What is the Difference Between TSC1 and TSC2

The key difference between TSC1 and TSC2 is that TSC1 is a gene located in chromosome 9 that causes tuberous sclerosis complex genetic disorder, while TSC2 is a gene located in chromosome 16 that causes tuberous sclerosis complex genetic disorder.

Tuberous sclerosis complex (TSC) is a genetic disorder. It is a result of a mutation in one of the two genes present in all cells of the human body. This disorder is characterized by the growth of numerous (benign) tumors in many parts of the body, including the brain, kidneys, heart, skin, and other organs. TSC1 and TSC2 are the two main genes that are responsible for the tuberous sclerosis complex.

CONTENTS

1. Overview and Key Difference
2. What is TSC1 
3. What is TSC2
4. Similarities – TSC1 and TSC2
5. TSC1 vs TSC2 in Tabular Form
6. Summary – TSC1 vs TSC2

What is TSC1?

TSC1 is a gene that causes tuberous sclerosis complex genetic disorder. This gene is located on chromosome 9. It codes for a protein called hamartin. Hamartin is also known as tuberous sclerosis 1 (TSC1) protein. Hamartin protein functions as a co-chaperone that inhibits the ATPase activity of the chaperone Hsp90 and decelerates its chaperone cycle. Moreover, hamartin protein functions as a facilitator of Hsp90 in chaperoning kinase and non-kinase clients, including TSC2. This prevents their ubiquitination and degradation in the proteasome. Hamartin (TSC1), TSC2, and TBC1D7 form a multi-protein complex called TSC complex. This complex negatively regulates mTORCI signalling by functioning as a GTPase activating protein (GAP) for the small GTPase Rheb. GTPase Rheb is an essential activator of mTORC1. TSC complex that consists of hamartin protein has been implicated as a tumor suppressor.

The defects (mutations) in the TSCI gene can cause tuberous sclerosis due to functional impairment of the TSC complex. Defects in the TSCI gene may also be a cause of focal cortical dysplasia. Furthermore, hamartin protein may also be involved in protecting brain neurons in the CA3 region of the hippocampus from the effects of stokes.

What is TSC2?

TSC2 is a gene that causes tuberous sclerosis complex genetic disorder. This gene is located on chromosome 16. TSC2 gene normally provides instructions for producing a protein called tuberin. In cells, tuberin interacts with hamartin, which is produced by the TSC1 gene. These two proteins help control cell growth and division (proliferation) and cell size. These proteins usually prevent cells from growing and dividing very fast or in an uncontrolled way. Thus, they work as tumor suppressor proteins.

Tuberin and hamartin carry out their tumor suppressor function by interacting with and regulating a wide variety of other proteins. The defective TSC2 gene variants cause a destructive rare lung disease called lymphangioleiomyomatosis (LAM). Furthermore, the defective TSC2 gene also causes a tuberous sclerosis complex that triggers noncancerous tumor growth in many parts of the body.

What are the Similarities Between TSC1 and TSC2?

• TSC1 and TSC2 are the two main genes that are responsible for causing tuberous sclerosis complex genetic disorders.
• Both genes produce proteins that act as tumor suppressors.
• Their proteins are important components of the TSC complex.
• Both genes can be mutated to cause other diseases as well.

What is the Difference Between TSC1 and TSC2?

TSC1 is a gene located in chromosome 9 that causes tuberous sclerosis complex genetic disorder, while TSC2 is a gene located in chromosome 16 that causes tuberous sclerosis complex genetic disorder. Thus, this is a key difference between TSC1 and TSC2. Furthermore, the TSC1 gene codes for a protein called hamartin, while the TSC2 gene codes for a protein called tuberin. So, this is also a main difference between TSC1 and TSC2.

The below infographic presents the differences between TSC1 and TSC2 in tabular form for side by side comparison.

Summary – TSC1 vs TSC2

TSC1 and TSC2 are two important genes found in all body cells. They code for proteins that are important components of the TSC tumor suppressor complex. Their mutation can cause a genetic disorder known as the tuberous sclerosis complex. TSC1 gene is located in chromosome 9, while TSC2 gene is located in chromosome 16. So, this is the summary of the difference between TSC1 and TSC2.

Reference:

1. “TSC1 Gene: Medlineplus Genetics.” MedlinePlus, U.S. National Library of Medicine, 4 Jan. 2022.
2. “TSC2 Gene: Medlineplus Genetics.” MedlinePlus, U.S. National Library of Medicine, 4 Jan. 2022.

Image Courtesy:

1. “Human chromosome 09 with ASD genes from IJMS-16-06464” By Merlin G. Butler, Syed K. Rafi, Ann M. Manzardo and Lorie Gavulic (illustration) – “High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders“; Int. J. Mol. Sci. 2015, 16(3), 6464-6495; doi:10.3390/ijms16036464 (CC BY 4.0) via Commons Wikimedia
2. “Human chromosome 16 with ASD genes from IJMS-16-06464” By Merlin G. Butler, Syed K. Rafi, Ann M. Manzardo and Lorie Gavulic (illustration) “High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders“; Int. J. Mol. Sci. 2015, 16(3), 6464-6495; doi:10.3390/ijms16036464 (CC BY 4.0) via Commons Wikimedia