HGSNAT

Chr 8AR

heparan-alpha-glucosaminide N-acetyltransferase

NCBI Gene: 138050ENSG00000165102UniProt: Q68CP4

Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase

Primary Disease Associations & Inheritance

Mucopolysaccharidosis type IIIC (Sanfilippo C)MIM #252930
AR
Retinitis pigmentosa 73MIM #616544
AR
586
ClinVar variants
76
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HGSNAT
🧬
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.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 165 VUS of 586 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.73LOEUF
pLI 0.000
Z-score 2.85
OE 0.49 (0.34–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.71Z-score
OE missense 0.89 (0.81–0.98)
283 obs / 318.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.34–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 18 / 36.6Missense obs/exp: 283 / 318.5Syn Z: 0.05

ClinVar Variant Classifications

586 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic30
VUS165
Likely Benign338
Benign5
Conflicting2
46
Pathogenic
30
Likely Pathogenic
165
VUS
338
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
0
23
0
46
Likely Pathogenic
18
8
4
0
30
VUS
1
119
38
7
165
Likely Benign
0
2
164
172
338
Benign
0
1
4
0
5
Conflicting
—2
Total42130233179586

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

HGSNAT-related mucopolysaccharidosis type IIIC

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

HGSNAT-related retinitis pigmentosa

limited
ARUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mucopolysaccharidosis type IIIC (Sanfilippo C)

MIM #252930

Molecular basis of disorder known

Autosomal recessive

Retinitis pigmentosa 73

MIM #616544

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — HGSNAT
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.
Feldhammer M et al.·Hum Mutat
2009Review
Mucopolysaccharidosis type IIIC in chinese mainland: clinical and molecular characteristics of ten patients and report of six novel variants in the HGSNAT gene.
Liang Y et al.·Metab Brain Dis
2023Cohort
Sanfilippo syndrome: Overall review.
Andrade F et al.·Pediatr Int
2015Review
Glucosamine amends CNS pathology in mucopolysaccharidosis IIIC mouse expressing misfolded HGSNAT.
Pan X et al.·J Exp Med
2022Functional
A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT, the gene associated with Sanfilippo C mucopolysaccharidosis.
Schiff ER et al.·Am J Med Genet C Semin Med Genet
2020
Histological characterization of retinal degeneration in mucopolysaccharidosis type IIIC.
Ludwig J et al.·Exp Eye Res
2023
Glycosaminoglycans and mucopolysaccharidosis type III.
Jakobkiewicz-Banecka J et al.·Front Biosci (Landmark Ed)
2016Review
How close are we to therapies for Sanfilippo disease?
Gaffke L et al.·Metab Brain Dis
2018Review
Expanding the phenotypic and genotypic spectrum of patients with HGSNAT-related retinopathy.
da Palma MM et al.·Ophthalmic Genet
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools