FBP2

protein-coding

fructose-bisphosphatase 2, the group of Fructose-1,6-bisphosphatases

Gene summary

This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003837.4

Inheritance

ClinVar variants

U:64B:6

Top phenotype

Leukodystrophy, childhood-onset, remitting

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr9:94,558,720-94,593,824

External References & Databases

Ensembl (ENSG00000130957)

Transcript & Mutation Effects

hg38 • Region Span ~35.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukodystrophy, childhood-onset, remittingMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859246

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Leukodystrophy, childhood-onset, remittingAD

Manifestation: Biochemical; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33977262

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBP2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 11

Leukodystrophy, childhood-onset, remittingTotal: 6

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003837.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			64 clinvar	1 clinvar	3 clinvar	68
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	64	2	4	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003837.4	RefSeq	NP_003828.2	7	MANE Select
ENST00000375337.4	Ensembl	ENSP00000364486.3	7	MANE Select
ENST00001134324.1	Ensembl	ENSP00000810528.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycolysis / Gluconeogenesis - Homo sapiens (human)
Fructose and mannose metabolism - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
Pentose phosphate pathway - Homo sapiens (human)
Insulin signaling pathway - Homo sapiens (human)

Biological Process

sucrose biosynthetic process
fructose metabolic process
fructose 6-phosphate metabolic process
gluconeogenesis
dephosphorylation

Molecular Function

protein binding
fructose 1,6-bisphosphate 1-phosphatase activity
identical protein binding
metal ion binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
plasma membrane
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375337
Coding exons: 7
Length: 35074
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.190	201	209	0.963	0.0000124	2172
Missense (PolyPhen)		65	75.015	0.8665		787
Synonymous	0.0346	92	92.4	0.995	0.00000626	704
Loss of Function	1.59	8	14.5	0.550	6.95e-7	185

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate. {ECO:0000269|PubMed:17350621, ECO:0000269|PubMed:18214967}.;

Recessive Scores

pRec: 0.233

Intolerance Scores

LoFtool: 0.462
RVIS EVS: 0.49
RVIS percentile EVS: 79.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.981

Gene Damage Prediction

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