Disease relevance of DLG5

• BACKGROUND AND AIMS: Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions [1].
• Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease [1].
• METHODS: A cohort of 2032 individuals was genotyped for disease-associated OCTN and DLG5 variants, including 981 patients with IBD (CD, n = 769; ulcerative colitis, n = 186; indeterminate colitis, n = 26) followed up at a tertiary IBD center [2].
• METHODS: Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205) [3].
• Investigation of association of the DLG5 gene with psoriatic arthritis [4].

High impact information on DLG5

• We found a significant difference in association of the 113A DLG5 variant with Crohn disease in affected individuals carrying the risk-associated CARD15 alleles versus those carrying non-risk-associated CARD15 alleles [5].
• Genetic variation in DLG5 is associated with inflammatory bowel disease [5].
• One of the risk-associated DLG5 haplotypes is distinguished from the common haplotype by a nonsynonymous single-nucleotide polymorphism 113G-->A, resulting in the amino acid substitution R30Q in the DUF622 domain of DLG5 [5].
• We refined our previously defined linkage region for IBD on chromosome 10q23 and used positional cloning to identify genetic variants in DLG5 associated with IBD [5].
• The carnitine/organic cation transporter (OCTN) on 5q31 (IBD5) is associated with Crohn's disease (CD) and DLG5 (10q23), a member of membrane-associated guanylate kinase (MAGUK) family, with IBD [2].

Chemical compound and disease context of DLG5

• HDLG5/KIAA0583, encoding a MAGUK-family protein, is a primary progesterone target gene in breast cancer cells [6].
• Here we report identification of a gene encoding a member of the MAGUK protein family, hDlg5 (also known as KIAA0583 and P-dlg), as being the primary progestin target gene in MCF-7 breast cancer cells [6].

Biological context of DLG5

• Recently, we described the association of genetic variation in the discs large homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) in a large European study sample (Stoll et al. in Nat Genet 36:476-480, 2004) [7].
• Further investigation of the observed TRD may contribute towards enlightening the role of DLG5 in physiological processes influencing transmission of chromosomes to the surviving offspring, which, in turn, may help in understanding its implication in the development of CD among men [7].
• Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease [8].
• For DLG5, there were no associations with a particular phenotype [2].
• The genomic sequence of the DLG5 gene spanned 79 KB with 32 exons and was shown to have ubiquitous human tissue expression including placenta, heart, skeletal muscle, liver and pancreas [9].

Anatomical context of DLG5

• Decreased levels of endogenous RAB6KIFL in PDAC cells altered the subcellular localization of DLG5 from cytoplasmic membranes to cytoplasm [10].
• These findings suggest that P-dlg forms a complex with p55 at the plasma membrane and plays roles in maintaining the structure of epithelial cells and transmitting extracellular signals to the membrane and cytoskeleton, which may negatively regulate cell proliferation [11].

Other interactions of DLG5

• Mutational analysis of ANX11, DLG5, and PPIF revealed no disease-associated mutations [12].
• A higher frequency of DLG5 113A was observed in CARD15-positive patients (12.2%) compared with CARD15-negative patients (8.7%; P = .033) [2].
• Association analysis of SLC22A4, SLC22A5 and DLG5 in Japanese patients with Crohn disease [13].
• Genetic variants in TNF-alpha but not DLG5 are associated with inflammatory bowel disease in a large United Kingdom cohort [14].

Analytical, diagnostic and therapeutic context of DLG5

• Co-immunoprecipitation experiments revealed that both endogenous and epitope-tagged deletion mutants of lp-dlg/KIAA0583 associated with beta-catenin [15].

References