TOX3
TOX high mobility group box family member 3 | |||||||
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Identifiers | |||||||
Symbol | TOX3 | ||||||
Alt. symbols | TNRC9, CAGF9 | ||||||
Chr. 16 q12.1 | |||||||
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TOX high mobility group box family member 3, also known as TOX3, is a human gene.[1][2]
The protein encoded by this gene is a member of a subfamily of transcription factors that also includes TOX, TOX2, and TOX4 that share almost identical HMG-box DNA-binding domains which function to modify chromatin structure by unwinding and bending DNA.[3] The protein TOX3 has a glutamine-rich C-terminus due to CAG repeats.[4] TOX3 is located on human chromosome band 16q12.1.[5] The gene consists of seven exons and is highly expressed in both the brain and luminal epithelial breast tissue.[6] Mutations in the gene are associated with increased susceptibility to breast cancer.[2] TOX3 plays a role in regulating calcium-dependent transcription and interacts with cAMP-response-element-binding protein (CREB) and CREB-binding protein (CBP).[7] It also increases transcription via interaction with CITED1, a transcription co-regulator that increases transcription factor activity.[7]
Disease linkage
Mutations in the TOX3 gene are associated with an increased risk of breast cancer.[1][2][8][9]
The risk allele rs3803662 is a low-penetrance SNP (single nucleotide polymorphism) associated with decreased expression of TOX3 and an increase in breast cancer risk.[7] The risk locus was reported to regulate affinity of FOXA1 binding to chromatin, potentially affecting TOX3 expression.[6] This locus also interacts with high-penetrance mutations BRCA1 and BRCA2 to increase risk.[10] The rs3803662 variant has a high frequency in the population, with a minor allele frequency of 0.25.[11]
Little is known of the transcriptional mechanisms and protein interactions of TOX3. However, a 2019 publication identified TOX3 as a cancer suppressor gene in
References
- ^ PMID 16636340.
- ^ PMID 17529967.
- PMID 12697058.
- ^ "TOX3 TOX high mobility group box family member 3 [Homo sapiens (human)]". Gene - NCBI. National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine.
- ^ "TOX3 (TOX high mobility group box family member 3)". Atlas of Genetics and Cytogenetics in Oncology and Haematology.
- ^ PMID 24069272.
- ^ PMID 23270421.
- S2CID 7346190.
- PMID 18355772.
- ^ "OMIM Entry - * 611416 - TOX HIGH MOBILITY GROUP BOX FAMILY MEMBER 3; TOX3". Online Mendelian Inheritance in Man (OMIM).
- PMID 20542480.
- ^ S2CID 73487599.