NDST1

Chr 5

N-deacetylase and N-sulfotransferase 1

Also known as: HSST, MRT46, NST1

NCBI Gene: 3340 ENSG00000070614 UniProt: P52848

This protein is a bifunctional enzyme that catalyzes both N-deacetylation and N-sulfation of glucosamine in heparan sulfate biosynthesis within the Golgi apparatus. Mutations cause autosomal recessive intellectual developmental disorder 46. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.19), indicating that biallelic pathogenic variants are required for disease manifestation.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal recessive 46

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.07 (0.03–0.19)

0≤0.351.4

Missense OE?0.65 (0.59–0.71)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 3 / 41.5Missense obs/exp: 353 / 545.1Syn Z: -0.13

Background carrier burden — how many people carry a rare variant somewhere in NDST1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

887 rare PASS variants

Rare truncating (LoF)

1 in 4,000

67 rare PASS variants

Rare synonymous (reference)

1 in 57

521 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NDST1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 87	1 in 3,400
South Asian	~43k	1 in 74	≈ 1 in 11,000
Remaining (unassigned)	~30k	1 in 78	≈ 1 in 15,000
European (Finnish)	~27k	1 in 240	1 in 4,400
Admixed American	~22k	1 in 71	≈ 1 in 5,600
African / African American	~21k	1 in 71	1 in 3,500
East Asian	~20k	1 in 63	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 59	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓