PFKL

protein-coding

phosphofructokinase, liver type

Gene summary

This gene encodes the liver (L) subunit of an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

MANE transcript

NM_002626.6

Inheritance

—

ClinVar variants

U:128B:26

Top phenotype

PFKL-related disorder

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr21:44,300,051-44,327,376

External References & Databases

Ensembl (ENSG00000141959)

Transcript & Mutation Effects

hg38 • Region Span ~27.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PFKL variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 108

PFKL-related disorderTotal: 20

not providedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002626.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	14 clinvar	1 clinvar	19
missense			106 clinvar	10 clinvar	1 clinvar	117
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			16 clinvar			16
Total	0	0	128	24	2	154

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 126 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002626.6	RefSeq	NP_002617.3	22	MANE Select
ENST00000349048.9	Ensembl	ENSP00000269848.6	22	MANE Select
NM_001002021.3	RefSeq	NP_001002021.2	23	Standard
ENST00000397961.6	Ensembl	ENSP00000381052.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

fructose 6-phosphate metabolic process
glucose catabolic process
glycolytic process
response to glucose
fructose 1,6-bisphosphate metabolic process

Molecular Function

6-phosphofructokinase activity
protein binding
ATP binding
AMP binding
kinase binding

Cellular Component

extracellular region
cytosol
6-phosphofructokinase complex
membrane
secretory granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000349048
Coding exons: 22
Length: 27326
Individuals with no LoFs: 125625
Homozygous LoFs: 0
Heterozygous LoFs: 84
Defined: 125709
p: 0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.68	403	510	0.791	0.0000346	5012
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00045	0.00043	rare
Latino/Admixed American	0.00036	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00035	0.00033	rare
Finnish	0.00015	0.00014	rare
European (Non-Finnish)	0.00038	0.00037	rare
South Asian	0.00045	0.00042	rare
Other	0.00020	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.435

Intolerance Scores

LoFtool: 0.507
RVIS EVS: -1.3
RVIS percentile EVS: 4.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.953

Gene Damage Prediction

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