HGSNAT

Chr 8AR

heparan-alpha-glucosaminide N-acetyltransferase

Also known as: HGNAT, MPS3C, RP73, TMEM76

This protein functions as a lysosomal acetyltransferase essential for heparan sulfate degradation. Mutations cause mucopolysaccharidosis type IIIC (Sanfilippo syndrome C), a lysosomal storage disorder resulting from impaired heparan sulfate breakdown, and retinitis pigmentosa 73, both inherited in an autosomal recessive pattern. The pathogenic mechanism involves deficient enzymatic activity leading to toxic accumulation of undegraded heparan sulfate in lysosomes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.732 OMIM phenotypes
Clinical SummaryHGSNAT
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Gene-Disease Validity (ClinGen)
inherited retinal dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
0.73LOEUF
pLI 0.000
Z-score 2.85
OE 0.49 (0.340.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.71Z-score
OE missense 0.89 (0.810.98)
283 obs / 318.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.340.73)
00.351.4
Missense OE0.89 (0.810.98)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 18 / 36.6Missense obs/exp: 283 / 318.5Syn Z: 0.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHGSNAT-related mucopolysaccharidosis type IIICLOFAR
limitedHGSNAT-related retinitis pigmentosaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.6151th %ile
LOF
0.3066th %ile

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HGSNAT · 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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