HS6ST1
protein-codingheparan sulfate 6-O-sulfotransferase 1, the group of Sulfotransferases, membrane bound
Gene summary
The protein encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biological activities. This enzyme is a type II integral membrane protein and is responsible for 6-O-sulfation of heparan sulfate. This enzyme does not share significant sequence similarity with other known sulfotransferases. A pseudogene located on chromosome 1 has been found for this gene. [provided by RefSeq, Jul 2008]
- HS6ST
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018800
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0018555
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0013946
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: Unknown
Disease ID:MONDO:0013946
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: AD
Disease ID:MONDO:0013946
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Musculoskeletal; Neurologic
Intervention: Endocrine
Rationale: Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to male fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required
Comments: Relatively complex models of inheritance such as digenic inheritance and interaction with other related loci (eg, FGF8-network-associated genes) have been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HS6ST1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004807.3. 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 | 3 | 42 | 7 | 52 | ||
| missense | 93 | 6 | 1 | 100 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 98 | 48 | 8 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004798.3 | 2 | MANE Select | |
| Ensembl | ENSP00000259241.6 | 2 | MANE Select | |
| Ensembl | ENSP00000794747.1 | 2 | Standard | |
| Ensembl | ENSP00000794748.1 | 2 | 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
- angiogenesis
- glycosaminoglycan biosynthetic process
- heparan sulfate proteoglycan biosynthetic process, enzymatic modification
- lung alveolus development
- neuron development
Molecular Function
- sulfotransferase activity
- heparan sulfate 6-O-sulfotransferase activity
Cellular Component
- Golgi membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000259241
- Coding exons
- 2
- Length
- 81862
- Individuals with no LoFs
- 122835
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1477
- Defined
- 124312
- p
- 0.00596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.92 | 178 | 266 | 0.668 | 0.0000191 | 2610 |
| Missense (PolyPhen) | 83 | 134.95 | 0.61503 | 1376 | ||
| Synonymous | -0.845 | 135 | 123 | 1.10 | 0.00000888 | 830 |
| Loss of Function | 3.03 | 1 | 12.6 | 0.0792 | 5.52e-7 | 137 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0026 | 0.0025 | notable |
| Latino/Admixed American | 0.0053 | 0.0053 | notable |
| Ashkenazi Jewish | 0.0052 | 0.0050 | notable |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.0063 | 0.0060 | notable |
| European (Non-Finnish) | 0.0087 | 0.0081 | notable |
| South Asian | 0.0041 | 0.0040 | notable |
| Other | 0.0088 | 0.0083 | notable |
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. Critical for normal neuronal development where it may play a role in neuron branching. May also play a role in limb development. May prefer iduronic acid. {ECO:0000269|PubMed:21700882}.;
- Disease
- DISEASE: Hypogonadotropic hypogonadism 15 with or without anosmia (HH15) [MIM:614880]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:21700882, ECO:0000269|PubMed:25077900}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.;
Recessive Scores
- pRec
- 0.156
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.323
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |