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

Gene ID: 10406, updated on 5-Mar-2024

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; AllianceGenome:HGNC:15939
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
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Genomic context

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Location:
20q13.12
Exon count:
4
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (45469753..45481532)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (47205608..47217387)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (44098393..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 ATAC-STARR-seq lymphoblastoid silent region 12958 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12959 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. Human epididymis protein 4 as a clinical biomarker in identifying interstitial lung disease in patients with idiopathic inflammatory myopathies. Sun F, et al. Int Immunopharmacol, 2023 Feb. PMID 36577160
  2. Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer(). Dubey H, et al. Cancer Treat Res Commun, 2023. PMID 36525756
  3. HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients. Braicu EI, et al. BMC Cancer, 2022 Jul 30. PMID 35907794, Free PMC Article
  4. Can serum human epididymis protein 4 (HE4) support the decision to refer a patient with an ovarian mass to an oncology hospital? Lof P, et al. Gynecol Oncol, 2022 Aug. PMID 35688656
  5. HE4 is associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients. Mi D, et al. J Obstet Gynaecol Res, 2022 Jul. PMID 35596602

See all (230) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.
    Title: Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.
  2. Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125) for Prediction of Optimal Primary Surgery in Non-Mucinous Epithelial Ovarian Cancer.
    Title: Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125) for Prediction of Optimal Primary Surgery in Non-Mucinous Epithelial Ovarian Cancer.
  3. Serum human epididymis protein 4 is associated with disease severity in patients with IgA nephropathy.
    Title: Serum human epididymis protein 4 is associated with disease severity in patients with IgA nephropathy.
  4. Elevated level of serum human epididymis protein 4 (HE4) predicts disease severity and mortality in COVID-19 pneumonia.
    Title: Elevated level of serum human epididymis protein 4 (HE4) predicts disease severity and mortality in COVID-19 pneumonia.
  5. Combination of serum CST1 and HE4 for early diagnosis of endometrial cancer.
    Title: Combination of serum CST1 and HE4 for early diagnosis of endometrial cancer.
  6. Effect of Serum Level of Human Epididymis Protein 4 and Interleukin-6 as Biomarkers in Patients with Adnexal Mass.
    Title: Effect of Serum Level of Human Epididymis Protein 4 and Interleukin-6 as Biomarkers in Patients with Adnexal Mass.
  7. Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis.
    Title: Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis.
  8. The Utility of Preoperative Serum CA125 Combined with HE4 to Predict Lymph Node Metastasis in Endometrial Cancer.
    Title: The Utility of Preoperative Serum CA125 Combined with HE4 to Predict Lymph Node Metastasis in Endometrial Cancer.
  9. Human epididymis protein 4 as a clinical biomarker in identifying interstitial lung disease in patients with idiopathic inflammatory myopathies.
    Title: Human epididymis protein 4 as a clinical biomarker in identifying interstitial lung disease in patients with idiopathic inflammatory myopathies.
  10. Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.
    Title: Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma.
Submit: New GeneRIF Correction See all GeneRIFs (213)

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

EBI GWAS Catalog

Description
Voxelwise genome-wide association study (vGWAS).
EBI GWAS Catalog

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

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
human epididymis protein 4
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
    A2A2A5, A2A2A6, A6PVD5, Q14508, Q6IB27, Q8WXV9, Q8WXW0, Q8WXW1, Q8WXW2, Q96KJ1
    UniProtKB/TrEMBL
    A0A384MTN6
    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: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

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

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    47205608..47217387
    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

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