GNS
Chr 12ARglucosamine (N-acetyl)-6-sulfatase
Also known as: G6S
This gene encodes a lysosomal enzyme that catabolizes heparin, heparan sulfate, and keratan sulfate. Mutations cause mucopolysaccharidosis type IIID (Sanfilippo D syndrome), the rarest subtype of Sanfilippo syndrome, through autosomal recessive inheritance. Enzyme deficiency leads to accumulation of undegraded substrate in lysosomes, resulting in progressive neurodegeneration.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 22 | 0 | 3 | 0 | 25 |
Likely Pathogenic | 18 | 1 | 2 | 0 | 21 |
VUS | 3 | 102 | 9 | 8 | 122 |
Likely Benign | 0 | 2 | 112 | 105 | 219 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 1 | |||
| Total | 43 | 105 | 128 | 113 | 390 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GNS · 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