HPSE2

protein-coding

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

Gene summary

This gene encodes a heparanase enzyme. The encoded protein is a endoglycosidase that degrades heparin sulfate proteoglycans located on the extracellular matrix and cell surface. This protein may be involved in biological processes involving remodeling of the extracellular matrix including angiogenesis and tumor progression. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Previous symbols:

MANE transcript

NM_021828.5

Inheritance

ClinVar variants

P:22U:148B:35

Top phenotype

Ochoa syndrome; Urofacial syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr10:98,457,077-99,235,862

External References & Databases

Ensembl (ENSG00000172987)

Transcript & Mutation Effects

hg38 • Region Span ~778.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ochoa syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000463

Submitter: Orphanet

urofacial syndrome type 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009368

Submitter: Ambry Genetics

urofacial syndrome type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009368

Submitter: PanelApp Australia

urofacial syndrome type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009368

Submitter: Labcorp Genetics (formerly Invitae)

urofacial syndrome type 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009368

Submitter: G2P

Clinical Genomic Database (CGD)

Ochoa syndrome; Urofacial syndrome 1AR

Manifestation: Craniofacial; Neurologic; Renal

Intervention: Renal

Rationale: 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

Refs: 11446407; 19839856; 19669792; 20560209; 20560210; 20605127; 21332471; 21450525

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HPSE2 variants in ClinVar

8 Conditions Cataloged

Urofacial syndrome type 1Total: 100

not providedTotal: 98

Inborn genetic diseasesTotal: 87

HPSE2-related disorderTotal: 13

not specifiedTotal: 9

Ochoa syndromeTotal: 3

Congenital anomaly of kidney and urinary tractTotal: 2

HPSE2-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021828.5. 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			4 clinvar	29 clinvar		33
missense	1 clinvar		142 clinvar	5 clinvar	1 clinvar	149
nonsense	3 clinvar	2 clinvar	1 clinvar			6
start loss						0
frameshift	3 clinvar	7 clinvar				10
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar	1 clinvar			7
Total	9	13	148	34	1	205

Highest pathogenic variant AF is 0.00041941786

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021828.5	RefSeq	NP_068600.4	12	MANE Select
ENST00000370552.8	Ensembl	ENSP00000359583.3	12	MANE Select
NM_001166244.1	RefSeq	NP_001159716.1	11	Standard
NM_001166245.1	RefSeq	NP_001159717.1	10	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)
Metabolism of carbohydrates
HS-GAG degradation
Heparan sulfate/heparin (HS-GAG) metabolism

Biological Process

glycosaminoglycan catabolic process
biological_process
positive regulation of cell population proliferation
extracellular matrix organization

Molecular Function

heparanase activity
heparan sulfate proteoglycan binding

Cellular Component

plasma membrane
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370552
Coding exons: 12
Length: 776745
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125748
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.245	316	329	0.962	0.0000189	3822
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.00052	0.00052	rare
South Asian	0.000065	0.000065	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.185

Intolerance Scores

LoFtool: 0.898
RVIS EVS: 0.09
RVIS percentile EVS: 60.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.303

Gene Damage Prediction

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