PKLR (pyruvate kinase L/R)

Gene

• Entrez ID: 5313
• Gene name: Pyruvate kinase L/R
• Gene symbol: PKLR
• Synonyms: CNSHA2, PK1, PKL, PKRL, RPK
• Chromosome: 1
• Chromosome location: 1q22
• 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs8177988	C>T	Conflicting-interpretations-of-pathogenicity, likely-pathogenic, uncertain-significance	Genic downstream transcript variant, missense variant, coding sequence variant
rs74315362	G>A	Pathogenic	Missense variant, 3 prime UTR variant, coding sequence variant
rs113403872	C>T	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant
rs116100695	G>A	Likely-pathogenic, pathogenic, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, missense variant, coding sequence variant
rs118204083	G>A	Pathogenic	Missense variant, coding sequence variant
rs118204084	G>T	Pathogenic	Genic downstream transcript variant, downstream transcript variant, missense variant, coding sequence variant
rs118204085	C>T	Pathogenic	Genic downstream transcript variant, downstream transcript variant, missense variant, coding sequence variant
rs118204087	C>A,T	Pathogenic	5 prime UTR variant, missense variant, intron variant, coding sequence variant
rs118204089	G>T	Pathogenic	Missense variant, coding sequence variant
rs138871700	G>A	Pathogenic	Missense variant, coding sequence variant
rs185753709	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs201953584	C>A	Pathogenic	Coding sequence variant, stop gained
rs752423472	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs762591322	C>T	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, downstream transcript variant, missense variant
rs764143249	G>A,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs771145576	C>A,T	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, downstream transcript variant, stop gained
rs772567442	G>A	Pathogenic	Stop gained, intron variant, coding sequence variant, 5 prime UTR variant
rs773626254	C>A,T	Pathogenic	Missense variant, coding sequence variant
rs774652817	C>A,T	Pathogenic	Coding sequence variant, synonymous variant, genic downstream transcript variant, downstream transcript variant
rs886045351	ATG>-	Likely-pathogenic	Inframe deletion, coding sequence variant
rs918627824	C>T	Pathogenic	Missense variant, coding sequence variant
rs1358047518	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1448381947	C>T	Pathogenic	Intron variant, splice acceptor variant
rs1572057140	C>T	Pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1237584	hsa-miR-3688-3p	CLIP-seq
MIRT1237585	hsa-miR-1270	CLIP-seq
MIRT1237586	hsa-miR-1273f	CLIP-seq
MIRT1237587	hsa-miR-1296	CLIP-seq
MIRT1237588	hsa-miR-147	CLIP-seq
MIRT1237589	hsa-miR-203	CLIP-seq
MIRT1237590	hsa-miR-2110	CLIP-seq
MIRT1237591	hsa-miR-2355-5p	CLIP-seq
MIRT1237592	hsa-miR-2861	CLIP-seq
MIRT1237593	hsa-miR-2909	CLIP-seq
MIRT1237594	hsa-miR-3179	CLIP-seq
MIRT1237595	hsa-miR-3202	CLIP-seq
MIRT1237596	hsa-miR-3650	CLIP-seq
MIRT1237584	hsa-miR-3688-3p	CLIP-seq
MIRT1237597	hsa-miR-370	CLIP-seq
MIRT1237598	hsa-miR-3911	CLIP-seq
MIRT1237599	hsa-miR-4271	CLIP-seq
MIRT1237600	hsa-miR-4434	CLIP-seq
MIRT1237601	hsa-miR-4436b-3p	CLIP-seq
MIRT1237602	hsa-miR-4468	CLIP-seq
MIRT1237603	hsa-miR-4512	CLIP-seq
MIRT1237604	hsa-miR-4516	CLIP-seq
MIRT1237605	hsa-miR-4648	CLIP-seq
MIRT1237606	hsa-miR-4654	CLIP-seq
MIRT1237607	hsa-miR-4663	CLIP-seq
MIRT1237608	hsa-miR-4667-5p	CLIP-seq
MIRT1237609	hsa-miR-4683	CLIP-seq
MIRT1237610	hsa-miR-4687-5p	CLIP-seq
MIRT1237611	hsa-miR-4688	CLIP-seq
MIRT1237612	hsa-miR-4694-3p	CLIP-seq
MIRT1237613	hsa-miR-4700-5p	CLIP-seq
MIRT1237614	hsa-miR-4713-5p	CLIP-seq
MIRT1237615	hsa-miR-4725-3p	CLIP-seq
MIRT1237616	hsa-miR-4747-5p	CLIP-seq
MIRT1237617	hsa-miR-4769-5p	CLIP-seq
MIRT1237618	hsa-miR-4775	CLIP-seq
MIRT1237619	hsa-miR-590-3p	CLIP-seq
MIRT1237620	hsa-miR-620	CLIP-seq
MIRT1237621	hsa-miR-644	CLIP-seq
MIRT1237622	hsa-miR-660	CLIP-seq
MIRT1237623	hsa-miR-661	CLIP-seq
MIRT1237584	hsa-miR-3688-3p	CLIP-seq
MIRT1237584	hsa-miR-3688-3p	CLIP-seq
MIRT1237618	hsa-miR-4775	CLIP-seq
MIRT1237619	hsa-miR-590-3p	CLIP-seq
MIRT1237622	hsa-miR-660	CLIP-seq
MIRT1237618	hsa-miR-4775	CLIP-seq
MIRT1237619	hsa-miR-590-3p	CLIP-seq
MIRT1237622	hsa-miR-660	CLIP-seq
MIRT2594558	hsa-miR-1253	CLIP-seq
MIRT2594559	hsa-miR-3123	CLIP-seq
MIRT2594560	hsa-miR-3925-5p	CLIP-seq
MIRT2594561	hsa-miR-3976	CLIP-seq
MIRT2594562	hsa-miR-873	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
USF1	Unknown	7852331
USF2	Unknown	7852331

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000287	Function	Magnesium ion binding	IEA
GO:0001666	Process	Response to hypoxia	IEA
GO:0004743	Function	Pyruvate kinase activity	IBA	21873635
GO:0004743	Function	Pyruvate kinase activity	NAS	1445295
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0006096	Process	Glycolytic process	IBA	21873635
GO:0006754	Process	ATP biosynthetic process	IEA
GO:0007584	Process	Response to nutrient	IEA
GO:0009408	Process	Response to heat	IEA
GO:0009749	Process	Response to glucose	IEA
GO:0010226	Process	Response to lithium ion	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0030955	Function	Potassium ion binding	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IBA	21873635
GO:0033198	Process	Response to ATP	IEA
GO:0042866	Process	Pyruvate biosynthetic process	IEA
GO:0051591	Process	Response to cAMP	IEA
GO:0061621	Process	Canonical glycolysis	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:0071872	Process	Cellular response to epinephrine stimulus	IEA

Other IDs

• MIM: 609712
• HGNC: 9020
• e!Ensembl: ENSG00000143627

Protein

• UniProt ID: P30613
• Protein name: Pyruvate kinase PKLR (EC 2.7.1.40) (Pyruvate kinase 1) (Pyruvate kinase isozymes L/R) (R-type/L-type pyruvate kinase) (Red cell/liver pyruvate kinase)
• Protein function: Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis.
• PDB: 2VGB, 2VGF, 2VGG, 2VGI, 4IMA, 4IP7, 5SC8, 5SC9, 5SCA, 5SCB, 5SCC, 5SCD, 5SCE, 5SCF, 5SCG, 5SCH, 5SCI, 5SCJ, 5SCK, 5SCL, 5SDT, 6NN4, 6NN5, 6NN7, 6NN8, 7FRV, 7FRW, 7FRX, 7FRY, 7FRZ, 7FS0, 7FS1, 7FS2, 7FS3, 7FS4, 7FS5, 7FS6, 7FS7, 7FS8, 7FS9, 7FSA, 7FSB, 7FSC, 7FSD, 7QDN, 7QZU, 8TBS, 8TBT, 8TBU, 8XFD
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00224	PK	85 → 438	Pyruvate kinase, barrel domain	Family
  PF02887	PK_C	453 → 571	Pyruvate kinase, alpha/beta domain	Domain

• Sequence:

  MSIQENISSLQLRSWVSKSQRDLAKSILIGAPGGPAGYLRRASVAQLTQELGTAFFQQQQ
  LPAAMADTFLEHLCLLDIDSEPVAARSTSIIATIGPASRSVERLKEMIKAGMNIARLNFS
  HGSHEYHAESIANVREAVESFAGSPLSYRPVAIALDTKGPEIRTGILQGGPESEVELVKG
  SQVLVTVDPAFRTRGNANTVWVDYPNIVRVVPVGGRIYIDDGLISLVVQKIGPEGLVTQV
  ENGGVLGSRKGVNLPGAQVDLPGLSEQDVRDLRFGVEHGVDIVFASFVRKASDVAAVRAA
  LGPEGHGIKIISKIENHEGVKRFDEILEVSDGIMVARGDLGIEIPAEKVFLAQKMMIGRC
  NLAGKPVVCATQMLESMITKPRPTRAETSDVANAVLDGADCIMLSGETAKGNFPVEAVKM
  QHAIAREAEAAVYHRQLFEELRRAAPLSRDPTEVTAIGAVEAAFKCCAAAIIVLTTTGRS
  AQLLSRYRPRAAVIAVTRSAQAARQVHLCRGVFPLLYREPPEAIWADDVDRRVQFGIESG
  KLRGFLRVGDLVIVVTGWRPGSGYTNIMRVLSIS

• Sequence length: 574

Pathways

KEGG:

Glycolysis / Gluconeogenesis
Pyruvate metabolism
Metabolic pathways
Carbon metabolism
Biosynthesis of amino acids
Insulin signaling pathway
Type II diabetes mellitus
Non-alcoholic fatty liver disease
Maturity onset diabetes of the young

Reactome:

Glycolysis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Hemolytic, Congenital	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Cholelithiasis	Cholelithiasis	rs121918440, rs72552778, rs387906528, rs759202962, rs377160065, rs1051861187, rs757693457, rs752563752
Deficiency of pyruvate kinase	Deficiency of pyruvate kinase	rs74315362, rs118204084, rs118204085, rs113403872, rs116100695, rs118204089, rs2147483647, rs771145576, rs774652817, rs201953584, rs886045351, rs918627824, rs185753709, rs752423472	11328279, 7948315, 19085939, 7706479, 8180378, 1896471, 9827908, 26658699, 27871768, 18759866, 8481523, 8483951, 21794208, 7919353, 15953013, 8476433, 2018831, 7655861, 28133914, 9057665, 8161798, 9389718, 26728349, 27346685, 11698298, 11960989, 10923218, 12393511, 11054094, 16704447, 21815188, 9886305, 17574881, 8664896, 1536957, 9482576
Erythrocytosis	Erythrocytosis familial, 1	rs119476044, rs119476045, rs137853036, rs137853037, rs35020585, rs33949869, rs33987903, rs36020563, rs35890959, rs1141387, rs35117167, rs33969677, rs33918338, rs33951978, rs33954595, rs33945777, rs35724775, rs35004220, rs34690599, rs33978134, rs1554393463, rs1554393458, rs1018129986, rs1596573335	22274579
Hemolytic anemia	Chronic hemolytic anemia, Hemolytic anemia due to red cell pyruvate kinase deficiency	rs104894025, rs104894026, rs397518435, rs397518436, rs104894027, rs397518437, rs104894028, rs397518438, rs104894029, rs137853583, rs137853585, rs137853586, rs137853587, rs267606851, rs267606852, rs267606853, rs137853249, rs33924146, rs104894101, rs104894102, rs137853203, rs137853204, rs137853205, rs387906582, rs387906583, rs398122379, rs1064794848, rs774419705, rs1555367318, rs1345036090, rs1586033745, rs1571436535, rs2022057
Hydrops fetalis	Hydrops Fetalis	rs28935477, rs1131691986
Hyperbilirubinemia	Unconjugated hyperbilirubinemia, Neonatal unconjugated hyperbilirubinemia	rs34993780, rs587784535, rs797046090, rs797046091

Unknown
Disease name	Disease term	dbSNP ID	References
Cholecystitis	Cholecystitis
Enzymopathy	Enzymopathy		1896471, 8664896
Mental depression	Major Depressive Disorder	rs587778876, rs587778877	29317602
Polycythemia	Polycythemia