PKM

pyruvate kinase M1/2

Basic information

Region (hg38): 15:72199028-72231819

Previous symbols: [ "PKM2" ]

Links

ENSG00000067225 ∙ NCBI:5315 ∙ OMIM:179050 ∙ HGNC:9021 ∙ Uniprot:P14618 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKM gene.

• Inborn genetic diseases (9 variants)
• not provided (5 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	4	6
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	9	2	4

Variants in PKM

This is a list of pathogenic ClinVar variants found in the PKM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-72199654-G-A		not specified	Uncertain significance (Feb 12, 2024)
15-72200629-C-T		not specified	Uncertain significance (Oct 17, 2023)
15-72202473-C-T		not specified	Uncertain significance (Nov 21, 2022)
15-72202513-G-A		not specified	Likely benign (Mar 28, 2016)
15-72202565-C-T		not specified	Uncertain significance (Feb 06, 2024)
15-72206853-G-A		not specified	Uncertain significance (Jan 03, 2022)
15-72207167-C-T		not specified	Uncertain significance (Feb 16, 2023)
15-72208625-G-A		not specified	Uncertain significance (Apr 25, 2022)
15-72208664-T-C		not specified	Uncertain significance (Jul 12, 2022)
15-72208731-C-T			Benign (Dec 31, 2019)
15-72208751-C-T		not specified	Uncertain significance (Jul 09, 2021)
15-72208758-G-A			Likely benign (May 16, 2018)
15-72208850-A-G			Benign (May 16, 2018)
15-72209723-C-T		not specified	Uncertain significance (Apr 05, 2023)
15-72209800-G-A		not specified	Benign (Mar 28, 2016)
15-72209809-C-T			Benign (Dec 31, 2019)
15-72209857-G-A			Likely benign (Dec 31, 2019)
15-72210382-T-C		not specified	Uncertain significance (Dec 28, 2023)
15-72210408-C-T		not specified	Uncertain significance (Jul 26, 2021)
15-72219076-C-T		not specified	Uncertain significance (Apr 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PKM	protein_coding	protein_coding	ENST00000319622	10	32795

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.855	0.145	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.09	221	327	0.675	0.0000210	3484
Missense in Polyphen		33	83.912	0.39327		1005
Synonymous	-0.606	124	116	1.07	0.00000689	1082
Loss of Function	3.78	4	23.9	0.167	0.00000154	257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival. {ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:21620138}.
• Pathway: Pyruvate metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Abacavir Pathway, Pharmacokinetics/Pharmacodynamics;Warburg Effect;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Photodynamic therapy-induced HIF-1 survival signaling;Amino Acid metabolism;Pathways in clear cell renal cell carcinoma;Glycolysis and Gluconeogenesis;Neutrophil degranulation;Metabolism of carbohydrates;Citrate cycle;Folate metabolism;Alanine Aspartate Asparagine metabolism;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;TCR;Purine metabolism;Innate Immune System;Immune System;Metabolism;Pyrimidine metabolism;Glycolysis;Purine nucleotides nucleosides metabolism;EGFR1;Pyruvate metabolism;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Glucose metabolism;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.181

Intolerance Scores

• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.777
• hipred: Y
• hipred_score: 0.825
• ghis: 0.588

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pkm
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; neoplasm

Gene ontology

• Biological process: response to hypoxia;liver development;glycolytic process;response to nutrient;response to gravity;programmed cell death;response to muscle inactivity;animal organ regeneration;cellular response to insulin stimulus;neutrophil degranulation;skeletal muscle tissue regeneration;protein homotetramerization;canonical glycolysis;positive regulation of sprouting angiogenesis
• Cellular component: extracellular region;nucleus;cytoplasm;mitochondrion;cytosol;cilium;vesicle;secretory granule lumen;myelin sheath;collagen-containing extracellular matrix;extracellular exosome;pyruvate kinase complex;extracellular vesicle;ficolin-1-rich granule lumen
• Molecular function: magnesium ion binding;RNA binding;pyruvate kinase activity;protein binding;ATP binding;kinase activity;MHC class II protein complex binding;potassium ion binding;identical protein binding;ADP binding;cadherin binding;thyroid hormone binding