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PKLR pyruvate kinase L/R [ Homo sapiens (human) ]

Gene ID: 5313, updated on 14-Nov-2024

Summary

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Official Symbol
PKLRprovided by HGNC
Official Full Name
pyruvate kinase L/Rprovided by HGNC
Primary source
HGNC:HGNC:9020
See related
Ensembl:ENSG00000143627 MIM:609712; AllianceGenome:HGNC:9020
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PK1; PKL; RPK; PKRL; CNSHA2
Summary
The protein encoded by this gene is a pyruvate kinase that catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP, which is the rate-limiting step of glycolysis. Defects in this enzyme, due to gene mutations or genetic variations, are the common cause of chronic hereditary nonspherocytic hemolytic anemia (CNSHA or HNSHA). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Biased expression in liver (RPKM 34.0), kidney (RPKM 20.1) and 3 other tissues See more
Orthologs
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Genomic context

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See PKLR in Genome Data Viewer
Location:
1q22
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (155289293..155308654, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (154427854..154447170, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (155259084..155271229, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene secretory carrier membrane protein 3 Neighboring gene CDC like kinase 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:155243888-155244388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155254443-155254943 Neighboring gene hyperpolarization activated cyclic nucleotide gated potassium channel 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:155263898-155264430 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:155275791-155276290 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1813 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1814 Neighboring gene farnesyl diphosphate synthase Neighboring gene RUSC1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1400 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155291392-155292375 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1401 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1402 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1403 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1405 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1815 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155295943-155296500 Neighboring gene RUN and SH3 domain containing 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Hematologically important mutations: red cell pyruvate kinase (Third update). Bianchi P, et al. Blood Cells Mol Dis, 2000 Feb. PMID 10772876
  2. Six children with pyruvate kinase deficiency from one small town: molecular characterization of the PK-LR gene. Christensen RD, et al. J Pediatr, 2011 Oct. PMID 21784452
  3. Genetic diversity in human erythrocyte pyruvate kinase. Berghout J, et al. Genes Immun, 2012 Jan. PMID 21833022
  4. Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia. Wang C, et al. Blood, 2001 Nov 15. PMID 11698298
  5. Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria. Machado P, et al. PLoS One, 2012. PMID 23082140, Free PMC Article

See all (141) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PKLR mutations in pyruvate kinase deficient Polish patients: Functional characteristics of c.101-1G > A and c.1058delAAG variants.
    Title: PKLR mutations in pyruvate kinase deficient Polish patients: Functional characteristics of c.101-1G > A and c.1058delAAG variants.
  2. Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine differentiation of castration-resistant prostate cancer.
    Title: Targeting PKLR/MYCN/ROMO1 signaling suppresses neuroendocrine differentiation of castration-resistant prostate cancer.
  3. Targeted next-generation sequencing identifies eighteen novel mutations expanding the molecular and clinical spectrum of PKLR gene disorders in the Indian population.
    Title: Targeted next-generation sequencing identifies eighteen novel mutations expanding the molecular and clinical spectrum of PKLR gene disorders in the Indian population.
  4. FLI1 accelerates leukemogenesis through transcriptional regulation of pyruvate kinase-L/R and other glycolytic genes.
    Title: FLI1 accelerates leukemogenesis through transcriptional regulation of pyruvate kinase-L/R and other glycolytic genes.
  5. Haematological profile of malaria patients with G6PD and PKLR variants (erythrocytic enzymopathies): a cross-sectional study in Thailand.
    Title: Haematological profile of malaria patients with G6PD and PKLR variants (erythrocytic enzymopathies): a cross-sectional study in Thailand.
  6. Genetic variants of PKLR are associated with acute pain in sickle cell disease.
    Title: Genetic variants of PKLR are associated with acute pain in sickle cell disease.
  7. Pyruvate kinase L/R links metabolism dysfunction to neuroendocrine differentiation of prostate cancer by ZBTB10 deficiency.
    Title: Pyruvate kinase L/R links metabolism dysfunction to neuroendocrine differentiation of prostate cancer by ZBTB10 deficiency.
  8. A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report.
    Title: A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report.
  9. Rheostat functional outcomes occur when substitutions are introduced at nonconserved positions that diverge with speciation.
    Title: Rheostat functional outcomes occur when substitutions are introduced at nonconserved positions that diverge with speciation.
  10. Liver Pyruvate Kinase Promotes NAFLD/NASH in Both Mice and Humans in a Sex-Specific Manner.
    Title: Liver Pyruvate Kinase Promotes NAFLD/NASH in Both Mice and Humans in a Sex-Specific Manner.
Submit: New GeneRIF Correction See all GeneRIFs (72)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Pyruvate kinase deficiency of red cells
MedGen: C0340968 OMIM: 266200 GeneReviews: Not available
Compare labs
Pyruvate kinase hyperactivity
MedGen: C1863224 OMIM: 102900 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.
EBI GWAS Catalog
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
EBI GWAS Catalog

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of pyruvate kinase, liver and RBC (PKLR) by siRNA has both activating and inhibiting activities on HIV-1 replication in HeLa P4/R5 cells, suggesting a regulatory role in HIV replication PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables magnesium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables monosaccharide binding IEA
Inferred from Electronic Annotation
more info
  
enables potassium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables pyruvate kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables pyruvate kinase activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cellular response to epinephrine stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to insulin stimulus IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glycolytic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glycolytic process IEA
Inferred from Electronic Annotation
more info
  
involved_in glycolytic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in pyruvate biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in response to ATP IEA
Inferred from Electronic Annotation
more info
  
involved_in response to cAMP IEA
Inferred from Electronic Annotation
more info
  
involved_in response to glucose IEA
Inferred from Electronic Annotation
more info
  
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in response to metal ion IEA
Inferred from Electronic Annotation
more info
  
involved_in response to nutrient IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
part_of pyruvate kinase complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
pyruvate kinase PKLR
Names
R-type/L-type pyruvate kinase
pyruvate kinase 1
pyruvate kinase isozyme R/L
pyruvate kinase isozymes L/R
pyruvate kinase isozymes R/L
pyruvate kinase type L
pyruvate kinase, liver and RBC
pyruvate kinase, liver and blood cell
red cell/liver pyruvate kinase
NP_000289.1
NP_870986.1
XP_006711449.1
XP_011507942.1
XP_016856982.1
XP_047278547.1
XP_047278548.1
XP_054185450.1
XP_054185451.1
XP_054185452.1
XP_054193047.1
XP_054193048.1
XP_054193049.1
XP_054193050.1
XP_054193051.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011677.1 RefSeqGene

    Range
    4997..17142
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1136

mRNA and Protein(s)

  1. NM_000298.6 → NP_000289.1  pyruvate kinase PKLR isoform 1

    See identical proteins and their annotated locations for NP_000289.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1). Isoform 1 is also known as type R.
    Source sequence(s)
    AL713999, BC025737, H77542
    Consensus CDS
    CCDS1109.1
    UniProtKB/Swiss-Prot
    O75758, P11973, P30613
    UniProtKB/TrEMBL
    A0A977JB91
    Related
    ENSP00000339933.4, ENST00000342741.6
    Conserved Domains (1) summary
    cd00288
    Location:85 → 573
    Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

  2. NM_181871.4 → NP_870986.1  pyruvate kinase PKLR isoform 2

    See identical proteins and their annotated locations for NP_870986.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a distinct and shorter N-terminus, as compared to isoform 1. Isoform 2 is also known as type L.
    Source sequence(s)
    AK225947, AL713999, BF110802, M15465
    Consensus CDS
    CCDS44240.1
    UniProtKB/TrEMBL
    Q16716
    Related
    ENSP00000376214.3, ENST00000392414.7
    Conserved Domains (2) summary
    cd00288
    Location:54 → 542
    Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
    TIGR01064
    Location:55 → 539
    pyruv_kin; pyruvate kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    155289293..155308654 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047422591.1 → XP_047278547.1  pyruvate kinase PKLR isoform X1

    UniProtKB/Swiss-Prot
    O75758, P11973, P30613

  2. XM_047422592.1 → XP_047278548.1  pyruvate kinase PKLR isoform X1

    UniProtKB/Swiss-Prot
    O75758, P11973, P30613

  3. XM_011509640.4 → XP_011507942.1  pyruvate kinase PKLR isoform X2

    See identical proteins and their annotated locations for XP_011507942.1

    UniProtKB/TrEMBL
    B4DPM0
    Conserved Domains (2) summary
    cd00288
    Location:21 → 509
    Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
    TIGR01064
    Location:22 → 506
    pyruv_kin; pyruvate kinase

  4. XM_006711386.5 → XP_006711449.1  pyruvate kinase PKLR isoform X2

    See identical proteins and their annotated locations for XP_006711449.1

    UniProtKB/TrEMBL
    B4DPM0
    Conserved Domains (2) summary
    cd00288
    Location:21 → 509
    Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
    TIGR01064
    Location:22 → 506
    pyruv_kin; pyruvate kinase

  5. XM_017001493.1 → XP_016856982.1  pyruvate kinase PKLR isoform X3

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NW_003315906.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    94316..106461 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054329475.1 → XP_054185450.1  pyruvate kinase PKLR isoform X2

  2. XM_054329476.1 → XP_054185451.1  pyruvate kinase PKLR isoform X2

  3. XM_054329477.1 → XP_054185452.1  pyruvate kinase PKLR isoform X4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    154427854..154447170 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054337072.1 → XP_054193047.1  pyruvate kinase PKLR isoform X1

    UniProtKB/Swiss-Prot
    O75758, P11973, P30613

  2. XM_054337073.1 → XP_054193048.1  pyruvate kinase PKLR isoform X1

    UniProtKB/Swiss-Prot
    O75758, P11973, P30613

  3. XM_054337074.1 → XP_054193049.1  pyruvate kinase PKLR isoform X2

  4. XM_054337075.1 → XP_054193050.1  pyruvate kinase PKLR isoform X2

  5. XM_054337076.1 → XP_054193051.1  pyruvate kinase PKLR isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P30613.2 GenPept UniProtKB/Swiss-Prot:P30613

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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