Full text data of LDHB
LDHB
[Confidence: high (present in two of the MS resources)]
L-lactate dehydrogenase B chain; LDH-B; 1.1.1.27 (LDH heart subunit; LDH-H; Renal carcinoma antigen NY-REN-46)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
L-lactate dehydrogenase B chain; LDH-B; 1.1.1.27 (LDH heart subunit; LDH-H; Renal carcinoma antigen NY-REN-46)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00219217
IPI00219217 Lactate dehydrogenase B (S)-lactate + NAD+ = pyruvate + NADH, anaerobic, final step, LDH-B soluble 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 n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00219217 Lactate dehydrogenase B (S)-lactate + NAD+ = pyruvate + NADH, anaerobic, final step, LDH-B soluble 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 n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P07195
ID LDHB_HUMAN Reviewed; 334 AA.
AC P07195;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 168.
DE RecName: Full=L-lactate dehydrogenase B chain;
DE Short=LDH-B;
DE EC=1.1.1.27;
DE AltName: Full=LDH heart subunit;
DE Short=LDH-H;
DE AltName: Full=Renal carcinoma antigen NY-REN-46;
GN Name=LDHB;
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].
RX PubMed=2930497;
RA Takeno T., Li S.S.-L.;
RT "Structure of the human lactate dehydrogenase B gene.";
RL Biochem. J. 257:921-924(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=T-cell;
RX PubMed=3435492;
RA Sakai I., Sharief F.S., Pan Y.-C.E., Li S.S.-L.;
RT "The cDNA and protein sequences of human lactate dehydrogenase B.";
RL Biochem. J. 248:933-936(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, and Urinary bladder;
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 [4]
RP PROTEIN SEQUENCE OF 2-23; 44-58; 78-100; 108-113; 120-127; 159-170;
RP 234-244; 271-279 AND 300-329, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAY-2005) to UniProtKB.
RN [5]
RP PROTEIN SEQUENCE OF 8-23; 44-58; 78-91; 108-113; 120-127; 159-170;
RP 234-244; 280-299 AND 300-318, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND TYR-240, AND MASS
RP 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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-7; LYS-58; LYS-119 AND
RP LYS-329, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240, 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 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NADH AND
RP SUBSTRATE ANALOG, AND HOMOTETRAMERIZATION.
RX PubMed=11276087;
RX DOI=10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#;
RA Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L.;
RT "Structural basis for altered activity of M- and H-isozyme forms of
RT human lactate dehydrogenase.";
RL Proteins 43:175-185(2001).
RN [13]
RP VARIANT LDHB DEFICIENCY GLU-7.
RX PubMed=8314553; DOI=10.1007/BF00217765;
RA Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T.;
RT "Analysis of a genetic mutation in an electrophoretic variant of the
RT human lactate dehydrogenase-B(H) subunit.";
RL Hum. Genet. 91:423-426(1993).
RN [14]
RP VARIANTS LDHB DEFICIENCY GLU-35; VAL-171 AND LEU-175.
RX PubMed=8462975; DOI=10.1007/BF00222718;
RA Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T.;
RT "Detection and characterization of new genetic mutations in
RT individuals heterozygous for lactate dehydrogenase-B(H) deficiency
RT using DNA conformation polymorphism analysis and silver staining.";
RL Hum. Genet. 91:163-168(1993).
RN [15]
RP VARIANTS LDHB DEFICIENCY ARG-129 AND HIS-172.
RX PubMed=1587525; DOI=10.1007/BF00217116;
RA Sudo K., Maekawa M., Tomonaga A., Tsukada T., Nakayama T.,
RA Kitamura M., Li S.S.-L., Kanno T., Toriumi J.;
RT "Molecular characterization of genetic mutations in human lactate
RT dehydrogenase (LDH) B (H) variant.";
RL Hum. Genet. 89:158-162(1992).
RN [16]
RP VARIANT LDHB DEFICIENCY HIS-172.
RX PubMed=2334429; DOI=10.1016/0006-291X(90)92373-8;
RA Sudo K., Maekawa M., Ikawa S., Machida K., Kitamura M., Li S.S.-L.;
RT "A missense mutation found in human lactate dehydrogenase-B (H)
RT variant gene.";
RL Biochem. Biophys. Res. Commun. 168:672-676(1990).
RN [17]
RP VARIANT LDHB DEFICIENCY VAL-322.
RA Maekawa M., Sudo K., Fujita K., Yoshioka N., Sakurabayashi I.,
RA Li S.S.-L., Kanno T.;
RT "DNA analysis of slow type of electrophoretic lactate dehydrogenase
RT B(H) variant.";
RL Seibutsu Butsuri Kagaku 38:25-29(1994).
RN [18]
RP VARIANT LDHB DEFICIENCY TRP-107.
RX PubMed=8611651; DOI=10.1016/0925-4439(95)00089-5;
RA Shonnard G.C., Hud N.V., Mohrenweiser H.W.;
RT "Arginine to tryptophan substitution in the active site of a human
RT lactate dehydrogenase variant -- LDHB GUA1: postulated effects on
RT subunit structure and catalysis.";
RL Biochim. Biophys. Acta 1315:9-14(1996).
RN [19]
RP VARIANT LDHB DEFICIENCY ASN-223 DEL.
RX PubMed=10211631; DOI=10.1016/S0009-9120(98)00097-6;
RA Sudo K., Maekawa M., Houki N., Okuda T., Akizuki S., Magara T.,
RA Kawano K.;
RT "A novel in-frame deletion mutation in a case of lactate dehydrogenase
RT (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in
RT serum and erythrocytes.";
RL Clin. Biochem. 32:137-141(1999).
RN [20]
RP VARIANT LDHB DEFICIENCY PRO-172.
RX PubMed=9929983; DOI=10.1007/s100380050111;
RA Hidaka K., Ueda N., Hirata I., Watanabe Y., Minatogawa Y., Iuchi I.;
RT "First case of missense mutation (LDH-H:R171P) in exon 4 of the
RT lactate dehydrogenase gene detected in a Japanese patient.";
RL J. Hum. Genet. 44:69-72(1999).
RN [21]
RP VARIANT LDHB DEFICIENCY GLU-69.
RX PubMed=11509017; DOI=10.1006/mgme.2001.3203;
RA Takatani T., Takaoka N., Tatsumi M., Kawamoto H., Okuno Y., Morita K.,
RA Masutani T., Murakawa K., Okamoto Y.;
RT "A novel missense mutation in human lactate dehydrogenase b-subunit
RT gene.";
RL Mol. Genet. Metab. 73:344-348(2001).
CC -!- CATALYTIC ACTIVITY: (S)-lactate + NAD(+) = pyruvate + NADH.
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-
CC lactate from pyruvate: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- POLYMORPHISM: Rare LDHB variants result in deficiency of lactate
CC dehydrogenase, a condition with no deleterious effects on health.
CC LDHB deficiency is of interest to laboratory medicine mainly
CC because it can cause misdiagnosis in those disorders in which
CC elevation of serum LDH is expected. Lactate dehydrogenase
CC deficiency can probably be considered a non-disease [MIM:614128].
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LDHB";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Lactate_dehydrogenase";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Another dark horse -
CC Issue 109 of September 2009;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt109.shtml";
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DR EMBL; X13794; CAA32033.1; -; Genomic_DNA.
DR EMBL; X13795; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13796; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13797; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13798; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13799; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13800; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; Y00711; CAA68701.1; -; mRNA.
DR EMBL; BC002362; AAH02362.1; -; mRNA.
DR EMBL; BC015122; AAH15122.1; -; mRNA.
DR EMBL; BC071860; AAH71860.1; -; mRNA.
DR PIR; S02795; DEHULH.
DR RefSeq; NP_001167568.1; NM_001174097.1.
DR RefSeq; NP_002291.1; NM_002300.6.
DR UniGene; Hs.446149; -.
DR PDB; 1I0Z; X-ray; 2.10 A; A/B=2-334.
DR PDB; 1T2F; X-ray; 3.00 A; A/B/C/D=2-334.
DR PDBsum; 1I0Z; -.
DR PDBsum; 1T2F; -.
DR ProteinModelPortal; P07195; -.
DR SMR; P07195; 2-333.
DR IntAct; P07195; 15.
DR MINT; MINT-1144561; -.
DR STRING; 9606.ENSP00000229319; -.
DR BindingDB; P07195; -.
DR ChEMBL; CHEMBL4940; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P07195; -.
DR DMDM; 126041; -.
DR DOSAC-COBS-2DPAGE; P07195; -.
DR OGP; P07195; -.
DR REPRODUCTION-2DPAGE; IPI00219217; -.
DR SWISS-2DPAGE; P07195; -.
DR UCD-2DPAGE; P07195; -.
DR PaxDb; P07195; -.
DR PRIDE; P07195; -.
DR DNASU; 3945; -.
DR Ensembl; ENST00000350669; ENSP00000229319; ENSG00000111716.
DR Ensembl; ENST00000396076; ENSP00000379386; ENSG00000111716.
DR GeneID; 3945; -.
DR KEGG; hsa:3945; -.
DR UCSC; uc001rfd.3; human.
DR CTD; 3945; -.
DR GeneCards; GC12M021788; -.
DR HGNC; HGNC:6541; LDHB.
DR HPA; CAB004641; -.
DR MIM; 150100; gene.
DR MIM; 614128; phenotype.
DR neXtProt; NX_P07195; -.
DR Orphanet; 284435; Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency.
DR PharmGKB; PA30325; -.
DR eggNOG; COG0039; -.
DR HOGENOM; HOG000213793; -.
DR HOVERGEN; HBG000462; -.
DR InParanoid; P07195; -.
DR KO; K00016; -.
DR OMA; SFNGWIL; -.
DR OrthoDB; EOG7X0VH3; -.
DR PhylomeDB; P07195; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; P07195; -.
DR UniPathway; UPA00554; UER00611.
DR ChiTaRS; LDHB; human.
DR EvolutionaryTrace; P07195; -.
DR GenomeRNAi; 3945; -.
DR NextBio; 15479; -.
DR PRO; PR:P07195; -.
DR ArrayExpress; P07195; -.
DR Bgee; P07195; -.
DR CleanEx; HS_LDHB; -.
DR Genevestigator; P07195; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0051287; F:NAD binding; IEA:Ensembl.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006096; P:glycolysis; IEA:UniProtKB-KW.
DR GO; GO:0006089; P:lactate metabolic process; IEA:Ensembl.
DR GO; GO:0019674; P:NAD metabolic process; IEA:Ensembl.
DR GO; GO:0006090; P:pyruvate metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.110.10; -; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
DR InterPro; IPR011304; L-lactate_DH.
DR InterPro; IPR018177; L-lactate_DH_AS.
DR InterPro; IPR022383; Lactate/malate_DH_C.
DR InterPro; IPR001236; Lactate/malate_DH_N.
DR InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11540; PTHR11540; 1.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR PRINTS; PR00086; LLDHDRGNASE.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1.
DR PROSITE; PS00064; L_LDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disease mutation; Glycolysis; NAD;
KW Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 334 L-lactate dehydrogenase B chain.
FT /FTId=PRO_0000168459.
FT NP_BIND 31 53 NAD (By similarity).
FT ACT_SITE 194 194 Proton acceptor.
FT BINDING 100 100 NAD.
FT BINDING 107 107 Substrate.
FT BINDING 139 139 NAD or substrate.
FT BINDING 170 170 Substrate.
FT BINDING 249 249 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 7 7 N6-acetyllysine.
FT MOD_RES 44 44 Phosphoserine.
FT MOD_RES 58 58 N6-acetyllysine.
FT MOD_RES 119 119 N6-acetyllysine.
FT MOD_RES 240 240 Phosphotyrosine.
FT MOD_RES 329 329 N6-acetyllysine.
FT VARIANT 7 7 K -> E (in LDHB deficiency; slightly
FT decreased activity).
FT /FTId=VAR_004173.
FT VARIANT 35 35 A -> E (in LDHB deficiency).
FT /FTId=VAR_004174.
FT VARIANT 69 69 G -> E (in LDHB deficiency).
FT /FTId=VAR_011634.
FT VARIANT 107 107 R -> W (in LDHB deficiency; inactive).
FT /FTId=VAR_011635.
FT VARIANT 129 129 S -> R (in LDHB deficiency).
FT /FTId=VAR_004175.
FT VARIANT 171 171 F -> V (in LDHB deficiency).
FT /FTId=VAR_004176.
FT VARIANT 172 172 R -> H (in LDHB deficiency; unstable).
FT /FTId=VAR_004177.
FT VARIANT 172 172 R -> P (in LDHB deficiency).
FT /FTId=VAR_011636.
FT VARIANT 175 175 M -> L (in LDHB deficiency).
FT /FTId=VAR_004178.
FT VARIANT 175 175 M -> V (in dbSNP:rs7966339).
FT /FTId=VAR_049758.
FT VARIANT 223 223 Missing (in LDHB deficiency).
FT /FTId=VAR_011637.
FT VARIANT 322 322 D -> V (in LDHB deficiency).
FT /FTId=VAR_004179.
FT VARIANT 325 325 W -> R (in LDHB deficiency).
FT /FTId=VAR_011638.
FT HELIX 4 8
FT STRAND 9 13
FT STRAND 21 27
FT HELIX 31 42
FT STRAND 47 52
FT HELIX 56 68
FT HELIX 69 72
FT STRAND 76 80
FT HELIX 84 87
FT STRAND 91 95
FT HELIX 107 110
FT HELIX 111 128
FT STRAND 133 136
FT STRAND 138 140
FT HELIX 141 152
FT HELIX 156 158
FT STRAND 159 161
FT HELIX 165 179
FT HELIX 183 185
FT STRAND 190 192
FT HELIX 202 204
FT HELIX 212 215
FT TURN 217 220
FT STRAND 221 223
FT STRAND 225 227
FT HELIX 229 246
FT HELIX 251 265
FT STRAND 270 277
FT TURN 279 282
FT STRAND 289 297
FT STRAND 300 304
FT HELIX 311 328
SQ SEQUENCE 334 AA; 36638 MW; 3AD605DEED0D54A2 CRC64;
MATLKEKLIA PVAEEEATVP NNKITVVGVG QVGMACAISI LGKSLADELA LVDVLEDKLK
GEMMDLQHGS LFLQTPKIVA DKDYSVTANS KIVVVTAGVR QQEGESRLNL VQRNVNVFKF
IIPQIVKYSP DCIIIVVSNP VDILTYVTWK LSGLPKHRVI GSGCNLDSAR FRYLMAEKLG
IHPSSCHGWI LGEHGDSSVA VWSGVNVAGV SLQELNPEMG TDNDSENWKE VHKMVVESAY
EVIKLKGYTN WAIGLSVADL IESMLKNLSR IHPVSTMVKG MYGIENEVFL SLPCILNARG
LTSVINQKLK DDEVAQLKKS ADTLWDIQKD LKDL
//
ID LDHB_HUMAN Reviewed; 334 AA.
AC P07195;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 168.
DE RecName: Full=L-lactate dehydrogenase B chain;
DE Short=LDH-B;
DE EC=1.1.1.27;
DE AltName: Full=LDH heart subunit;
DE Short=LDH-H;
DE AltName: Full=Renal carcinoma antigen NY-REN-46;
GN Name=LDHB;
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].
RX PubMed=2930497;
RA Takeno T., Li S.S.-L.;
RT "Structure of the human lactate dehydrogenase B gene.";
RL Biochem. J. 257:921-924(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=T-cell;
RX PubMed=3435492;
RA Sakai I., Sharief F.S., Pan Y.-C.E., Li S.S.-L.;
RT "The cDNA and protein sequences of human lactate dehydrogenase B.";
RL Biochem. J. 248:933-936(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, and Urinary bladder;
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 [4]
RP PROTEIN SEQUENCE OF 2-23; 44-58; 78-100; 108-113; 120-127; 159-170;
RP 234-244; 271-279 AND 300-329, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAY-2005) to UniProtKB.
RN [5]
RP PROTEIN SEQUENCE OF 8-23; 44-58; 78-91; 108-113; 120-127; 159-170;
RP 234-244; 280-299 AND 300-318, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND TYR-240, AND MASS
RP 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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-7; LYS-58; LYS-119 AND
RP LYS-329, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240, 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 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NADH AND
RP SUBSTRATE ANALOG, AND HOMOTETRAMERIZATION.
RX PubMed=11276087;
RX DOI=10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#;
RA Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L.;
RT "Structural basis for altered activity of M- and H-isozyme forms of
RT human lactate dehydrogenase.";
RL Proteins 43:175-185(2001).
RN [13]
RP VARIANT LDHB DEFICIENCY GLU-7.
RX PubMed=8314553; DOI=10.1007/BF00217765;
RA Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T.;
RT "Analysis of a genetic mutation in an electrophoretic variant of the
RT human lactate dehydrogenase-B(H) subunit.";
RL Hum. Genet. 91:423-426(1993).
RN [14]
RP VARIANTS LDHB DEFICIENCY GLU-35; VAL-171 AND LEU-175.
RX PubMed=8462975; DOI=10.1007/BF00222718;
RA Maekawa M., Sudo K., Kitajima M., Matsuura Y., Li S.S.-L., Kanno T.;
RT "Detection and characterization of new genetic mutations in
RT individuals heterozygous for lactate dehydrogenase-B(H) deficiency
RT using DNA conformation polymorphism analysis and silver staining.";
RL Hum. Genet. 91:163-168(1993).
RN [15]
RP VARIANTS LDHB DEFICIENCY ARG-129 AND HIS-172.
RX PubMed=1587525; DOI=10.1007/BF00217116;
RA Sudo K., Maekawa M., Tomonaga A., Tsukada T., Nakayama T.,
RA Kitamura M., Li S.S.-L., Kanno T., Toriumi J.;
RT "Molecular characterization of genetic mutations in human lactate
RT dehydrogenase (LDH) B (H) variant.";
RL Hum. Genet. 89:158-162(1992).
RN [16]
RP VARIANT LDHB DEFICIENCY HIS-172.
RX PubMed=2334429; DOI=10.1016/0006-291X(90)92373-8;
RA Sudo K., Maekawa M., Ikawa S., Machida K., Kitamura M., Li S.S.-L.;
RT "A missense mutation found in human lactate dehydrogenase-B (H)
RT variant gene.";
RL Biochem. Biophys. Res. Commun. 168:672-676(1990).
RN [17]
RP VARIANT LDHB DEFICIENCY VAL-322.
RA Maekawa M., Sudo K., Fujita K., Yoshioka N., Sakurabayashi I.,
RA Li S.S.-L., Kanno T.;
RT "DNA analysis of slow type of electrophoretic lactate dehydrogenase
RT B(H) variant.";
RL Seibutsu Butsuri Kagaku 38:25-29(1994).
RN [18]
RP VARIANT LDHB DEFICIENCY TRP-107.
RX PubMed=8611651; DOI=10.1016/0925-4439(95)00089-5;
RA Shonnard G.C., Hud N.V., Mohrenweiser H.W.;
RT "Arginine to tryptophan substitution in the active site of a human
RT lactate dehydrogenase variant -- LDHB GUA1: postulated effects on
RT subunit structure and catalysis.";
RL Biochim. Biophys. Acta 1315:9-14(1996).
RN [19]
RP VARIANT LDHB DEFICIENCY ASN-223 DEL.
RX PubMed=10211631; DOI=10.1016/S0009-9120(98)00097-6;
RA Sudo K., Maekawa M., Houki N., Okuda T., Akizuki S., Magara T.,
RA Kawano K.;
RT "A novel in-frame deletion mutation in a case of lactate dehydrogenase
RT (LD) H subunit deficiency showing an atypical LD isoenzyme pattern in
RT serum and erythrocytes.";
RL Clin. Biochem. 32:137-141(1999).
RN [20]
RP VARIANT LDHB DEFICIENCY PRO-172.
RX PubMed=9929983; DOI=10.1007/s100380050111;
RA Hidaka K., Ueda N., Hirata I., Watanabe Y., Minatogawa Y., Iuchi I.;
RT "First case of missense mutation (LDH-H:R171P) in exon 4 of the
RT lactate dehydrogenase gene detected in a Japanese patient.";
RL J. Hum. Genet. 44:69-72(1999).
RN [21]
RP VARIANT LDHB DEFICIENCY GLU-69.
RX PubMed=11509017; DOI=10.1006/mgme.2001.3203;
RA Takatani T., Takaoka N., Tatsumi M., Kawamoto H., Okuno Y., Morita K.,
RA Masutani T., Murakawa K., Okamoto Y.;
RT "A novel missense mutation in human lactate dehydrogenase b-subunit
RT gene.";
RL Mol. Genet. Metab. 73:344-348(2001).
CC -!- CATALYTIC ACTIVITY: (S)-lactate + NAD(+) = pyruvate + NADH.
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-
CC lactate from pyruvate: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- POLYMORPHISM: Rare LDHB variants result in deficiency of lactate
CC dehydrogenase, a condition with no deleterious effects on health.
CC LDHB deficiency is of interest to laboratory medicine mainly
CC because it can cause misdiagnosis in those disorders in which
CC elevation of serum LDH is expected. Lactate dehydrogenase
CC deficiency can probably be considered a non-disease [MIM:614128].
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LDHB";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactate dehydrogenase entry;
CC URL="http://en.wikipedia.org/wiki/Lactate_dehydrogenase";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Another dark horse -
CC Issue 109 of September 2009;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt109.shtml";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X13794; CAA32033.1; -; Genomic_DNA.
DR EMBL; X13795; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13796; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13797; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13798; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13799; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; X13800; CAA32033.1; JOINED; Genomic_DNA.
DR EMBL; Y00711; CAA68701.1; -; mRNA.
DR EMBL; BC002362; AAH02362.1; -; mRNA.
DR EMBL; BC015122; AAH15122.1; -; mRNA.
DR EMBL; BC071860; AAH71860.1; -; mRNA.
DR PIR; S02795; DEHULH.
DR RefSeq; NP_001167568.1; NM_001174097.1.
DR RefSeq; NP_002291.1; NM_002300.6.
DR UniGene; Hs.446149; -.
DR PDB; 1I0Z; X-ray; 2.10 A; A/B=2-334.
DR PDB; 1T2F; X-ray; 3.00 A; A/B/C/D=2-334.
DR PDBsum; 1I0Z; -.
DR PDBsum; 1T2F; -.
DR ProteinModelPortal; P07195; -.
DR SMR; P07195; 2-333.
DR IntAct; P07195; 15.
DR MINT; MINT-1144561; -.
DR STRING; 9606.ENSP00000229319; -.
DR BindingDB; P07195; -.
DR ChEMBL; CHEMBL4940; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P07195; -.
DR DMDM; 126041; -.
DR DOSAC-COBS-2DPAGE; P07195; -.
DR OGP; P07195; -.
DR REPRODUCTION-2DPAGE; IPI00219217; -.
DR SWISS-2DPAGE; P07195; -.
DR UCD-2DPAGE; P07195; -.
DR PaxDb; P07195; -.
DR PRIDE; P07195; -.
DR DNASU; 3945; -.
DR Ensembl; ENST00000350669; ENSP00000229319; ENSG00000111716.
DR Ensembl; ENST00000396076; ENSP00000379386; ENSG00000111716.
DR GeneID; 3945; -.
DR KEGG; hsa:3945; -.
DR UCSC; uc001rfd.3; human.
DR CTD; 3945; -.
DR GeneCards; GC12M021788; -.
DR HGNC; HGNC:6541; LDHB.
DR HPA; CAB004641; -.
DR MIM; 150100; gene.
DR MIM; 614128; phenotype.
DR neXtProt; NX_P07195; -.
DR Orphanet; 284435; Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency.
DR PharmGKB; PA30325; -.
DR eggNOG; COG0039; -.
DR HOGENOM; HOG000213793; -.
DR HOVERGEN; HBG000462; -.
DR InParanoid; P07195; -.
DR KO; K00016; -.
DR OMA; SFNGWIL; -.
DR OrthoDB; EOG7X0VH3; -.
DR PhylomeDB; P07195; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; P07195; -.
DR UniPathway; UPA00554; UER00611.
DR ChiTaRS; LDHB; human.
DR EvolutionaryTrace; P07195; -.
DR GenomeRNAi; 3945; -.
DR NextBio; 15479; -.
DR PRO; PR:P07195; -.
DR ArrayExpress; P07195; -.
DR Bgee; P07195; -.
DR CleanEx; HS_LDHB; -.
DR Genevestigator; P07195; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0051287; F:NAD binding; IEA:Ensembl.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006096; P:glycolysis; IEA:UniProtKB-KW.
DR GO; GO:0006089; P:lactate metabolic process; IEA:Ensembl.
DR GO; GO:0019674; P:NAD metabolic process; IEA:Ensembl.
DR GO; GO:0006090; P:pyruvate metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.110.10; -; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
DR InterPro; IPR011304; L-lactate_DH.
DR InterPro; IPR018177; L-lactate_DH_AS.
DR InterPro; IPR022383; Lactate/malate_DH_C.
DR InterPro; IPR001236; Lactate/malate_DH_N.
DR InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR PANTHER; PTHR11540; PTHR11540; 1.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR PRINTS; PR00086; LLDHDRGNASE.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1.
DR PROSITE; PS00064; L_LDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disease mutation; Glycolysis; NAD;
KW Oxidoreductase; Phosphoprotein; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 334 L-lactate dehydrogenase B chain.
FT /FTId=PRO_0000168459.
FT NP_BIND 31 53 NAD (By similarity).
FT ACT_SITE 194 194 Proton acceptor.
FT BINDING 100 100 NAD.
FT BINDING 107 107 Substrate.
FT BINDING 139 139 NAD or substrate.
FT BINDING 170 170 Substrate.
FT BINDING 249 249 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 7 7 N6-acetyllysine.
FT MOD_RES 44 44 Phosphoserine.
FT MOD_RES 58 58 N6-acetyllysine.
FT MOD_RES 119 119 N6-acetyllysine.
FT MOD_RES 240 240 Phosphotyrosine.
FT MOD_RES 329 329 N6-acetyllysine.
FT VARIANT 7 7 K -> E (in LDHB deficiency; slightly
FT decreased activity).
FT /FTId=VAR_004173.
FT VARIANT 35 35 A -> E (in LDHB deficiency).
FT /FTId=VAR_004174.
FT VARIANT 69 69 G -> E (in LDHB deficiency).
FT /FTId=VAR_011634.
FT VARIANT 107 107 R -> W (in LDHB deficiency; inactive).
FT /FTId=VAR_011635.
FT VARIANT 129 129 S -> R (in LDHB deficiency).
FT /FTId=VAR_004175.
FT VARIANT 171 171 F -> V (in LDHB deficiency).
FT /FTId=VAR_004176.
FT VARIANT 172 172 R -> H (in LDHB deficiency; unstable).
FT /FTId=VAR_004177.
FT VARIANT 172 172 R -> P (in LDHB deficiency).
FT /FTId=VAR_011636.
FT VARIANT 175 175 M -> L (in LDHB deficiency).
FT /FTId=VAR_004178.
FT VARIANT 175 175 M -> V (in dbSNP:rs7966339).
FT /FTId=VAR_049758.
FT VARIANT 223 223 Missing (in LDHB deficiency).
FT /FTId=VAR_011637.
FT VARIANT 322 322 D -> V (in LDHB deficiency).
FT /FTId=VAR_004179.
FT VARIANT 325 325 W -> R (in LDHB deficiency).
FT /FTId=VAR_011638.
FT HELIX 4 8
FT STRAND 9 13
FT STRAND 21 27
FT HELIX 31 42
FT STRAND 47 52
FT HELIX 56 68
FT HELIX 69 72
FT STRAND 76 80
FT HELIX 84 87
FT STRAND 91 95
FT HELIX 107 110
FT HELIX 111 128
FT STRAND 133 136
FT STRAND 138 140
FT HELIX 141 152
FT HELIX 156 158
FT STRAND 159 161
FT HELIX 165 179
FT HELIX 183 185
FT STRAND 190 192
FT HELIX 202 204
FT HELIX 212 215
FT TURN 217 220
FT STRAND 221 223
FT STRAND 225 227
FT HELIX 229 246
FT HELIX 251 265
FT STRAND 270 277
FT TURN 279 282
FT STRAND 289 297
FT STRAND 300 304
FT HELIX 311 328
SQ SEQUENCE 334 AA; 36638 MW; 3AD605DEED0D54A2 CRC64;
MATLKEKLIA PVAEEEATVP NNKITVVGVG QVGMACAISI LGKSLADELA LVDVLEDKLK
GEMMDLQHGS LFLQTPKIVA DKDYSVTANS KIVVVTAGVR QQEGESRLNL VQRNVNVFKF
IIPQIVKYSP DCIIIVVSNP VDILTYVTWK LSGLPKHRVI GSGCNLDSAR FRYLMAEKLG
IHPSSCHGWI LGEHGDSSVA VWSGVNVAGV SLQELNPEMG TDNDSENWKE VHKMVVESAY
EVIKLKGYTN WAIGLSVADL IESMLKNLSR IHPVSTMVKG MYGIENEVFL SLPCILNARG
LTSVINQKLK DDEVAQLKKS ADTLWDIQKD LKDL
//
MIM
150100
*RECORD*
*FIELD* NO
150100
*FIELD* TI
*150100 LACTATE DEHYDROGENASE B; LDHB
;;LDH, SUBUNIT H
*FIELD* TX
The LDHB gene encodes the B subunit of lactate dehydrogenase (EC
read more1.1.1.27), an enzyme that catalyzes the interconversion of lactate and
pyruvate (summary by Markert, 1984).
CLONING
Sakai et al. (1987) isolated and sequenced LDHB cDNA. The deduced LDHB
protein contains 333 amino acids. Nucleotide and amino acid sequences
for the LDHB enzyme showed 68% and 75% identity, respectively, with
those of LDHA (150000).
GENE STRUCTURE
Takeno and Li (1989) determined that the LDHB gene contains 7 coding
exons.
MAPPING
LDHB and peptidase B (169900) are linked (Santachiara et al., 1970) and
both loci are on chromosome 12 (Chen et al., 1973). In a case of
deletion of the short arm of chromosome 12, Weiss et al. (1973) found
evidence that LDHB is located there.
From study of somatic cell hybrids Hamerton et al. (1975) concluded that
LDHB is in the 12pter-q21 region. Rethore et al. (1975) found
augmentation of LDHB activity in a boy trisomic for the short arm of
chromosome 12. From study of 3 patients with different deletions of
chromosome 12, Rethore et al. (1976) concluded that the G3PD locus
(138400) is on the distal part of 12p and that the LDHB locus is on the
middle third between 12p12.1 and 12p12.2.
Steinbach and Rehder (1987) demonstrated dosage effect with LDHB in a
case of tetrasomy of 12p.
- Pseudogenes
Sudo et al. (1990) demonstrated 93% homology between an LDHB processed
pseudogene and the functional gene. The pseudogene was mapped to the X
chromosome by dot-blot analysis.
GENE FUNCTION
The LDHB AND LDHA (150000) subunits generate 5 tetrameric isozymes.
Although all LDH isozymes catalyze the interconversion of pyruvate and
lactate, they do so with different kinetics. The B subunits in heart
muscle are bound to NAD. Heart muscle B4 isozymes function principally
to oxidize lactic acid to pyruvate with the generation of NADH which, in
turn, is oxidized through the cytochrome system to generate energy to
support the normal physiology of the heart. Through a negative feedback
system involving LDHB, a constant ratio of NAD to NADH is maintained
(summary by Markert, 1984).
MOLECULAR GENETICS
Mohrenweiser and Neel (1981) identified thermolabile variants of lactate
dehydrogenase B, glucosephosphate isomerase, and glucose-6-phosphate
dehydrogenase. None was detectable as a variant by standard
electrophoretic techniques. All were inherited.
In a clinically normal 43-year-old male who was found to have low LDH
activity in serum by Houki et al. (1986), Sudo et al. (1990) identified
a homozygous mutation in the LDHB gene (150100.0001). LDHB mutations
have been found in other individuals with LDHB deficiency (see, e.g.,
150100.0002-150100.0004).
Okumura et al. (1999) tabulated the LDHB variants caused by missense
mutations.
*FIELD* AV
.0001
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, ARG173HIS
Houki et al. (1986) found low LDH activity (614128) in the serum of a
clinically normal 43-year-old male who was undergoing health
examination. Findings on electrophoresis suggested the synthesis of
unstable LDHB subunits in vivo. Studying the mutant gene in this case,
Sudo et al. (1990) demonstrated an A-to-G substitution in exon 4 causing
a substitution of histidine for arginine at residue 173; the arginine
coded by CGC is a highly conserved residue which is involved in an
anion-binding site at the P-axis of LDH subunits. Sudo et al. (1992)
demonstrated that the subject was homozygous for the arg173-to-his
mutation.
.0002
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, SER131ARG
In a 44-year-old male, Sudo et al. (1992) found low serum LDH activity
(614128). The man had 'similar symptoms to case 1' (see 150100.0001),
but in neither case were the symptoms detailed. They demonstrated in
exon 3 of the LDHB gene a transversion from AGT (ser) to CGT (arg) at
residue 131. The proband was homozygous. Two of his children were
heterozygous.
.0003
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, LYS6GLU
Maekawa et al. (1993) described the mutational basis of an
electrophoretically fast LDHB variant found in a 65-year-old male with
diabetes mellitus and slightly decreased LDH activity (614128). An
A-to-G transition, which changed codon 6 from AAA to GAA, resulted in
the replacement of a lysine by a glutamic acid (K6E). The change may
result in heat instability and affect the net charge of the variant
subunit.
.0004
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, TRP323ARG
Okumura et al. (1999) described homozygosity and heterozygosity for a
trp323-to-arg mutation in LDHB in individuals with lactate dehydrogenase
B deficiency (614128). They designated the homozygous and heterozygous
types as Matsumoto I and Matsumoto II, respectively. The substitution of
the positively charged arg residue for an uncharged trp residue was
consistent with a decrease in net negative charge (slow-type) of the
variant LDHB subunit observed by isoenzyme analysis. The 2 subjects were
not known to be related. The homozygote was a 58-year-old woman with
coronary artery disease; the heterozygote was a 35-year-old healthy man.
*FIELD* SA
Boyer et al. (1963); Herbschleb-Voogt and Meera Khan (1981); Malpuech
et al. (1975); Mayeda et al. (1974); Van Someren et al. (1972)
*FIELD* RF
1. Boyer, S. H.; Fainer, D. C.; Watson-Williams, E. J.: Lactate dehydrogenase
variant from human blood: evidence for molecular subunits. Science 141:
642-643, 1963.
2. Chen, T.-R.; McMorris, F. A.; Creagan, R.; Ricciuti, F. C.; Tischfield,
J.; Ruddle, F. H.: Assignment of the genes for malate oxidoreductase
decarboxylating to chromosome 6 and peptidase B and lactate dehydrogenase
B to chromosome 12 in man. Am. J. Hum. Genet. 25: 200-207, 1973.
3. Hamerton, J. L.; Mohandas, T.; McAlpine, P. J.; Douglas, G. R.
: Localization of human gene loci using spontaneous chromosome rearrangements
in human-Chinese hamster somatic cell hybrids. Am. J. Hum. Genet. 27:
595-608, 1975.
4. Herbschleb-Voogt, E.; Meera Khan, P.: Defining the locus of origin
of a genetically determined electrophoretic variant of a multilocus
enzyme system; the Calcutta-1 of human LDH system is a B-locus variant. Hum.
Genet. 57: 290-295, 1981.
5. Houki, N.; Matsushima, Y.; Kitamura, M.; Tukada, T.; Nishina, T.;
Nakayama, T.: A case of deficiency of lactate dehydrogenase H-subunit. Jpn.
J. Clin. Chem. 15: 85-90, 1986.
6. Maekawa, M.; Sudo, K.; Kitajima, M.; Matsuura, Y.; Li, S. S.-L.;
Kanno, T.: Analysis of a genetic mutation in an electrophoretic variant
of the human lactate dehydrogenase-B(H) subunit. Hum. Genet. 91:
423-426, 1993.
7. Malpuech, G.; Kaplan, J. C.; Rethore, M. O.; Junien, C.; Geneix,
A.: Une observation de deletion partielle du bras court du chromosome
12: localisation du gene de la lacticodeshydrogenase B. Lyon Med. 233:
275-279, 1975.
8. Markert, C. L.: Lactate dehydrogenase: biochemistry and function
of lactate dehydrogenase. Cell Biochem. Func. 2: 131-134, 1984.
9. Mayeda, K.; Weiss, L.; Lindahl, R.; Dully, M.: Localization of
the human lactate dehydrogenase B gene on the short arm of chromosome
12. Am. J. Hum. Genet. 26: 59-64, 1974.
10. Mohrenweiser, H. W.; Neel, J. V.: Frequency of thermostability
variants: estimation of total 'rare' variant frequency in human populations. Proc.
Nat. Acad. Sci. 78: 5729-5733, 1981.
11. Okumura, N.; Terasawa, F.; Ueno, I.; Oki, K.; Yamauchi, K.; Hidaka,
H.; Tozuka, M.; Okura, M.; Katsuyama, T.: Genetic analyses in homozygous
and heterozygous variants of lactate dehydrogenase-B (H) subunit:
LD-B Matsumoto I and II (LD-B W323R). Clin. Chim. Acta 287: 163-171,
1999.
12. Rethore, M.-O.; Junien, C.; Malpuech, G.; Baccichetti, C.; Tenconi,
R.; Kaplan, J. C.; de Romeuf, J.; Lejeune, J.: Localisation du gene
de la glyceraldehyde 3-phosphate dehydrogenase (G3PD) sur le segment
distal du bras court du chromosome 12. Ann. Genet. 19: 140-142,
1976.
13. Rethore, M.-O.; Kaplan, J.-C.; Junien, C.; Cruveiller, J.; Dutrillaux,
B.; Aurias, A.; Carpentier, S.; Lafourcade, J.; Lejeune, J.: Augmentation
de l'activite de la LDH-B chez un garcon trisomique 12p par malsegregation
d'une translocation maternelle t(12;14)(q12;p11). Ann. Genet. 18:
81-87, 1975.
14. Sakai, I.; Sharief, F. S.; Pan, Y.-C. E.; Li, S. S.-L.: The cDNA
and protein sequences of human lactate dehydrogenase B. Biochem.
J. 248: 933-936, 1987.
15. Santachiara, A. S.; Nabholz, M.; Miggiano, V.; Darlington, A.
J.; Bodmer, W. F.: Linkage between human lactate dehydrogenase B
and peptidase B genes. Nature 227: 248-251, 1970.
16. Steinbach, P.; Rehder, H.: Tetrasomy for the short arm of chromosome
12 with accessory isochromosome (+i[12p]) and a marked LDH-B gene
dosage effect. Clin. Genet. 32: 1-4, 1987.
17. Sudo, K.; Maekawa, M.; Ikawa, S.; Machida, K.; Kitamura, M.; Li,
S. S.-L.: A missense mutation found in human lactate dehydrogenase-B
(H) variant gene. Biochem. Biophys. Res. Commun. 168: 672-676, 1990.
18. Sudo, K.; Maekawa, M.; Luedemann, M. M.; Deaven, L. L.; Li, S.
S.-L.: Human lactate dehydrogenase-B processed pseudogene: nucleotide
sequence analysis and assignment to the X-chromosome. Biochem. Biophys.
Res. Commun. 171: 67-74, 1990.
19. Sudo, K.; Maekawa, M.; Tomonaga, A.; Tsukada, T.; Nakayama, T.;
Kitamura, M.; Li, S. S.-L.; Kanno, T.; Toriumi, J.: Molecular characterization
of genetic mutations in human lactate dehydrogenase (LDH)B (H) variant. Hum.
Genet. 89: 158-162, 1992.
20. Takeno, T.; Li, S. S.-L.: Structure of the human lactate dehydrogenase
B gene. Biochem. J. 257: 921-924, 1989.
21. Van Someren, H.; Meera Khan, P.; Westerveld, A.; Bootsma, D.:
Human genetics--two new linkage groups carrying different loci for
LDH and glutamic-pyruvic transaminase found. Nature 240: 221-222,
1972.
22. Weiss, L.; Mayeda, K.; Lindahl, R.; Dully, M.: Localization of
human LDH-B gene of the short arm of chromosome 12. (Abstract) Am.
J. Hum. Genet. 25: 85A only, 1973.
*FIELD* CN
Victor A. McKusick - updated: 12/13/1999
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 08/02/2011
carol: 7/27/2011
carol: 5/17/2006
terry: 5/17/2005
mgross: 3/17/2004
carol: 12/20/1999
mcapotos: 12/15/1999
terry: 12/13/1999
mark: 1/12/1998
alopez: 6/2/1997
terry: 5/13/1994
mimadm: 4/7/1994
carol: 3/18/1994
carol: 11/5/1993
carol: 8/18/1993
carol: 6/23/1993
*RECORD*
*FIELD* NO
150100
*FIELD* TI
*150100 LACTATE DEHYDROGENASE B; LDHB
;;LDH, SUBUNIT H
*FIELD* TX
The LDHB gene encodes the B subunit of lactate dehydrogenase (EC
read more1.1.1.27), an enzyme that catalyzes the interconversion of lactate and
pyruvate (summary by Markert, 1984).
CLONING
Sakai et al. (1987) isolated and sequenced LDHB cDNA. The deduced LDHB
protein contains 333 amino acids. Nucleotide and amino acid sequences
for the LDHB enzyme showed 68% and 75% identity, respectively, with
those of LDHA (150000).
GENE STRUCTURE
Takeno and Li (1989) determined that the LDHB gene contains 7 coding
exons.
MAPPING
LDHB and peptidase B (169900) are linked (Santachiara et al., 1970) and
both loci are on chromosome 12 (Chen et al., 1973). In a case of
deletion of the short arm of chromosome 12, Weiss et al. (1973) found
evidence that LDHB is located there.
From study of somatic cell hybrids Hamerton et al. (1975) concluded that
LDHB is in the 12pter-q21 region. Rethore et al. (1975) found
augmentation of LDHB activity in a boy trisomic for the short arm of
chromosome 12. From study of 3 patients with different deletions of
chromosome 12, Rethore et al. (1976) concluded that the G3PD locus
(138400) is on the distal part of 12p and that the LDHB locus is on the
middle third between 12p12.1 and 12p12.2.
Steinbach and Rehder (1987) demonstrated dosage effect with LDHB in a
case of tetrasomy of 12p.
- Pseudogenes
Sudo et al. (1990) demonstrated 93% homology between an LDHB processed
pseudogene and the functional gene. The pseudogene was mapped to the X
chromosome by dot-blot analysis.
GENE FUNCTION
The LDHB AND LDHA (150000) subunits generate 5 tetrameric isozymes.
Although all LDH isozymes catalyze the interconversion of pyruvate and
lactate, they do so with different kinetics. The B subunits in heart
muscle are bound to NAD. Heart muscle B4 isozymes function principally
to oxidize lactic acid to pyruvate with the generation of NADH which, in
turn, is oxidized through the cytochrome system to generate energy to
support the normal physiology of the heart. Through a negative feedback
system involving LDHB, a constant ratio of NAD to NADH is maintained
(summary by Markert, 1984).
MOLECULAR GENETICS
Mohrenweiser and Neel (1981) identified thermolabile variants of lactate
dehydrogenase B, glucosephosphate isomerase, and glucose-6-phosphate
dehydrogenase. None was detectable as a variant by standard
electrophoretic techniques. All were inherited.
In a clinically normal 43-year-old male who was found to have low LDH
activity in serum by Houki et al. (1986), Sudo et al. (1990) identified
a homozygous mutation in the LDHB gene (150100.0001). LDHB mutations
have been found in other individuals with LDHB deficiency (see, e.g.,
150100.0002-150100.0004).
Okumura et al. (1999) tabulated the LDHB variants caused by missense
mutations.
*FIELD* AV
.0001
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, ARG173HIS
Houki et al. (1986) found low LDH activity (614128) in the serum of a
clinically normal 43-year-old male who was undergoing health
examination. Findings on electrophoresis suggested the synthesis of
unstable LDHB subunits in vivo. Studying the mutant gene in this case,
Sudo et al. (1990) demonstrated an A-to-G substitution in exon 4 causing
a substitution of histidine for arginine at residue 173; the arginine
coded by CGC is a highly conserved residue which is involved in an
anion-binding site at the P-axis of LDH subunits. Sudo et al. (1992)
demonstrated that the subject was homozygous for the arg173-to-his
mutation.
.0002
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, SER131ARG
In a 44-year-old male, Sudo et al. (1992) found low serum LDH activity
(614128). The man had 'similar symptoms to case 1' (see 150100.0001),
but in neither case were the symptoms detailed. They demonstrated in
exon 3 of the LDHB gene a transversion from AGT (ser) to CGT (arg) at
residue 131. The proband was homozygous. Two of his children were
heterozygous.
.0003
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, LYS6GLU
Maekawa et al. (1993) described the mutational basis of an
electrophoretically fast LDHB variant found in a 65-year-old male with
diabetes mellitus and slightly decreased LDH activity (614128). An
A-to-G transition, which changed codon 6 from AAA to GAA, resulted in
the replacement of a lysine by a glutamic acid (K6E). The change may
result in heat instability and affect the net charge of the variant
subunit.
.0004
LACTATE DEHYDROGENASE B DEFICIENCY
LDHB, TRP323ARG
Okumura et al. (1999) described homozygosity and heterozygosity for a
trp323-to-arg mutation in LDHB in individuals with lactate dehydrogenase
B deficiency (614128). They designated the homozygous and heterozygous
types as Matsumoto I and Matsumoto II, respectively. The substitution of
the positively charged arg residue for an uncharged trp residue was
consistent with a decrease in net negative charge (slow-type) of the
variant LDHB subunit observed by isoenzyme analysis. The 2 subjects were
not known to be related. The homozygote was a 58-year-old woman with
coronary artery disease; the heterozygote was a 35-year-old healthy man.
*FIELD* SA
Boyer et al. (1963); Herbschleb-Voogt and Meera Khan (1981); Malpuech
et al. (1975); Mayeda et al. (1974); Van Someren et al. (1972)
*FIELD* RF
1. Boyer, S. H.; Fainer, D. C.; Watson-Williams, E. J.: Lactate dehydrogenase
variant from human blood: evidence for molecular subunits. Science 141:
642-643, 1963.
2. Chen, T.-R.; McMorris, F. A.; Creagan, R.; Ricciuti, F. C.; Tischfield,
J.; Ruddle, F. H.: Assignment of the genes for malate oxidoreductase
decarboxylating to chromosome 6 and peptidase B and lactate dehydrogenase
B to chromosome 12 in man. Am. J. Hum. Genet. 25: 200-207, 1973.
3. Hamerton, J. L.; Mohandas, T.; McAlpine, P. J.; Douglas, G. R.
: Localization of human gene loci using spontaneous chromosome rearrangements
in human-Chinese hamster somatic cell hybrids. Am. J. Hum. Genet. 27:
595-608, 1975.
4. Herbschleb-Voogt, E.; Meera Khan, P.: Defining the locus of origin
of a genetically determined electrophoretic variant of a multilocus
enzyme system; the Calcutta-1 of human LDH system is a B-locus variant. Hum.
Genet. 57: 290-295, 1981.
5. Houki, N.; Matsushima, Y.; Kitamura, M.; Tukada, T.; Nishina, T.;
Nakayama, T.: A case of deficiency of lactate dehydrogenase H-subunit. Jpn.
J. Clin. Chem. 15: 85-90, 1986.
6. Maekawa, M.; Sudo, K.; Kitajima, M.; Matsuura, Y.; Li, S. S.-L.;
Kanno, T.: Analysis of a genetic mutation in an electrophoretic variant
of the human lactate dehydrogenase-B(H) subunit. Hum. Genet. 91:
423-426, 1993.
7. Malpuech, G.; Kaplan, J. C.; Rethore, M. O.; Junien, C.; Geneix,
A.: Une observation de deletion partielle du bras court du chromosome
12: localisation du gene de la lacticodeshydrogenase B. Lyon Med. 233:
275-279, 1975.
8. Markert, C. L.: Lactate dehydrogenase: biochemistry and function
of lactate dehydrogenase. Cell Biochem. Func. 2: 131-134, 1984.
9. Mayeda, K.; Weiss, L.; Lindahl, R.; Dully, M.: Localization of
the human lactate dehydrogenase B gene on the short arm of chromosome
12. Am. J. Hum. Genet. 26: 59-64, 1974.
10. Mohrenweiser, H. W.; Neel, J. V.: Frequency of thermostability
variants: estimation of total 'rare' variant frequency in human populations. Proc.
Nat. Acad. Sci. 78: 5729-5733, 1981.
11. Okumura, N.; Terasawa, F.; Ueno, I.; Oki, K.; Yamauchi, K.; Hidaka,
H.; Tozuka, M.; Okura, M.; Katsuyama, T.: Genetic analyses in homozygous
and heterozygous variants of lactate dehydrogenase-B (H) subunit:
LD-B Matsumoto I and II (LD-B W323R). Clin. Chim. Acta 287: 163-171,
1999.
12. Rethore, M.-O.; Junien, C.; Malpuech, G.; Baccichetti, C.; Tenconi,
R.; Kaplan, J. C.; de Romeuf, J.; Lejeune, J.: Localisation du gene
de la glyceraldehyde 3-phosphate dehydrogenase (G3PD) sur le segment
distal du bras court du chromosome 12. Ann. Genet. 19: 140-142,
1976.
13. Rethore, M.-O.; Kaplan, J.-C.; Junien, C.; Cruveiller, J.; Dutrillaux,
B.; Aurias, A.; Carpentier, S.; Lafourcade, J.; Lejeune, J.: Augmentation
de l'activite de la LDH-B chez un garcon trisomique 12p par malsegregation
d'une translocation maternelle t(12;14)(q12;p11). Ann. Genet. 18:
81-87, 1975.
14. Sakai, I.; Sharief, F. S.; Pan, Y.-C. E.; Li, S. S.-L.: The cDNA
and protein sequences of human lactate dehydrogenase B. Biochem.
J. 248: 933-936, 1987.
15. Santachiara, A. S.; Nabholz, M.; Miggiano, V.; Darlington, A.
J.; Bodmer, W. F.: Linkage between human lactate dehydrogenase B
and peptidase B genes. Nature 227: 248-251, 1970.
16. Steinbach, P.; Rehder, H.: Tetrasomy for the short arm of chromosome
12 with accessory isochromosome (+i[12p]) and a marked LDH-B gene
dosage effect. Clin. Genet. 32: 1-4, 1987.
17. Sudo, K.; Maekawa, M.; Ikawa, S.; Machida, K.; Kitamura, M.; Li,
S. S.-L.: A missense mutation found in human lactate dehydrogenase-B
(H) variant gene. Biochem. Biophys. Res. Commun. 168: 672-676, 1990.
18. Sudo, K.; Maekawa, M.; Luedemann, M. M.; Deaven, L. L.; Li, S.
S.-L.: Human lactate dehydrogenase-B processed pseudogene: nucleotide
sequence analysis and assignment to the X-chromosome. Biochem. Biophys.
Res. Commun. 171: 67-74, 1990.
19. Sudo, K.; Maekawa, M.; Tomonaga, A.; Tsukada, T.; Nakayama, T.;
Kitamura, M.; Li, S. S.-L.; Kanno, T.; Toriumi, J.: Molecular characterization
of genetic mutations in human lactate dehydrogenase (LDH)B (H) variant. Hum.
Genet. 89: 158-162, 1992.
20. Takeno, T.; Li, S. S.-L.: Structure of the human lactate dehydrogenase
B gene. Biochem. J. 257: 921-924, 1989.
21. Van Someren, H.; Meera Khan, P.; Westerveld, A.; Bootsma, D.:
Human genetics--two new linkage groups carrying different loci for
LDH and glutamic-pyruvic transaminase found. Nature 240: 221-222,
1972.
22. Weiss, L.; Mayeda, K.; Lindahl, R.; Dully, M.: Localization of
human LDH-B gene of the short arm of chromosome 12. (Abstract) Am.
J. Hum. Genet. 25: 85A only, 1973.
*FIELD* CN
Victor A. McKusick - updated: 12/13/1999
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 08/02/2011
carol: 7/27/2011
carol: 5/17/2006
terry: 5/17/2005
mgross: 3/17/2004
carol: 12/20/1999
mcapotos: 12/15/1999
terry: 12/13/1999
mark: 1/12/1998
alopez: 6/2/1997
terry: 5/13/1994
mimadm: 4/7/1994
carol: 3/18/1994
carol: 11/5/1993
carol: 8/18/1993
carol: 6/23/1993
MIM
614128
*RECORD*
*FIELD* NO
614128
*FIELD* TI
#614128 LACTATE DEHYDROGENASE B DEFICIENCY; LDHBD
*FIELD* TX
A number sign (#) is used with this entry because lactate dehydrogenase
read moreB deficiency is caused by heterozygous or homozygous mutation in the
LDHB gene (150100) on chromosome 12p12.
CLINICAL FEATURES
Kitamura et al. (1971) reported the first case of a complete deficiency
of lactate dehydrogenase subunit H(B) in serum, saliva, and erythrocytes
of a 64-year-old male with mild diabetes. Study made on family members
revealed low LDH activity in their serum also linked with decreased
relative activity of the H4(B4) fraction. Based on the comparison of the
calculated ratio of H to M subunits in normal and affected family
members, it was hypothesized that the proband is homozygous while the
abnormal family members are heterozygous, assuming a single gene is
involved. Red cell metabolism in the proband was studied by Miwa et al.
(1971); neither reticulocytosis nor hemolytic anemia was present. Thus,
although LDHA deficiency (612933) leads to myoglobinuria and risk of
renal failure after strenuous exercise, LDHB deficiency probably has no
clear symptomatic consequences.
Markert (1984) noted that 30 families with LDHB deficiency had been
reported and in none were deleterious effects on health observed. As
pointed out by Sudo (1993), LDHB deficiency is of interest to laboratory
medicine mainly because it can cause misdiagnosis in those disorders in
which elevation of serum LDH is expected. LDHB deficiency can probably
be considered a 'nondisease.'
In a screening of 2,880 blood samples from healthy persons in the
Fukuoka Prefecture in Japan, Maekawa et al. (1994) found that the
frequency of heterozygotes for either LDHA deficiency or LDHB deficiency
was 0.104% at each locus. These estimated frequencies were slightly
lower than, but not significantly different from, those found previously
in the Shizuoka Prefecture.
MOLECULAR GENETICS
In a clinically normal 43-year-old male who was found to have low LDH
activity in serum by Houki et al. (1986), Sudo et al. (1990) identified
a homozygous mutation in the LDHB gene (150100.0001). LDHB mutations
have been found in other individuals with LDHB deficiency (see, e.g.,
150100.0002-150100.0004).
Okumura et al. (1999) tabulated the LDHB variants caused by missense
mutations.
*FIELD* RF
1. Houki, N.; Matsushima, Y.; Kitamura, M.; Tukada, T.; Nishina, T.;
Nakayama, T.: A case of deficiency of lactate dehydrogenase H-subunit. Jpn.
J. Clin. Chem. 15: 85-90, 1986.
2. Kitamura, M.; Iijima, N.; Hashimoto, F.; Hiratsuka, A.: Hereditary
deficiency of subunit H of lactate dehydrogenase. Clin. Chim. Acta 34:
419-423, 1971.
3. Maekawa, M.; Sudo, K.; Nagura, K.; Li, S. S.-L.; Kanno, T.: Population
screening of lactate dehydrogenase deficiencies in Fukuoka Prefecture
in Japan and molecular characterization of three independent mutations
in the lactate dehydrogenase-B(H) gene. Hum. Genet. 93: 74-76, 1994.
4. Markert, C. L.: Lactate dehydrogenase: biochemistry and function
of lactate dehydrogenase. Cell Biochem. Func. 2: 131-134, 1984.
5. Miwa, S.; Nishima, T.; Kanehashi, Y.; Kitamura, M.; Hiratsuka,
A.; Shizume, K.: Studies on erythrocyte metabolism in a case with
hereditary deficiency of H-subunit of lactate dehydrogenase. Acta
Haemat. Jpn. 34: 228-232, 1971.
6. Okumura, N.; Terasawa, F.; Ueno, I.; Oki, K.; Yamauchi, K.; Hidaka,
H.; Tozuka, M.; Okura, M.; Katsuyama, T.: Genetic analyses in homozygous
and heterozygous variants of lactate dehydrogenase-B (H) subunit:
LD-B Matsumoto I and II (LD-B W323R). Clin. Chim. Acta 287: 163-171,
1999.
7. Sudo, K.: Personal Communication. Komae City, Japan 7/12/1993.
8. Sudo, K.; Maekawa, M.; Ikawa, S.; Machida, K.; Kitamura, M.; Li,
S. S.-L.: A missense mutation found in human lactate dehydrogenase-B
(H) variant gene. Biochem. Biophys. Res. Commun. 168: 672-676, 1990.
*FIELD* CD
Carol A. Bocchini: 7/27/2011
*FIELD* ED
joanna: 07/27/2011
carol: 7/27/2011
*RECORD*
*FIELD* NO
614128
*FIELD* TI
#614128 LACTATE DEHYDROGENASE B DEFICIENCY; LDHBD
*FIELD* TX
A number sign (#) is used with this entry because lactate dehydrogenase
read moreB deficiency is caused by heterozygous or homozygous mutation in the
LDHB gene (150100) on chromosome 12p12.
CLINICAL FEATURES
Kitamura et al. (1971) reported the first case of a complete deficiency
of lactate dehydrogenase subunit H(B) in serum, saliva, and erythrocytes
of a 64-year-old male with mild diabetes. Study made on family members
revealed low LDH activity in their serum also linked with decreased
relative activity of the H4(B4) fraction. Based on the comparison of the
calculated ratio of H to M subunits in normal and affected family
members, it was hypothesized that the proband is homozygous while the
abnormal family members are heterozygous, assuming a single gene is
involved. Red cell metabolism in the proband was studied by Miwa et al.
(1971); neither reticulocytosis nor hemolytic anemia was present. Thus,
although LDHA deficiency (612933) leads to myoglobinuria and risk of
renal failure after strenuous exercise, LDHB deficiency probably has no
clear symptomatic consequences.
Markert (1984) noted that 30 families with LDHB deficiency had been
reported and in none were deleterious effects on health observed. As
pointed out by Sudo (1993), LDHB deficiency is of interest to laboratory
medicine mainly because it can cause misdiagnosis in those disorders in
which elevation of serum LDH is expected. LDHB deficiency can probably
be considered a 'nondisease.'
In a screening of 2,880 blood samples from healthy persons in the
Fukuoka Prefecture in Japan, Maekawa et al. (1994) found that the
frequency of heterozygotes for either LDHA deficiency or LDHB deficiency
was 0.104% at each locus. These estimated frequencies were slightly
lower than, but not significantly different from, those found previously
in the Shizuoka Prefecture.
MOLECULAR GENETICS
In a clinically normal 43-year-old male who was found to have low LDH
activity in serum by Houki et al. (1986), Sudo et al. (1990) identified
a homozygous mutation in the LDHB gene (150100.0001). LDHB mutations
have been found in other individuals with LDHB deficiency (see, e.g.,
150100.0002-150100.0004).
Okumura et al. (1999) tabulated the LDHB variants caused by missense
mutations.
*FIELD* RF
1. Houki, N.; Matsushima, Y.; Kitamura, M.; Tukada, T.; Nishina, T.;
Nakayama, T.: A case of deficiency of lactate dehydrogenase H-subunit. Jpn.
J. Clin. Chem. 15: 85-90, 1986.
2. Kitamura, M.; Iijima, N.; Hashimoto, F.; Hiratsuka, A.: Hereditary
deficiency of subunit H of lactate dehydrogenase. Clin. Chim. Acta 34:
419-423, 1971.
3. Maekawa, M.; Sudo, K.; Nagura, K.; Li, S. S.-L.; Kanno, T.: Population
screening of lactate dehydrogenase deficiencies in Fukuoka Prefecture
in Japan and molecular characterization of three independent mutations
in the lactate dehydrogenase-B(H) gene. Hum. Genet. 93: 74-76, 1994.
4. Markert, C. L.: Lactate dehydrogenase: biochemistry and function
of lactate dehydrogenase. Cell Biochem. Func. 2: 131-134, 1984.
5. Miwa, S.; Nishima, T.; Kanehashi, Y.; Kitamura, M.; Hiratsuka,
A.; Shizume, K.: Studies on erythrocyte metabolism in a case with
hereditary deficiency of H-subunit of lactate dehydrogenase. Acta
Haemat. Jpn. 34: 228-232, 1971.
6. Okumura, N.; Terasawa, F.; Ueno, I.; Oki, K.; Yamauchi, K.; Hidaka,
H.; Tozuka, M.; Okura, M.; Katsuyama, T.: Genetic analyses in homozygous
and heterozygous variants of lactate dehydrogenase-B (H) subunit:
LD-B Matsumoto I and II (LD-B W323R). Clin. Chim. Acta 287: 163-171,
1999.
7. Sudo, K.: Personal Communication. Komae City, Japan 7/12/1993.
8. Sudo, K.; Maekawa, M.; Ikawa, S.; Machida, K.; Kitamura, M.; Li,
S. S.-L.: A missense mutation found in human lactate dehydrogenase-B
(H) variant gene. Biochem. Biophys. Res. Commun. 168: 672-676, 1990.
*FIELD* CD
Carol A. Bocchini: 7/27/2011
*FIELD* ED
joanna: 07/27/2011
carol: 7/27/2011