G6PC1

Chr 17AR

glucose-6-phosphatase catalytic subunit 1

Also known as: G6PC, G6PT, G6Pase, GSD1, GSD1a

Glucose-6-phosphatase hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum and is the key enzyme in homeostatic regulation of blood glucose levels through the terminal step of glycogenolysis and gluconeogenesis. Mutations cause glycogen storage disease type Ia (von Gierke disease), an autosomal recessive metabolic disorder characterized by severe hypoglycemia and accumulation of glycogen and fat in the liver and kidneys. The gene shows low constraint to loss-of-function variation, consistent with the recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.011 OMIM phenotype
Clinical SummaryG6PC1
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Gene-Disease Validity (ClinGen)
glycogen storage disease I · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
120 unique Pathogenic / Likely Pathogenic· 136 VUS of 500 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — G6PC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.54
OE 0.60 (0.371.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.27Z-score
OE missense 0.95 (0.841.07)
182 obs / 192.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.371.01)
00.351.4
Missense OE0.95 (0.841.07)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 10 / 16.8Missense obs/exp: 182 / 192.4Syn Z: -1.58
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveG6PC1-related glycogen storage diseaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.6932th %ile
LOF
0.2582th %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

500 submitted variants in ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic64
VUS136
Likely Benign206
Benign18
Conflicting17
56
Pathogenic
64
Likely Pathogenic
136
VUS
206
Likely Benign
18
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
39
9
8
0
56
Likely Pathogenic
29
34
1
0
64
VUS
2
97
34
3
136
Likely Benign
1
17
59
129
206
Benign
0
1
17
0
18
Conflicting
17
Total71158119132497

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

View in ClinVar →

Protein Context — Lollipop Plot

G6PC1 · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC