FBP1

Chr 9AR

fructose-bisphosphatase 1

Also known as: FBP

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 SummaryFBP1
🧬
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.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 62 VUS of 300 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.079
Z-score 2.25
OE 0.32 (0.150.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.74Z-score
OE missense 0.85 (0.750.97)
170 obs / 199.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.150.72)
00.351.4
Missense OE0.85 (0.750.97)
00.61.4
Synonymous OE1.20
01.21.6
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

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 →