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WFDC2 WAP four-disulfide core domain 2 [ Homo sapiens (human) ]

Gene ID: 10406, updated on 24-Nov-2020

Summary

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Official Symbol
WFDC2provided by HGNC
Official Full Name
WAP four-disulfide core domain 2provided by HGNC
Primary source
HGNC:HGNC:15939
See related
Ensembl:ENSG00000101443 MIM:617548
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HE4; WAP5; EDDM4; dJ461P17.6
Summary
This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation. [provided by RefSeq, Jul 2008]
Expression
Biased expression in salivary gland (RPKM 317.9), endometrium (RPKM 117.3) and 8 other tissues See more
Orthologs
mouse all

Genomic context

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See WFDC2 in Genome Data Viewer
Location:
20q13.12
Exon count:
4
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 20 NC_000020.11 (45469753..45481532)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (44098229..44110172)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372631 Neighboring gene phosphatidylinositol glycan anchor biosynthesis class T Neighboring gene microRNA 6812 Neighboring gene uncharacterized LOC107987282 Neighboring gene ribosomal protein L5 pseudogene 2 Neighboring gene serine peptidase inhibitor, Kunitz type 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis. Li L, et al. Clin Chim Acta, 2020 Mar. PMID 31730821
  2. Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer. Yang WL, et al. Cancer, 2020 Feb 15. PMID 31714597,
  3. Diagnostic value of human epididymis protein 4 in malignant pleural effusion in lung cancer. Lv M, et al. Cancer Biomark, 2019. PMID 31658049
  4. Diagnostic performance of HE4 and ROMA among Chinese women. Shen Y, et al. Clin Chim Acta, 2020 Jan. PMID 31626761
  5. Urinary Human Epididymis Secretory Protein 4 as a Useful Biomarker for Subclinical Acute Rejection Three Months after Kidney Transplantation. Tajima S, et al. Int J Mol Sci, 2019 Sep 22. PMID 31546745, Free PMC Article

See all (197) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Endometriomas with low-risk malignancy potential in ultrasonography with high human epididymis protein 4 and risk of ovarian malignancy algorithm: a cases series.
    Title: Endometriomas with low-risk malignancy potential in ultrasonography with high human epididymis protein 4 and risk of ovarian malignancy algorithm: a cases series.
  2. Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis.
    Title: Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis.
  3. The differential diagnostic value and clinical significance of serum HE4 in ovarian disease with elevated CA125.
    Title: The differential diagnostic value and clinical significance of serum HE4 in ovarian disease with elevated CA125.
  4. Diagnostic accuracy of CA125 and HE4 in ovarian carcinoma patients and the effect of confounders on their serum levels.
    Title: Diagnostic accuracy of CA125 and HE4 in ovarian carcinoma patients and the effect of confounders on their serum levels.
  5. Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer.
    Title: Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer.
  6. Data demonstrated that HE4 augments the activity of trypsin, thereby enhancing PAR2 signaling, and leading to increased ovarian cancer cell proliferation. HE4 was found to inhibit trypsin degradation, increasing its stability and ultimately its enzymatic potential.
    Title: Role of trypsin and protease-activated receptor-2 in ovarian cancer.
  7. There was no significant difference in the 2 year survival rates of lung cancer patients with high and low HE4 concentrations in pleural fluid (P= 0.882).
    Title: Diagnostic value of human epididymis protein 4 in malignant pleural effusion in lung cancer.
  8. diagnostic use of HE4 in ovarian cancer
    Title: Diagnostic performance of HE4 and ROMA among Chinese women.
  9. Serum HE4 level in women with borderline ovarian tumors and epithelial ovarian cancer at early stages.
    Title: CPH-I and HE4 Are More Favorable Than CA125 in Differentiating Borderline Ovarian Tumors from Epithelial Ovarian Cancer at Early Stages.
  10. In the multivariate logistic regression analysis, HE4 was independently associated with acute heart failure in patients with chronic kidney disease (odds ratio, 2.120; 95% con fi dence interval, 1.034-4.344; P = .04).
    Title: Human Epididymis Protein 4 as an Indicator of Acute Heart Failure in Patients with Chronic Kidney Disease.
Submit: New GeneRIF Correction See all GeneRIFs (174)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Voxelwise genome-wide association study (vGWAS).
GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC57529

Gene Ontology Provided by GOA

Function Evidence Code Pubs
aspartic-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
cysteine-type endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
serine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
serine-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
antibacterial humoral response IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
innate immune response IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
proteolysis TAS
Traceable Author Statement
more info
 PubMed 
spermatogenesis TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
extracellular exosome HDA PubMed 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 

General protein information

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Preferred Names
WAP four-disulfide core domain protein 2
Names
WAP domain containing protein HE4-V4
epididymal protein 4
epididymal secretory protein E4
epididymis secretory sperm binding protein
epididymis-specific, whey-acidic protein type, four-disulfide core
major epididymis-specific protein E4
putative protease inhibitor WAP5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_006103.4 → NP_006094.3  WAP four-disulfide core domain protein 2 precursor

    See identical proteins and their annotated locations for NP_006094.3

    Status: REVIEWED

    Source sequence(s)
    AL031663, BI759775, X63187
    Consensus CDS
    CCDS35501.1
    UniProtKB/Swiss-Prot
    Q14508
    Related
    ENSP00000361761.3, ENST00000372676.8
    Conserved Domains (2) summary
    smart00217
    Location:76 → 123
    WAP; Four-disulfide core domains
    pfam00095
    Location:32 → 73
    WAP; WAP-type (Whey Acidic Protein) 'four-disulfide core'

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p13 Primary Assembly

    Range
    45469753..45481532
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_080733.1: Suppressed sequence

    Description
    NM_080733.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

  2. NM_080734.1: Suppressed sequence

    Description
    NM_080734.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  3. NM_080735.1: Suppressed sequence

    Description
    NM_080735.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  4. NM_080736.1: Suppressed sequence

    Description
    NM_080736.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14508.2 GenPept UniProtKB/Swiss-Prot:Q14508

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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