PFKFB1
protein-coding6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1, the group of 6-phosphofructo-2-kinases/fructose-2,6-biphosphatases
Gene summary
This gene encodes a member of the family of bifunctional 6-phosphofructo-2-kinase:fructose-2,6-biphosphatase enzymes. The enzyme forms a homodimer that catalyzes both the synthesis and degradation of fructose-2,6-biphosphate using independent catalytic domains. Fructose-2,6-biphosphate is an activator of the glycolysis pathway and an inhibitor of the gluconeogenesis pathway. Consequently, regulating fructose-2,6-biphosphate levels through the activity of this enzyme is thought to regulate glucose homeostasis. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2012]
- PFRX
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~65.6 kbGenCC 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 PFKFB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002625.4. 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 | 5 | ||||
| missense | 67 | 5 | 72 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 16 | 16 | ||||
| Total | 0 | 0 | 89 | 5 | 0 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002616.2 | 14 | MANE Select | |
| Ensembl | ENSP00000364145.3 | 14 | MANE Select | |
| RefSeq | NP_001258733.1 | 14 | Standard | |
| RefSeq | NP_001258734.1 | 13 | 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)
- Glucagon signaling pathway - Homo sapiens (human)
- Fructose intolerance, hereditary
- Fructose and Mannose Degradation
Biological Process
- fructose metabolic process
- fructose 2,6-bisphosphate metabolic process
- gluconeogenesis
- glycolytic process
- dephosphorylation
Molecular Function
- 6-phosphofructo-2-kinase activity
- fructose-2,6-bisphosphate 2-phosphatase activity
- protein binding
- ATP binding
- kinase binding
Cellular Component
- cytosol
- 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375006
- Coding exons
- 14
- Length
- 65574
- Individuals with no LoFs
- 125692
- Homozygous LoFs
- 19
- Heterozygous LoFs
- 36
- Defined
- 125747
- p
- 0.000219
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0481 | 192 | 190 | 1.01 | 0.0000152 | 3083 |
| Missense (PolyPhen) | 87 | 99.726 | 0.87239 | 1508 | ||
| Synonymous | 0.578 | 60 | 66.0 | 0.909 | 0.00000478 | 891 |
| Loss of Function | 1.97 | 14 | 24.5 | 0.571 | 0.00000222 | 344 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.00086 | notable |
| Latino/Admixed American | 0.00030 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00026 | 0.00018 | rare |
| European (Non-Finnish) | 0.00031 | 0.00022 | rare |
| South Asian | 0.00011 | 0.000065 | rare |
| Other | 0.00045 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate.;
Recessive Scores
- pRec
- 0.235
Intolerance Scores
- LoFtool
- 0.448
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.700
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |