WFDC6 Gene

HGNC Family	WAP four-disulfide core domain containing (WFDC)
Name	WAP four-disulfide core domain 6
Description	This gene encodes a member of the WAP-type four-disulfide core (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. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Read-through transcription exists between this gene and the upstream SPINLW1 (serine peptidase inhibitor-like, with Kunitz and WAP domains 1) gene. [provided by RefSeq, Nov 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIt appears that none of the provided abstracts address WFDC6; rather, their focus is on AGAP1, a multidomain ArfGAP protein that integrates multiple signaling pathways. In one study, AGAP1 was shown to bind specifically to the muscarinic M5 receptor in midbrain dopaminergic neurons (20664521). This interaction facilitates the loading of the AP-3 adaptor complex onto M5, promoting receptor endocytic recycling and thereby preserving cell surface receptor density during sustained stimulation—a process essential for potentiating presynaptic dopamine release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "In a second report, AGAP1 was identified as a binding partner of nitric oxide (NO)–sensitive soluble guanylyl cyclase (sGC) (15381706). The interaction, which occurs through AGAP1’s carboxyl terminal region, is enhanced by tyrosine phosphorylation mediated by Src-like kinases, suggesting that AGAP1 may integrate signals from Arf GTPases, the NO/cGMP pathway, and receptor tyrosine kinases to modulate sGC activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "A third study further revealed that AGAP proteins, including AGAP1, are allosterically regulated through binding of small GTPases such as RhoA to their G-protein-like domains (22453919). This binding, which occurs independently of nucleotide state, enhances AGAP1’s GAP activity towards Arf1, thereby playing a critical role in post-Golgi membrane trafficking. Collectively, these results highlight AGAP1 as an important mediator of receptor recycling and signaling pathway crosstalk by linking GPCR, NO/cGMP, and cytoskeletal regulatory mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jacob Bendor, José E Lizardi-Ortiz, Robert I Westphalen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGAP1/AP-3-dependent endocytic recycling of M5 muscarinic receptors promotes dopamine release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.154"}], "href": "https://doi.org/10.1038/emboj.2010.154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20664521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20664521"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sabine Meurer, Sylke Pioch, Kristina Wagner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AGAP1, a novel binding partner of nitric oxide-sensitive guanylyl cyclase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410565200"}], "href": "https://doi.org/10.1074/jbc.M410565200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15381706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15381706"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ruibai Luo, Itoro O Akpan, Ryo Hayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GTP-binding protein-like domain of AGAP1 is protein binding site that allosterically regulates ArfGAP protein catalytic activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.334458"}], "href": "https://doi.org/10.1074/jbc.M111.334458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22453919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22453919"}]}]}]}
Synonyms	C20ORF171, DJ461P17.11, WAP6, HEL-S-295
Proteins	WFDC6_HUMAN
NCBI Gene ID	140870
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WFDC6 has 1,601 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 44 datasets.

Click the + buttons to view associations for WFDC6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WFDC6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of WFDC6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of WFDC6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WFDC6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WFDC6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of WFDC6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WFDC6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WFDC6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of WFDC6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of WFDC6 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WFDC6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with WFDC6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of WFDC6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WFDC6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by WFDC6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with WFDC6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at WFDC6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WFDC6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of WFDC6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of WFDC6 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of WFDC6 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
	GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations	transcription factor perturbations changing expression of WFDC6 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Viral Infections	virus perturbations changing expression of WFDC6 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
	GTEx eQTL 2025	SNPs regulating expression of WFDC6 gene from the GTEx eQTL 2025 dataset.
	GTEx Tissue Gene Expression Profiles	tissues with high or low expression of WFDC6 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
	GTEx Tissue Gene Expression Profiles 2023	tissues with high or low expression of WFDC6 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
	InterPro Predicted Protein Domain Annotations	protein domains predicted for WFDC6 protein from the InterPro Predicted Protein Domain Annotations dataset.
	JASPAR Predicted Human Transcription Factor Targets 2025	transcription factors regulating expression of WFDC6 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
	JASPAR Predicted Transcription Factor Targets	transcription factors regulating expression of WFDC6 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
	Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles	cell lines with high or low copy number of WFDC6 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
	KnockTF Gene Expression Profiles with Transcription Factor Perturbations	transcription factor perturbations changing expression of WFDC6 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
	LOCATE Predicted Protein Localization Annotations	cellular components predicted to contain WFDC6 protein from the LOCATE Predicted Protein Localization Annotations dataset.
	MiRTarBase microRNA Targets	microRNAs targeting WFDC6 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
	MotifMap Predicted Transcription Factor Targets	transcription factors regulating expression of WFDC6 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
	Roadmap Epigenomics Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at WFDC6 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
	Rummagene Transcription Factor Associations 2026	transcription factors regulating expression of WFDC6 gene from the Rummagene Transcription Factor Associations 2026 dataset.
	RummaGEO Drug Perturbation Signatures	drug perturbations changing expression of WFDC6 gene from the RummaGEO Drug Perturbation Signatures dataset.
	RummaGEO Gene Perturbation Signatures	gene perturbations changing expression of WFDC6 gene from the RummaGEO Gene Perturbation Signatures dataset.
	TargetScan Predicted Conserved microRNA Targets	microRNAs regulating expression of WFDC6 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
	TargetScan Predicted Nonconserved microRNA Targets	microRNAs regulating expression of WFDC6 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
	TCGA Signatures of Differentially Expressed Genes for Tumors	tissue samples with high or low expression of WFDC6 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
	TISSUES Curated Tissue Protein Expression Evidence Scores	tissues with high expression of WFDC6 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
	TISSUES Curated Tissue Protein Expression Evidence Scores 2025	tissues with high expression of WFDC6 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
	TISSUES Experimental Tissue Protein Expression Evidence Scores	tissues with high expression of WFDC6 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
	TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025	tissues co-occuring with WFDC6 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.