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P014 FAM167A/BLK is a susceptibility locus in autoimmune diseases: characterisation of the FAM167 gene family
  1. L Mentlein,
  2. GE Thorlacius,
  3. L Meneghel,
  4. JI Ramirez Sepulveda,
  5. S Brauner,
  6. A Espinosa,
  7. M Wahren-Herlenius
  1. Unit of Rheumatology, Department of Medicine Solna, Karolinska Institute, Solna, Sweden


Introduction Genome-wide association studies of multiple autoimmune diseases, including Sjögren’s syndrome, systemic lupus erythematosus and rheumatoid arthritis have identified associations in the FAM167A/BLK locus. eQTL (expression quantitative loci) analyses in peripheral blood cells show a significantly increased expression of FAM167A for the disease associated genotypes. While BLK acts downstream of the B cell receptor, the function of FAM167A is unknown. Additionally, the role of the only homologous protein, its gene family member FAM167B, remains unexplored.

Objectives To elucidate the potential role of these proteins in susceptibility, or pathogenesis of autoimmune disease, we aim to characterise the FAM167 gene family by both bioinformatic and experimental approaches.

Methods Public databases, including NCBI, GEO, Uniprot, CCLE, PhylomeDB were searched for information on the FAM167 gene family and its two members. The FAM167 protein sequences were analysed with structure prediction tools including YASPIN and D2P2 server. The mRNA levels of the genes of interest were determined by qPCR analysis on organs from 12 week old C57BL/6 mice and cells of selected human cancer cell lines.

Results After protein sequence analysis we found that the FAM167 gene family shows no homology to any other annotated genes but is highly conserved in vertebrates. The FAM167A and FAM167B proteins don’t comprise any previously known protein domains and are predicted to contain both helical and disordered protein structures. Based on the analysis of their protein structure prediction and their conservation we propose that the FAM167 proteins contain two distinct modules linked by a variable linker accounting for the different size of 24 and 18 kDa for FAM167A and B, respectively. Database research revealed that FAM167A is expressed in many cancer cell lines whereas FAM167B shows a specifically high expression only within melanoma lines according to CCLE. FAM167A expression was confirmed for the myeloma cell line LP1 and the monocytic cell line THP1 experimentally. High FAM167B expression was found in the melanoma cell line SKMEL28. Expression profiling of mouse organs collected from C57BL/6 mice revealed high expression of Fam167a in lung, spleen, skeletal muscle and brain. Fam167b had its peak expression in adrenal glands, kidney and liver, with low or no expression observed in other analysed organs.

Conclusions The FAM167A/B genes show distinct expression profiles both at the organ and the cellular level. Further in vitro and in vivo studies will be implemented to unravel the function of this gene family.

Disclosure of interest None declared

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