HS6ST2
protein-codingheparan sulfate 6-O-sulfotransferase 2, the group of Sulfotransferases, membrane bound
Gene summary
Heparan sulfate proteoglycans are ubiquitous components of the cell surface, extracellular matrix, and basement membranes, and interact with various ligands to influence cell growth, differentiation, adhesion, and migration. This gene encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS. Different family members and isoforms are thought to synthesize heparan sulfates with tissue-specific structures and functions. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~335.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0026724
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0026724
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HS6ST2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001394073.1. 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 | 3 | 13 | 1 | 17 | ||
| missense | 1 | 98 | 11 | 3 | 113 | |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 1 | 103 | 24 | 5 | 134 |
Highest pathogenic variant AF is 9.384173e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001381002.1 | 5 | MANE Select | |
| Ensembl | ENSP00000359870.3 | 5 | MANE Select | |
| RefSeq | NP_001070656.1 | 5 | Standard | |
| RefSeq | NP_001381003.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hs6st2 | Danio rerio | Structure: hyaloid vessel Quality: irregular spatial pattern abnormal |
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
- glycosaminoglycan biosynthetic process
- heparan sulfate proteoglycan biosynthetic process, enzymatic modification
Molecular Function
- heparan sulfate 6-O-sulfotransferase activity
Cellular Component
- Golgi membrane
- nucleoplasm
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000521489
- Coding exons
- 5
- Length
- 335380
- Individuals with no LoFs
- 124342
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 5
- Defined
- 124349
- p
- 0.0000281
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 187 | 249 | 0.751 | 0.0000186 | 4183 |
| Missense (PolyPhen) | 55 | 110.85 | 0.49616 | 1854 | ||
| Synonymous | 0.752 | 98 | 108 | 0.908 | 0.00000811 | 1304 |
| Loss of Function | 1.75 | 7 | 14.1 | 0.496 | 9.67e-7 | 243 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000081 | 0.000065 | rare |
| Latino/Admixed American | 0.000075 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000079 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000014 | 0.0000089 | rare |
| South Asian | 0.00011 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.526
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 69.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.111
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |