PFKFB4

protein-coding

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4, the group of MicroRNA protein coding host genes|6-phosphofructo-2-kinases/fructose-2,6-biphosphatases

Gene summary

The protein encoded by this gene is one of four bifunctional kinase/phosphatases that regulate the concentration of the glycolytic byproduct fructose-2,6-bisphosphate (F2,6BP). The encoded protein is highly expressed in cancer cells and is induced by hypoxia. This protein is essential to the survival of cancer cells under conditions of hypoxia, because it increases the amount of F2,6BP and ATP at a time when the cell cannot produce much of them. This finding suggests that this protein may be a good target for disruption in cancer cells, hopefully imperiling their survival. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

MANE transcript

NM_004567.4

Inheritance

—

ClinVar variants

U:66

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr3:48,517,684-48,562,015

External References & Databases

Ensembl (ENSG00000114268)

Transcript & Mutation Effects

hg38 • Region Span ~44.3 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 PFKFB4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 59

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004567.4. 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			3 clinvar			3
missense			61 clinvar			61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	66	0	0	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004567.4	RefSeq	NP_004558.1	14	MANE Select
ENST00000232375.8	Ensembl	ENSP00000232375.3	14	MANE Select
NM_001317134.2	RefSeq	NP_001304063.1	15	Standard
NM_001317135.2	RefSeq	NP_001304064.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fructose and mannose metabolism - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
Focal Adhesion-PI3K-Akt-mTOR-signaling pathway
PI3K-AKT-mTOR - VitD3 Signalling
Aminosugars metabolism

Biological Process

fructose metabolic process
fructose 2,6-bisphosphate metabolic process
dephosphorylation
positive regulation of glycolytic process
carbohydrate phosphorylation

Molecular Function

6-phosphofructo-2-kinase activity
fructose-2,6-bisphosphate 2-phosphatase activity
ATP binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000232375
Coding exons: 14
Length: 44332
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.36	231	297	0.778	0.0000189	3072
Missense (PolyPhen)		116	135.48	0.85619		1391
Synonymous	0.853	106	118	0.900	0.00000742	906
Loss of Function	1.74	18	27.9	0.645	0.00000134	313

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00027	0.00026	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.304
RVIS EVS: -0.93
RVIS percentile EVS: 9.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.943

Gene Damage Prediction

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