell PFK
activity and no increase of blood lactate during ischemic exercise
testing. Electrophoresis of red cell PFK showed complete absence of the
PFK muscle isozyme.

Etiemble et al.(1976), Etiemble et al. (1980), Miwa et al. (1972), and
Kahn et al. (1975) reported cases of hereditary nonspherocytic hemolytic
anemia associated with partial erythrocyte phosphofructokinase
deficiency (about 60% of normal). Although none of the patients had
muscle symptoms, studies showed that the PFKM isoform was unstable. Vora
et al. (1980) speculated that the heterogeneous group of hemolytic
syndromes associated with partial red cell PFK deficiency without
myopathy (Boulard et al., 1974; Kahn et al., 1975) may represent total
absence of PFKL subunits or qualitative defects of M or L subunits. Vora
et al. (1983) suggested that GSD VII could be classified clinically into
5 phenotypic subtypes: type I is the classic syndrome characterized by
exertional myopathy and hemolysis; type II by isolated myopathy; type
III by isolated hemolysis; and type IV by asymptomatic partial
deficiency of red cell PFK. Type V could represent the rare progressive,
fatal myopathy of infancy (see below).

Hays et al. (1981) described muscle phosphofructokinase deficiency in a
61-year-old woman who had mild limb weakness all her life but no cramps
or myoglobinuria. Limb weakness had worsened progressively in the
previous 5 years. An abnormal polysaccharide was identified in muscle
and thought to be related to a greatly elevated concentration of muscle
glucose-6-phosphate, an activator of the chain-elongating enzyme
glycogen synthase. Zanella et al. (1982) studied a 61-year-old man of
northern Italian extraction, born of consanguineous parents, who had a
lifelong intolerance for prolonged exercise and developed spontaneous
muscle cramps. He also had intermittent mild jaundice from the age of
46: cholecystectomy was performed for gallstones at age 51, and, at age
54, he developed anemia and marked jaundice. Creatine phosphokinase
levels were greatly increased. PFK activity was absent from muscle and
was 39% of normal in red cells. Biochemical studies showed that the PFKM
subunit was structurally abnormal and catalytically inactive.

Vora et al. (1987) reported an 80-year-old man who presented with a
10-year history of progressive weakness of the legs as the only symptom.
Residual red cell PFK showed the presence of a few M-containing isozymes
in addition to the predominant L4 species, suggesting that the genetic
lesion in this patient was a 'leaky' mutation of the gene coding for the
M subunit. Danon et al. (1988) described a 75-year-old man with a
10-year history of slowly progressive limb weakness without cramps or
myoglobinuria associated with PFKM deficiency. His asymptomatic daughter
had 63% erythrocyte PFK activity. Argov et al. (1994) suggested that
late-onset myopathy may represent a natural course of PFK deficiency
rather than a separate nosologic entity because many patients give a
history of easy fatigability and exercise intolerance since childhood.

Tsujino et al. (1994) reported a 17-year-old Italian man who complained
since childhood of myalgia and cramps after intense exercise. He had had
no episodes of myoglobinuria. His red cell count and hemoglobin were
normal, but he had reticulocytosis (6.1%), indicating compensated
hemolysis. Muscle biopsy showed myopathic changes with subsarcolemmal
glycogen accumulation. A brother was also affected.

Nakagawa et al. (1995) and Hamaguchi et al. (1996) reported a
22-year-old Japanese man with a mild form of PFKM deficiency. He was
brought to medical attention because of a gastric ulcer. While treated
for the ulcer, he reported a history of mild fatigability and nausea and
vomiting with strenuous exercise, and recurrent gouty arthritis, but no
muscle pain, cramps, or dark urine. His parents were first cousins.
Exercise testing resulted in increased serum creatine kinase, mild
increase in serum lactate, and increased serum uric acid. Muscle studies
showed almost complete absence of PFK activity and increased glycogen
content. Molecular analysis identified a mutation in the PFKM gene
(610681.0008).

- Rapidly Progressive Fatal Infantile Form

There are rare reports of a rapidly progressive fatal infantile form of
PFKM deficiency. Servidei et al. (1986) reported an unusually severe
case of PFKM deficiency. An affected girl had onset in infancy of limb
weakness, seizures, cortical blindness, and corneal clouding, with death
at age 7 months of respiratory failure. Amit et al. (1992) described a
similar case of fatal infantile glycogen storage disease with
multisystem manifestations in an infant girl born of consanguineous
Bedouin parents. An older brother had suffered from similar weakness and
cardiomyopathy; both sibs died at the age of 21 months.
Phosphofructokinase activity was lacking in both liver and muscle. Amit
et al. (1992) found reports of only 4 other cases (Danon et al., 1981)
and 1 other family (Guibaud et al., 1978), and suggested that this
multisystem form of phosphofructokinase deficiency may be related to the
absence of an unknown activator common to all the PFK isozymes. Raben
and Sherman (1995) noted that none of the patients with the rapidly
progressive fatal infantile form of the disorder had evidence of
hemolysis.

BIOCHEMICAL FEATURES

Vora et al. (1983) studied 3 patients with exertional myopathy of
varying severity and a total lack of PFKM. All had high-normal
hemoglobin levels despite hemolysis and early-onset hyperuricemia. In
red cells, the levels of hexose monophosphates were elevated and those
of 2,3-diphosphoglycerate (2,3-DPG) were depressed, causing strikingly
increased hemoglobin-oxygen affinity. Residual red cell PFK consisted
exclusively of L4 isozyme; however, with a monoclonal antibody, an
immunoreactive M subunit was demonstrated in cultured fibroblasts.
Early-onset hyperuricemia and gout occurred in this disorder as in type
I glycogenosis (GSD1; 232200). In both GSD I and GSD VII, increased
shunting of fructose-6-phosphate via the hexose monophosphate shunt is
proposed to result in increased production of 5-phosphoribosyl
pyrophosphate (PRPP).

Davidson et al. (1983) demonstrated immunoreactive M subunits of PFK
despite a lack of enzyme activity in 3 cases of muscle
phosphofructokinase deficiency. The findings suggested that the disease
mutation is in the structural gene for the M subunit of PFK.

Mineo et al. (1987) provided an explanation for the hyperuricemia of GSD
type VII. In the disorder, there is a net degradation of ATP and an
accumulation of ADP or AMP. These accumulated adenine nucleotides are
then degraded at a more rapid rate to several purine metabolites,
including uric acid. A similar mechanism may explain the reports of uric
acid nephropathy after heavy exertion and the association between
ethanol ingestion and hyperuricemia.

Some patients with PFKM deficiency have reported that fatigue of active
muscles occurs more rapidly after a high-carbohydrate meal. In 4 such
patients, Haller and Lewis (1991) observed that the oxidative capacity
of muscle and the capacity for aerobic exercise varied according to the
availability of blood-borne fuels. The authors concluded that glucose
infusion lowers exercise tolerance by inhibiting lipolysis and thus
depriving muscle of oxidative substrate (plasma free fatty acids and
ketones); this impairs the capacity of working muscle to extract oxygen
and lowers maximal oxygen consumption.

Ristow et al. (1997) studied 4 members (2 parents and 2 sons) of an
Ashkenazi Jewish family with Tarui disease reported by Vorgerd et al.
(1996). Both the father and the older son reported early fatigue with
exercise from early childhood, whereas the mother and younger son were
asymptomatic. In addition, the father had typical diabetic background
retinopathy and the older son reported an episode of insulin treatment
during hepatitis A infection. The father and older son were compound
heterozygotes for 2 PFKM mutations, whereas the mother and the younger
son were heterozygous for a PFKM mutation (see 610681.0009). The father
showed impaired glucose tolerance and the mother showed
noninsulin-dependent diabetes mellitus (NIDDM; 125853). By intravenous
glucose tolerance tests, both parents and the older son had decreased
first-phase insulin secretion and a diminished glucose disappearance
rate. The insulin-sensitivity test (IST) using octreotide showed marked
insulin resistance in both parents and in the older, homozygous son, and
moderate resistance in the younger son. Ristow et al. (1997) concluded
that PFKM deficiency can cause impaired insulin secretion in response to
glucose, demonstrating its participation in islet glucose metabolism and
peripheral insulin resistance. These combined metabolic sequelae of PFKM
deficiency identified PFMK as a candidate gene predisposing to NIDDM.

MOLECULAR GENETICS

In 1 of the original Japanese patients with glycogen storage disease
type VII reported by Tarui et al. (1965), Nakajima et al. (1990)
identified a homozygous mutation in the PFKM gene (610681.0001).

In 2 Ashkenazi Jewish sisters with GSD VII, Raben et al. (1993)
identified a homozygous splice site mutation in the PFKM gene resulting
in the deletion of exon 5 (610681.0005). Sherman et al. (1994)
identified the exon 5 deletion mutation in 11 (61%) of 18 abnormal
alleles in 9 Ashkenazi Jewish families with GSD VII, making it as the
most common PFKM mutation in this population.

In 4 Italian patients, including 2 brothers, with GSD VII, Tsujino et
al. (1994) identified 3 novel mutations in the PFKM gene
(610681.0002-610681.0004). The authors emphasized that these patients
were not of Ashkenazi Jewish descent.

Raben and Sherman (1995) tabulated 15 GSD VII disease-inducing mutations
of the PFKM gene.

In a 22-year-old Japanese man, born of consanguineous parents, with a
mild form of GSD VII, Nakagawa et al. (1995) and Hamaguchi et al. (1996)
identified a homozygous mutation in the PFKM gene (610681.0008).

POPULATION GENETICS

Raben and Sherman (1995) tabulated 15 GSD VII disease-inducing mutations
of the PFKM gene and noted that the disorder is especially prevalent
among people of Ashkenazi Jewish descent. The authors found that the
frequent exon 5 splicing defect (610681.0005) accounted for
approximately 68% of mutant alleles in Ashkenazim.

ANIMAL MODEL

Giger et al. (1985) and Vora et al. (1985) reported naturally occurring
Pfkm deficiency in English springer spaniel dogs. The dogs had a history
of chronic hemolytic anemia and sporadic hemolytic crises. Induced
hyperventilation resulted in hemoglobinuria and severe bilirubinemia.
Erythrocytes showed increased erythrocyte alkaline fragility, and
erythrocyte 2,3-diphosphoglycerate content was reduced. Pfkm levels were
10% of normal controls.

Giger et al. (1992) reported Pfkm deficiency in an American cocker
spaniel. Smith et al. (1996) determined that canine Pfkm deficiency is
caused by a nonsense mutation in the canine Pfkm gene, leading to rapid
degradation of a truncated protein and loss of enzyme activity.

*FIELD* SA
Nishikawa et al. (1965); Raben et al. (1993); Yamasaki et al. (1991)
*FIELD* RF
1. Amit, R.; Bashan, N.; Abarbanel, J. M.; Shapira, Y.; Sofer, S.;
Moses, S.: Fatal familial infantile glycogen storage disease: multisystem
phosphofructokinase deficiency. Muscle Nerve 15: 455-458, 1992.

2. Argov, Z.; Barash, V.; Soffer, D.; Sherman, J.; Raben, N.: Late-onset
muscular weakness in phosphofructokinase deficiency due to exon 5/intron
5 junction point mutation: a unique disorder or the natural course
of this glycolytic disorder? Neurology 44: 1097-1100, 1994.

3. Boulard, M. R.; Bois, M.; Reviron, M.; Najean, Y.: Red-cell phosphofructokinase
deficiency. New Eng. J. Med. 291: 978-979, 1974.

4. Danon, M. J.; Carpenter, S.; Manaligod, J. R.; Schliselfeld, L.
H.: Fatal infantile glycogen storage disease: deficiency of phosphofructokinase
and phosphorylase b kinase. Neurology 31: 1303-1307, 1981.

5. Danon, M. J.; Servidei, S.; DiMauro, S.; Vora, S.: Late-onset
muscle phosphofructokinase deficiency. Neurology 38: 956-960, 1988.

6. Davidson, M.; Miranda, A. F.; Bender, A. N.; DiMauro, S.; Vora,
S.: Muscle phosphofructokinase deficiency: biochemical and immunological
studies of phosphofructokinase isozymes in muscle culture. J. Clin.
Invest. 72: 545-550, 1983.

7. Etiemble, J.; Kahn, A.; Boivin, P.; Bernard, J. F.; Goudemand,
M.: Hereditary hemolytic anemia with erythrocyte phosphofructokinase
deficiency. Hum. Genet. 31: 83-91, 1976.

8. Etiemble, J.; Picat, C.; Simeon, J.; Blatrix, C.; Boivin, P.:
Inherited erythrocyte phosphofructokinase deficiency: molecular mechanism. Hum.
Genet. 55: 383-390, 1980.

9. Giger, U.; Harvey, J. W.; Yamaguchi, R. A.; McNulty, P. K.; Chiapella,
A.; Beutler, E.: Inherited phosphofructokinase deficiency in dogs
with hyperventilation-induced hemolysis: increased in vitro and in
vivo alkaline fragility of erythrocytes. Blood 65: 345-351, 1985.

10. Giger, U.; Smith, B. F.; Woods, C. B.; Patterson, D. F.; Stedman,
H.: Inherited phosphofructokinase deficiency in an American cocker
spaniel. J. Am. Vet. Med. Assoc. 201: 1569-1571, 1992.

11. Guibaud, P.; Carrier, H.; Mathieu, M.; Dorche, C.; Parchoux, B.;
Bethenod, M.; Larbre, F.: Observation familiale de dystrophie musculaire
congenitale par deficit en phosphofructokinase. Arch. Franc. Pediat. 35:
1105-1115, 1978.

12. Haller, R. G.; Lewis, S. F.: Glucose-induced exertional fatigue
in muscle phosphofructokinase deficiency. New Eng. J. Med. 324:
364-369, 1991.

13. Hamaguchi, T.; Nakajima, H.; Noguchi, T.; Nakagawa, C.; Kuwajima,
M.; Kono, N.; Tarui, S.; Matsuzawa, Y.: Novel missense mutation (W686C)
of the phosphofructokinase-M gene in a Japanese patient with a mild
form of glycogenosis VII. Hum. Mutat. 8: 273-275, 1996.

14. Hays, A. P.; Hallett, M.; Delfs, J.; Morris, J.; Sotrel, A.; Shevchuk,
M. M.; DiMauro, S.: Muscle phosphofructokinase deficiency: abnormal
polysaccharide in a case of late-onset myopathy. Neurology 31: 1077-1086,
1981.

15. Kahn, A.; Etiemble, J.; Meienhofer, M. C.; Boivin, P.: Erythrocyte
phosphofructokinase deficiency associated with an unstable variant
of muscle phosphofructokinase. Clin. Chim. Acta 61: 415-419, 1975.

16. Layzer, R. B.; Rowland, L. P.; Ranney, H. M.: Muscle phosphofructokinase
deficiency. Arch. Neurol. 17: 512-523, 1967.

17. Mineo, I.; Kono, N.; Hara, N.; Shimizu, T.; Yamada, Y.; Kawachi,
M.; Kiyokawa, H.; Wang, Y. L.; Tarui, S.: Myogenic hyperuricemia:
a common pathophysiologic feature of glycogenosis types III, V, and
VII. New Eng. J. Med. 317: 75-80, 1987.

18. Miwa, S.; Sato, T.; Murao, H.; Kozuru, M.; Ibayashi, H.: A new
type of phosphofructokinase deficiency: hereditary nonspherocytic
hemolytic anemia. Acta Haemat. Jpn. 35: 113-118, 1972.

19. Nakagawa, C.; Mineo, I.; Kaido, M.; Fujimura, H.; Shimizu, T.;
Hamaguchi, T.; Nakajima, H.; Tarui, S.: A new variant case of muscle
phosphofructokinase deficiency, coexisting with gastric ulcer, gouty
arthritis, and increased hemolysis. Muscle Nerve 3 (Suppl): S39-S44,
1995.

20. Nakajima, H.; Kono, N.; Yamasaki, T.; Hotta, K.; Kawachi, M.;
Kuwajima, M.; Noguchi, T.; Tanaka, T.; Tarui, S.: Genetic defect
in muscle phosphofructokinase deficiency: abnormal splicing of the
muscle phosphofructokinase gene due to a point mutation at the 5-prime-splice
site. J. Biol. Chem. 265: 9392-9395, 1990.

21. Nishikawa, M.; Tsukiyama, K.; Enomoto, T.; Tarui, S.; Okuno, G.;
Ueda, K.; Ikura, T.; Tsujii, T.; Sugase, T.; Suda, M.; Tanaka, T.
: A new type of skeletal muscle glycogenosis due to phosphofructokinase
deficiency. Proc. Jpn. Acad. 41: 350-353, 1965.

22. Raben, N.; Sherman, J.; Miller, F.; Mena, H.; Plotz, P.: A 5-prime
splice junction mutation leading to exon deletion in an Ashkenazic
Jewish family with phosphofructokinase deficiency (Tarui disease). J.
Biol. Chem. 268: 4963-4967, 1993.

23. Raben, N.; Sherman, J.; Nicastri, C.; Adams, E.; Argov, Z.; Nakajima,
H.; Plotz, P.: A limited number of mutations in the phosphofructokinase
gene in Ashkenazi Jewish patients with glycogenosis VII (Tarui disease).
(Abstract) Am. J. Hum. Genet. 53 (suppl.): A942, 1993.

24. Raben, N.; Sherman, J. B.: Mutations in muscle phosphofructokinase
gene. Hum. Mutat. 6: 1-6, 1995.

25. Ristow, M.; Vorgerd, M.; Mohlig, M.; Schatz, H.; Pfeiffer, A.
: Deficiency of phosphofructo-1-kinase/muscle subtype in humans impairs
insulin secretion and causes insulin resistance. J. Clin. Invest. 100:
2833-2841, 1997.

26. Satoyoshi, E.; Kowa, H.: A myopathy due to glycolytic abnormality. Arch.
Neurol. 17: 248-256, 1967.

27. Servidei, S.; Bonilla, E.; Diedrich, R. G.; Kornfeld, M.; Oates,
J. D.; Davidson, M.; Vora, S.; DiMauro, S.: Fatal infantile form
of muscle phosphofructokinase deficiency. Neurology 36: 1465-1470,
1986.

28. Sherman, J. B.; Raben, N.; Nicastri, C.; Argov, Z.; Nakajima,
H.; Adams, E. M.; Eng, C. M.; Cowan, T. M.; Plotz, P. H.: Common
mutations in the phosphofructokinase-M gene in Ashkenazi Jewish patients
with glycogenesis (sic) VII--and their population frequency. Am.
J. Hum. Genet. 55: 305-313, 1994.

29. Smith, B. F.; Stedman, H.; Rajpurohit, Y.; Henthorn, P. S.; Wolfe,
J. H.; Patterson, D. F.; Giger, U.: Molecular basis of canine muscle
type phosphofructokinase deficiency. J. Biol. Chem. 271: 20070-20074,
1996.

30. Tani, K.; Fujii, H.; Takegawa, S.; Miwa, S.; Koyama, W.; Kanayama,
M.; Imanaka, A.; Imanaka, F.; Kuramoto, A.: Two cases of phosphofructokinase
deficiency associated with congenital hemolytic anemia found in Japan. Am.
J. Hemat. 14: 165-174, 1983.

31. Tarui, S.; Okuno, G.; Ikura, Y.; Tanaka, T.; Suda, M.; Nishikawa,
M.: Phosphofructokinase deficiency in skeletal muscle: a new type
of glycogenosis. Biochem. Biophys. Res. Commun. 19: 517-523, 1965.

32. Tsujino, S.; Servidei, S.; Tonin, P.; Shanske, S.; Azan, G.; DiMauro,
S.: Identification of three novel mutations in non-Ashkenazi Italian
patients with muscle phosphofructokinase deficiency. Am. J. Hum.
Genet. 54: 812-819, 1994.

33. Vora, S.; Corash, L.; Engel, W. K.; Durham, S.; Seaman, C.; Piomelli,
S.: The molecular mechanism of the inherited phosphofructokinase
deficiency associated with hemolysis and myopathy. Blood 55: 629-635,
1980.

34. Vora, S.; Davidson, M.; Seaman, C.; Miranda, A. F.; Noble, N.
A.; Tanaka, K. R.; Frenkel, E. P.; DiMauro, S.: Heterogeneity of
the molecular lesions in inherited phosphofructokinase deficiency. J.
Clin. Invest. 72: 1995-2006, 1983.

35. Vora, S.; DiMauro, S.; Spear, D.; Harker, D.; Danon, M. J.: Characterization
of the enzymatic defect in late-onset muscle phosphofructokinase deficiency:
new subtype of glycogen storage disease type VII. J. Clin. Invest. 80:
1479-1485, 1987.

36. Vora, S.; Giger, U.; Turchen, S.; Harvey, J. W.: Characterization
of the enzymatic lesion in inherited phosphofructokinase deficiency
in the dog: an animal analogue of human glycogen storage disease type
VII. Proc. Nat. Acad. Sci. 82: 8109-8113, 1985.

37. Vora, S.; Seaman, C.; Durham, S.; Piomelli, S.: Isozymes of human
phosphofructokinase: identification and subunit structural characterization
of a new system. Proc. Nat. Acad. Sci. 77: 62-66, 1980.

38. Vorgerd, M.; Karitzky, J.; Ristow, M.; Van Schaftingen, E.; Tegenthoff,
M.; Jerusalem, F.; Malin, J. P.: Muscle phosphofructokinase deficiency
in two generations. J. Neurol. Sci. 141: 95-99, 1996.

39. Waterbury, L.; Frenkel, E. P.: Hereditary nonspherocytic hemolysis
with erythrocyte phosphofructokinase deficiency. Blood 39: 415-425,
1972.

40. Yamasaki,; Nakajima, H.; Kono, N.; Hotta, K.; Yamada, K.; Imai,
E.; Kuwajima, M.; Noguchi, T.; Tanaka, T.; Tarui, S.: Structure of
the entire human muscle phosphofructokinase-encoding gene: a two-promoter
system. Gene 104: 277-282, 1991.

41. Zanella, A.; Mariani, M.; Meola, G.; Fagnani, G.; Sirchia, G.
: Phosphofructokinase (PFK) deficiency due to a catalytically inactive
mutant M-type subunit. Am. J. Hemat. 12: 215-225, 1982.

*FIELD* CS
INHERITANCE:
Autosomal recessive

ABDOMEN:
[Liver];
Gallstones due to hemolytic anemia;
Jaundice due to hemolytic anemia

SKELETAL:
[Feet];
Gout due to increased uric acid

SKIN, NAILS, HAIR:
[Skin];
Jaundice due to hemolytic anemia

MUSCLE, SOFT TISSUE:
Exercise intolerance;
Muscle weakness;
Muscle cramps with exertion;
Muscle fibers may contain abnormal polysaccharide;
Increased muscle glycogen content

HEMATOLOGY:
Hemolytic anemia

LABORATORY ABNORMALITIES:
Muscle phosphofructokinase deficiency;
Myoglobinuria with extreme exertion;
Hyperuricemia;
Increased bilirubin;
Increased reticulocyte count;
Decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG);
No increase of muscle lactate with ischemic exercise testing

MISCELLANEOUS:
Variable severity;
Exercise intolerance often evident in childhood;
Late-adult onset has been reported;
A severe infantile variant has been rarely reported

MOLECULAR BASIS:
Caused by mutation in the muscle phosphofructokinase gene (PFKM, 610681.0001)

*FIELD* CN
Cassandra L. Kniffin - updated: 2/26/2007
Kelly A. Przylepa - revised: 9/19/2000

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

*FIELD* ED
joanna: 05/23/2007
ckniffin: 2/26/2007
joanna: 3/18/2002
kayiaros: 9/19/2000

*FIELD* CN
Cassandra L. Kniffin - reorganized: 3/8/2007
Cassandra L. Kniffin - updated: 2/26/2007
Victor A. McKusick - updated: 7/7/1998
Victor A. McKusick - updated: 1/15/1998
Victor A. McKusick - updated: 8/12/1997

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

*FIELD* ED
carol: 04/17/2007
carol: 3/8/2007
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MIM 610681
*RECORD*
*FIELD* NO
610681
*FIELD* TI
*610681 PHOSPHOFRUCTOKINASE, MUSCLE TYPE; PFKM
;;PFK, MUSCLE TYPE
*FIELD* TX

DESCRIPTION
read more
The PFKM gene encodes the muscle isoform of phosphofructokinase (PFK)
(ATP:D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11). PFK
catalyzes the irreversible conversion of fructose-6-phosphate to
fructose-1,6-bisphosphate and is a key regulatory enzyme in glycolysis.

Mammalian PFK is a tetramer made up of various combinations of 3
subunits: muscle (PFKM), liver (PFKL; 171860), and platelet (PFKP;
171840), the genes for which are located on chromosomes 12q13, 21q22,
and 10p, respectively. The composition of the tetramers differs
according to the tissue type. Muscle and liver PFK are a homotetramers
of 4M and 4L subunits, respectively. Erythrocytes contain both L and M
subunits, which randomly tetramerize to form M4, L4, and M3L, M2L2, and
ML3 hybrid forms of the holoenzyme (Vora et al., 1980; Raben and
Sherman, 1995).

CLONING

Layzer et al. (1969) demonstrated that PFK of muscle and erythrocyte are
immunologically related but not identical. Layzer et al. (1967)
suggested that red cell PFK is composed of 2 different subunits.

Nakajima et al. (1987) reported the cloning of a full-length cDNA
corresponding to the human PFKM gene. The deduced 779-residue protein
has a molecular mass of 85 kD and shares 95% homology with the rabbit
protein.

Nakajima et al. (1990) found that the human PFKM gene encodes 3
different mRNAs, termed A (131 bp), B (220 bp), and C (54 bp). Type B is
the major gene product and contains an extra noncoding sequence within
the 5-prime untranslated region of type A mRNA. Types A and B share a
common promoter and undergo alternative splicing, whereas type C appears
to have a different promoter. Yamasaki et al. (1991) confirmed that the
PFKM gene contains 2 promoters in the upstream regions of exons 1 and 2,
respectively. Promoter 1 contains Sp1 (SP1; 189906)-binding sites and
drives the transcription of type C mRNA; promoter 2 contains a
TATA-box-like sequence and a CAAT-box-like sequence and drives the
expression of types A and B mRNA.

GENE STRUCTURE

Yamasaki et al. (1991) determined that the PFKM gene contains 24 exons
and spans approximately 30 kb.

GENE FUNCTION

Yi et al. (2012) demonstrated that the dynamic posttranslational
modification of proteins by O-linked beta-N-acetylglucosamine
(O-GlcNAcylation) is a key metabolic regulator of glucose metabolism.
O-GlcNAcylation was induced at ser529 of phosphofructokinase-1 (PFK1) in
response to hypoxia. Glycosylation inhibited PFK1 activity and
redirected glucose flux through the pentose phosphate pathway, thereby
conferring a selective growth advantage on cancer cells. Blocking
glycosylation of PFK1 at ser529 reduced cancer cell proliferation in
vitro and impaired tumor formation in vivo.

MAPPING

Using mouse/human somatic cell hybridization, Ashley et al. (1987)
identified an expressed PFK gene on human chromosome 12, which turned
out to represent PFKM (see HISTORY). The authors assigned the homologous
mouse gene to chromosome 15 using a panel of hamster/mouse somatic cell
hybrids.

By fluorescence in situ hybridization with a CEPH YAC, Howard et al.
(1996) localized the PFKM gene to chromosome 12q13, centromeric to the
diacylglycerol kinase gene (DGKA; 125855) at 12q13.3. A highly
informative genetic marker isolated from the same YAC was used to map
PFKM between markers D12S1090 and D12S390.

MOLECULAR GENETICS

In 1 of the original Japanese patients with glycogen storage disease
type VII (GSD7; 232800) reported by Tarui et al. (1965), Nakajima et al.
(1990) identified a homozygous mutation in the PFKM gene (610681.0001).

In 2 Ashkenazi Jewish sisters with GSD VII, Raben et al. (1993)
identified a homozygous splice site mutation in the PFKM gene resulting
in the deletion of exon 5 (610681.0005). Sherman et al. (1994)
identified the exon 5 deletion mutation in 11 (61%) of 18 abnormal
alleles in 9 Ashkenazi Jewish families with GSD VII, making it as the
most common PFKM mutation in this population.

Raben and Sherman (1995) tabulated 15 GSD VII disease-inducing mutations
of the PFKM gene and several polymorphisms and noted that the disorder
is especially prevalent among people of Ashkenazi Jewish descent. The
authors found that the frequent exon 5 splicing defect accounted for
approximately 68% of mutant alleles in Ashkenazim.

In 4 Italian patients, including 2 brothers, with GSD VII, Tsujino et
al. (1994) identified 3 novel mutations in the PFKM gene
(610681.0002-610681.0004). The authors emphasized that these patients
were not of Ashkenazi Jewish descent.

In a 22-year-old Japanese man, born of consanguineous parents, with a
mild form of GSD VII, Nakagawa et al. (1995) and Hamaguchi et al. (1996)
identified a homozygous mutation in the PFKM gene (610681.0008).

HISTORY

Vora et al. (1982) originally assigned the PFKM gene to chromosome
1cen-q32 by somatic cell hybridization. Because of this assignment,
Ashley et al. (1987) concluded that the PFK gene they identified on
chromosome 12 was a different gene, which they termed 'PFKX.' With
subsequent confirmation of the mapping of PFKM to chromosome 12 (Howard
et al., 1996), it was determined that the 'PFKX' locus actually
represents the PFKM locus.

*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE VII
PFKM, IVS15DS, G-T, +1

In 1 of the original Japanese patients with glycogen storage disease
type VII (232800) reported by Tarui et al. (1965), Nakajima et al.
(1990) identified a G-to-T transversion at the 5-prime end of intron 13
of the PFKM gene, resulting in a splice site mutation and a 75-bp
(25-residue) in-frame deletion in the 3-prime portion of exon 13. A
cryptic splice site located 75 bases upstream from the normal splice
site was identified. The mutation was predicted to result in drastic
configurational changes in the protein, leading to loss of catalytic
activity. Since the parents were consanguineous, Nakajima et al. (1990)
assumed that the mutation was homozygous.

Nakajima (1997) noted that at the original publication of this mutation
in 1990, only the rabbit gene was sequenced; therefore, the exon
numbering followed that of rabbit Pfkm. Later studies by Yamasaki et al.
(1991) determined the full genomic structure of the gene and showed that
intron 15 is the appropriate numbering for this mutation.

.0002
GLYCOGEN STORAGE DISEASE VII
PFKM, IVS6AS, A-C, -2

In an Italian patient with glycogen storage disease VII (232800),
Tsujino et al. (1994) identified a homozygous A-to-C transversion at the
3-prime end of intron 6 of the PFKM gene, resulting in a splicing
defect. The mutation led to activation of 2 cryptic splice sites in exon
7, resulting in one 5 bp- and one 12 bp-deleted transcript. An affected
brother was also homozygous, and both parents were heterozygous, for the
splice junction mutation.

.0003
GLYCOGEN STORAGE DISEASE VII
PFKM, ARG39PRO

In an Italian patient with GSD VII (232800), born of consanguineous
parents, Tsujino et al. (1994) identified a homozygous 116G-C
transversion in the PFKM gene, resulting in an arg39-to-pro (R39P)
substitution. The proband was a 35-year-old man who had complained since
adolescence of exercise intolerance, exercise-related myalgia, and
cramps, with a few episodes of myoglobinuria after intense exercise. He
had first been seen by an internist for mild jaundice.

Bruno et al. (1998) described a 14-year-old boy with exercise-related
myalgia and cramps who had had several episodes of myoglobinuria since
early childhood. An episode at 2 years of age had caused acute renal
failure. Histochemical and biochemical analysis of muscle showed a
combined defect of phosphofructokinase and adenosine monophosphate
deaminase-1 (AMPD1; 102770). DNA analysis showed that the patient was
homozygous for the PFKM R39P substitution and also homozygous for a
common mutation found in AMP deaminase deficiency (102770.0001); the
latter mutation is found in homozygous state in about 2% of muscle
biopsies.

Another pathogenic mutation in the PFKM gene has been described in the
same codon (R39L; 610681.0006) (Sherman et al., 1994).

.0004
GLYCOGEN STORAGE DISEASE VII
PFKM, ASP543ALA

In an Italian patient with GSD VII (232800), Tsujino et al. (1994)
identified compound heterozygosity for 2 mutations in the PFKM gene. One
allele carried an A-to-C transversion in exon 18, resulting in an
asp543-to-ala (D543A) substitution, and the other allele did not express
the PFKM gene at all; however, sequencing of the reported regulatory
region of the gene revealed no mutation. The proband was a 43-year-old
man who had difficulty in keeping up with his peers in physical
activities since childhood. At age 33, he developed proximal weakness,
myalgia, and exercise intolerance. He was jaundiced, but because he had
no signs of hemolysis, Gilbert syndrome (143500) had originally been
diagnosed clinically.

.0005
GLYCOGEN STORAGE DISEASE VII
PFKM, IVS5DS, G-A, +1

In 2 Ashkenazi Jewish sisters with GSD VII (232800), Raben et al. (1993)
identified a homozygous G-to-A transition at the 5-prime end of intron 5
of the PFKM gene, resulting in a splicing defect and an in-frame
deletion of exon 5.

Sherman et al. (1994) identified this splice site mutation in 11 (61%)
of 18 abnormal alleles in 9 Ashkenazi Jewish families with GSD VII,
making it the most common PFKM mutation in this population.

Ristow et al. (1997) reported an Ashkenazi Jewish family in which a a
father and son with GSD VII were compound heterozygous for 2 mutations
in the PFKM gene: the common exon 5 deletion and a 1-bp deletion in exon
22 (610681.0010). The family had previously been reported by Vorgerd et
al. (1996) and was unusual because 2 members in subsequent generations
were affected.

.0006
GLYCOGEN STORAGE DISEASE VII
PFKM, ARG39LEU

In an Ashkenazi Jewish patient with GSD VII (232800), Sherman et al.
(1994) identified compound heterozygosity for 2 mutations in the PFKM
gene: a 116G-T transversion in exon 4 of the PFKM gene resulting in an
arg39-to-leu (R39L) substitution and the common exon 5 deletion
(610681.0005). Another pathogenic mutation in the PFKM gene has been
described in the same codon (R39P; 610681.0003).

.0007
GLYCOGEN STORAGE DISEASE VII
PFKM, ARG95TER

In 3 affected members of an Ashkenazi Jewish family with GSD VII
(232800), Vasconcelos et al. (1995) identified a homozygous C-to-T
transition in exon 6 of the PFKM gene, resulting in an arg95-to-ter
(R95X) substitution. In addition, RT-PCR studies identified an unusual
transcript resulting from a 252-bp insertion corresponding to intron 10,
which the authors postulated resulted from differential pre-mRNA
processing. The R95X substitution was considered to be solely
responsible for the disease phenotype. The family showed
pseudodominance: an affected woman married to her uncle had 2 affected
daughters. She herself was the product of a first-cousin marriage.

.0008
GLYCOGEN STORAGE DISEASE VII
PFKM, TRP686CYS

In a 22-year-old Japanese man, born of consanguineous parents, with a
mild form of GSD VII (232800), Nakagawa et al. (1995) and Hamaguchi et
al. (1996) identified a homozygous 2058G-T transversion in exon 22 of
the PFKM gene, resulting in a trp686-to-cys (W686C) substitution. The
patient was a 22-year-old man with gastric ulcer, gouty arthritis, and
compensated hemolysis. An episodic increase in serum creatine kinase
after exercising was detected. Although he did not experience muscle
pain or cramps, PFK activity in a skeletal muscle specimen was
approximately 1% of normal.

.0009
REMOVED FROM DATABASE
.0010
GLYCOGEN STORAGE DISEASE VII
PFKM, 1-BP DEL, 2003C

In Ashkenazi Jewish patients with GSD VII (232800), Sherman et al.
(1994) identified a 1-bp deletion (2003delC) in exon 22 of the PFKM
gene, resulting in a frameshift and a truncated PFKM protein with 16
altered amino acids at the C terminus. Two patients were homozygous for
the mutation and 2 were compound heterozygous for the deletion and
another pathogenic mutation.

Ristow et al. (1997) identified the 1-bp deletion in compound
heterozygosity with the common exon 5 deletion (610681.0005) in an
Ashkenazi Jewish father and son with GSD VII. The family had previously
been reported by Vorgerd et al. (1996) and was unusual because 2 members
in subsequent generations were affected.

*FIELD* RF
1. Ashley, P. L.; Price, E. R.; Lebo, R. V.; Cox, D. R.: An expressed
phosphofructokinase gene (PFKX) maps to human chromosome 12 and mouse
chromosome 15. (Abstract) Cytogenet. Cell Genet. 46: 573 only, 1987.

2. Bruno, C.; Minetti, C.; Shanske, S.; Morreale, G.; Bado, M.; Cordone,
G.; DiMauro, S.: Combined defects of muscle phosphofructokinase and
AMP deaminase in a child with myoglobinuria. Neurology 50: 296-298,
1998.

3. Hamaguchi, T.; Nakajima, H.; Noguchi, T.; Nakagawa, C.; Kuwajima,
M.; Kono, N.; Tarui, S.; Matsuzawa, Y.: Novel missense mutation (W686C)
of the phosphofructokinase-M gene in a Japanese patient with a mild
form of glycogenosis VII. Hum. Mutat. 8: 273-275, 1996.

4. Howard, T. D.; Akots, G.; Bowden, D. W.: Physical and genetic
mapping of the muscle phosphofructokinase gene (PFKM): reassignment
to human chromosome 12q. Genomics 34: 122-127, 1996.

5. Layzer, R. B.; Rowland, L. P.; Bank, W. J.: Physical and kinetic
properties of human phosphofructokinase from skeletal muscle and erythrocytes. J.
Biol. Chem. 244: 3823-3831, 1969.

6. Layzer, R. B.; Rowland, L. P.; Ranney, H. M.: Muscle phosphofructokinase
deficiency. Arch. Neurol. 17: 512-523, 1967.

7. Nakagawa, C.; Mineo, I.; Kaido, M.; Fujimura, H.; Shimizu, T.;
Hamaguchi, T.; Nakajima, H.; Tarui, S.: A new variant case of muscle
phosphofructokinase deficiency, coexisting with gastric ulcer, gouty
arthritis, and increased hemolysis. Muscle Nerve Suppl. 3: S39-S44,
1995.

8. Nakajima, H.: Personal Communication. Osaka, Japan 6/15/1997.

9. Nakajima, H.; Kono, N.; Yamasaki, T.; Hotta, K.; Kawachi, M.; Kuwajima,
M.; Noguchi, T.; Tanaka, T.; Tarui, S.: Genetic defect in muscle
phosphofructokinase deficiency: abnormal splicing of the muscle phosphofructokinase
gene due to a point mutation at the 5-prime-splice site. J. Biol.
Chem. 265: 9392-9395, 1990.

10. Nakajima, H.; Noguchi, T.; Yamasaki, T.; Kono, N.; Tanaka, T.;
Tarui, S.: Cloning of human muscle phosphofructokinase cDNA. FEBS
Lett. 223: 113-116, 1987.

11. Nakajima, H.; Yamasaki, T.; Noguchi, T.; Tanaka, T.; Kono, N.;
Tarui, S.: Evidence for alternative RNA splicing and possible alternative
promoters in the human muscle phosphofructokinase gene at the 5-prime
untranslated region. Biochem. Biophys. Res. Commun. 166: 637-641,
1990.

12. Raben, N.; Sherman, J.; Miller, F.; Mena, H.; Plotz, P.: A 5-prime
splice junction mutation leading to exon deletion in an Ashkenazic
Jewish family with phosphofructokinase deficiency (Tarui disease). J.
Biol. Chem. 268: 4963-4967, 1993.

13. Raben, N.; Sherman, J. B.: Mutations in muscle phosphofructokinase
gene. Hum. Mutat. 6: 1-6, 1995.

14. Ristow, M.; Vorgerd, M.; Mohlig, M.; Schatz, H.; Pfeiffer, A.
: Deficiency of phosphofructo-1-kinase/muscle subtype in humans impairs
insulin secretion and causes insulin resistance. J. Clin. Invest. 100:
2833-2841, 1997.

15. Sherman, J. B.; Raben, N.; Nicastri, C.; Argov, Z.; Nakajima,
H.; Adams, E. M.; Eng, C. M.; Cowan, T. M.; Plotz, P. H.: Common
mutations in the phosphofructokinase-M gene in Ashkenazi Jewish patients
with glycogenesis (sic) VII--and their population frequency. Am.
J. Hum. Genet. 55: 305-313, 1994.

16. Tarui, S.; Okuno, G.; Ikura, Y.; Tanaka, T.; Suda, M.; Nishikawa,
M.: Phosphofructokinase deficiency in skeletal muscle: a new type
of glycogenosis. Biochem. Biophys. Res. Commun. 19: 517-523, 1965.

17. Tsujino, S.; Servidei, S.; Tonin, P.; Shanske, S.; Azan, G.; DiMauro,
S.: Identification of three novel mutations in non-Ashkenazi Italian
patients with muscle phosphofructokinase deficiency. Am. J. Hum.
Genet. 54: 812-819, 1994.

18. Vasconcelos, O.; Sivakumar, K.; Dalakas, M. C.; Quezado, M.; Nagle,
J.; Leon-Monzon, M.; Dubnick, M.; Gajdusek, D. C.; Goldfarb, L. G.
: Nonsense mutation in the phosphofructokinase muscle subunit gene
associated with retention of intron 10 in one of the isolated transcripts
in Ashkenazi Jewish patients with Tarui disease. Proc. Nat. Acad.
Sci. 92: 10322-10326, 1995.

19. Vora, S.; Durham, S.; de Martinville, B.; Francke, U.: Assignment
of the human gene for muscle-type phosphofructokinase (PFKM) to chromosome
1 (region cen-q32) using somatic cell hybrids and monoclonal anti-M
antibody. Somat. Cell Genet. 8: 95-104, 1982.

20. Vora, S.; Seaman, C.; Durham, S.; Piomelli, S.: Isozymes of human
phosphofructokinase: identification and subunit structural characterization
of a new system. Proc. Nat. Acad. Sci. 77: 62-66, 1980.

21. Vorgerd, M.; Karitzky, J.; Ristow, M.; Van Schaftingen, E.; Tegenthoff,
M.; Jerusalem, F.; Malin, J. P.: Muscle phosphofructokinase deficiency
in two generations. J. Neurol. Sci. 141: 95-99, 1996.

22. Yamasaki,; Nakajima, H.; Kono, N.; Hotta, K.; Yamada, K.; Imai,
E.; Kuwajima, M.; Noguchi, T.; Tanaka, T.; Tarui, S.: Structure of
the entire human muscle phosphofructokinase-encoding gene: a two-promoter
system. Gene 104: 277-282, 1991.

23. Yi, W.; Clark, P. M.; Mason, D. E.; Keenan, M. C.; Hill, C.; Goddard,
W. A., III; Peters, E. C.; Driggers, E. M.; Hsieh-Wilson, L. C.:
Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337:
975-980, 2012.

*FIELD* CN
Ada Hamosh - updated: 9/6/2012

*FIELD* CD
Cassandra L. Kniffin: 1/3/2007

*FIELD* ED
alopez: 09/07/2012
terry: 9/6/2012
carol: 3/8/2007
ckniffin: 2/26/2007