G6PC3

Chr 17AR

glucose-6-phosphatase catalytic subunit 3

NCBI Gene: 92579ENSG00000141349UniProt: Q9BUM1

Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function

Primary Disease Associations & Inheritance

Dursun syndromeMIM #612541
AR
Neutropenia, severe congenital 4, autosomal recessiveMIM #612541
AR
705
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— G6PC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 138 VUS of 705 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.000
Z-score 1.47
OE 0.62 (0.39–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.70Z-score
OE missense 0.86 (0.75–0.98)
161 obs / 187.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.39–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.75–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20
0≤1.21.6
LoF obs/exp: 11 / 17.7Missense obs/exp: 161 / 187.8Syn Z: -1.37

ClinVar Variant Classifications

705 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic1
VUS138
Likely Benign55
3
Pathogenic
1
Likely Pathogenic
138
VUS
55
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
1
0
3
Likely Pathogenic
0
1
0
0
1
VUS
0
138
0
0
138
Likely Benign
0
9
5
41
55
Benign
0
0
0
0
0
Total1149641197

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

View in ClinVar →

Protein Context — Lollipop Plot

G6PC3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dursun syndrome

MIM #612541

Molecular basis of disorder known

Autosomal recessive

Neutropenia, severe congenital 4, autosomal recessive

MIM #612541

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review.
Lava SAG et al.·Paediatr Drugs
2024Review
Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency.
Zhen X et al.·J Clin Immunol
2024
A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations.
Banka S et al.·Orphanet J Rare Dis
2013Review
An Integrated Taxonomy for Monogenic Inflammatory Bowel Disease.
Bolton C et al.·Gastroenterology
2022
G6PC3 promotes genome maintenance and is a candidate mammary tumor suppressor.
Li X et al.·JCI Insight
2025
Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel.
Yeshareem L et al.·Eur J Haematol
2024
The metabolic basis of inherited neutropenias.
Oyarbide U et al.·Br J Haematol
2024Review
Novel G6PC3 Mutations in Patients with Congenital Neutropenia: Case Reports and Review of the Literature.
Maroufi SF et al.·Endocr Metab Immune Disord Drug Targets
2021Review
Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses.
Parisi X et al.·J Clin Pathol
2024Review
Neutropenia in primary immunodeficiency.
Sokolic R·Curr Opin Hematol
2013Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools