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

Summary

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: mouse all
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Genomic context

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

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	not available
Pyruvate kinase hyperactivity MedGen: C1863224 OMIM: 102900 GeneReviews: Not available	not available

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH16325 (e-PCR)
- UniSTS:31774

D1S1153 (e-PCR)
- UniSTS:149041

GDB:366638 (e-PCR)
- UniSTS:156817

D1S3522 (e-PCR)
- UniSTS:70038

RH10977 (e-PCR)
- UniSTS:7630

PKLR__7008 (e-PCR)
- UniSTS:466399

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 phosphorylation	IEA Inferred from Electronic Annotation more info
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 more info	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

EC 2.7.1.40

NP_870986.1

EC 2.7.1.40

XP_006711449.1

EC 2.7.1.40

XP_011507942.1

EC 2.7.1.40

XP_016856982.1

EC 2.7.1.40

XP_047278547.1

EC 2.7.1.40

XP_047278548.1

EC 2.7.1.40

XP_054185450.1

EC 2.7.1.40

XP_054185451.1

EC 2.7.1.40

XP_054185452.1

EC 2.7.1.40

XP_054193047.1

EC 2.7.1.40

XP_054193048.1

EC 2.7.1.40

XP_054193049.1

EC 2.7.1.40

XP_054193050.1

EC 2.7.1.40

XP_054193051.1

EC 2.7.1.40

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

NG_011677.1 RefSeqGene

Range

4997..17142

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1136

mRNA and Protein(s)

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 ...
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

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

155289293..155308654 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

O75758, P11973, P30613
XM_047422592.1 → XP_047278548.1 pyruvate kinase PKLR isoform X1

UniProtKB/Swiss-Prot

O75758, P11973, P30613
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
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
XM_017001493.1 → XP_016856982.1 pyruvate kinase PKLR isoform X3