NDST3
protein-codingN-deacetylase and N-sulfotransferase 3, the group of Sulfotransferases, membrane bound
Gene summary
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. This monomeric bifunctional enzyme catalyzes the N-deacetylation and N-sulfation of N-acetylglucosamine residues in heparan sulfate and heparin, which are the initial chemical modifications required for the biosynthesis of the functional oligosaccharide sequences that define the specific ligand binding activities of heparan sulfate and heparin. [provided by RefSeq, Nov 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~225.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NDST3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004784.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 76 | 1 | 77 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 79 | 1 | 0 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004775.1 | 13 | MANE Select | |
| Ensembl | ENSP00000296499.5 | 13 | MANE Select | |
| Ensembl | ENSP00000522930.1 | 13 | Standard | |
| Ensembl | ENSP00000522930.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human)
- Metapathway biotransformation Phase I and II
- Metabolism of carbohydrates
- HS-GAG biosynthesis
- Heparan sulfate/heparin (HS-GAG) metabolism
Biological Process
- heparan sulfate proteoglycan biosynthetic process
- heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process
- heparin biosynthetic process
Molecular Function
- [heparan sulfate]-glucosamine N-sulfotransferase activity
- deacetylase activity
- heparan sulfate sulfotransferase activity
- heparan sulfate N-acetylglucosaminyltransferase activity
Cellular Component
- Golgi membrane
- cellular_component
- Golgi apparatus
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296499
- Coding exons
- 13
- Length
- 225031
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125748
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.59 | 300 | 456 | 0.659 | 0.0000222 | 5776 |
| Missense (PolyPhen) | 98 | 185.81 | 0.52742 | 2452 | ||
| Synonymous | 0.151 | 162 | 164 | 0.985 | 0.00000837 | 1624 |
| Loss of Function | 3.67 | 16 | 41.5 | 0.386 | 0.00000213 | 503 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential bifunctional enzyme that catalyzes both the N- deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Has high deacetylase activity but low sulfotransferase activity. {ECO:0000269|PubMed:9915799}.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.567
- RVIS EVS
- -1
- RVIS percentile EVS
- 8.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.292
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |