FBP1

Chr 9AR

fructose-bisphosphatase 1

Also known as: FBP

NCBI Gene: 2203ENSG00000165140UniProt: P09467OMIM: 611570

The protein catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate as a key regulatory enzyme in gluconeogenesis. Biallelic mutations cause fructose-1,6-bisphosphatase deficiency, an autosomal recessive disorder presenting with hypoglycemia and metabolic acidosis. The pathogenic mechanism involves loss of function leading to impaired glucose production during fasting states.

OMIMResearchSummary from RefSeq, OMIM, Mechanism
LOFmechanismARLOEUF 0.721 OMIM phenotype
Clinical Summary— FBP1
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Gene-Disease Validity (ClinGen)
fructose-1,6-bisphosphatase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
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ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 62 VUS of 300 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.079
Z-score 2.25
OE 0.32 (0.15–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.74Z-score
OE missense 0.85 (0.75–0.97)
170 obs / 199.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.15–0.72)
0≤0.351.4
Missense OE0.85 (0.75–0.97)
0≤0.61.4
Synonymous OE1.20
0≤1.21.6
LoF obs/exp: 4 / 12.7Missense obs/exp: 170 / 199.4Syn Z: -1.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFBP1-related fructose-1,6-bisphosphatase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.72top 25%
LOF
0.2679th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic22
VUS62
Likely Benign149
Benign14
Conflicting10
39
Pathogenic
22
Likely Pathogenic
62
VUS
149
Likely Benign
14
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
2
16
0
39
Likely Pathogenic
9
7
6
0
22
VUS
1
47
12
2
62
Likely Benign
0
2
51
96
149
Benign
0
1
13
0
14
Conflicting
—10
Total31599898296

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FBP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Fructose-bisphosphatase1 (FBP1) alleviates experimental osteoarthritis by regulating Protein crumbs homolog 3 (CRB3)
Wang Z et al.·Arthritis Res Ther
2023
Deubiquitination of FBP1 by USP7 blocks FBP1-DNMT1 interaction and decreases the sensitivity of pancreatic cancer cells to PARP inhibitors
Cheng X et al.·Mol Oncol
2022
Down-regulation of FBP1 in lung adenocarcinoma cells promotes proliferation and invasion through SLUG mediated epithelial mesenchymal transformation
Wang Z et al.·Transl Cancer Res
2023
Fructose 1,6-bisphosphatase 1 is a potential biomarker affecting the malignant phenotype and aerobic glycolysis in glioblastoma
Lu W et al.·PeerJ
2025
The Ancient Drug Salicylate Indirectly Targets Fructose-1,6-Bisphosphatase to Suppress Liver Glucose Production in Diet-Induced Obese Mice
Nisr RB et al.·Acta Physiol (Oxf)
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Fusobacterium nucleatum alleviates alcohol-associated liver disease through mannose-mediated elevation of Fbp1 and modulation of gut microbiota.
Shu H et al.·J Hepatol
2026
The RNA molecule or the transcription process: which is critical in the regulation of fbp1 gene activation mediated by metabolic stress-induced lncRNA (mlonRNA) in fission yeast.
Oe H et al.·Biochem Biophys Res Commun
2026
Correction: Retraction: Downregulation of FBP1 promotes tumor metastasis and indicates poor prognosis in gastric cancer via regulating epithelial-mesenchymal transition.
PLOS One Editors.·PLoS One
2026Open Access
Improving erectile function in diabetic male mice by rescuing depalmitoylated FBP1 to reduce cavernosal lactate.
Xiao M et al.·Nat Commun
2026Open Access
FBP1/HIF-1α Axis mediates macrophage metabolic reprogramming and serves as diagnostic biomarkers in atherosclerosis.
Li M et al.·Int Immunopharmacol
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients