PFKL

phosphofructokinase, liver type

Basic information

Region (hg38): 21:44300050-44327376

Links

ENSG00000141959 ∙ NCBI:5211 ∙ OMIM:171860 ∙ HGNC:8876 ∙ Uniprot:P17858 ∙ 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 PFKL gene.

• Inborn genetic diseases (32 variants)
• not specified (9 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PFKL 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				1	2	3
missense			33	3	2	38
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					2	2
Total	0	0	33	4	6

Variants in PFKL

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

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

Position	Type	Phenotype	Significance	ClinVar
21-44300101-C-T			Benign (Oct 04, 2017)
21-44300136-G-A		not specified	Uncertain significance (Mar 31, 2023)
21-44300142-G-T		not specified	Uncertain significance (Jun 23, 2023)
21-44305823-C-T			Benign (Oct 17, 2017)
21-44305863-C-T		PFKL-related disorder	Benign (Jun 05, 2020)
21-44311021-G-A		not specified	Uncertain significance (Feb 27, 2023)
21-44311072-A-G		not specified	Uncertain significance (Feb 26, 2024)
21-44312152-G-C		not specified	Uncertain significance (Aug 12, 2021)
21-44312160-G-A		not specified	Uncertain significance (May 17, 2023)
21-44312165-G-A		not specified	Likely benign (May 23, 2023)
21-44312210-G-A			Uncertain significance (May 13, 2018)
21-44312233-C-T		not specified	Benign (Jan 09, 2019)
21-44313002-G-A		not specified	Likely benign (Aug 16, 2021)
21-44313003-G-C		PFKL-related disorder	Likely benign (Mar 22, 2023)
21-44313022-A-G		not specified	Uncertain significance (Jul 20, 2022)
21-44313681-G-A		not specified	Uncertain significance (Nov 13, 2023)
21-44313984-A-T		not specified	Benign (Nov 15, 2018)
21-44314028-G-A		not specified	Benign (Dec 16, 2018)
21-44316253-C-T		not specified	Uncertain significance (Apr 28, 2022)
21-44316254-G-A		not specified	Uncertain significance (Feb 14, 2023)
21-44316301-C-T		not specified	Uncertain significance (Aug 16, 2021)
21-44316305-A-G		not specified	Uncertain significance (May 25, 2022)
21-44316307-G-A		not specified	Uncertain significance (Sep 01, 2021)
21-44316325-A-G		not specified	Uncertain significance (Jun 26, 2023)
21-44316430-A-G			Uncertain significance (Apr 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PFKL	protein_coding	protein_coding	ENST00000349048	22	27326

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.70e-17	0.208	125625	0	84	125709	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.68	403	510	0.791	0.0000346	5012
Missense in Polyphen		173	237.93	0.72709		2234
Synonymous	-0.275	224	219	1.02	0.0000170	1566
Loss of Function	1.37	31	40.4	0.767	0.00000191	458

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000804	0.000786
Ashkenazi Jewish	0.00	0.00
East Asian	0.000345	0.000326
Finnish	0.000150	0.000139
European (Non-Finnish)	0.000378	0.000369
Middle Eastern	0.000345	0.000326
South Asian	0.000446	0.000425
Other	0.000196	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (By similarity). {ECO:0000250|UniProtKB:P12382, ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Fructose and mannose metabolism - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);RNA degradation - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Warburg Effect;Pentose Phosphate Pathway;Fructose intolerance, hereditary;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Transaldolase deficiency;Fructose and Mannose Degradation;Fructosuria;Photodynamic therapy-induced HIF-1 survival signaling;Pathways in clear cell renal cell carcinoma;Insulin Signaling;Glycolysis and Gluconeogenesis;Neutrophil degranulation;phosphoinositides and their downstream targets;Metabolism of carbohydrates;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Innate Immune System;Immune System;Metabolism;Pentose phosphate cycle;Glycolysis;Galactose 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: 0.435

Intolerance Scores

• loftool: 0.507
• rvis_EVS: -1.3
• rvis_percentile_EVS: 4.95

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.533
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.953

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pfkl

Gene ontology

• Biological process: fructose 6-phosphate metabolic process;glucose catabolic process;glycolytic process;response to glucose;fructose 1,6-bisphosphate metabolic process;neutrophil degranulation;negative regulation of insulin secretion;protein complex oligomerization;protein homotetramerization;canonical glycolysis
• Cellular component: extracellular region;cytosol;6-phosphofructokinase complex;membrane;secretory granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: 6-phosphofructokinase activity;protein binding;ATP binding;AMP binding;kinase binding;identical protein binding;metal ion binding;monosaccharide binding;fructose binding;fructose-6-phosphate binding