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TSEN54 gene

tRNA splicing endonuclease subunit 54

Normal Function

The TSEN54 gene provides instructions for making one part (subunit) of an enzyme called the tRNA splicing endonuclease complex. This complex helps process several types of RNA molecules, which are chemical cousins of DNA.

The tRNA splicing endonuclease complex is particularly important for the normal processing of a form of RNA known as transfer RNA (tRNA). tRNA molecules help assemble protein building blocks called amino acids into full-length proteins. However, before they can assemble proteins, tRNAs must be processed into mature molecules. In particular, regions called introns need to be removed from some tRNAs for the molecules to be functional. The tRNA splicing endonuclease complex recognizes and then removes introns to help produce mature tRNA molecules.

Studies suggest that the tRNA splicing endonuclease complex may also be involved in processing another form of RNA known as messenger RNA (mRNA). mRNA serves as a genetic blueprint for making proteins. Researchers suspect that the tRNA splicing endonuclease complex cuts (cleaves) one end of mRNA molecules so a string of adenines (one of the building blocks of RNA) can be added. This process is known as polyadenylation, and the string of adenines is known as a poly(A) tail. The poly(A) tail signals the stopping point for protein production and protects mRNA from being broken down before protein production occurs.

Health Conditions Related to Genetic Changes

Pontocerebellar hypoplasia

Several mutations in the TSEN54 gene have been identified in people with a disorder of brain development called pontocerebellar hypoplasia. The major features of this condition include delayed development, problems with movement, and intellectual disability. TSEN54 gene mutations are the most frequent cause of a form of the disorder designated pontocerebellar hypoplasia type 2 (PCH2). When PCH2 results from TSEN54 gene mutations, it is sometimes categorized more specifically as PCH2A. Mutations in the TSEN54 gene also cause pontocerebellar hypoplasia type 4 (PCH4) and appear to be a rare cause of pontocerebellar hypoplasia type 1 (PCH1).

The most common mutation in the TSEN54 gene replaces the amino acid alanine with the amino acid serine at position 307 in the TSEN54 protein (written as Ala307Ser or A307S). About 90 percent of all people with PCH2 have this mutation in both copies of the TSEN54 gene in each cell. At least one person diagnosed with PCH1 also had the mutation in both copies of the gene. Most individuals with PCH4 have the common Ala307Ser mutation in one copy of the TSEN54 gene in each cell and a different mutation in the other copy of the gene.

The TSEN54 gene mutations that cause pontocerebellar hypoplasia impair the function of the tRNA splicing endonuclease complex, which likely disrupts the processing of RNA molecules and affects the production of many types of proteins. Before birth, these changes appear to have the most severe impact on fast-growing tissues, such as those in the brain. However, it is unknown exactly how reduced function of the tRNA splicing endonuclease complex leads to abnormal brain development in people with pontocerebellar hypoplasia.

More About This Health Condition

Other Names for This Gene

  • FLJ37147
  • SEN54
  • SEN54L
  • tRNA splicing endonuclease 54 homolog
  • tRNA splicing endonuclease 54 homolog (S. cerevisiae)
  • tRNA-intron endonuclease Sen54
  • TSEN54 tRNA splicing endonuclease subunit

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Bailey KA, Aldinger KA. Mutations in the tRNA splicing endonuclease complex cause pontocerebellar hypoplasia. Clin Genet. 2009 May;75(5):427-8. doi: 10.1111/j.1399-0004.2009.01186_3.x. No abstract available. Citation on PubMed
  • Battini R, D'Arrigo S, Cassandrini D, Guzzetta A, Fiorillo C, Pantaleoni C, Romano A, Alfei E, Cioni G, Santorelli FM. Novel mutations in TSEN54 in pontocerebellar hypoplasia type 2. J Child Neurol. 2014 Apr;29(4):520-5. doi: 10.1177/0883073812470002. Epub 2013 Jan 9. Citation on PubMed
  • Budde BS, Namavar Y, Barth PG, Poll-The BT, Nurnberg G, Becker C, van Ruissen F, Weterman MA, Fluiter K, te Beek ET, Aronica E, van der Knaap MS, Hohne W, Toliat MR, Crow YJ, Steinling M, Voit T, Roelenso F, Brussel W, Brockmann K, Kyllerman M, Boltshauser E, Hammersen G, Willemsen M, Basel-Vanagaite L, Krageloh-Mann I, de Vries LS, Sztriha L, Muntoni F, Ferrie CD, Battini R, Hennekam RC, Grillo E, Beemer FA, Stoets LM, Wollnik B, Nurnberg P, Baas F. tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat Genet. 2008 Sep;40(9):1113-8. doi: 10.1038/ng.204. Citation on PubMed
  • Namavar Y, Barth PG, Kasher PR, van Ruissen F, Brockmann K, Bernert G, Writzl K, Ventura K, Cheng EY, Ferriero DM, Basel-Vanagaite L, Eggens VR, Krageloh-Mann I, De Meirleir L, King M, Graham JM Jr, von Moers A, Knoers N, Sztriha L, Korinthenberg R; PCH Consortium; Dobyns WB, Baas F, Poll-The BT. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain. 2011 Jan;134(Pt 1):143-56. doi: 10.1093/brain/awq287. Epub 2010 Oct 15. Citation on PubMed
  • Rudaks LI, Moore L, Shand KL, Wilkinson C, Barnett CP. Novel TSEN54 mutation causing pontocerebellar hypoplasia type 4. Pediatr Neurol. 2011 Sep;45(3):185-8. doi: 10.1016/j.pediatrneurol.2011.05.009. Citation on PubMed
  • Simonati A, Cassandrini D, Bazan D, Santorelli FM. TSEN54 mutation in a child with pontocerebellar hypoplasia type 1. Acta Neuropathol. 2011 May;121(5):671-3. doi: 10.1007/s00401-011-0823-1. Epub 2011 Apr 6. No abstract available. Citation on PubMed
  • van Dijk T, Baas F. TSEN54 Pontocerebellar Hypoplasia. 2009 Sep 8 [updated 2020 May 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from Citation on PubMed

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