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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PFKFB1
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1
Chromosome X · Xp11.21
NCBI Gene: 5207Ensembl: ENSG00000158571.12HGNC: HGNC:8872UniProt: I1Z9G4
30PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein binding6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complexidentical protein bindingfructose-2,6-bisphosphate 2-phosphatase activityhypertensionRomano-Ward syndromefamilial long QT syndromediabetes mellitus
✦AI Summary

PFKFB1 encodes a bifunctional enzyme that catalyzes both the synthesis and degradation of fructose-2,6-bisphosphate (F-2,6-BP), a critical regulator of glycolysis 12. This enzyme controls glycolytic flux by modulating the steady-state concentration of F-2,6-BP, which allosterically activates 6-phosphofructo-1-kinase, a rate-limiting enzyme in glycolysis 2. The gene is located on chromosome X at position Xp11.21, approximately 250 kb telomeric to the ALAS2 gene 3. PFKFB1 expression is transcriptionally regulated by SREBP-1a through a sterol regulatory element in its promoter, mediating postprandial activation in response to glucose and insulin 1. Multiple mRNA variants exist, including a novel fetal liver-specific isoform that may facilitate the metabolic transition from fetal to adult liver metabolism 4. In disease contexts, PFKFB1 has been implicated in multiple myeloma progression through the STAT3-PFKFB1 pathway 5. While PFKFB family members are considered potential therapeutic targets for cancer treatment due to their role in tumor cell glycolysis 67, PFKFB1's specific role in cancer metabolism requires further investigation.

Sources cited
1
PFKFB1 catalyzes synthesis and degradation of fructose-2,6-bisphosphate and is transcriptionally regulated by SREBP-1a
PMID: 16614080
2
PFKFB enzymes control glycolytic flux by regulating fructose-2,6-bisphosphate levels which activate 6-phosphofructo-1-kinase
PMID: 16912547
3
PFKFB1 gene is located on chromosome X at position Xp11.21, approximately 250 kb telomeric to ALAS2
PMID: 9119406
4
Novel PFKFB1 mRNA variants exist in fetal liver that may modulate metabolic transition
PMID: 23291237
5
PFKFB1 is involved in multiple myeloma progression through STAT3-PFKFB1 pathway
PMID: 39025844
6
PFKFB family members are potential therapeutic targets for cancer treatment
PMID: 40639515
7
PFKFB enzymes are essential for glycolytic and oncogenic properties in tumor cells
PMID: 40538377
Disease Associationsⓘ20
hypertensionOpen Targets
0.13Weak
familial long QT syndromeOpen Targets
0.12Weak
Romano-Ward syndromeOpen Targets
0.12Weak
diabetes mellitusOpen Targets
0.08Suggestive
Miyoshi myopathyOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
colorectal cancerOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
Neoplasm of the lungOpen Targets
0.02Suggestive
prostate cancerOpen Targets
0.02Suggestive
Acute hepatic failureOpen Targets
0.01Suggestive
COVID-19Open Targets
0.01Suggestive
rheumatoid arthritisOpen Targets
0.01Suggestive
papillary thyroid carcinomaOpen Targets
0.01Suggestive
melanomaOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
lumbar disc degenerationOpen Targets
0.01Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PRKACBProtein interaction99%PFKMProtein interaction98%HK2Protein interaction98%PRKACGProtein interaction97%MPIProtein interaction96%TIGARProtein interaction96%
Tissue Expression6 tissues
Liver
100%
Brain
1%
Lung
1%
Bone Marrow
0%
Heart
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
PFKFB1PRKACBPFKMHK2PRKACGMPITIGAR
PROTEIN STRUCTURE
Preparing viewer…
PDB1K6M · 2.40 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.56–0.98]
RankingsWhere PFKFB1 stands among ~20K protein-coding genes
  • #12,001of 20,598
    Most Researched30
  • #9,299of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedPFKFB1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway.
PMID: 39025844
Cell Death Dis · 2024
1.00
2
Potential applications of PFKFB in cancer treatment strategies.
PMID: 40639515
Int J Biol Macromol · 2025
0.90
3
Regulatory mechanisms of PFKFB2 in glycolysis and tumor metabolism: implications for cancer therapy.
PMID: 40538377
Carcinogenesis · 2025
0.80
4
Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene promoter.
PMID: 16614080
Endocrinology · 2006
0.70
5
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis.
PMID: 16912547
Curr Opin Clin Nutr Metab Care · 2006
0.60