Human perforin gene variation is geographically distributed

Robin C. Willenbring, Yasuhiro Ikeda, Larry R. Pease, Aaron J. Johnson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Deleterious mutations in PRF1 result in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, not all mutations in PRF1 are deleterious and result in FHL 2. Currently, these nondeleterious mutations are being investigated in the onset of numerous disorders, such as lymphomas and diabetes. Yet, there is still an overwhelmingly large amount of PRF1 mutations that are not associated with disease. Methods: We conducted a post hoc analysis of the PRF1 mutations in the coding region using the recently published Exome Aggregation Consortium genomes, Leiden Open Variation Database, NCBI SNP database, and primary literature to better understand PRF1 variation in the human population. Results: This study catalogs 460 PRF1 mutations in the coding region, and demonstrates PRF1 is more variant then previously predicted. We identify key PRF1 mutations with high allelic frequency and are only found in certain populations. Additionally, we define PRF1 SNVs are geographically distributed. Conclusions: This study concludes with a novel hypothesis that nondeleterious mutation in PRF1, which decreases perforin expression and/or activity, may be an example of selective advantage in the context of environmental stressors prevalent near the equator. Our studies illustrate how perforin deficiency can be protective from injuries resulting in blood–brain barrier (BBB) disruption.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalMolecular Genetics and Genomic Medicine
Issue number1
StatePublished - Jan 2018


  • familial hemophagocytic lymphohistiocytosis type 2
  • human genetics
  • pathogen
  • perforin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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