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DEF6

Chr 6p21.31

DEF6 guanine nucleotide exchange factor

Aliases:
IBP, SLAT, SWAP70L
MANE:
ENST00000316637.7

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Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • COVID-19 research

    BIALLELIC, autosomal or pseudoautosomal
  • Primary immunodeficiency or monogenic inflammatory bowel disease

    BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

  • immunodeficiency 87 and autoimmunity

    0.69
  • hypothyroidism

    0.40
  • Graves disease

    0.25
  • asthma

    0.16
  • childhood onset asthma

    0.14
  • respiratory system disorder

    0.11
  • breast cancer

    0.09
  • breast carcinoma

    0.09
  • cancer

    0.08
  • celiac disease

    0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Defensin-6

Host-defense peptide that contributes to intestinal innate immunity and mediates homeostasis at mucosal surfaces by forming higher-order oligomers that capture bacteria and prevent microbial invasion of the epithelium (PubMed:15616305, PubMed:17088326, PubMed:25158166, PubMed:25354318, PubMed:28026958). After binding to bacterial surface proteins, undergoes ordered self-assembly to form fibril-like nanonets that surround and entangle bacteria and thereby prevent bacterial invasion across the epithelial barrier (PubMed:22722251). Entangles and agglutinates Gram-negative bacteria, such as E.coli, S.typhimurium and Y.enterocolitica, and Gram-positive bacteria such as L.monocytogenes, thereby protecting the intestine against invasion by enteric bacterial pathogens (PubMed:22722251, PubMed:25158166, PubMed:27076903). Blocks adhesion of C.albicans to intestinal epithelial cells and thereby suppresses fungal invasion of epithelial cells and biofilm formation (PubMed:28026958). Under reducing conditions and in an acidic environment similar to the intestinal milieu, exhibits inhibitory activity against anaerobic bacteria such as B.adolescentis, L.acidophilus and B.breve, as well as B.longum and S.thermophilus, possibly by leading to alterations in bacterial cell envelope structures (PubMed:25354318). The disulfide-linked oxidized form exhibits negligible antimicrobial activity against Gram-negative and Gram-positive bacteria, as compared to the enteric defensin DEFA5 (PubMed:15616305, PubMed:17088326)

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.