RBCC

Full text data of PHKA2

PHKA2 (PHKLA, PYK) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Phosphorylase b kinase regulatory subunit alpha, liver isoform; Phosphorylase kinase alpha L subunit

UniProt P46019
ID KPB2_HUMAN Reviewed; 1235 AA.
AC P46019; A8K1T1; Q6LAJ5; Q7Z6W0; Q96CR3; Q9UDA1;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Phosphorylase b kinase regulatory subunit alpha, liver isoform;
DE Short=Phosphorylase kinase alpha L subunit;
GN Name=PHKA2; Synonyms=PHKLA, PYK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GSD9A PHE-141 DEL AND
RP LEU-1205.
RC TISSUE=Liver;
RX PubMed=7847371;
RA van den Berg I.E.T., van Beurden E.A.C.M., Malingre H.E.M.,
RA Ploos van Amstel H.K., Poll-The B.T., Smeitink J.A.M., Lamers W.H.,
RA Berger R.;
RT "X-linked liver phosphorylase kinase deficiency is associated with
RT mutations in the human liver phosphorylase kinase alpha subunit.";
RL Am. J. Hum. Genet. 56:381-387(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GSD9A VAL-193.
RC TISSUE=Liver;
RX PubMed=7549948;
RA Hirono H., Hayasaka K., Sato W., Takahashi T., Takada G.;
RT "Isolation of cDNA encoding the human liver phosphorylase kinase alpha
RT subunit (PHKA2) and identification of a missense mutation of the PHKA2
RT gene in a family with liver phosphorylase kinase deficiency.";
RL Biochem. Mol. Biol. Int. 36:505-511(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GSD9A CYS-186;
RP HIS-186; 189-LYS-THR-190 DEL; HIS-295 AND LYS-1125.
RC TISSUE=Liver;
RX PubMed=10330341; DOI=10.1086/302399;
RA Hendrickx J., Lee P., Keating J.P., Carton D., Sardharwalla I.B.,
RA Tuchman M., Baussan C., Willems P.J.;
RT "Complete genomic structure and mutational spectrum of PHKA2 in
RT patients with X-linked liver glycogenosis type I and II.";
RL Am. J. Hum. Genet. 64:1541-1549(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-206, AND VARIANTS GSD9A
RP GLU-189; SER-399; 818-GLN--TYR-825 DEL; 953-ASN--LEU-954 DELINS ILE
RP AND TRP-1207.
RX PubMed=9600238; DOI=10.1007/s004390050715;
RA Burwinkel B., Amat L., Gray R.G., Matsuo N., Muroya K., Narisawa K.,
RA Sokol R.J., Vilaseca M.A., Kilimann M.W.;
RT "Variability of biochemical and clinical phenotype in X-linked liver
RT glycogenosis with mutations in the phosphorylase kinase PHKA2 gene.";
RL Hum. Genet. 102:423-429(1998).
RN [9]
RP NUCLEOTIDE SEQUENCE OF 750-1126.
RC TISSUE=Liver;
RX PubMed=8518797; DOI=10.1093/hmg/2.5.583;
RA Hendrickx J., Coucke P., Bossuyt P., Wauters J., Raeymaekers P.,
RA Marchau F., Smit G.P., Stolte I., Sardharwalla I.B., Berthelot J.;
RT "X-linked liver glycogenosis: localization and isolation of a
RT candidate gene.";
RL Hum. Mol. Genet. 2:583-589(1993).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 977-1080.
RC TISSUE=Liver;
RX PubMed=8226841;
RA Wuellrich A., Hamacher C., Schneider A., Kilimann M.W.;
RT "The multiphosphorylation domain of the phosphorylase kinase alpha M
RT and alpha L subunits is a hotspot of differential mRNA processing and
RT of molecular evolution.";
RL J. Biol. Chem. 268:23208-23214(1993).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729; SER-735 AND
RP SER-1015, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1015, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729 AND SER-1015, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-729 AND SER-735, AND
RP MASS 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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP VARIANTS GSD9A CYS-186; THR-251 DEL; THR-ARG-1111 INS AND ILE-1114.
RX PubMed=8733133; DOI=10.1093/hmg/5.5.649;
RA Hendrickx J., Dams E., Coucke P., Lee P., Fernandes J., Willems P.J.;
RT "X-linked liver glycogenosis type II (XLG II) is caused by mutations
RT in PHKA2, the gene encoding the liver alpha subunit of phosphorylase
RT kinase.";
RL Hum. Mol. Genet. 5:649-652(1996).
RN [19]
RP VARIANTS GSD9A PRO-132; TYR-132; HIS-186 AND GLY-299.
RX PubMed=8733134; DOI=10.1093/hmg/5.5.653;
RA Burwinkel B., Shin Y.S., Bakker H.D., Deutsch J., Lozano M.J.,
RA Maire I., Kilimann M.W.;
RT "Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis
RT due to phosphorylase kinase deficiency with atypical activity in blood
RT cells (XLG2).";
RL Hum. Mol. Genet. 5:653-658(1996).
RN [20]
RP VARIANTS GSD9A TYR-ASN-THR-ALA-THR-120 INS; GLY-299; LEU-498; ARG-869;
RP TRP-916; ARG-1070 DEL AND ILE-1113.
RX PubMed=17689125; DOI=10.1016/j.ymgme.2007.06.007;
RA Beauchamp N.J., Dalton A., Ramaswami U., Niinikoski H., Mention K.,
RA Kenny P., Kolho K.L., Raiman J., Walter J., Treacy E., Tanner S.,
RA Sharrard M.;
RT "Glycogen storage disease type IX: High variability in clinical
RT phenotype.";
RL Mol. Genet. Metab. 92:88-99(2007).
CC -!- FUNCTION: Phosphorylase b kinase catalyzes the phosphorylation of
CC serine in certain substrates, including troponin I. The alpha
CC chain may bind calmodulin.
CC -!- ENZYME REGULATION: By phosphorylation of various serine residues
CC and by calcium.
CC -!- PATHWAY: Glycan biosynthesis; glycogen metabolism.
CC -!- SUBUNIT: Hexadecamer of 4 heterotetramers, each composed of alpha,
CC beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta
CC (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the
CC catalytic subunit, and delta is calmodulin.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (Potential).
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver and other
CC non-muscle tissues.
CC -!- PTM: Although the final Cys may be farnesylated, the terminal
CC tripeptide is probably not removed, and the C-terminus is not
CC methylated (By similarity).
CC -!- DISEASE: Glycogen storage disease 9A (GSD9A) [MIM:306000]: A
CC metabolic disorder resulting in a mild liver glycogenosis with
CC clinical symptoms that include hepatomegaly, growth retardation,
CC muscle weakness, elevation of glutamate-pyruvate transaminase and
CC glutamate-oxaloacetate transaminase, hypercholesterolemia,
CC hypertriglyceridemia, and fasting hyperketosis. Two subtypes are
CC known: type 1 or classic type with no phosphorylase kinase
CC activity in liver or erythrocytes, and type 2 or variant type with
CC no phosphorylase kinase activity in liver, but normal activity in
CC erythrocytes. Unlike other glycogenosis diseases, glycogen storage
CC disease type 9A is generally a benign condition. Patients improve
CC with age and are often asymptomatic as adults. Accurate diagnosis
CC is therefore also of prognostic interest. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the phosphorylase b kinase regulatory chain
CC family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PHKA2";
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DR EMBL; X80497; CAA56662.1; -; mRNA.
DR EMBL; D38616; BAA07606.1; -; mRNA.
DR EMBL; AF044572; AAD32846.1; -; Genomic_DNA.
DR EMBL; AF044540; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044541; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044542; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044543; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044544; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044545; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044546; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044547; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044548; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044549; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044550; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044551; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044552; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044553; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044554; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044555; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044556; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044557; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044558; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044559; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044560; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044561; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044562; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044563; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044564; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044565; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044566; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044567; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044568; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044569; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044570; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AF044571; AAD32846.1; JOINED; Genomic_DNA.
DR EMBL; AK289996; BAF82685.1; -; mRNA.
DR EMBL; AL096700; CAB86408.2; -; Genomic_DNA.
DR EMBL; AL732509; CAB86408.2; JOINED; Genomic_DNA.
DR EMBL; AL732509; CAI41680.1; -; Genomic_DNA.
DR EMBL; AL096700; CAI41680.1; JOINED; Genomic_DNA.
DR EMBL; CH471074; EAW98951.1; -; Genomic_DNA.
DR EMBL; BC014036; AAH14036.1; -; mRNA.
DR EMBL; Y15154; CAA75421.1; -; Genomic_DNA.
DR EMBL; X73875; CAA52084.1; -; mRNA.
DR RefSeq; NP_000283.1; NM_000292.2.
DR UniGene; Hs.54941; -.
DR ProteinModelPortal; P46019; -.
DR IntAct; P46019; 4.
DR MINT; MINT-1185164; -.
DR STRING; 9606.ENSP00000369274; -.
DR BindingDB; P46019; -.
DR ChEMBL; CHEMBL2111324; -.
DR PhosphoSite; P46019; -.
DR DMDM; 1170685; -.
DR PaxDb; P46019; -.
DR PRIDE; P46019; -.
DR DNASU; 5256; -.
DR Ensembl; ENST00000379942; ENSP00000369274; ENSG00000044446.
DR GeneID; 5256; -.
DR KEGG; hsa:5256; -.
DR UCSC; uc004cyv.4; human.
DR CTD; 5256; -.
DR GeneCards; GC0XM018910; -.
DR H-InvDB; HIX0176778; -.
DR HGNC; HGNC:8926; PHKA2.
DR HPA; HPA002912; -.
DR MIM; 300798; gene.
DR MIM; 306000; phenotype.
DR neXtProt; NX_P46019; -.
DR Orphanet; 264580; Glycogen storage disease due to liver phosphorylase kinase deficiency.
DR PharmGKB; PA33267; -.
DR eggNOG; NOG82518; -.
DR HOGENOM; HOG000231478; -.
DR HOVERGEN; HBG000273; -.
DR InParanoid; P46019; -.
DR KO; K07190; -.
DR OMA; TEMNSIG; -.
DR OrthoDB; EOG73V6JF; -.
DR PhylomeDB; P46019; -.
DR BioCyc; MetaCyc:HS00576-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00163; -.
DR GeneWiki; PHKA2; -.
DR GenomeRNAi; 5256; -.
DR NextBio; 20304; -.
DR PRO; PR:P46019; -.
DR Bgee; P46019; -.
DR CleanEx; HS_PHKA2; -.
DR Genevestigator; P46019; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005964; C:phosphorylase kinase complex; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IEA:InterPro.
DR GO; GO:0004689; F:phosphorylase kinase activity; TAS:ProtInc.
DR GO; GO:0006006; P:glucose metabolic process; TAS:Reactome.
DR GO; GO:0005980; P:glycogen catabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR008928; 6-hairpin_glycosidase-like.
DR InterPro; IPR012341; 6hp_glycosidase.
DR InterPro; IPR011613; Glyco_hydro_15.
DR InterPro; IPR008734; PHK_A/B_su.
DR PANTHER; PTHR10749; PTHR10749; 1.
DR Pfam; PF00723; Glyco_hydro_15; 1.
DR SUPFAM; SSF48208; SSF48208; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; Carbohydrate metabolism; Cell membrane;
KW Complete proteome; Disease mutation; Glycogen metabolism;
KW Glycogen storage disease; Lipoprotein; Membrane; Phosphoprotein;
KW Polymorphism; Prenylation; Reference proteome.
FT CHAIN 1 1235 Phosphorylase b kinase regulatory subunit
FT alpha, liver isoform.
FT /FTId=PRO_0000057730.
FT REGION 807 837 Calmodulin-binding (Potential).
FT REGION 1059 1099 Calmodulin-binding (Potential).
FT MOD_RES 729 729 Phosphoserine.
FT MOD_RES 735 735 Phosphoserine.
FT MOD_RES 1015 1015 Phosphoserine.
FT LIPID 1232 1232 S-farnesyl cysteine (By similarity).
FT VARIANT 38 38 E -> Q (in dbSNP:rs17313469).
FT /FTId=VAR_024563.
FT VARIANT 120 120 T -> TYNTAT (in GSD9A).
FT /FTId=VAR_062393.
FT VARIANT 132 132 H -> P (in GSD9A; type 2).
FT /FTId=VAR_006177.
FT VARIANT 132 132 H -> Y (in GSD9A; type 2).
FT /FTId=VAR_006178.
FT VARIANT 141 141 Missing (in GSD9A; type 1).
FT /FTId=VAR_006179.
FT VARIANT 186 186 R -> C (in GSD9A; type 2).
FT /FTId=VAR_006180.
FT VARIANT 186 186 R -> H (in GSD9A; type 2).
FT /FTId=VAR_006181.
FT VARIANT 189 190 Missing (in GSD9A; type 2).
FT /FTId=VAR_012270.
FT VARIANT 189 189 K -> E (in GSD9A; type 2).
FT /FTId=VAR_012269.
FT VARIANT 193 193 G -> V (in GSD9A; type 2).
FT /FTId=VAR_012271.
FT VARIANT 251 251 Missing (in GSD9A; type 2).
FT /FTId=VAR_006182.
FT VARIANT 295 295 R -> H (in GSD9A; type 1 and type 2).
FT /FTId=VAR_012272.
FT VARIANT 299 299 D -> G (in GSD9A; type 2).
FT /FTId=VAR_006183.
FT VARIANT 399 399 P -> S (in GSD9A; type 1).
FT /FTId=VAR_012273.
FT VARIANT 416 416 G -> R (in dbSNP:rs16980929).
FT /FTId=VAR_050518.
FT VARIANT 498 498 P -> L (in GSD9A).
FT /FTId=VAR_062394.
FT VARIANT 818 825 Missing (in GSD9A; type 1).
FT /FTId=VAR_012274.
FT VARIANT 869 869 P -> R (in GSD9A).
FT /FTId=VAR_062395.
FT VARIANT 916 916 R -> W (in GSD9A).
FT /FTId=VAR_062396.
FT VARIANT 953 954 NL -> I (in GSD9A; type 1).
FT /FTId=VAR_012275.
FT VARIANT 1070 1070 Missing (in GSD9A).
FT /FTId=VAR_062397.
FT VARIANT 1111 1111 R -> RTR (in GSD9A; type 2).
FT /FTId=VAR_006184.
FT VARIANT 1113 1113 M -> I (in GSD9A).
FT /FTId=VAR_062398.
FT VARIANT 1114 1114 T -> I (in GSD9A; type 2).
FT /FTId=VAR_006185.
FT VARIANT 1125 1125 E -> K (in GSD9A; type 1).
FT /FTId=VAR_012276.
FT VARIANT 1205 1205 P -> L (in GSD9A; type 1).
FT /FTId=VAR_006186.
FT VARIANT 1207 1207 G -> W (in GSD9A; type 1).
FT /FTId=VAR_012277.
FT CONFLICT 527 527 Q -> E (in Ref. 7; AAH14036).
FT CONFLICT 756 756 G -> S (in Ref. 7; AAH14036).
SQ SEQUENCE 1235 AA; 138408 MW; 6CA10CFFA86A582A CRC64;
MRSRSNSGVR LDGYARLVQQ TILCYQNPVT GLLSASHEQK DAWVRDNIYS ILAVWGLGMA
YRKNADRDED KAKAYELEQN VVKLMRGLLQ CMMRQVAKVE KFKHTQSTKD SLHAKYNTAT
CGTVVGDDQW GHLQVDATSL FLLFLAQMTA SGLRIIFTLD EVAFIQNLVF YIEAAYKVAD
YGMWERGDKT NQGIPELNAS SVGMAKAALE AIDELDLFGA HGGRKSVIHV LPDEVEHCQS
ILFSMLPRAS TSKEIDAGLL SIISFPAFAV EDVNLVNVTK NEIISKLQGR YGCCRFLRDG
YKTPREDPNR LHYDPAELKL FENIECEWPV FWTYFIIDGV FSGDAVQVQE YREALEGILI
RGKNGIRLVP ELYAVPPNKV DEEYKNPHTV DRVPMGKVPH LWGQSLYILS SLLAEGFLAA
GEIDPLNRRF STSVKPDVVV QVTVLAENNH IKDLLRKHGV NVQSIADIHP IQVQPGRILS
HIYAKLGRNK NMNLSGRPYR HIGVLGTSKL YVIRNQIFTF TPQFTDQHHF YLALDNEMIV
EMLRIELAYL CTCWRMTGRP TLTFPISRTM LTNDGSDIHS AVLSTIRKLE DGYFGGARVK
LGNLSEFLTT SFYTYLTFLD PDCDEKLFDN ASEGTFSPDS DSDLVGYLED TCNQESQDEL
DHYINHLLQS TSLRSYLPPL CKNTEDRHVF SAIHSTRDIL SVMAKAKGLE VPFVPMTLPT
KVLSAHRKSL NLVDSPQPLL EKVPESDFQW PRDDHGDVDC EKLVEQLKDC SNLQDQADIL
YILYVIKGPS WDTNLSGQHG VTVQNLLGEL YGKAGLNQEW GLIRYISGLL RKKVEVLAEA
CTDLLSHQKQ LTVGLPPEPR EKIISAPLPP EELTKLIYEA SGQDISIAVL TQEIVVYLAM
YVRAQPSLFV EMLRLRIGLI IQVMATELAR SLNCSGEEAS ESLMNLSPFD MKNLLHHILS
GKEFGVERSV RPIHSSTSSP TISIHEVGHT GVTKTERSGI NRLRSEMKQM TRRFSADEQF
FSVGQAASSS AHSSKSARSS TPSSPTGTSS SDSGGHHIGW GERQGQWLRR RRLDGAINRV
PVGFYQRVWK ILQKCHGLSI DGYVLPSSTT REMTPHEIKF AVHVESVLNR VPQPEYRQLL
VEAIMVLTLL SDTEMTSIGG IIHVDQIVQM ASQLFLQDQV SIGAMDTLEK DQATGICHFF
YDSAPSGAYG TMTYLTRAVA SYLQELLPNS GCQMQ
//

MIM 300798
*RECORD*
*FIELD* NO
300798
*FIELD* TI
*300798 PHOSPHORYLASE KINASE, LIVER, ALPHA-2 SUBUNIT; PHKA2
*FIELD* TX

DESCRIPTION
read more
The PHKA2 gene on chromosome Xp22 encodes the alpha subunit of hepatic
phosphorylase kinase (PHK; EC 2.7.11.19). Hepatic phosphorylase kinase
is a hexadecameric enzyme comprising 4 copies each of 4 unique subunits
encoded by 4 different genes: alpha (PHKA2), beta (PHKB, 172490), gamma
(PHKG2, (172471)), and delta. The delta subunit can be encoded by 3
different genes (CALM1, 114180; CALM2, 114182; or CALM3, 114183). The
PHKA1 (311870) and PHKG1 (172470) genes encode the alpha and gamma
subunits, respectively, of muscle phosphorylase kinase; the beta subunit
is the same in both isoforms. The gamma subunits contain the active site
of the enzyme, whereas the alpha and beta subunits have regulatory
functions controlled by phosphorylation. The delta subunit, which
encodes calmodulin, mediates the dependence of the enzyme on calcium
concentration (Beauchamp et al., 2007).

CLONING

Davidson et al. (1992) isolated clones corresponding to the Phka2 gene
from a rabbit cDNA library. The deduced 1,235-residue protein showed 68%
sequence similarity to the rabbit Phka1 gene. The placement of
nucleotide and residue differences indicated that Phka1 and Phka2 are
encoded by 2 separate genes, rather than being generated by alternative
splicing of a single gene. Northern blot analysis identified a 4.3-kb
mRNA Phka2 transcript with high expression in liver and brain, but not
in muscle.

Hendrickx et al. (1992, 1993) isolated a clone for the human PHKA2 gene
from a human hepatoma cDNA library. The protein showed 93.5% homology to
the rabbit protein. Two calmodulin binding sites identified in rabbit
Phka1 are highly conserved in rabbit and human PHKA2. Differential
splicing was observed.

MAPPING

Using the rabbit Phka2 gene, Davidson et al. (1992) mapped the human
homolog, PHKA2, to chromosome Xp22.2-p22.1. By in situ hybridization,
Wauters et al. (1992) demonstrated that the PHKA2 gene is located in the
distal part of Xp in the same region as the mutation for X-linked liver
glycogenosis (GSD IXa; 306000). By fluorescence in situ hybridization,
Hendrickx et al. (1992, 1993) mapped the human PHKA2 gene to Xp22. It is
noteworthy that PHKA1 and PHKA2 are located on Xq and Xp, respectively.

In the mouse, Ryder-Cook et al. (1989) mapped the alpha subunit of
phosphorylase kinase to the X chromosome. They noted that the beta,
gamma, and delta subunits are autosomal.

GENE STRUCTURE

Hendrickx et al. (1999) determined that the human PHKA2 gene contains 33
exons and spans 65 kb or more.

MOLECULAR GENETICS

In patients with X-linked hepatic glycogen storage disease (GSD9A; see
306000), Hendrickx et al. (1995) identified 4 different mutations in the
PHKA2 gene (300798.0001-300798.0004).

Van den Berg et al. (1995) identified mutations in the PHKA2 gene
(300798.0005 and 300798.0006) in affected members of 2 Dutch families
with GSD IXa1. One of the families had been reported by Huijing and
Fernandez (1969).

Burwinkel et al. (1996) identified mutations in the PHKA2 gene in
patients with GSD IXa2 (306000.0007-306000.0010). The mutations appeared
to cluster in limited sequence regions. Burwinkel et al. (1996) stressed
that the clustering of GSD IXa2 mutations would further facilitate
analysis by RT-PCR of blood cell mRNA and thus help avoid liver biopsy
in the diagnosis.

In a Japanese boy with classic GSD IXa2, Fukao et al. (2007) identified
a hemizygous 10-kb deletion in the PHKA2 gene, resulting in the deletion
of exons 20 to 26. Studies of the breakpoint regions showed that the
deletion resulted from Alu element-mediated unequal homologous
recombination.

GENOTYPE/PHENOTYPE CORRELATIONS

In 4 unrelated patients with GSD IXa2, Hendrickx et al. (1996)
identified 4 different mutations in the PHKA2 gene
(306000.0011-306000.0014). The mutations resulted in minor abnormalities
in the primary structure of the protein. These mutations are found in a
conserved RXX(X)T motif, resembling known phosphorylation sites that may
be involved in the regulation of PHK. Hendrickx et al. (1996) postulated
that PHK activity may be regulated by phosphorylation of these sites and
that type II GSD9A may be due to impaired activation of PHK activity.
The findings may explain why the in vitro PHK enzymatic activity is not
deficient in type II, whereas it is in type I.

Hendrickx et al. (1999) identified PHKA2 mutations in 10 patients with
GSD9A, types I and II. They proposed that mutations in GSD type I, in
which PHK activity is decreased in both liver and erythrocytes, results
from truncation or disruption of the PHKA2 protein. In contrast, all
type II mutations, which result in residual activity in erythrocytes,
were missense mutations or small in-frame deletions and insertions.
These results suggested that the biochemical differences between the 2
types of GSD IXa are due to the different nature of the disease-causing
mutations in PHKA2. Type I mutations may lead to absence of the alpha
subunit, which causes an unstable PHK holoenzyme and deficient enzyme
activity, whereas type II mutations may lead to in vivo deregulation of
PHK, which might be difficult to demonstrate in vitro.

*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, GLN1009TER

In a Belgian boy with glycogen storage disease IXa1 (306000), Hendrickx
et al. (1995) identified a C-to-T transition in exon 8, resulting in a
gln1009-to-ter (Q1009X) substitution. This led to a truncated protein
that lacked the C terminus, the phosphorylation site, and a putative
calmodulin-binding site. The patient had hepatomegaly, elevated liver
enzymes, and growth retardation that decreased with puberty. PHK
activity was completely absent from erythrocytes and liver.

.0002
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, GLN766TER

In a French boy with GSD type IXa1 (306000), Hendrickx et al. (1995)
found a C-to-T transition in exon 2 of the PHKA gene, resulting in a
gln766-to-ter (Q766X) substitution. This led to a truncated protein that
lacked the C terminus, the phosphorylation site, and both putative
calmodulin-binding sites. The patient had hepatomegaly, elevated liver
enzymes, and growth retardation. Erythrocyte PHK activity was 2% of
control values. His mildly affected sister had only hepatomegaly; her
erythrocyte PHK activity was 30% of control values.

.0003
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, IVS7DS, G-T, +1

In twin boys from the U.K. with GSD type IXa1 (306000), Hendrickx et al.
(1995) found a G-to-T transversion at position +1 of intron 7 of the
PHKA2 gene. This resulted in complete skipping of exon 7 and a PHKA2
protein lacking the 34 amino acids of this exon. Both patients had
hepatomegaly, growth retardation, and hypertriglyceridemia, but not
hypercholesterolemia. Only 1 had increased liver enzymes. Hepatomegaly
disappeared in both boys between ages 8 and 10 years. Erythrocyte
activity was 8 and 4% of control values, respectively.

.0004
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, SER1049TER

In 2 brothers from the U.K. with GSD type IXa1 (306000), Hendrickx et
al. (1995) found a C-to-A transversion in exon 11 of the PHKA2 gene,
resulting in a ser1049-to-ter (S1049X) substitution and protein lacking
more than 180 amino acids of the C terminus, including the 3-prime
putative calmodulin binding site. Both patients had growth retardation,
hepatomegaly, and elevated liver enzymes. Erythrocyte PHK activity was
5.7 and 16.9% of control values, respectively.

.0005
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, PRO1205LEU

In affected members of a large Dutch family with GSD type IXa1 (306000)
previously described by Huijing and Fernandez (1969) and Willems et al.
(1990), van den Berg et al. (1995) found a 3614C-T transition in the
PHKA2 gene, resulting in a pro1205-to-leu (P1205L) substitution in a
highly conserved region of the protein.

.0006
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, 3-BP DEL, 419TCT

In a Dutch boy with GSD type IXa1 (306000), van den Berg et al. (1995)
found a 3-bp deletion (419_421), resulting in deletion of
phenylalanine-141 from the gene product. The same deletion was found in
the PHKA2 coding sequence from lymphocytes of the patient's mother in
heterozygous state. This phenylalanine is a highly conserved amino acid
between species.

.0007
GLYCOGEN STORAGE DISEASE, TYPE IXa1
PHKA2, ASP299GLY

Burwinkel et al. (1996) identified an A-to-G transition in the PHKA2
gene, resulting in an asp299-to-gly (D299G) substitution, in a patient
they classified as having X-linked GSD IXa2 (see 306000). However,
Beauchamp et al. (2007) identified the D299G mutation in a patient with
reduced PHK activity in erythrocytes and leukocytes, consistent with GSD
IXa1 (306000). They suggested that D299G should be reclassified as a GSD
IXa1 mutation.

.0008
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, ARG186HIS

In a patient with X-linked GSD IXa2 (see 306000), Burwinkel et al.
(1996) identified a G-to-A transition in the PHKA2 gene, resulting in an
arg186-to-his (R186H) substitution.

Hendrickx et al. (1998) presented clinical, biochemical, and molecular
findings in a patient with type II X-linked liver glycogenosis and the
R186H mutation in the PHKA2 gene. The patient had been followed for 40
years. Although growth was retarded early in life, he achieved a height
of 182 cm at the age of 33 years. Thyroid therapy appeared to be helpful
in this patient. Five male relatives also had liver glycogenosis.

.0009
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, HIS132PRO

In a patient with GSD IXa2 (see 306000), Burwinkel et al. (1996)
identified an A-to-C transversion in the PHKA2 gene, resulting in a
his132-to-pro (H132P) substitution.

.0010
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, HIS132TYR

In a patient with GSD IXa2 (see 306000), Burwinkel et al. (1996)
identified a C-to-T change in the PHKA2 gene, resulting in a
his132-to-tyr (H132Y) substitution.

.0011
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, THR1114ILE

In a patient with X-linked GSD IXa2 (see 306000), Hendrickx et al.
(1996) identified a 3341C-T change in the PHKA2 gene, resulting in a
thr1114-to-ile (T1114I) substitution.

.0012
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, ARG556CYS

In a patient with X-linked GSD type IXa2 (see 306000), Hendrickx et al.
(1996) identified a 556C-T transition in the PHKA2 gene, resulting in an
arg556-to-cys (R556C) substitution.

.0013
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, 3-BP DEL, NT750

In a patient with X-linked GSD IXa2 (see 306000), Hendrickx et al.
(1996) identified an in-frame 3-bp deletion (750_752) in the PHKA2 gene,
resulting in the deletion of thr251.

.0014
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, 6-BP INS, NT3331

In a patient with X-linked GSD type IXa2 (see 306000), Hendrickx et al.
(1996) identified an in-frame 6-bp insertion between nucleotides 3331
and 3332 of the PHKA2 gene, resulting in the insertion of a threonine
and an arginine residue between arg1111 and glu1112 (R1111insTR).

.0015
GLYCOGEN STORAGE DISEASE, TYPE IXa2
PHKA2, LYS189GLU

In a patient with X-linked GSD IXa2 (see 306000), Burwinkel et al.
(1998) described an A-to-G transition in the PHKA2 coding sequence,
resulting in a lys189-to-glu (K189E) substitution. The phenotype in the
patient was that of low PHK activity in liver tissue, but activity in
erythrocytes was 4-fold higher than normal.

*FIELD* SA
Davisson (1987); Hendrickx et al. (1994); Huijing and Fernandez (1970);
Krebs et al. (1964); Lyon et al. (1967); Willems et al. (1991)
*FIELD* RF
1. Beauchamp, N. J.; Dalton, A.; Ramaswami, U.; Niinikoski, H.; Mention,
K.; Kenny, P.; Kolho, K.-L.; Raiman, J.; Walter, J.; Treacy, E.; Tanner,
S.; Sharrard, M.: Glycogen storage disease type IX: high variability
in clinical phenotype. Molec. Genet. Metab. 92: 88-99, 2007.

2. Burwinkel, B.; Amat, L.; Gray, R. G. F.; Matsuo, N.; Muroya, K.;
Narisawa, K.; Sokol, R. J.; Vilaseca, M. A.; Kilimann, M. W.: Variability
of biochemical and clinical phenotype in X-linked liver glycogenosis
with mutations in the phosphorylase kinase PHKA2 gene. Hum. Genet. 102:
423-429, 1998.

3. Burwinkel, B.; Shin, Y. S.; Bakker, H. D.; Deutsch, J.; Lozano,
M. J.; Maire, I.; Kilimann, M. W.: Mutation hotspots in the PHKA2
gene in X-linked liver glycogenosis due to phosphorylase kinase deficiency
with atypical activity in blood cells (XLG2). Hum. Molec. Genet. 5:
653-658, 1996.

4. Davidson, J. J.; Ozcelik, T.; Hamacher, C.; Willems, P. J.; Francke,
U.; Kilimann, M. W.: cDNA cloning of a liver isoform of the phosphorylase
kinase alpha subunit and mapping of the gene to Xp22.2-p22.1, the
region of human X-linked liver glycogenosis. Proc. Nat. Acad. Sci. 89:
2096-2100, 1992.

5. Davisson, M. T.: X-linked genetic homologies between mouse and
man. Genomics 1: 213-227, 1987.

6. Fukao, T.; Zhang, G.; Aoki, Y.; Arai, T.; Teramoto, T.; Kaneko,
H.; Sugie, H.; Kondo, N.: Identification of Alu-mediated, large deletion-spanning
introns 19-26 in PHKA2 in a patient with X-linked liver glycogenosis
(hepatic phosphorylase kinase deficiency). Molec. Genet. Metab. 92:
179-182, 2007.

7. Hendrickx, J.; Bosshard, N. U.; Willems, P.; Gitzelmann, R.: Clinical,
biochemical and molecular findings in a patient with X-linked liver
glycogenosis followed for 40 years. Europ. J. Pediat. 157: 919-923,
1998.

8. Hendrickx, J.; Coucke, P.; Bossuyt, P.; Wauters, J.; Raeymaekers,
P.; Marchau, F.; Smit, G. P. A.; Stolte, I.; Sardharwalla, I. B.;
Berthelot, J.; Van den Bergh, I.; Berger, R.; Van Broeckhoven, C.;
Baussan, C.; Wapenaar, M.; Fernandes, J.; Willems, P. J.: X-linked
liver glycogenosis: localization and isolation of a candidate gene. Hum.
Molec. Genet. 2: 583-589, 1993.

9. Hendrickx, J.; Coucke, P.; Dams, E.; Lee, P.; Odievre, M.; Corbeel,
L.; Fernandes, J. F.; Willems, P. J.: Mutations in the phosphorylase
kinase gene PHKA2 are responsible for X-linked liver glycogen storage
disease. Hum. Molec. Genet. 4: 77-83, 1995.

10. Hendrickx, J.; Coucke, P.; Hors-Cayla, M.-C.; Smit, G. P. A.;
Shin, Y. S.; Deutsch, J.; Smeitink, J.; Berger, R.; Lee, P.; Fernandes,
J.; Willems, P. J.: Localization of a new type of X-linked liver
glycogenosis to the chromosomal region Xp22 containing the liver alpha-subunit
of phosphorylase kinase (PHKA2). Genomics 21: 620-625, 1994.

11. Hendrickx, J.; Coucke, P.; Raeymaekers, P.; Willems, P. J.: X-linked
liver glycogenosis: localization and isolation of a strong candidate
gene. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A190 only, 1992.

12. Hendrickx, J.; Dams, E.; Coucke, P.; Lee, P.; Fernandes, J.; Willems,
P. J.: X-linked liver glycogenosis type II (XLG II) is caused by
mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase
kinase. Hum. Molec. Genet. 5: 649-652, 1996.

13. Hendrickx, J.; Lee, P.; Keating, J. P.; Carton, D.; Sardharwalla,
I. B.; Tuchman, M.; Baussan, C.; Willems, P. J.: Complete genomic
structure and mutational spectrum of PHKA2 in patients with X-linked
liver glycogenosis type I and II. Am. J. Hum. Genet. 64: 1541-1549,
1999.

14. Huijing, F.; Fernandez, J.: X-chromosomal inheritance of liver
glycogenosis with phosphorylase kinase deficiency. Am. J. Hum. Genet. 21:
275-284, 1969.

15. Huijing, F.; Fernandez, J.: Liver glycogenosis and phosphorylase
kinase deficiency. (Letter) Am. J. Hum. Genet. 22: 484-485, 1970.

16. Krebs, E. G.; Love, D. S.; Bratvold, G. E.; Trayser, K. A.; Meyer,
W. L.; Fischer, E. H.: Purification and properties of rabbit skeletal
muscle phosphorylase B kinase. Biochemistry 3: 1022-1033, 1964.

17. Lyon, J. B., Jr.; Porter, J.; Robertson, M.: Phosphorylase B
kinase inheritance in mice. Science 155: 1550-1551, 1967.

18. Ryder-Cook, A. S.; Derry, J. M. J.; Barnard, P. J.: Localization
of the phosphorylase kinase alpha subunit gene on the mouse X chromosome.
(Abstract) Cytogenet. Cell Genet. 51: 1071-1072, 1989.

19. van den Berg, I. E. T.; van Beurden, E. A. C. M.; Malingre, H.
E. M.; Ploos van Amstel, H. K.; Poll-The, B. T.; Smeitink, J. A. M.;
Lamers, W. H.; Berger, R.: X-linked liver phosphorylase kinase deficiency
is associated with mutations in the human liver phosphorylase kinase
alpha subunit. Am. J. Hum. Genet. 56: 381-387, 1995.

20. Wauters, J. G.; Bossuyt, P. J.; Davidson, J.; Hendrickx, J.; Kilimann,
M. W.; Willems, P. J.: Regional mapping of a liver alpha-subunit
gene of phosphorylase kinase (PHKA) to the distal region of human
chromosome Xp. Cytogenet. Cell Genet. 60: 194-196, 1992.

21. Willems, P. J.; Gerver, W. J. M.; Berger, R.; Fernandes, J.:
The natural history of liver glycogenosis due to phosphorylase kinase
deficiency: a longitudinal study of 41 patients. Europ. J. Pediat. 149:
268-271, 1990.

22. Willems, P. J.; Hendrickx, J.; Van der Auwera, B. J.; Vits, L.;
Raeymaekers, P.; Coucke, P. J.; Van den Bergh, I.; Berger, R.; Smit,
G. P. A.; Van Broeckhoven, C.; Kilimann, M. W.; Van Elsen, A. F.;
Fernandes, J. F.: Mapping of the gene for X-linked liver glycogenosis
due to phosphorylase kinase deficiency to human chromosome region
Xp22. Genomics 9: 565-569, 1991.

*FIELD* CN
Cassandra L. Kniffin - updated: 10/9/2009

*FIELD* CD
Cassandra L. Kniffin: 9/20/2009

*FIELD* ED
wwang: 11/05/2009
ckniffin: 10/9/2009
carol: 10/1/2009
ckniffin: 9/24/2009

MIM 306000
*RECORD*
*FIELD* NO
306000
*FIELD* TI
#306000 GLYCOGEN STORAGE DISEASE IXa1; GSD9A1
;;GSD IXa1;;
LIVER GLYCOGENOSIS, X-LINKED, TYPE I; XLG1;;
read moreGLYCOGEN STORAGE DISEASE VIII, FORMERLY;;
GSD VIII, FORMERLY; GSD8, FORMERLY
GLYCOGEN STORAGE DISEASE IXa2, INCLUDED;;
GSD IXa2, INCLUDED; GSD9A2, INCLUDED;;
LIVER GLYCOGENOSIS, X-LINKED, TYPE II, INCLUDED; XLG2, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease type IXa (GSD9a) is caused by mutation in the gene encoding the
alpha-2 subunit of hepatic phosphorylase kinase (PHKA2; 300798).

DESCRIPTION

Glycogen storage disease type IX is a metabolic disorder resulting from
a deficiency of hepatic phosphorylase kinase, a hexadecameric enzyme
comprising 4 copies each of 4 unique subunits encoded by 4 different
genes: alpha (PHKA2), beta (PHKB; 172490), gamma (PHKG2; 172471), and
delta (CALM1; 114180). Mutations within the PHKA2, PHKB, and PHKG2 genes
result in GSD9a, GSD9b (261750), and GSD9c (613027), respectively. GSD9a
is an X-linked recessive disorder, whereas the others are autosomal
recessive.

See also X-linked muscle PHK deficiency (GSD9D; 300559), caused by
mutation in the gene encoding the muscle-specific alpha PHK subunit
(PHKA1; 311870).

GSD IXa has been further divided into types IXa1 (GSD9A1), with no PHK
activity in liver or erythrocytes, and IXa2 (GSD9A2), with no PHK in
liver, but normal activity in erythrocytes. The clinical presentation of
both subtypes is the same, and both are caused by mutations in the PHKA2
gene. However, mutations that result in IXa2 are either missense or
small in-frame deletions or insertions enabling residual enzyme
expression in erythrocytes (Keating et al., 1985; Hendrickx et al.,
1994; Beauchamp et al., 2007).

CLINICAL FEATURES

Glycogen storage disease IXa is one of the mildest of the glycogenoses
of man. Clinical symptoms include hepatomegaly, growth retardation,
elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate
transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting
hyperketosis These clinical and biochemical abnormalities gradually
disappear with age, and most adult patients are asymptomatic (Schimke et
al., 1973; Willems et al., 1990).

Hendrickx et al. (1998) presented clinical, biochemical, and molecular
findings in a patient with GSD IXa2 who had been followed for 40 years.
Although growth was retarded early in life, he achieved a height of 182
cm at the age of 33 years. Thyroid therapy appeared to be helpful in
this patient. Five male relatives also had liver glycogenosis. Genetic
analysis identified a mutation in the PHKA2 gene (R186H; 300798.0008)

Beauchamp et al. (2007) reported 10 patients from 8 families with GSD
IXa confirmed by genetic analysis. Age at diagnosis ranged from 12
months to 7 years. Clinical features were variable, and included
hepatomegaly, short stature, liver dysfunction, hypoglycemia,
hyperuricemia, hyperlipidemia, fasting ketosis, and mild motor delay.
Five of the 8 probands had a demonstrable reduction of PHK activity in
erythrocytes, consistent with GSD IXa1. The majority of patients had
private mutations. The authors emphasized that molecular analysis
results in accurate diagnosis for GSD IX when enzymology is
uninformative, and thus allows for proper genetic counseling.

CLINICAL MANAGEMENT

In 4 boys with X-linked PHK-deficient glycogenosis, aged 29 months to 43
months, Garibaldi et al. (1978) found that dextrothyroxine (D-T4) had
dramatic effects: the liver, previously greatly enlarged, returned to
normal size; serum GOT, GPT, and triglycerides fell to normal; and
hypoglycemia was corrected.

INHERITANCE

Williams and Field (1961) found low leukocyte phosphorylase activity in
2 affected brothers, and normal activity in an unaffected brother and in
the father. An intermediately low level in the mother, together with
affected males, suggested X-linked inheritance. Wallis et al. (1966)
restudied the family and with new methods found support for X-linkage.

Huijing and Fernandez (1969) studied 2 kindreds, one of which had 6
affected males and 2 possibly affected males. The other had 20 affected
males, 2 affected females, and 7 probably affected males. X-linked
inheritance was suggested. Huijing and Fernandez (1970) suggested that
affected females studied by Hug et al. (1969) were heterozygotes.

By cloning cells of an obligate heterozygous female with GSD due to
phosphorylase kinase deficiency, Migeon and Huijing (1974) demonstrated
that some fibroblasts had enzymatic levels similar to those of affected
hemizygotes. This was presented as proof of X-linkage and X-inactivation
of the phosphorylase kinase locus.

MAPPING

Willems et al. (1991) performed linkage analysis with X-chromosomal
polymorphic DNA markers in 2 families with X-linked liver glycogenosis.
Multipoint linkage analysis indicated that the mutation responsible for
X-linked liver glycogenosis was located on Xp22 between DXS143 and
DXS41. Linkage to the muscle PHKA1 region on Xq12-q13 was excluded.

Hendrickx et al. (1992, 1993) found a combined multipoint lod score of
16.79 for linkage of X-linked liver glycogenosis to chromosome Xp22.

Hendrickx et al. (1994) performed linkage analysis in 4 families with
GSD IXa2, who had residual PHK activity in erythrocytes, and showed that
this form was also linked to Xp22. The authors concluded that this
biochemical variant type was allelic to GSD IXa1, and that both diseases
are likely caused by mutations in PHKA2. Hendrickx et al. (1994)
proposed the classification of XLG into types I and II.

MOLECULAR GENETICS

In affected members of 4 unrelated families with GSD IXa1, Hendrickx et
al. (1995) identified 4 different mutations in the PHKA2 gene
(300798.0001-300798.0004). Clinical features were somewhat variable, but
included growth retardation, hepatomegaly, elevated liver enzymes, and
normalization of symptoms with age. PHK activity was decreased to less
than 20% of control values in erythrocytes and in liver, when measured.

Van den Berg et al. (1995) identified mutations in the PHKA2 gene
(300798.0005 and 300798.0006) in affected members of 2 Dutch families
with GSD IXa1. One of the families had been reported by Huijing and
Fernandez (1969).

Burwinkel et al. (1996) identified mutations in the PHKA2 gene in
patients with GSD IXa2 (see 306000.0008-306000.0010). The mutations
appeared to cluster in limited sequence regions. Burwinkel et al. (1996)
stressed that the clustering of type II mutations would further
facilitate analysis by RT-PCR of blood cell mRNA and thus help avoid
liver biopsy in the diagnosis.

GENOTYPE/PHENOTYPE CORRELATIONS

In 4 unrelated patients with GSD IXa2, Hendrickx et al. (1996)
identified 4 different mutations in the PHKA2 gene
(306000.0011-306000.0014). The mutations resulted in minor abnormalities
in the primary structure of the protein. These mutations are found in a
conserved RXX(X)T motif, resembling known phosphorylation sites that may
be involved in the regulation of PHK. Hendrickx et al. (1996) postulated
that PHK activity may be regulated by phosphorylation of these sites and
that type II GSD9a may be due to impaired activation of PHK activity.
The findings may explain why the in vitro PHK enzymatic activity is not
deficient in type II, whereas it is in type I.

Burwinkel et al. (1998) described 8 new mutations and phenotypic
consequences in patients with X-linked liver glycogenosis. One of the
patients reported by Burwinkel et al. (1998) had low PHK activity in the
liver but elevated levels in erythrocytes, typical of XLG type II. This
patient had a lys189-to-glu missense mutation (K189E; 306000.0015). The
authors noted that this observation adds to the growing body of evidence
that the XLG phenotype is associated with missense mutations clustering
at a few sites in the PHKA2 gene.

Hendrickx et al. (1999) identified PHKA2 mutations in 10 patients with
XLG types I and II. They proposed that mutations in XLG type I, in which
PHK activity is decreased in both liver and erythrocytes, results from
truncation or disruption of the PHKA2 protein. In contrast, all type II
mutations, which result in residual activity in erythrocytes, were
missense mutations or small in-frame deletions and insertions. These
results suggested that the biochemical differences between the 2 types
of XLG are due to the different nature of the disease-causing mutations
in PHKA2. Type I mutations may lead to absence of the alpha subunit,
which causes an unstable PHK holoenzyme and deficient enzyme activity,
whereas type II mutations may lead to in vivo deregulation of PHK, which
might be difficult to demonstrate in vitro.

NOMENCLATURE

The classification, particularly the numbering, of the glycogenoses has
long been a matter of dispute. For example, Huijing (1970) referred to
this disorder as glycogen storage disease type VIA; Hug (1974) assigned
number VIII to a presumedly recessive form of phosphorylase deficiency
with brain involvement and number IX to phosphorylase kinase deficiency
(see Schimke et al., 1973). McAdams et al. (1974) presented information
on classification and morphology of the glycogenoses.

ANIMAL MODEL

Schneider et al. (1993) reviewed the animal mutants that result in
PHK-linked glycogenoses. Two different X-linked disorders are known, as
well as an autosomal recessive PHK deficiency affecting the liver and
most other tissues but not muscle, in the rat.

*FIELD* SA
Goji et al. (1985); Hers (1959); Huijing (1967); Huijing (1970);
Varsanyi et al. (1980)
*FIELD* RF
1. Beauchamp, N. J.; Dalton, A.; Ramaswami, U.; Niinikoski, H.; Mention,
K.; Kenny, P.; Kolho, K.-L.; Raiman, J.; Walter, J.; Treacy, E.; Tanner,
S.; Sharrard, M.: Glycogen storage disease type IX: high variability
in clinical phenotype. Molec. Genet. Metab. 92: 88-99, 2007.

2. Burwinkel, B.; Amat, L.; Gray, R. G. F.; Matsuo, N.; Muroya, K.;
Narisawa, K.; Sokol, R. J.; Vilaseca, M. A.; Kilimann, M. W.: Variability
of biochemical and clinical phenotype in X-linked liver glycogenosis
with mutations in the phosphorylase kinase PHKA2 gene. Hum. Genet. 102:
423-429, 1998.

3. Burwinkel, B.; Shin, Y. S.; Bakker, H. D.; Deutsch, J.; Lozano,
M. J.; Maire, I.; Kilimann, M. W.: Mutation hotspots in the PHKA2
gene in X-linked liver glycogenosis due to phosphorylase kinase deficiency
with atypical activity in blood cells (XLG2). Hum. Molec. Genet. 5:
653-658, 1996.

4. Garibaldi, L. R.; Borrone, C.; De Martini, I.; Battistini, E.:
Dextrothyroxine treatment of phosphorylase-kinase deficiency glycogenosis
in four boys. Helv. Paediat. Acta 33: 435-444, 1978.

5. Goji, K.; Morishita, Y.; Kodama, S.; Takahashi, T.; Matsuo, T.
: Lymphocyte phosphorylase kinase activities in the sex-linked form
of liver phosphorylase kinase deficiency. Europ. J. Pediat. 143:
179-182, 1985.

6. Hendrickx, J.; Bosshard, N. U.; Willems, P.; Gitzelmann, R.: Clinical,
biochemical and molecular findings in a patient with X-linked liver
glycogenosis followed for 40 years. Europ. J. Pediat. 157: 919-923,
1998.

7. Hendrickx, J.; Coucke, P.; Bossuyt, P.; Wauters, J.; Raeymaekers,
P.; Marchau, F.; Smit, G. P. A.; Stolte, I.; Sardharwalla, I. B.;
Berthelot, J.; Van den Bergh, I.; Berger, R.; Van Broeckhoven, C.;
Baussan, C.; Wapenaar, M.; Fernandes, J.; Willems, P. J.: X-linked
liver glycogenosis: localization and isolation of a candidate gene. Hum.
Molec. Genet. 2: 583-589, 1993.

8. Hendrickx, J.; Coucke, P.; Dams, E.; Lee, P.; Odievre, M.; Corbeel,
L.; Fernandes, J. F.; Willems, P. J.: Mutations in the phosphorylase
kinase gene PHKA2 are responsible for X-linked liver glycogen storage
disease. Hum. Molec. Genet. 4: 77-83, 1995.

9. Hendrickx, J.; Coucke, P.; Hors-Cayla, M.-C.; Smit, G. P. A.; Shin,
Y. S.; Deutsch, J.; Smeitink, J.; Berger, R.; Lee, P.; Fernandes,
J.; Willems, P. J.: Localization of a new type of X-linked liver
glycogenosis to the chromosomal region Xp22 containing the liver alpha-subunit
of phosphorylase kinase (PHKA2). Genomics 21: 620-625, 1994.

10. Hendrickx, J.; Coucke, P.; Raeymaekers, P.; Willems, P. J.: X-linked
liver glycogenosis: localization and isolation of a strong candidate
gene. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A190 only, 1992.

11. Hendrickx, J.; Dams, E.; Coucke, P.; Lee, P.; Fernandes, J.; Willems,
P. J.: X-linked liver glycogenosis type II (XLG II) is caused by
mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase
kinase. Hum. Molec. Genet. 5: 649-652, 1996.

12. Hendrickx, J.; Lee, P.; Keating, J. P.; Carton, D.; Sardharwalla,
I. B.; Tuchman, M.; Baussan, C.; Willems, P. J.: Complete genomic
structure and mutational spectrum of PHKA2 in patients with X-linked
liver glycogenosis type I and II. Am. J. Hum. Genet. 64: 1541-1549,
1999.

13. Hers, H. G.: Etudes enzymatiques sur fragments hepatiques: application
a la classification des glycogenoses. Rev. Int. Hepat. 9: 35-55,
1959.

14. Hug, G.: Personal Communication. Cincinnati, Ohio 1974.

15. Hug, G.; Schubert, W. K.; Chuck, G.: Deficient activity of dephosphophosphorylase
kinase and accumulation of glycogen in the liver. J. Clin. Invest. 48:
704-715, 1969.

16. Huijing, F.: Glycogen-storage disease type VIa: low phosphorylase
kinase activity caused by a low enzyme-substrate affinity. Biochim.
Biophys. Acta 206: 199-201, 1970.

17. Huijing, F.: Phosphorylase kinase in leucocytes of normal subjects
and of patients with glycogen-storage disease. Biochim. Biophys.
Acta 148: 601-603, 1967.

18. Huijing, F.: Phosphorylase kinase deficiency. Biochem. Genet. 4:
187-194, 1970.

19. Huijing, F.; Fernandez, J.: X-chromosomal inheritance of liver
glycogenosis with phosphorylase kinase deficiency. Am. J. Hum. Genet. 21:
275-284, 1969.

20. Huijing, F.; Fernandez, J.: Liver glycogenosis and phosphorylase
kinase deficiency. (Letter) Am. J. Hum. Genet. 22: 484-485, 1970.

21. Keating, J. P.; Brown, B. I.; White, N. H.; DiMauro, S.: X-linked
glycogen storage disease: a cause of hypotonia, hyperuricemia, and
growth retardation. Am. J. Dis. Child. 139: 609-613, 1985.

22. McAdams, A. J.; Hug, G.; Bove, K. E.: Glycogen storage disease,
type I to X: criteria for morphologic diagnosis. Hum. Path. 5: 463-487,
1974.

23. Migeon, B. R.; Huijing, F.: Glycogen-storage disease associated
with phosphorylase kinase deficiency: evidence for X inactivation. Am.
J. Hum. Genet. 26: 360-368, 1974.

24. Schimke, R. N.; Zakheim, R. M.; Corder, R. C.; Hug, G.: Glycogen
storage disease type IX: benign glycogenosis of liver and hepatic
phosphorylase kinase deficiency. J. Pediat. 83: 1031-1034, 1973.

25. Schneider, A.; Davidson, J. J.; Wullrich, A.; Kilimann, M. W.
: Phosphorylase kinase deficiency in I-strain mice is associated with
a frameshift mutation in the alpha-subunit muscle isoform. Nature
Genet. 5: 381-385, 1993.

26. van den Berg, I. E. T.; van Beurden, E. A. C. M.; Malingre, H.
E. M.; Ploos van Amstel, H. K.; Poll-The, B. T.; Smeitink, J. A. M.;
Lamers, W. H.; Berger, R.: X-linked liver phosphorylase kinase deficiency
is associated with mutations in the human liver phosphorylase kinase
alpha subunit. Am. J. Hum. Genet. 56: 381-387, 1995.

27. Varsanyi, M.; Vrbica, A.; Heilmeyer, L. M. G., Jr.: X-linked
dominant inheritance of partial phosphorylase kinase deficiency in
mice. Biochem. Genet. 18: 247-261, 1980.

28. Wallis, P. G.; Sidbury, J. B., Jr.; Harris, R. C.: Hepatic phosphorylase
defect. Studies on peripheral blood. Am. J. Dis. Child. 111: 278-282,
1966.

29. Willems, P. J.; Gerver, W. J. M.; Berger, R.; Fernandes, J.:
The natural history of liver glycogenosis due to phosphorylase kinase
deficiency: a longitudinal study of 41 patients. Europ. J. Pediat. 149:
268-271, 1990.

30. Willems, P. J.; Hendrickx, J.; Van der Auwera, B. J.; Vits, L.;
Raeymaekers, P.; Coucke, P. J.; Van den Bergh, I.; Berger, R.; Smit,
G. P. A.; Van Broeckhoven, C.; Kilimann, M. W.; Van Elsen, A. F.;
Fernandes, J. F.: Mapping of the gene for X-linked liver glycogenosis
due to phosphorylase kinase deficiency to human chromosome region
Xp22. Genomics 9: 565-569, 1991.

31. Williams, H. E.; Field, J. B.: Low leukocyte phosphorylase in
hepatic phosphorylase deficient glycogen storage disease. J. Clin.
Invest. 40: 1841-1845, 1961.

*FIELD* CS
INHERITANCE:
X-linked recessive

GROWTH:
[Height];
Growth retardation;
Normal final adult height

ABDOMEN:
[Liver];
Hepatomegaly;
Liver histology reveals glycogen-distended hepatocytes

NEUROLOGIC:
[Central nervous system];
Mild motor development delay

LABORATORY ABNORMALITIES:
Liver phosphorylase kinase (PHK) deficiency;
Phosphorylase kinase normal in muscle;
Variable hypoglycemia;
Mild elevation of transaminases;
Mild elevation of cholesterol;
Mild elevation of triglycerides;
Fasting ketosis

MISCELLANEOUS:
Clinical and biochemical abnormalities disappear with age

MOLECULAR BASIS:
Caused by mutations in the liver phosphorylase alpha-2 subunit gene
(PHKA2, 306000.0001)

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

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

*FIELD* ED
joanna: 03/18/2002
kayiaros: 9/20/2000

*FIELD* CN
Cassandra L. Kniffin - reorganized: 10/1/2009
Cassandra L. Kniffin - updated: 9/24/2009
Victor A. McKusick - updated: 5/28/1999
Victor A. McKusick - updated: 2/3/1999
Victor A. McKusick - updated: 1/25/1999
Clair A. Francomano - updated: 5/27/1998
Victor A. McKusick - updated: 11/17/1997
Moyra Smith - updated: 6/12/1996

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

*FIELD* ED
carol: 12/01/2010
carol: 10/1/2009
ckniffin: 9/24/2009
carol: 1/6/2009
carol: 4/17/2007
alopez: 2/3/2006
terry: 4/6/2005
carol: 3/17/2004
mgross: 6/14/1999
mgross: 6/3/1999
terry: 5/28/1999
carol: 2/12/1999
terry: 2/3/1999
carol: 2/1/1999
terry: 1/25/1999
carol: 6/19/1998
terry: 6/16/1998
dholmes: 5/28/1998
dholmes: 5/27/1998
dholmes: 5/21/1998
alopez: 5/8/1998
jenny: 11/20/1997
jenny: 11/19/1997
terry: 11/17/1997
alopez: 7/8/1997
mark: 3/27/1997
terry: 10/31/1996
carol: 6/12/1996
carol: 2/27/1995
davew: 8/22/1994
jason: 7/13/1994
warfield: 4/20/1994
mimadm: 4/13/1994
carol: 12/17/1993

RBCC Red Blood Cell Collection

Full text data of PHKA2