NDST1

Chr 5AR

N-deacetylase and N-sulfotransferase 1

Also known as: HSST, MRT46, NST1

NCBI Gene: 3340ENSG00000070614UniProt: P52848

This gene encodes a member of the heparan sulfate/heparin GlcNAc N-deacetylase/ N-sulfotransferase family. The encoded enzyme is a type II transmembrane protein that resides in the Golgi apparatus. The encoded protein catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to nitrogen of glucosamine in heparan sulfate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 46MIM #616116
AR
100
ClinVar variants
1
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NDST1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 66 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.19LOEUF
pLI 1.000
Z-score 5.54
OE 0.07 (0.03–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.92Z-score
OE missense 0.65 (0.59–0.71)
353 obs / 545.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.07 (0.03–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.59–0.71)
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.1.01
0≤1.21.6
LoF obs/exp: 3 / 41.5Missense obs/exp: 353 / 545.1Syn Z: -0.13

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS66
Likely Benign30
Benign2
Conflicting1
1
Pathogenic
66
VUS
30
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
63
3
0
66
Likely Benign
0
2
11
17
30
Benign
0
0
0
2
2
Conflicting
—1
Total0651519100

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

View in ClinVar →

Protein Context — Lollipop Plot

NDST1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NDST1-related intellectual disability with or without seizures

moderate
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 46

MIM #616116

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss of NDST1 N-sulfotransferase activity is associated with autosomal recessive intellectual disability.
Khosrowabadi E et al.·Hum Mol Genet
2024
NDST1 missense mutations in autosomal recessive intellectual disability.
Reuter MS et al.·Am J Med Genet A
2014
Heparan sulfate N-deacetylase/N-sulfotransferase-1 regulates glioblastoma cell migration and invasion.
Spyrou A et al.·Matrix Biol
2025
A dominant negative splice variant of the heparan sulfate biosynthesis enzyme NDST1 reduces heparan sulfate sulfation.
Missaghian P et al.·Glycobiology
2022
Integrated clinical and omics approach to rare diseases: novel genes and oligogenic inheritance in holoprosencephaly.
Kim A et al.·Brain
2019
N-Sulfated Heparan Sulfate Promotes Reelin Signaling as a Co-receptor.
Pan L et al.·J Am Chem Soc
2025
Identification of NDST1 variant as a cause of intellectual disability.
Rosales-Castillo A et al.·Med Clin (Barc)
2024Case report
Methylation-regulated miR-149 modulates chemoresistance by targeting GlcNAc N-deacetylase/N-sulfotransferase-1 in human breast cancer.
He DX et al.·FEBS J
2014
Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth.
El Ghazal R et al.·Neoplasia
2016
Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants.
Khan A et al.·Genes (Basel)
2020Case report
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