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

    Gene ID: 10406, updated on 10-Dec-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; BENP; 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
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    Genomic context

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    See WFDC2 in Genome Data Viewer
    Location:
    20q13.12
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (45469753..45481532)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (47205608..47217387)
    RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Overexpression of Lewis y antigen promotes human epididymis protein 4-mediated invasion and metastasis of ovarian cancer cells. Zhuang H, et al. Biochimie, 2014 Oct. PMID 24998328
    2. Increased human epididymis protein 4 in benign gynecological diseases complicated with chronic renal insufficiency patients. Lv YW, et al. Genet Mol Res, 2015 Mar 27. PMID 25867363
    3. Selection of DNA aptamers for ovarian cancer biomarker HE4 using CE-SELEX and high-throughput sequencing. Eaton RM, et al. Anal Bioanal Chem, 2015 Sep. PMID 25863801, Free PMC Article
    4. Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance. Brennan DJ, et al. BMC Cancer, 2015 Feb 6. PMID 25655024, Free PMC Article
    5. Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study. Capriglione S, et al. Tumour Biol, 2015 Jun. PMID 25577252

    See all (240) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Silencing HE4 alleviates the renal fibrosis in lupus nephritis mice by regulating the C3/MMPs/prss axis.
      Title: Silencing HE4 alleviates the renal fibrosis in lupus nephritis mice by regulating the C3/MMPs/prss axis.
    2. Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling.
      Title: Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling.
    3. Relationship between human epididymal protein 4 and depth of tumor invasion, postoperative recurrence, and metastasis of epithelial epithelial ovarian cancer.
      Title: Relationship between human epididymal protein 4 and depth of tumor invasion, postoperative recurrence, and metastasis of epithelial epithelial ovarian cancer.
    4. Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.
      Title: Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.
    5. Human epididymis protein 4: Analysis of national health and nutrition examination survey data.
      Title: Human epididymis protein 4: Analysis of national health and nutrition examination survey data.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (216)

    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)

    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 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
    		  
    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_2024_08

    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

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

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