CHST4
protein-codingcarbohydrate sulfotransferase 4, the group of Sulfotransferases, membrane bound
Gene summary
This gene encodes an N-acetylglucosamine 6-O sulfotransferase. The encoded enzyme transfers sulfate from 3'phosphoadenosine 5'phospho-sulfate to the 6-hydroxyl group of N-acetylglucosamine on glycoproteins. This protein is localized to the Golgi and is involved in the modification of glycan structures on ligands of the lymphocyte homing receptor L-selectin. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.5 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 CHST4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001166395.2. 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 | 0 | |||||
| missense | 68 | 10 | 78 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 68 | 10 | 0 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001159867.1 | 1 | MANE Select | |
| Ensembl | ENSP00000441204.3 | 1 | MANE Select | |
| RefSeq | NP_005760.1 | 1 | Standard | |
| Ensembl | ENSP00000341206.5 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosaminoglycan biosynthesis - keratan sulfate - Homo sapiens (human)
- Metapathway biotransformation Phase I and II
- Post-translational protein modification
- Metabolism of proteins
- O-linked glycosylation of mucins
Biological Process
- carbohydrate metabolic process
- N-acetylglucosamine metabolic process
- protein sulfation
- sulfur compound metabolic process
- inflammatory response
Molecular Function
- N-acetylglucosamine 6-O-sulfotransferase activity
- sulfotransferase activity
Cellular Component
- Golgi membrane
- trans-Golgi network
- integral component of membrane
- intrinsic component of Golgi membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338482
- Coding exons
- 1
- Length
- 13514
- Individuals with no LoFs
- 125682
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 61
- Defined
- 125743
- p
- 0.000243
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.256 | 231 | 242 | 0.954 | 0.0000151 | 2539 |
| Missense (PolyPhen) | 102 | 109.74 | 0.92949 | 1077 | ||
| Synonymous | 0.599 | 87 | 94.4 | 0.922 | 0.00000551 | 776 |
| Loss of Function | -0.172 | 13 | 12.3 | 1.05 | 7.70e-7 | 107 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00038 | 0.00037 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000065 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues within mucin-associated glycans that ultimately serve as SELL ligands. SELL ligands are present in high endothelial cells (HEVs) and play a central role in lymphocyte homing at sites of inflammation. Participates in biosynthesis of the SELL ligand sialyl 6-sulfo Lewis X on receptors SPN/CD43, GLYCAM1 and MADCAM1. Also involved in biosynthesis of SELL ligand recognized by MECA-79 antibody. Plays a central role in lymphocyte trafficking during chronic inflammation. Has a catalytic preference for core 2- branched mucin-type O-glycans. Can use GlcNAcbeta1-6[Galbeta1- 3]GalNAc-pNP (core 2), GlcNAcbeta1-6ManOMe and GlcNAcbeta1-2Man oligosaccharide structures as acceptors. Has also activity toward core 3 of GlcNAcbeta1-3GalNAc-pNP. Its substrate specificity may be influenced by its subcellular location. {ECO:0000269|PubMed:10330415}.;
Recessive Scores
- pRec
- 0.134
Intolerance Scores
- LoFtool
- 0.151
- RVIS EVS
- -0.02
- RVIS percentile EVS
- 52.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.722
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |