FBP1

fructose-bisphosphatase 1, the group of Fructose-1,6-bisphosphatases

Basic information

Region (hg38): 9:94603132-94640249

Previous symbols: [ "FBP" ]

Links

ENSG00000165140 ∙ NCBI:2203 ∙ OMIM:611570 ∙ HGNC:3606 ∙ Uniprot:P09467 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fructose-1,6-bisphosphatase deficiency (Definitive), mode of inheritance: AR
• fructose-1,6-bisphosphatase deficiency (Strong), mode of inheritance: AR
• fructose-1,6-bisphosphatase deficiency (Strong), mode of inheritance: AR
• fructose-1,6-bisphosphatase deficiency (Strong), mode of inheritance: AR
• fructose-1,6-bisphosphatase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fructose-1,6-bisphosphatase deficiency	AR	Biochemical	The condition may be lethal in the perinatal period, but prompt recognition and treatment of lactic acidosis and hypoglycemia (eg, with IV/oral glucose, sodium bicarbonate) can be effective	Biochemical	4193749; 4335192; 4341454; 4341015; 175754; 2347355; 1995492; 9382095; 12126934; 17705024; 19259699; 20096900; 22158280

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBP1 gene.

• Fructose-biphosphatase deficiency (159 variants)
• not provided (45 variants)
• not specified (29 variants)
• Inborn genetic diseases (9 variants)
• Abnormality of acid-base homeostasis;Impaired gluconeogenesis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	37	3	41
missense	2	10	38	4	1	55
nonsense	4	1				5
start loss	1					1
frameshift	9	3	1			13
inframe indel		1				1
splice donor/acceptor (+/-2bp)	3	1				4
splice region		1	4	7	1	13
non coding			8	19	11	38
Total	19	16	48	60	15

Highest pathogenic variant AF is 0.0000197

Variants in FBP1

This is a list of pathogenic ClinVar variants found in the FBP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-94603132-CT-C		Fructose-biphosphatase deficiency	Benign/Likely benign (Jun 29, 2018)
9-94603229-G-A		Fructose-biphosphatase deficiency	Uncertain significance (Jan 13, 2018)
9-94603254-G-A		Fructose-biphosphatase deficiency	Uncertain significance (Jan 13, 2018)
9-94603260-A-C		Fructose-biphosphatase deficiency	Conflicting classifications of pathogenicity (Oct 27, 2020)
9-94603360-G-A		not specified • Fructose-biphosphatase deficiency	Benign (Aug 10, 2021)
9-94603377-G-A		not specified	Likely benign (Apr 04, 2016)
9-94603385-TG-T		Fructose-biphosphatase deficiency	Uncertain significance (Sep 07, 2022)
9-94603389-C-A		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
9-94603390-A-G		Fructose-biphosphatase deficiency	Likely benign (May 19, 2023)
9-94603401-C-T		Fructose-biphosphatase deficiency	Uncertain significance (Jan 12, 2018)
9-94603412-A-G		Fructose-biphosphatase deficiency	Pathogenic/Likely pathogenic (Dec 06, 2023)
9-94603413-G-T		Fructose-biphosphatase deficiency	Uncertain significance (Feb 05, 2022)
9-94603414-G-A		Fructose-biphosphatase deficiency	Likely benign (Jul 07, 2023)
9-94603417-C-T		Fructose-biphosphatase deficiency	Likely benign (Dec 04, 2023)
9-94603420-G-A		Fructose-biphosphatase deficiency	Likely benign (Oct 19, 2023)
9-94603420-G-C		Fructose-biphosphatase deficiency	Likely benign (Dec 18, 2023)
9-94603421-A-G		Fructose-biphosphatase deficiency	Uncertain significance (Oct 14, 2021)
9-94603422-G-C		not specified	Likely benign (Mar 06, 2014)
9-94603426-G-A		Fructose-biphosphatase deficiency	Likely benign (Jun 03, 2023)
9-94603427-T-C		Fructose-biphosphatase deficiency	Uncertain significance (Dec 27, 2019)
9-94603428-C-T		Fructose-biphosphatase deficiency	Uncertain significance (Dec 20, 2021)
9-94603429-G-A		Fructose-biphosphatase deficiency	Likely benign (Sep 20, 2023)
9-94603431-CG-C		Fructose-biphosphatase deficiency	Conflicting classifications of pathogenicity (Jan 16, 2024)
9-94603432-G-A		Fructose-biphosphatase deficiency	Likely benign (Dec 26, 2023)
9-94603436-G-GA		Fructose-biphosphatase deficiency	Pathogenic (May 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBP1	protein_coding	protein_coding	ENST00000415431	7	37117

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0791	0.911	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.740	170	199	0.853	0.0000110	2189
Missense in Polyphen		50	73.921	0.67639		787
Synonymous	-1.45	100	83.2	1.20	0.00000532	673
Loss of Function	2.25	4	12.7	0.316	5.40e-7	174

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000114	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.000114	0.000109
South Asian	0.000131	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000269|PubMed:16497803, ECO:0000269|PubMed:18375435, ECO:0000269|PubMed:22517657}.
• Disease: DISEASE: Fructose-1,6-bisphosphatase deficiency (FBP1D) [MIM:229700]: An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, and episodes of hypoglycemia and metabolic acidosis that can be lethal in newborn infants or young children. {ECO:0000269|PubMed:12126934, ECO:0000269|PubMed:25601412, ECO:0000269|PubMed:9382095}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Fructose and mannose metabolism - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Pentose Phosphate Pathway;Fructose intolerance, hereditary;Gluconeogenesis;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Transaldolase deficiency;Fructose and Mannose Degradation;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Fructosuria;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Angiopoietin Like Protein 8 Regulatory Pathway;Glycolysis and Gluconeogenesis;Metabolism of carbohydrates;Fructose Mannose metabolism;Glycolysis Gluconeogenesis;Metabolism;Pentose phosphate cycle;gluconeogenesis;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.507

Intolerance Scores

• loftool: 0.460
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.374
• hipred: Y
• hipred_score: 0.754
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fbp1

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;sucrose biosynthetic process;fructose metabolic process;fructose 6-phosphate metabolic process;gluconeogenesis;regulation of gluconeogenesis;dephosphorylation;negative regulation of cell growth;fructose 1,6-bisphosphate metabolic process;cellular response to drug;negative regulation of glycolytic process;negative regulation of Ras protein signal transduction;protein homotetramerization;cellular response to magnesium ion
• Cellular component: nucleus;cytoplasm;cytosol;extracellular exosome
• Molecular function: protein binding;AMP binding;fructose 1,6-bisphosphate 1-phosphatase activity;identical protein binding;metal ion binding;monosaccharide binding