HPSE
protein-codingheparanase, the group of Heparanases
Gene summary
Heparan sulfate proteoglycans are major components of the basement membrane and extracellular matrix. The protein encoded by this gene is an enzyme that cleaves heparan sulfate proteoglycans to permit cell movement through remodeling of the extracellular matrix. In addition, this cleavage can release bioactive molecules from the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.7 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 HPSE variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001098540.3. 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 | 2 | 1 | 4 | ||
| missense | 73 | 7 | 1 | 81 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 80 | 9 | 2 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001092010.1 | 12 | MANE Select | |
| Ensembl | ENSP00000308107.5 | 12 | MANE Select | |
| RefSeq | NP_001159970.1 | 10 | Standard | |
| RefSeq | NP_001186759.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Proteoglycans in cancer - Homo sapiens (human)
- Glycosaminoglycan degradation - Homo sapiens (human)
- Neutrophil degranulation
- Metabolism of carbohydrates
- HS-GAG degradation
Biological Process
- glycosaminoglycan catabolic process
- proteoglycan metabolic process
- cell-matrix adhesion
- positive regulation of vascular endothelial growth factor production
- positive regulation of blood coagulation
Molecular Function
- beta-glucuronidase activity
- protein binding
- heparanase activity
- syndecan binding
- protein dimerization activity
Cellular Component
- extracellular region
- nucleus
- nucleoplasm
- lysosome
- lysosomal membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000405413
- Coding exons
- 12
- Length
- 42693
- Individuals with no LoFs
- 125108
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 636
- Defined
- 125747
- p
- 0.00254
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.558 | 256 | 282 | 0.907 | 0.0000140 | 3468 |
| Missense (PolyPhen) | 80 | 88.153 | 0.90751 | 1127 | ||
| Synonymous | 1.52 | 95 | 116 | 0.820 | 0.00000572 | 1090 |
| Loss of Function | 0.878 | 24 | 29.1 | 0.824 | 0.00000153 | 356 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00071 | 0.00068 | rare |
| Latino/Admixed American | 0.0020 | 0.0019 | notable |
| Ashkenazi Jewish | 0.0018 | 0.0017 | notable |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.0049 | 0.0049 | notable |
| European (Non-Finnish) | 0.0033 | 0.0033 | notable |
| South Asian | 0.0014 | 0.0014 | notable |
| Other | 0.0037 | 0.0036 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up- regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis. {ECO:0000269|PubMed:12213822, ECO:0000269|PubMed:12773484, ECO:0000269|PubMed:15044433, ECO:0000269|PubMed:16452201, ECO:0000269|PubMed:18557927, ECO:0000269|PubMed:18798279, ECO:0000269|PubMed:19244131, ECO:0000269|PubMed:20097882, ECO:0000269|PubMed:20181948, ECO:0000269|PubMed:20309870, ECO:0000269|PubMed:20561914, ECO:0000269|PubMed:21131364}.;
Recessive Scores
- pRec
- 0.325
Intolerance Scores
- LoFtool
- 0.994
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0780
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |