G6PC2

Chr 2

glucose-6-phosphatase catalytic subunit 2

Also known as: IGRP

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]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 1.80
Clinical SummaryG6PC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 VUS of 41 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.80LOEUF
pLI 0.000
Z-score -1.09
OE 1.29 (0.911.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.24Z-score
OE missense 1.05 (0.931.18)
194 obs / 184.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.29 (0.911.80)
00.351.4
Missense OE?1.05 (0.931.18)
00.61.4
Synonymous OE?1.28
01.21.6
LoF obs/exp: 21 / 16.2Missense obs/exp: 194 / 184.9Syn Z: -1.84

This gene — mechanism propensity

DN
0.6841th %ile
GOF
0.5955th %ile
LOF
0.3455th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

41 submitted variants in ClinVar

Classification Summary

VUS36
Likely Benign2
Benign3
36
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
35
0
0
36
Likely Benign
0
0
0
2
2
Benign
0
2
1
0
3
Total1371241

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap G6PC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

G6PC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →