HPN

protein-coding

hepsin, the group of Type II transmembrane serine proteases|Scavenger receptor cysteine rich domain containing

Gene summary

This gene encodes a type II transmembrane serine protease that may be involved in diverse cellular functions, including blood coagulation and the maintenance of cell morphology. Expression of the encoded protein is associated with the growth and progression of cancers, particularly prostate cancer. The protein is cleaved into a catalytic serine protease chain and a non-catalytic scavenger receptor cysteine-rich chain, which associate via a single disulfide bond. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

MANE transcript

NM_001384133.1

Inheritance

—

ClinVar variants

U:70B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr19:35,040,506-35,066,573

External References & Databases

Ensembl (ENSG00000105707)

Transcript & Mutation Effects

hg38 • Region Span ~26.1 kb

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GenCC 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 HPN variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001384133.1. 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 clinvar		2 clinvar	5
missense			61 clinvar	2 clinvar		63
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	70	2	2	74

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 151 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001384133.1	RefSeq	NP_001371062.1	12	MANE Select
ENST00000672452.2	Ensembl	ENSP00000500664.1	12	MANE Select
NM_001375441.3	RefSeq	NP_001362370.1	12	Standard
NM_002151.5	RefSeq	NP_002142.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
hpn	Danio rerio	Structure: blood coagulation, fibrin clot formation Quality: delayed abnormal

Gene / Model

Organism

Observed Phenotype

hpn

Danio rerio

Structure: blood coagulation, fibrin clot formation

Quality: delayed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Viral carcinogenesis - Homo sapiens (human)
Signal Transduction
MET Receptor Activation
Signaling by MET
Signaling by MST1

Biological Process

proteolysis
regulation of cell shape
positive regulation of gene expression
negative regulation of epithelial to mesenchymal transition
positive regulation of plasminogen activation

Molecular Function

serine-type endopeptidase activity
protein binding
peptidase activity
serine-type peptidase activity
calcium-activated potassium channel activity

Cellular Component

endoplasmic reticulum membrane
plasma membrane
integral component of plasma membrane
cell-cell junction
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262626
Coding exons: 12
Length: 26066
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125743
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.79	181	263	0.689	0.0000176	2651
Missense (PolyPhen)		40	88.28	0.4531		908
Synonymous	0.696	104	113	0.917	0.00000828	858
Loss of Function	4.42	1	24.7	0.0404	0.00000136	247

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000053	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (PubMed:21875933, PubMed:15839837). Plays a role in cell growth and maintenance of cell morphology (PubMed:8346233, PubMed:21875933). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890). {ECO:0000269|PubMed:15839837, ECO:0000269|PubMed:21875933, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:8346233}.;

Recessive Scores

pRec: 0.262

Intolerance Scores

RVIS EVS: -0.47
RVIS percentile EVS: 23.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.538

Gene Damage Prediction

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