GNPDA2

Chr 4

glucosamine-6-phosphate deaminase 2

Also known as: GNP2, SB52

The protein catalyzes the reversible conversion of glucosamine-6-phosphate to fructose-6-phosphate and ammonium, regulating UDP-N-acetylglucosamine biosynthesis through the hexosamine pathway and influencing hyaluronan synthesis during tissue remodeling. GNPDA2 variants have been associated with body mass index regulation and obesity susceptibility, though the gene shows low constraint to loss-of-function variation. The inheritance pattern and specific neurological phenotypes associated with pathogenic variants in this gene are not well-established in the current literature.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.95
Clinical SummaryGNPDA2
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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.008
Z-score 1.68
OE 0.45 (0.240.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.09Z-score
OE missense 0.74 (0.630.87)
106 obs / 142.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.240.95)
00.351.4
Missense OE0.74 (0.630.87)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 5 / 11.0Missense obs/exp: 106 / 142.6Syn Z: 0.06
DN
0.77top 25%
GOF
0.76top 25%
LOF
0.2385th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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