FBP1

Chr 9AR

fructose-bisphosphatase 1

Also known as: FBP

NCBI Gene: 2203 ENSG00000165140 UniProt: P09467 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, Mechanism

Fructose-1,6-bisphosphatase 1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. Fructose-1,6-diphosphatase deficiency is associated with hypoglycemia and metabolic acidosis. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.721 OMIM phenotype

Clinical Summary— FBP1

🧬

Gene-Disease Validity (ClinGen)

fructose-1,6-bisphosphatase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

💊

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 OE?0.32 (0.15–0.72)

0≤0.351.4

Missense OE?0.85 (0.75–0.97)

0≤0.61.4

Synonymous OE?1.20

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

This gene — mechanism propensity

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

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.