What is TBL1XR1?

TBL1XR1 is a gene, located on chromosome 3q26.32, that is present in all humans. Genes contain instructions to make proteins. Proteins perform many critical roles in the body, including maintaining the structure, function, and regulation of tissues and organs.

Research indicates that the TBL1XR1 gene plays an important role in human development, in particular for brain function. TBL1XR1 also plays an important role in regulating gene pathways (turning various genes “on” and “off”).

Articles on TBL1XR1 gene and TBL1XR1-related disorder:

The Spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects, Orphanet Journal of Rare Disease (2024):

The spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects | Orphanet Journal of Rare Diseases | Full Text (biomedcentral.com)

TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway, Frontiers in Cell & Developmental Biology (2021): https://www.frontiersin.org/articles/10.3389/fcell.2021.641410/full

Expanding the spectrum of TBL1XR1 deletion: Report of a patient with brain and cardiac malformations, European Journal of Medical Genetics (2018): https://www.sciencedirect.com/science/article/pii/S1769721216304943

A specific mutation in TBL1XR1 causes Pierpont syndrome, Journal of Medical Genetics (2015): https://jmg.bmj.com/content/53/5/330

Linkage between TBL1XR1 and autism: https://www.the-scientist.com/features/the-genes-underlying-autism-are-coming-into-focus-33113 (must create login, but free to read).

TBL1XR1 in physiological and pathological states, American Journal of Clinical and Experimental Urology (2015): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446378/

What does it mean to have a TBL1XR1 gene variant?

Individuals with TBL1XR1 gene variants are part of the rare disease community. Rare (or orphan) diseases affect an estimated 400 million people worldwide. The vast majority of the 7,000+ rare diseases have no known treatments.

Much is still unknown about the disease-causing role of TBL1XR1 gene variants. Although the effect of having a TBL1XR1 gene variant can vary greatly from one person to another, common symptoms include:

  • Intellectual and Developmental Disabilities

  • Epilepsy (Seizures)

  • Autism Spectrum Disorder

  • ADHD

  • Chiari Malformation (brain)

  • Heart Defects

  • Kidney Defects

  • Strabismus (vision)

  • Feeding Intolerance

  • Hypotonia (low muscle tone)