GNPDA2

Chr 4

glucosamine-6-phosphate deaminase 2

Also known as: GNP2, SB52

NCBI Gene: 132789ENSG00000163281UniProt: Q8TDQ7

The protein encoded by this gene is an allosteric enzyme that catalyzes the reversible reaction converting D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium. Variations of this gene have been reported to be associated with influencing body mass index and susceptibility to obesity. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

0
ClinVar variants
0
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— GNPDA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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.
0.95LOEUF
pLI 0.008
Z-score 1.68
OE 0.45 (0.24–0.95)
Tolerant

Typical tolerance to LoF variation

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.
1.09Z-score
OE missense 0.74 (0.63–0.87)
106 obs / 142.6 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.0.45 (0.24–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.63–0.87)
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.0.99
0≤1.21.6
LoF obs/exp: 5 / 11.0Missense obs/exp: 106 / 142.6Syn Z: 0.06

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GNPDA2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population.
Hotta K et al.·J Hum Genet
2009
Genetic risk score for gestational weight gain.
Mikołajczyk-Stecyna J et al.·Eur J Obstet Gynecol Reprod Biol
2024
A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.
Bradfield JP et al.·Hum Mol Genet
2019Meta-analysis
Associations of obesity susceptibility loci with hypertension in Chinese children.
Xi B et al.·Int J Obes (Lond)
2013
Genetic risk profiles for a childhood with severe overweight.
González JR et al.·Pediatr Obes
2014
Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals.
Kilpeläinen TO et al.·Am J Clin Nutr
2011Meta-analysis
Deployment of Label-Free Quantitative Olfactory Proteomics to Detect Cerebrospinal Fluid Biomarker Candidates in Synucleinopathies.
Lachén-Montes M et al.·Methods Mol Biol
2019
Expression of obesity-related genes in human spermatozoa affects the outcomes of reproductive treatments.
Pereira SC et al.·F S Sci
2021
[Impact of obesity-related gene polymorphism on risk of obesity and metabolic disorder in childhood].
Zhang M et al.·Zhonghua Yu Fang Yi Xue Za Zhi
2014
Fine Mapping and Identification of BMI Loci in African Americans.
Gong J et al.·Am J Hum Genet
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms.
Lachén-Montes M et al.·Biomolecules
2024🔓 Open AccessFunctional
CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis.
Gutierrez-Aguilar R et al.·Front Nutr
2021🔓 Open Access
GNPDA2 Gene Affects Adipogenesis and Alters the Transcriptome Profile of Human Adipose-Derived Mesenchymal Stem Cells.
Wu L et al.·Int J Endocrinol
2019🔓 Open Access
[Association between rs10938397 polymorphism in GNPDA2 and obesity in children at different stages of development].
Gao LW et al.·Zhonghua Liu Xing Bing Xue Za Zhi
2018
Identification, expression and variation of the GNPDA2 gene, and its association with body weight and fatness traits in chicken.
Ouyang H et al.·PeerJ
2016🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools