HPSE2

heparanase 2 (inactive), the group of MicroRNA protein coding host genes|Heparanases

Basic information

Region (hg38): 10:98457076-99235862

Previous symbols: [ "UFS" ]

Links

ENSG00000172987 ∙ NCBI:60495 ∙ OMIM:613469 ∙ HGNC:18374 ∙ Uniprot:Q8WWQ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• urofacial syndrome type 1 (Definitive), mode of inheritance: AR
• urofacial syndrome type 1 (Moderate), mode of inheritance: AR
• Ochoa syndrome (Supportive), mode of inheritance: AR
• urofacial syndrome type 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ochoa syndrome; Urofacial syndrome 1	AR	Renal	Individuals are at high risk of infantile-onset vesicoureteral reflux leading to kidney damage, hypertension, and eventual renal failure, and surveillance and preventive measures related to manifestations such as urinary tract/renal infections may be beneficial	Craniofacial; Neurologic; Renal	11446407; 19839856; 19669792; 20560209; 20560210; 20605127; 21332471; 21450525

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPSE2 gene.

• not provided (103 variants)
• Inborn genetic diseases (25 variants)
• Urofacial syndrome type 1 (22 variants)
• Ochoa syndrome (2 variants)
• not specified (1 variants)
• HPSE2-related condition (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPSE2 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				15	1	16
missense			42	5	2	49
nonsense	4	1				5
start loss						0
frameshift	1	1				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2				3
splice region				3		3
non coding				10	39	49
Total	6	4	43	30	42

Highest pathogenic variant AF is 0.0000395

Variants in HPSE2

This is a list of pathogenic ClinVar variants found in the HPSE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-98459505-G-T			Benign (Jun 20, 2021)
10-98459557-G-A		Urofacial syndrome type 1	Benign (Aug 10, 2021)
10-98459584-C-T		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
10-98459585-G-T		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
10-98459590-G-T		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
10-98459592-C-T			Likely benign (Mar 11, 2022)
10-98459599-T-C		Inborn genetic diseases	Uncertain significance (May 17, 2023)
10-98459603-C-T		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
10-98459617-T-A		Urofacial syndrome type 1	Benign (Jan 30, 2024)
10-98459646-C-G		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
10-98459649-T-C			Benign (Nov 07, 2023)
10-98459657-C-T		Urofacial syndrome type 1 • Inborn genetic diseases	Uncertain significance (Nov 08, 2021)
10-98459664-A-G			Likely benign (Nov 08, 2022)
10-98459689-A-C			Uncertain significance (Aug 17, 2023)
10-98459725-T-A		Urofacial syndrome type 1	Pathogenic (Jan 01, 2012)
10-98459735-C-G			Benign/Likely benign (Dec 13, 2023)
10-98459739-C-A			Uncertain significance (May 19, 2022)
10-98459762-G-A		Urofacial syndrome type 1	Benign (Aug 10, 2021)
10-98459926-AC-A			Benign (Nov 12, 2018)
10-98461509-T-C			Benign (Nov 12, 2018)
10-98461839-G-A			Benign (Jun 20, 2021)
10-98482352-T-G			Benign (Nov 12, 2018)
10-98482438-C-T			Benign (Nov 12, 2018)
10-98482588-C-G			Benign (Nov 12, 2018)
10-98482629-C-T			Likely benign (Aug 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPSE2	protein_coding	protein_coding	ENST00000370552	12	776745

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000151	0.998	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.245	316	329	0.962	0.0000189	3822
Missense in Polyphen		122	135.08	0.90319		1580
Synonymous	-0.814	144	132	1.09	0.00000677	1224
Loss of Function	2.79	11	26.5	0.415	0.00000136	327

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000579	0.000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000945	0.0000924
European (Non-Finnish)	0.000520	0.000519
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro). {ECO:0000269|PubMed:20576607}.
• Disease: DISEASE: Urofacial syndrome 1 (UFS1) [MIM:236730]: A rare autosomal recessive disorder characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. Affected individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. {ECO:0000269|PubMed:20560209, ECO:0000269|PubMed:20560210}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteoglycans in cancer - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Metabolism of carbohydrates;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;Metabolism (Consensus)

Recessive Scores

• pRec: 0.185

Intolerance Scores

• loftool: 0.898
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.57

Haploinsufficiency Scores

• pHI: 0.297
• hipred: N
• hipred_score: 0.454
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.303

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hpse2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: glycosaminoglycan catabolic process;biological_process;positive regulation of cell population proliferation;extracellular matrix organization
• Cellular component: plasma membrane;extracellular matrix
• Molecular function: heparanase activity;heparan sulfate proteoglycan binding