RBCC

Full text data of PHKB

PHKB [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Phosphorylase b kinase regulatory subunit beta; Phosphorylase kinase subunit beta

UniProt Q93100
ID KPBB_HUMAN Reviewed; 1093 AA.
AC Q93100; Q8N4T5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Phosphorylase b kinase regulatory subunit beta;
DE Short=Phosphorylase kinase subunit beta;
GN Name=PHKB;
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 / MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=8681948; DOI=10.1111/j.1432-1033.1996.0374z.x;
RA Wuellrich-Schmoll A., Kilimann M.W.;
RT "Structure of the human gene encoding the phosphorylase kinase beta
RT subunit (PHKB).";
RL Eur. J. Biochem. 238:374-380(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Uterus;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, 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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORMS 2 AND 4),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4 (ISOFORMS 2 AND 4),
RP MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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 [8]
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 [9]
RP VARIANT CYS-770.
RX PubMed=9326319;
RA van den Berg I.E.T., van Beurden E.A.C.M., de Klerk J.B.C.,
RA van Diggelen O.P., Malingre H.E.M., Boer M.M., Berger R.;
RT "Autosomal recessive phosphorylase kinase deficiency in liver, caused
RT by mutations in the gene encoding the beta subunit (PHKB).";
RL Am. J. Hum. Genet. 61:539-546(1997).
RN [10]
RP VARIANT GSD9B PRO-118.
RX PubMed=9402963; DOI=10.1007/s004390050608;
RA Burwinkel B., Moses S.W., Kilimann M.W.;
RT "Phosphorylase-kinase-deficient liver glycogenosis with an unusual
RT biochemical phenotype in blood cells associated with a missense
RT mutation in the beta subunit gene (PHKB).";
RL Hum. Genet. 101:170-174(1997).
RN [11]
RP VARIANTS LYS-657 AND CYS-770.
RX PubMed=12825073; DOI=10.1038/sj.ejhg.5200996;
RA Burwinkel B., Hu B., Schroers A., Clemens P.R., Moses S.W., Shin Y.S.,
RA Pongratz D., Vorgerd M., Kilimann M.W.;
RT "Muscle glycogenosis with low phosphorylase kinase activity: mutations
RT in PHKA1, PHKG1 or six other candidate genes explain only a minority
RT of cases.";
RL Eur. J. Hum. Genet. 11:516-526(2003).
RN [12]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-867 AND ARG-877.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Phosphorylase b kinase catalyzes the phosphorylation of
CC serine in certain substrates, including troponin I. The beta chain
CC acts as a regulatory unit and modulates the activity of the
CC holoenzyme in response to phosphorylation.
CC -!- ENZYME REGULATION: By phosphorylation of various serine residues
CC (By similarity).
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 -!- INTERACTION:
CC Q96RG2:PASK; NbExp=2; IntAct=EBI-740559, EBI-1042651;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic
CC side (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q93100-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q93100-2; Sequence=VSP_012445;
CC Note=Initiator Met-1 is removed. Contains a N-acetylalanine at
CC position 2. Contains a phosphoserine at position 4;
CC Name=3;
CC IsoId=Q93100-3; Sequence=VSP_012446;
CC Name=4;
CC IsoId=Q93100-4; Sequence=VSP_012445, VSP_012446;
CC Note=Initiator Met-1 is removed. Contains a N-acetylalanine at
CC position 2. Contains a phosphoserine at position 4;
CC -!- PTM: Ser-701 is probably phosphorylated by PKA.
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 9B (GSD9B) [MIM:261750]: A
CC metabolic disorder characterized by hepatomegaly, only slightly
CC elevated transaminases and plasma lipids, clinical improvement
CC with increasing age, and remarkably no clinical muscle
CC involvement. Biochemical observations suggest that this mild
CC phenotype is caused by an incomplete holoenzyme that lacks the
CC beta subunit, but that may possess residual activity. Note=The
CC disease is caused by mutations affecting the gene represented in
CC 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/PHKB";
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DR EMBL; X84909; CAA59333.1; -; Genomic_DNA.
DR EMBL; X84911; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84912; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84913; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84914; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84915; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84916; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84917; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84918; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84919; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84920; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84921; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84922; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84923; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84924; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84925; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84926; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84927; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84928; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84929; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84930; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84931; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84933; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84934; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84935; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84936; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84937; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84938; CAA59333.1; JOINED; Genomic_DNA.
DR EMBL; X84908; CAA59332.1; -; mRNA.
DR EMBL; BC033657; AAH33657.1; -; mRNA.
DR PIR; S74250; S74250.
DR PIR; S74251; S74251.
DR RefSeq; NP_000284.1; NM_000293.2.
DR RefSeq; NP_001027005.1; NM_001031835.2.
DR RefSeq; XP_005256040.1; XM_005255983.1.
DR RefSeq; XP_005256041.1; XM_005255984.1.
DR UniGene; Hs.78060; -.
DR ProteinModelPortal; Q93100; -.
DR IntAct; Q93100; 5.
DR MINT; MINT-1444943; -.
DR STRING; 9606.ENSP00000313504; -.
DR BindingDB; Q93100; -.
DR ChEMBL; CHEMBL2111324; -.
DR PhosphoSite; Q93100; -.
DR DMDM; 2499582; -.
DR PaxDb; Q93100; -.
DR PRIDE; Q93100; -.
DR DNASU; 5257; -.
DR Ensembl; ENST00000299167; ENSP00000299167; ENSG00000102893.
DR Ensembl; ENST00000323584; ENSP00000313504; ENSG00000102893.
DR Ensembl; ENST00000455779; ENSP00000414345; ENSG00000102893.
DR Ensembl; ENST00000566044; ENSP00000456729; ENSG00000102893.
DR GeneID; 5257; -.
DR KEGG; hsa:5257; -.
DR UCSC; uc002eev.4; human.
DR CTD; 5257; -.
DR GeneCards; GC16P047436; -.
DR HGNC; HGNC:8927; PHKB.
DR MIM; 172490; gene.
DR MIM; 261750; phenotype.
DR neXtProt; NX_Q93100; -.
DR Orphanet; 79240; Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency.
DR PharmGKB; PA33268; -.
DR eggNOG; NOG82518; -.
DR HOGENOM; HOG000231477; -.
DR HOVERGEN; HBG097309; -.
DR InParanoid; Q93100; -.
DR KO; K07190; -.
DR OMA; LKGKYGF; -.
DR OrthoDB; EOG73Z2SM; -.
DR PhylomeDB; Q93100; -.
DR BioCyc; MetaCyc:HS02424-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00163; -.
DR ChiTaRS; PHKB; human.
DR GeneWiki; PHKB; -.
DR GenomeRNAi; 5257; -.
DR NextBio; 20308; -.
DR PRO; PR:Q93100; -.
DR ArrayExpress; Q93100; -.
DR Bgee; Q93100; -.
DR CleanEx; HS_PHKB; -.
DR Genevestigator; Q93100; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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: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 InterPro; IPR008928; 6-hairpin_glycosidase-like.
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 Acetylation; Alternative splicing; Calmodulin-binding;
KW Carbohydrate metabolism; Cell membrane; Complete proteome;
KW Disease mutation; Glycogen metabolism; Glycogen storage disease;
KW Lipoprotein; Membrane; Phosphoprotein; Polymorphism; Prenylation;
KW Reference proteome.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 1093 Phosphorylase b kinase regulatory subunit
FT beta.
FT /FTId=PRO_0000057736.
FT REGION 7 29 Calmodulin-binding (Potential).
FT REGION 768 795 Calmodulin-binding (Potential).
FT REGION 920 951 Calmodulin-binding (Potential).
FT MOD_RES 2 2 N-acetylalanine (By similarity).
FT MOD_RES 12 12 Phosphoserine; by autocatalysis (By
FT similarity).
FT MOD_RES 27 27 Phosphoserine.
FT MOD_RES 701 701 Phosphoserine (By similarity).
FT LIPID 1090 1090 S-farnesyl cysteine (By similarity).
FT VAR_SEQ 1 23 MAGAAGLTAEVSWKVLERRARTK -> MACSPDAVVSPSSA
FT FL (in isoform 2 and isoform 4).
FT /FTId=VSP_012445.
FT VAR_SEQ 780 806 LAVRYGAAFTQKFSSSIAPHITTFLVH -> SVVRRAASLL
FT SKVVDSLAPSITNVLVQ (in isoform 3 and
FT isoform 4).
FT /FTId=VSP_012446.
FT VARIANT 118 118 A -> P (in GSD9B).
FT /FTId=VAR_015536.
FT VARIANT 657 657 Q -> K (in dbSNP:rs34667348).
FT /FTId=VAR_020857.
FT VARIANT 770 770 Y -> C (in dbSNP:rs16945474).
FT /FTId=VAR_006187.
FT VARIANT 820 820 E -> V (in dbSNP:rs9934849).
FT /FTId=VAR_034056.
FT VARIANT 867 867 L -> V (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036486.
FT VARIANT 877 877 G -> R (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036487.
SQ SEQUENCE 1093 AA; 124884 MW; 48F05EE306195472 CRC64;
MAGAAGLTAE VSWKVLERRA RTKRSGSVYE PLKSINLPRP DNETLWDKLD HYYRIVKSTL
LLYQSPTTGL FPTKTCGGDQ KAKIQDSLYC AAGAWALALA YRRIDDDKGR THELEHSAIK
CMRGILYCYM RQADKVQQFK QDPRPTTCLH SVFNVHTGDE LLSYEEYGHL QINAVSLYLL
YLVEMISSGL QIIYNTDEVS FIQNLVFCVE RVYRVPDFGV WERGSKYNNG STELHSSSVG
LAKAALEAIN GFNLFGNQGC SWSVIFVDLD AHNRNRQTLC SLLPRESRSH NTDAALLPCI
SYPAFALDDE VLFSQTLDKV VRKLKGKYGF KRFLRDGYRT SLEDPNRCYY KPAEIKLFDG
IECEFPIFFL YMMIDGVFRG NPKQVQEYQD LLTPVLHHTT EGYPVVPKYY YVPADFVEYE
KNNPGSQKRF PSNCGRDGKL FLWGQALYII AKLLADELIS PKDIDPVQRY VPLKDQRNVS
MRFSNQGPLE NDLVVHVALI AESQRLQVFL NTYGIQTQTP QQVEPIQIWP QQELVKAYLQ
LGINEKLGLS GRPDRPIGCL GTSKIYRILG KTVVCYPIIF DLSDFYMSQD VFLLIDDIKN
ALQFIKQYWK MHGRPLFLVL IREDNIRGSR FNPILDMLAA LKKGIIGGVK VHVDRLQTLI
SGAVVEQLDF LRISDTEELP EFKSFEELEP PKHSKVKRQS STPSAPELGQ QPDVNISEWK
DKPTHEILQK LNDCSCLASQ AILLGILLKR EGPNFITKEG TVSDHIERVY RRAGSQKLWL
AVRYGAAFTQ KFSSSIAPHI TTFLVHGKQV TLGAFGHEEE VISNPLSPRV IQNIIYYKCN
THDEREAVIQ QELVIHIGWI ISNNPELFSG MLKIRIGWII HAMEYELQIR GGDKPALDLY
QLSPSEVKQL LLDILQPQQN GRCWLNRRQI DGSLNRTPTG FYDRVWQILE RTPNGIIVAG
KHLPQQPTLS DMTMYEMNFS LLVEDTLGNI DQPQYRQIVV ELLMVVSIVL ERNPELEFQD
KVDLDRLVKE AFNEFQKDQS RLKEIEKQDD MTSFYNTPPL GKRGTCSYLT KAVMNLLLEG
EVKPNNDDPC LIS
//

MIM 172490
*RECORD*
*FIELD* NO
172490
*FIELD* TI
*172490 PHOSPHORYLASE KINASE, BETA SUBUNIT; PHKB
*FIELD* TX

DESCRIPTION

The PHKB gene encodes the beta subunit of phosphorylase kinase (PHK; EC
read more2.7.11.19). Phosphorylase kinase is a hexadecameric enzyme comprising 4
copies each of 4 unique subunits encoded by 4 different genes: alpha
(PHKA1 (311870) and PHKA2 (300798), the skeletal muscle and hepatic
isoforms, respectively); beta (PHKB); gamma (PHKG1 (172470) and PHKG2
(172471), the skeletal muscle and hepatic isoforms, respectively); and
delta. The delta subunit can be encoded by 3 different genes (CALM1,
114180, CALM2, 114182, or CALM3, 114183). The beta subunit is the same
in both the muscle and hepatic 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

Kilimann et al. (1988) and Zander et al. (1988) cloned DNA sequences
encoding the alpha and beta PHK subunits from a rabbit muscle cDNA
library. The deduced alpha and beta polypeptides are 1,237 and 1,092
amino acids long, respectively, and contain extensive regions of
sequence homology.

Wullrich-Schmoll and Kilimann (1996) cloned the human PHKB gene and
found that the deduced protein shares 95% amino acid sequence identity
with the rabbit protein.

GENE STRUCTURE

Wullrich-Schmoll and Kilimann (1996) determined that the PHKB gene
contains 33 exons and spans at least 140 kb. Exons 26 and 27 are 2
homologous, mutually exclusively spliced exons in the middle of the
gene; exon 2 is a facultatively utilized cassette exon encoding an
alternative N terminus of the beta-subunit.

MAPPING

By Southern blot analysis of rodent-human somatic cell hybrids and by in
situ hybridization, Francke et al. (1989) mapped the human PHKB gene to
chromosome 16q12-q13.

Wullrich-Schmoll and Kilimann (1996) confirmed location of the PHKB gene
to chromosome 16 by screening of a chromosome 16-specific genomic
library. Two processed pseudogenes were identified.

MOLECULAR GENETICS

In 1 female and 4 male patients with glycogen storage disease IXb
(GSD9B; 261750) and PHK deficiency in both liver and muscle, Burwinkel
et al. (1997) identified biallelic mutations in the PHKB gene. There
were 5 different nonsense mutations (see, e.g., 172490.0002), a 1-bp
insertion (172490.0001), a splice site mutation, and a large deletion
involving the loss of exon 8. Although the mutations disrupted
translation severely and occurred in constitutively expressed sequences
of the only known beta-subunit gene of phosphorylase kinase, they were
associated with a surprisingly mild clinical phenotype, affecting
virtually only the liver, and with a relatively high residual enzyme
activity of approximately 10%. Inheritance was autosomal recessive.

*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE IXb
PHKB, 1-BP INS

In a patient with glycogen storage disease IXb (261750), Burwinkel et
al. (1997) identified compound heterozygosity for 2 mutations in the
PHKB gene. On 1 allele, a stretch of 7 A residues in exon 14 was
extended by an additional A, resulting in a frameshift in codon 421 and
translation termination at the following triplet; on the other allele, a
C-to-T transition in exon 21 resulted in a gln656-to-ter (Q656X;
172490.0002) substitution. Studies in the parents indicated that the
frameshift mutation had been inherited from the father and the nonsense
mutation from the mother. The patient was the only child of unrelated,
healthy German parents and presented at the age of 22 months because of
distended abdomen due to hepatomegaly. At the age of 4 years, the child
had a height at the tenth percentile and weight at the fiftieth
percentile, hepatomegaly, and a tendency to develop hypoglycemic
symptoms after several hours of fasting or physical activity. There were
no clinical indications of muscle involvement.

.0002
GLYCOGEN STORAGE DISEASE IXb
PHKB, GLN656TER

See 172490.0001 and Burwinkel et al. (1997).

.0003
GLYCOGEN STORAGE DISEASE IXb
PHKB, TYR418TER

In a Norwegian boy with GSD IXb (261750), Burwinkel et al. (1997)
identified compound heterozygosity for 2 mutations in the PHKB gene: a
tyr418-to-ter (Y418X) substitution, and a double mutation, glu975-to-ter
(E975X) and tyr974-to-his (Y974H) (172490.0004). The patient and his
affected sister were children of unaffected, unrelated parents. They
came to medical attention as infants because of hepatomegaly; glucagon
response was normal in both (Lederer et al., 1975). Residual
phosphorylase kinase activities were 18% of normal in red cell hemolysis
of both, 5% in liver of the sister, and 0 to 13% (depending on pH) in
muscle of the male. At the age of approximately 25, both patients were
fully capable of everyday physical activities, but tended to develop
hypoglycemic symptoms upon activity or fasting that were ameliorated by
carbohydrate intake. Hepatomegaly had receded; clinical muscle symptoms
had never been noted. RT-PCR analysis of RNA from both parents did not
yield significant sequence signals for any of the 3 mutations in these
sibs. As translation-terminating mutations often result in reduced
abundance of the mRNA, Burwinkel et al. (1997) suspected that this might
also be the case for both mutant alleles in this family, so that they
would be detectable together in the patient but missed against the
background of the higher levels of mRNA from the normal alleles in the
parents. In genomic DNA they indeed could identify the Y418X mutation in
the father and the double mutation in the mother.

.0004
GLYCOGEN STORAGE DISEASE IXb
PHKB, TYR974HIS AND GLU975TER

See 172490.0003 and Burwinkel et al. (1997).

.0005
GLYCOGEN STORAGE DISEASE IXb
PHKB, ALA117PRO

In a patient with GSD IXb (261750), Burwinkel et al. (1997) found
compound heterozygosity for 2 mutations in the PHKB gene: a splice site
mutation, IVS4AS-2 A-to-G (172490.0006), causing a reading
frame-disrupting deletion of exon 5 in the mRNA, and an ala117-to-pro
(A117P) missense mutation, also in exon 5. They stated that this was the
first missense mutation identified in PHKB; 9 translation-terminating
mutations had been described to that time. The patient was a
22-month-old child of North African-Jewish heritage with hepatomegaly
and slightly disturbed liver function tests.

.0006
GLYCOGEN STORAGE DISEASE IXb
PHKB, IVS4AS, A-G, -2

See 172490.0005 and Burwinkel et al. (1997).

*FIELD* SA
Bashan et al. (1981); Lederer et al. (1975)
*FIELD* RF
1. Bashan, N.; Iancu, T. C.; Lerner, A.; Fraser, D.; Potashnik, R.;
Moses, S. W.: Glycogenosis due to liver and muscle phosphorylase
kinase deficiency. Pediat. Res. 15: 299-303, 1981.

2. 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.

3. Burwinkel, B.; Maichele, A. J.; Aagenaes, O.; Bakker, H. D.; Lerner,
A.; Shin, Y. S.; Strachan, J. A.; Kilimann, M. W.: Autosomal glycogenosis
of liver and muscle due to phosphorylase kinase deficiency is caused
by mutations in the phosphorylase kinase beta subunit (PHKB). Hum.
Molec. Genet. 6: 1109-1115, 1997.

4. Burwinkel, B.; Moses, S. W.; Kilimann, M. W.: Phosphorylase-kinase-deficient
liver glycogenosis with an unusual biochemical phenotype in blood
cells associated with a missense mutation in the beta subunit gene
(PHKB). Hum. Genet. 101: 170-174, 1997.

5. Francke, U.; Darras, B. T.; Zander, N. F.; Kilimann, M. W.: Assignment
of human genes for phosphorylase kinase subunits alpha (PHKA) to Xq12-q13
and beta (PHKB) to 16q12-q13. Am. J. Hum. Genet. 45: 276-282, 1989.

6. Kilimann, M. W.; Zander, N. F.; Kuhn, C. C.; Crabb, J. W.; Meyer,
H. E.; Heilmeyer, L. M. G., Jr.: The alpha and beta subunits of phosphorylase
kinase are homologous: cDNA cloning and primary structure of the beta
subunit. Proc. Nat. Acad. Sci. 85: 9381-9385, 1988.

7. Lederer, B.; Van Hoof, F.; Van den Berghe, G.; Hers, H. G.: Glycogen
phosphorylase and its converter enzymes in haemolysates of normal
human subjects and of patients with type VI glycogen storage disease:
a study of phosphorylase kinase deficiency. Biochem. J. 147: 23-35,
1975.

8. Wullrich-Schmoll, A.; Kilimann, M. W.: Structure of the human
gene encoding the phosphorylase kinase beta subunit (PHKB). Europ.
J. Biochem. 238: 374-380, 1996.

9. Zander, N. F.; Meyer, H. E.; Hoffmann-Posorske, E.; Crabb, J. W.;
Heilmeyer, L. M. G., Jr.; Kilimann, M. W.: cDNA cloning and complete
primary structure of skeletal muscle phosphorylase kinase (alpha subunit). Proc.
Nat. Acad. Sci. 85: 2929-2933, 1988.

*FIELD* CN
Cassandra L. Kniffin - updated: 9/24/2009
Victor A. McKusick - updated: 12/2/1997
Victor A. McKusick - updated: 8/15/1997

*FIELD* CD
Victor A. McKusick: 9/4/1989

*FIELD* ED
carol: 10/01/2009
ckniffin: 9/24/2009
carol: 2/14/2000
terry: 7/24/1998
mark: 12/9/1997
terry: 12/2/1997
jenny: 8/19/1997
terry: 8/15/1997
mark: 12/2/1996
terry: 11/7/1996
supermim: 3/16/1992
carol: 1/8/1991
supermim: 3/20/1990
carol: 12/7/1989
ddp: 10/27/1989
carol: 9/4/1989

MIM 261750
*RECORD*
*FIELD* NO
261750
*FIELD* TI
#261750 GLYCOGEN STORAGE DISEASE IXb; GSD9B
;;GSD IXb;;
GLYCOGENOSIS OF LIVER AND MUSCLE, AUTOSOMAL RECESSIVE;;
read morePHOSPHORYLASE KINASE DEFICIENCY OF LIVER AND MUSCLE, AUTOSOMAL RECESSIVE
*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease type IXb (GSD9B) is caused by mutation in the gene encoding the
beta subunit of phosphorylase kinase (PHKB; 172490).

For a discussion of genetic heterogeneity of GSD IX (GSD9), see X-linked
GSD IXa (GSD9A; 306000).

CLINICAL FEATURES

In an Israeli Arab family reported by Bashan et al. (1981), a 4-year-old
brother and 2 sisters had marked hepatomegaly and marked accumulation of
glycogen in both liver and muscle, without clinical symptoms. Liver
phosphorylase kinase (PK) activity was 20% of normal, resulting in
undetectable activity of phosphorylase a. Muscle PK was about 25% of
normal, resulting in a marked decrease of phosphorylase a activity. This
finding of a seemingly autosomal recessive form of phosphorylase kinase
deficiency suggests that there are at least 2 different structural
genes, only one of which is X-linked, that code for subunits of the
enzyme.

Mild clinical manifestations of muscle involvement were observed by
Fernandes et al. (1974) in a 4-year-old patient, and Abarbanel et al.
(1986) found symptoms resembling McArdle disease (232600) in a
35-year-old man. Ohtani et al. (1982) reported histochemical and
biochemical study of a female child who lacked phosphorylase kinase in
muscle.

Gray et al. (1983) described affected sister and 2 brothers with
unrelated parents. Normal level of enzyme activity in the mother and
comparable levels in an affected brother and sister argued against
X-linked inheritance (306000). The sister presented at 15 months with
hepatomegaly, short stature, and acute attacks of diarrhea.

Burwinkel et al. (1997) reported 3 children, including 2 sibs, with GSD
IXb. The first child was German, and presented at age 22 months with
distended abdomen due to hepatomegaly. At the age of 4 years, the child
had a height at the tenth percentile and weight at the fiftieth
percentile, hepatomegaly, and a tendency to develop hypoglycemic
symptoms after several hours of fasting or physical activity. There were
no clinical indications of muscle involvement. The second child and his
affected sister came to medical attention as infants because of
hepatomegaly. Residual phosphorylase kinase activities were 18% of
normal in red cells, 5% in liver of the sister, and 0 to 13% (depending
on pH) in muscle of the male. At the age of approximately 25, both
patients were fully capable of everyday physical activities, but tended
to develop hypoglycemic symptoms upon activity or fasting that were
ameliorated by carbohydrate intake. Hepatomegaly had receded; clinical
muscle symptoms had never been noted.

Beauchamp et al. (2007) reported 3 patients from 2 families with GSD IXb
confirmed by genetic analysis. Clinical features were variable, and
included hepatomegaly, short stature, liver dysfunction, hypoglycemia,
fasting ketosis, and hypotonia. The authors emphasized that molecular
analysis results in accurate diagnosis for GSD IX when enzymology is
uninformative, and thus allows for proper genetic counseling.

MOLECULAR GENETICS

In 1 female and 4 male patients with glycogen storage disease IXb,
Burwinkel et al. (1997) identified mutations in the PHKB gene. There
were 5 different nonsense mutations (see, e.g., 172490.0002), a 1-bp
insertion (172490.0001), a splice site mutation, and a large deletion
involving the loss of exon 8. Although the mutations severely disrupted
translation and occurred in constitutively expressed sequences of the
only known beta-subunit gene of phosphorylase kinase, they were
associated with a surprisingly mild clinical phenotype, affecting
virtually only the liver, and with a relatively high residual enzyme
activity of approximately 10%. Inheritance was autosomal recessive.

NOMENCLATURE

Lederer et al. (1975) pointed out that what had been numbered glycogen
storage disease VI includes at least 3 different genetic defects:
X-linked phosphorylase b kinase deficiency, in which the muscle enzyme
is unaffected (called here glycogen storage disease VIII; 306000); the
autosomal kinase deficiency discussed here; and deficiency of liver
phosphorylase (called here glycogen storage disease VI; 232700).

*FIELD* SA
Hug et al. (1970)
*FIELD* RF
1. Abarbanel, J. M.; Bashan, N.; Potashnik, R.; Osimani, A.; Moses,
S. W.; Herishanu, Y.: Adult muscle phosphorylase 'b' kinase deficiency. Neurology 36:
560-562, 1986.

2. Bashan, N.; Iancu, T. C.; Lerner, A.; Fraser, D.; Potashnik, R.;
Moses, S. W.: Glycogenosis due to liver and muscle phosphorylase
kinase deficiency. Pediat. Res. 15: 299-303, 1981.

3. 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.

4. Burwinkel, B.; Maichele, A. J.; Aagenaes, O.; Bakker, H. D.; Lerner,
A.; Shin, Y. S.; Strachan, J. A.; Kilimann, M. W.: Autosomal glycogenosis
of liver and muscle due to phosphorylase kinase deficiency is caused
by mutations in the phosphorylase kinase beta subunit (PHKB). Hum.
Molec. Genet. 6: 1109-1115, 1997.

5. Fernandes, J.; Koster, J. F.; Grose, W. F. A.; Sorgedrager, N.
: Hepatic phosphorylase deficiency: its differentiation from other
hepatic glycogenoses. Arch. Dis. Child. 49: 186-191, 1974.

6. Gray, R. G. F.; Kumar, D.; Whitfield, A. E.: Glycogen phosphorylase
b kinase deficiency in three siblings. J. Inherit. Metab. Dis. 6:
107 only, 1983.

7. Hug, G.; Schubert, W. K.; Chuck, G.: Loss of cyclic 3-prime-5-prime-AMP
dependent kinase and reduction of phosphorylase kinase in skeletal
muscle of a girl with deactivated phosphorylase and glycogenosis of
liver and muscle. Biochem. Biophys. Res. Commun. 40: 982-988, 1970.

8. Lederer, B.; Van Hoof, F.; Van den Berghe, G.; Hers, H. G.: Glycogen
phosphorylase and its converter enzymes in haemolysates of normal
human subjects and of patients with type VI glycogen storage disease:
a study of phosphorylase kinase deficiency. Biochem. J. 147: 23-35,
1975.

9. Ohtani, Y.; Matsuda, I.; Iwamasa, T.; Tamari, H.; Origuchi, Y.;
Miike, T.: Infantile glycogen storage myopathy in a girl with phosphorylase
kinase deficiency. Neurology 32: 833-838, 1982.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Height];
Short stature, postnatal onset

ABDOMEN:
[Liver];
Hepatomegaly;
[Gastrointestinal];
Diarrhea

MUSCLE, SOFT TISSUE:
Hypotonia;
Mild weakness

LABORATORY ABNORMALITIES:
Phosphorylase kinase deficiency in liver and muscle;
Glycogen accumulation in both liver and muscle

MOLECULAR BASIS:
Caused by mutation in phosphorylase kinase, beta subunit (PHKB, 172490.0001)

*FIELD* CN
Ada Hamosh - revised: 2/14/2000

*FIELD* ED
joanna: 07/02/2013
joanna: 6/9/2009
mgross: 2/14/2000

*FIELD* CN
Cassandra L. Kniffin - updated: 9/24/2009

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

*FIELD* ED
carol: 12/01/2010
carol: 10/1/2009
ckniffin: 9/24/2009
carol: 4/17/2007
carol: 2/14/2000
mimadm: 3/11/1994
supermim: 3/17/1992
carol: 12/14/1990
supermim: 3/20/1990
ddp: 10/27/1989
root: 9/14/1989

RBCC Red Blood Cell Collection

Full text data of PHKB