POGLUT1
Chr 3ADARprotein O-glucosyltransferase 1
Also known as: C3orf9, CLP46, KDELCL1, KTELC1, LGMD2Z, LGMDR21, MDS010, MDSRP
The protein is a dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose to serine residues in extracellular EGF repeats of proteins including NOTCH2, acting as a positive regulator of Notch signaling during muscle development and early gastrulation. Mutations cause Dowling-Degos disease 4 (autosomal dominant) and limb-girdle muscular dystrophy type 21 (autosomal recessive), affecting skin and muscle systems respectively. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating intolerance to protein-disrupting mutations.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
POGLUT1 · 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