A Gene For Intelligence: SHANK3
The SHANK3 gene encodes the production of a protein, primarily found in the brain, referred to as the SHANK3 protein. The protein's involvement in support of synapses and maturation of dendritic spines makes it an important factor in intellectual ability (SHANK3 gene 2017).
The SHANK3 gene supports signaling at the synapse, or the connection between two neurons. It also plays a role in the formation and maturation of dendritic spines, the protrusions from neuron's dendrites which receive inputs from a single axon (Purves 2001).
Pain sensitivity has also been shown to correlate to SHANK3 expression. SHANK3 deficiency is associated with an increase in pain sensitivity especially in patients with autism spectrum disorder. While studying this phenomenon, in mice model organisms, complete knockout of the gene results in impaired heat hyperalgesia in inflammatory and neuropathic pain (Han 2016).
On the other hand, over-expression of the same gene can also have large impacts. In mice, over-expression of SHANK3 leads to manic-like behaviors including hyperactivity, impulsivity, elevated mood, reduced anxiety, and decreased need for sleep (Lee 2017). This may have implications in bipolar disorder which is characterized by manic and depressive episodes.
Other aliases: DEL22q13.3, PROSAP2, PSAP2, SCZD15, SPANK-2
The SHANK3 gene supports signaling at the synapse, or the connection between two neurons. It also plays a role in the formation and maturation of dendritic spines, the protrusions from neuron's dendrites which receive inputs from a single axon (Purves 2001).
Pain sensitivity has also been shown to correlate to SHANK3 expression. SHANK3 deficiency is associated with an increase in pain sensitivity especially in patients with autism spectrum disorder. While studying this phenomenon, in mice model organisms, complete knockout of the gene results in impaired heat hyperalgesia in inflammatory and neuropathic pain (Han 2016).
On the other hand, over-expression of the same gene can also have large impacts. In mice, over-expression of SHANK3 leads to manic-like behaviors including hyperactivity, impulsivity, elevated mood, reduced anxiety, and decreased need for sleep (Lee 2017). This may have implications in bipolar disorder which is characterized by manic and depressive episodes.
Other aliases: DEL22q13.3, PROSAP2, PSAP2, SCZD15, SPANK-2
SHANK3 Chromosomal Location
Molecular Location:
chromosome 22, base pairs 50,674,642- 50,733,212
chromosome 22, base pairs 50,674,642- 50,733,212
What Defines Intelligence?
Throughout the years, there has been much debate about the specific definition of intelligence. The question of how to determine intelligence differences between individuals has also been widely debated. The most widely agreed upon definition terms intelligence as the mental capacity for reasoning, problem solving, and learning. An understanding of intelligence is gathered through the integration of perception, attention, memory, language, and planning. These many contributing components make measurement of intelligence more difficult.
Psychologists have developed hundreds of standardized intelligence tests attempting to capture a measurement of said components. The most widely accepted and used tests are those which determine an individual's g factor, or general intelligence. This factor provides a numerical representation of the level of difficulty an individual is capable of handling through induction, reasoning, visualization, or language comprehension tests. It has been shown that the g factor accounts for over 50 percent of the total variance in cognitive ability. A commonly used test of the g factor is the Wechsler Adult Intelligence Scale (WAIS) which measures g, as well as several additional cognitive abilities and specific skills (Colom 2010). In general, in our discussion of the SHANK3 gene and its relation to intelligence, we will discuss intelligence in terms of g factor.
Psychologists have developed hundreds of standardized intelligence tests attempting to capture a measurement of said components. The most widely accepted and used tests are those which determine an individual's g factor, or general intelligence. This factor provides a numerical representation of the level of difficulty an individual is capable of handling through induction, reasoning, visualization, or language comprehension tests. It has been shown that the g factor accounts for over 50 percent of the total variance in cognitive ability. A commonly used test of the g factor is the Wechsler Adult Intelligence Scale (WAIS) which measures g, as well as several additional cognitive abilities and specific skills (Colom 2010). In general, in our discussion of the SHANK3 gene and its relation to intelligence, we will discuss intelligence in terms of g factor.
Mutation to the SHANK3 Gene
22q13.3 deletion syndrome22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome, is characterized by developmental delay, intellectual disability, and the inability to speak fluently. The condition is caused by a deletion of many genes of chromosome 22, including the SHANK3 gene. Therefore, affected individuals have one copy of the SHANK3 gene rather than two. Researchers believe that the deletion of the SHANK3 gene, specifically, leads to the phenotypic outcome of those with 22q13.3 Deletion syndrome. The deletion leads to decreased functioning of synapses and communication between neurons which is thought to cause the developmental and intellectual deficits observed (SHANK3 gene 2017).
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Autism spectrum disorderAutism spectrum disorder (ASD) is characterized by a spectrum of impairment of communication and socialization skills couple with repetitive behaviors. Over 43 different SHANK3 gene mutations have been found in people with ASD which either prevent production of or disrupt the function of the SHANK3 protein. Although the exact mechanism is unclear, it is hypothesized that the SHANK3 mutations disrupt communication between neurons which plays a role in the risk of developing the disorder. This disruption coupled with other mutations and extrinsic factors probably contribute to the development of Autism spectrum disorder (SHANK3 gene 2017).
Environmental, genetic, and epigenetic factors can all act as risk factors for development of ASD. Suggested environmental factors include chemicals, dietary factors, and physical or psychological stressors (Dietert 2011). These factors, if correlated with methylation of the SHANK3 gene, may play a role in the impairments associated with ASD through an epigenetic mechanism. |
Discussion
Study of SHANK3 opens avenues for research advancements in intellectual function as well as diseases and disorders including but not limited to autism spectrum disorder, 22q13.3 deletion syndrome, and other neurodevelopmental disorders. Navigate this website to learn more about gene and protein interactions and functions as well as some potential research aims. This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison in 2018. Feel free to contact me with any questions or comments.
References
Colom, R., Karama, S., Jung, R. E., & Haier, R. J. (2010). Human intelligence and brain networks. Dialogues in Clinical Neuroscience, 12(4), 489–501.
Dietert, R. R., Dietert, J. M., & Dewitt, J. C. (2011). Environmental risk factors for autism. Emerging Health Threats Journal, 4, 10.3402/ehtj.v4i0.7111. http://doi.org/10.3402/ehtj.v4i0.7111
Han, Q., Kim, Y. H., Wang, X., Liu, D., Zhang, Z.-J., Bey, A. L., … Ji, R.-R. (2016). SHANK3 deficiency impairs heat hyperalgesia and TRPV1 signaling in primary sensory neurons. Neuron, 92(6), 1279–1293. http://doi.org/10.1016/j.neuron.2016.11.007
Lee, Y., Kim, S. G., Lee, B., Zhang, Y., Kim, Y., Kim, S., … Han, K. (2017). Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling. Frontiers in Molecular Neuroscience, 10, 201. http://doi.org/10.3389/fnmol.2017.00201
Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Chapter 5, Synaptic Transmission. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11001/
SHANK3 gene - Genetics Home Reference. (2017, January). Retrieved January 31, 2018, from https://ghr.nlm.nih.gov/gene/SHANK3#sourcesforpage
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https://psychology-spot.com/did-you-know-that-intelligence-is/
Colom, R., Karama, S., Jung, R. E., & Haier, R. J. (2010). Human intelligence and brain networks. Dialogues in Clinical Neuroscience, 12(4), 489–501.
Dietert, R. R., Dietert, J. M., & Dewitt, J. C. (2011). Environmental risk factors for autism. Emerging Health Threats Journal, 4, 10.3402/ehtj.v4i0.7111. http://doi.org/10.3402/ehtj.v4i0.7111
Han, Q., Kim, Y. H., Wang, X., Liu, D., Zhang, Z.-J., Bey, A. L., … Ji, R.-R. (2016). SHANK3 deficiency impairs heat hyperalgesia and TRPV1 signaling in primary sensory neurons. Neuron, 92(6), 1279–1293. http://doi.org/10.1016/j.neuron.2016.11.007
Lee, Y., Kim, S. G., Lee, B., Zhang, Y., Kim, Y., Kim, S., … Han, K. (2017). Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling. Frontiers in Molecular Neuroscience, 10, 201. http://doi.org/10.3389/fnmol.2017.00201
Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Chapter 5, Synaptic Transmission. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11001/
SHANK3 gene - Genetics Home Reference. (2017, January). Retrieved January 31, 2018, from https://ghr.nlm.nih.gov/gene/SHANK3#sourcesforpage
Header Image
https://psychology-spot.com/did-you-know-that-intelligence-is/
Alyssa Fleischman | [email protected]
University of Wisconsin - Madison, 2019
B.S. Genetics and Genomics, Neurobiology
Last updated: May 7, 2018
University of Wisconsin - Madison, 2019
B.S. Genetics and Genomics, Neurobiology
Last updated: May 7, 2018
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.