G6PC2
protein-codingglucose-6-phosphatase catalytic subunit 2, the group of Glucose 6-phosphatases, catalytic
Gene summary
This gene encodes an enzyme belonging to the glucose-6-phosphatase catalytic subunit family. These enzymes are part of a multicomponent integral membrane system that catalyzes the hydrolysis of glucose-6-phosphate, the terminal step in gluconeogenic and glycogenolytic pathways, allowing the release of glucose into the bloodstream. The family member encoded by this gene is found in pancreatic islets and does not exhibit phosphohydrolase activity, but it is a major target of cell-mediated autoimmunity in diabetes. Several alternatively spliced transcript variants of this gene have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to G6PC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021176.3. 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 | 2 | 2 | ||||
| missense | 35 | 1 | 36 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 36 | 2 | 1 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066999.1 | 5 | MANE Select | |
| Ensembl | ENSP00000364512.3 | 5 | MANE Select | |
| RefSeq | NP_001075155.1 | 4 | Standard | |
| Ensembl | ENSP00000282075.4 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Adipocytokine signaling pathway - Homo sapiens (human)
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Insulin resistance - Homo sapiens (human)
- Starch and sucrose metabolism - Homo sapiens (human)
Biological Process
- gluconeogenesis
- dephosphorylation
- glucose homeostasis
- regulation of insulin secretion
- glucose 6-phosphate metabolic process
Molecular Function
- glucose-6-phosphatase activity
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375363
- Coding exons
- 5
- Length
- 8756
- Individuals with no LoFs
- 125242
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 504
- Defined
- 125748
- p
- 0.00201
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.237 | 194 | 185 | 1.05 | 0.00000937 | 2339 |
| Missense (PolyPhen) | 61 | 56.01 | 1.0891 | 759 | ||
| Synonymous | -1.84 | 90 | 70.4 | 1.28 | 0.00000393 | 689 |
| Loss of Function | -1.09 | 21 | 16.2 | 1.29 | 8.57e-7 | 166 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0013 | 0.0013 | notable |
| Latino/Admixed American | 0.0021 | 0.0021 | notable |
| Ashkenazi Jewish | 0.0038 | 0.0038 | notable |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0028 | 0.0028 | notable |
| South Asian | 0.0010 | 0.0010 | notable |
| Other | 0.0033 | 0.0033 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- LoFtool
- 0.623
- RVIS EVS
- 0.69
- RVIS percentile EVS
- 85.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.633
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |