HPSE

heparanase, the group of Heparanases

Basic information

Region (hg38): 4:83292460-83335153

Links

ENSG00000173083 ∙ NCBI:10855 ∙ OMIM:604724 ∙ HGNC:5164 ∙ Uniprot:Q9Y251 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPSE gene.

• Inborn genetic diseases (22 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPSE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			19	4		23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	19	5	1

Variants in HPSE

This is a list of pathogenic ClinVar variants found in the HPSE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-83295426-C-T		not specified	Uncertain significance (May 24, 2023)
4-83295427-G-A		not specified	Uncertain significance (Apr 06, 2022)
4-83295481-T-G		not specified	Uncertain significance (Aug 04, 2023)
4-83301004-A-C		HPSE-related disorder	Likely benign (Sep 20, 2022)
4-83301035-A-G		not specified	Uncertain significance (Mar 01, 2024)
4-83301038-C-T		not specified	Likely benign (Nov 30, 2021)
4-83301055-A-G		HPSE-related disorder	Benign (Nov 06, 2019)
4-83301080-G-C		not specified	Uncertain significance (Nov 02, 2023)
4-83302167-A-G		HPSE-related disorder	Likely benign (Aug 12, 2019)
4-83302204-T-C		not specified	Uncertain significance (Jun 18, 2021)
4-83306206-T-A		not specified	Uncertain significance (Nov 17, 2022)
4-83306243-C-T		not specified	Uncertain significance (Nov 18, 2022)
4-83306266-C-T		not specified	Uncertain significance (Jul 26, 2022)
4-83306300-C-T			Likely benign (Jun 23, 2018)
4-83308880-C-T		HPSE-related disorder	Likely benign (Feb 14, 2020)
4-83308891-C-T		not specified	Uncertain significance (Jan 24, 2023)
4-83309451-T-C		not specified	Uncertain significance (Jan 10, 2023)
4-83309463-T-G		not specified	Uncertain significance (Jul 15, 2021)
4-83309466-T-C		HPSE-related disorder	Benign (Oct 17, 2019)
4-83309473-C-T		not specified	Uncertain significance (Sep 20, 2023)
4-83310056-C-G		not specified	Uncertain significance (Dec 18, 2023)
4-83310068-C-T		not specified	Uncertain significance (Sep 27, 2021)
4-83310773-T-C		not specified	Uncertain significance (Sep 06, 2022)
4-83310857-A-C		HPSE-related disorder	Likely benign (Feb 11, 2020)
4-83313106-G-T			Benign (Apr 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPSE	protein_coding	protein_coding	ENST00000405413	12	42693

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.27e-14	0.117	125108	3	636	125747	0.00254

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.558	256	282	0.907	0.0000140	3468
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00268	0.00265
Ashkenazi Jewish	0.00180	0.00169
East Asian	0.000163	0.000163
Finnish	0.00485	0.00486
European (Non-Finnish)	0.00335	0.00329
Middle Eastern	0.000163	0.000163
South Asian	0.00145	0.00137
Other	0.00366	0.00359

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Proteoglycans in cancer - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Neutrophil degranulation;Metabolism of carbohydrates;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;Innate Immune System;Immune System;Metabolism;Syndecan-1-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.325

Intolerance Scores

• loftool: 0.994
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.69

Haploinsufficiency Scores

• pHI: 0.0749
• hipred: N
• hipred_score: 0.144
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0780

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hpse
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; limbs/digits/tail phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; respiratory system phenotype; skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: glycosaminoglycan catabolic process;proteoglycan metabolic process;cell-matrix adhesion;positive regulation of vascular endothelial growth factor production;positive regulation of blood coagulation;heparan sulfate proteoglycan catabolic process;positive regulation of osteoblast proliferation;neutrophil degranulation;regulation of hair follicle development;positive regulation of hair follicle development;positive regulation of protein kinase B signaling;angiogenesis involved in wound healing;vascular wound healing
• Cellular component: extracellular region;nucleus;nucleoplasm;lysosome;lysosomal membrane;extracellular matrix;specific granule lumen;lysosomal lumen;intracellular membrane-bounded organelle;membrane raft
• Molecular function: beta-glucuronidase activity;protein binding;heparanase activity;syndecan binding;protein dimerization activity