NT5C2
Chr 10AR5'-nucleotidase, cytosolic II
Also known as: GMP, NT5B, PNT5, SPG45, SPG65, cN-II
The protein encoded by this gene is a cytosolic 5'-nucleotidase that dephosphorylates purine nucleoside monophosphates, particularly IMP and GMP, and also functions as a phosphotransferase to regulate cellular purine nucleotide pools. Mutations cause spastic paraplegia 45, an autosomal recessive disorder. The pathogenic mechanism likely involves disruption of purine metabolism leading to spasticity and progressive weakness of the lower limbs.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is dominant-negative.
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
NT5C2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools