PFKFB3

protein-coding

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, the group of 6-phosphofructo-2-kinases/fructose-2,6-biphosphatases|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

MANE transcript

NM_004566.4

Inheritance

—

ClinVar variants

U:78B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr10:6,144,934-6,254,644

External References & Databases

Ensembl (ENSG00000170525)

Transcript & Mutation Effects

hg38 • Region Span ~109.7 kb

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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 PFKFB3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004566.4. 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			5 clinvar	2 clinvar	1 clinvar	8
missense			70 clinvar			70
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	78	2	1	81

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004566.4	RefSeq	NP_004557.1	15	MANE Select
ENST00000379775.9	Ensembl	ENSP00000369100.4	15	MANE Select
NM_001145443.3	RefSeq	NP_001138915.1	15	Standard
NM_001282630.3	RefSeq	NP_001269559.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fructose and mannose metabolism - Homo sapiens (human)
HIF-1 signaling pathway - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
AMP-activated Protein Kinase (AMPK) Signaling
Focal Adhesion-PI3K-Akt-mTOR-signaling pathway

Biological Process

fructose metabolic process
fructose 2,6-bisphosphate metabolic process
brain development
dephosphorylation
positive regulation of glycolytic process

Molecular Function

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

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379775
Coding exons: 15
Length: 90615
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.66	262	349	0.750	0.0000241	3402
Missense (PolyPhen)		77	149.45	0.51522		1492
Synonymous	-0.801	160	148	1.08	0.0000109	996
Loss of Function	3.83	7	29.4	0.238	0.00000125	350

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.348

Intolerance Scores

LoFtool: 0.125
RVIS EVS: -1.4
RVIS percentile EVS: 4.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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