[3][4][5][6] The TREX complex plays an important role in genome stability and neurodegenerative diseases.

UAP56 then dissociates, allowing the heterodimeric export receptor NXF1-NXT1 to bind as it recognizes the mRNA indirectly through ALYREF.

Mutational variants of THOC2 have been associated with syndromic intellectual disabilities, causing seizures, tremors, speech delays, and more.

[citation needed] DDX39, or U2AF65-associated protein 56 (UAP56, Sub2 in yeast) is a DEAD-box ATPase essential for pre-mRNA splicing,[13] but is also a key component of the TREX complex.

[21] UIF is speculated to associate with alternative TREX complexes in place of ALYREF, perhaps acting on certain types or mRNAs.

[30] CHTOP is speculated to associate with alternative TREX complexes in place of UAP56, perhaps acting on specific types or mRNAs.

[30][33] NXF1(Mex67p in yeast), also known as nuclear RNA export factor 1, is a multi-domain protein composed of one conserved N-terminal RNA recognition and four leucine-rich repeat motifs, a central NTF2-like domain, and a C-terminal ubiquitin associated domain that mediates interactions with nucleoporins.

The two proteins interact with each other as well as the TREX complex in facilitating the mRNA export from the nucleus to the cytoplasm.

Newly formed RNA strands can hybridize with the single-stranded template DNA sequence during transcription, leading to an R-loop.

For example, missense mutations, or a change in a nucleotide that results in the encoding of a different amino acid, in this gene and translocations on the X chromosome are associated with intellectual disabilities.

Mutations on this gene leads to the incorrect localization of the protein in the cytoplasm, an essential process for neural and organ development.

[7] A homozygous mutation in this gene can lead to not only intellectual disability, but cardiac defects and brain malformation.

[7] Mutations in other genes can also have an indirect dependence on the TREX complex and lead to disease, including familial amyotrophic lateral sclerosis(ALS).

ALS is a rare neurodegenerative disease that leads to the death of motor neurons in the brain, resulting in the loss of voluntary movement.