PFKFB2

protein-coding

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2, the group of 6-phosphofructo-2-kinases/fructose-2,6-biphosphatases

Gene summary

The protein encoded by this gene is 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, and a fructose-2,6-biphosphatase activity that catalyzes the degradation of fructose-2,6-bisphosphate. This protein regulates fructose-2,6-bisphosphate levels in the heart, while a related enzyme encoded by a different gene regulates fructose-2,6-bisphosphate levels in the liver and muscle. This enzyme functions as a homodimer. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006212.2

Inheritance

—

ClinVar variants

U:65B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr1:207,034,366-207,081,024

External References & Databases

Ensembl (ENSG00000123836)

Transcript & Mutation Effects

hg38 • Region Span ~46.7 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 PFKFB2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 57

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006212.2. 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			4
missense			58 clinvar	1 clinvar		59
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	65	1	0	66

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006212.2	RefSeq	NP_006203.2	14	MANE Select
ENST00000367080.8	Ensembl	ENSP00000356047.3	14	MANE Select
NM_001018053.2	RefSeq	NP_001018063.1	14	Standard
ENST00000367079.3	Ensembl	ENSP00000356046.2	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)
Thyroid hormone signaling pathway - Homo sapiens (human)
Focal Adhesion-PI3K-Akt-mTOR-signaling pathway
Aminosugars metabolism

Biological Process

fructose metabolic process
fructose 2,6-bisphosphate metabolic process
glucose catabolic process
lactate metabolic process
glycolytic process

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367080
Coding exons: 14
Length: 31569
Individuals with no LoFs: 125681
Homozygous LoFs: 0
Heterozygous LoFs: 67
Defined: 125748
p: 0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.45	183	303	0.604	0.0000180	3322
Missense (PolyPhen)		81	176.31	0.45943		1853
Synonymous	0.0105	110	110	0.999	0.00000637	944
Loss of Function	2.54	16	31.3	0.510	0.00000169	353

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00089	0.00089	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00036	0.00036	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: 0.173

Intolerance Scores

LoFtool: 0.188
RVIS EVS: -0.67
RVIS percentile EVS: 15.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.961

Gene Damage Prediction

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