NPAS4
Description
The NPAS4 (neuronal PAS domain protein 4) is a protein-coding gene located on chromosome 11.
Neuronal PAS domain protein 4 is a protein that in humans is encoded by the NPAS4 gene. The NPAS4 gene is a neuronal activity-dependent immediate early gene that has been identified as a transcription factor. The protein regulates the transcription of genes that control inhibitory synapse development, synaptic plasticity and most recently reported also behavior.
== Function == NPAS4 is a member of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]. NPAS4 has been shown by Dr. Brenda Bloodgood to play critical roles in regulating the plasticity of inhibitory neurons. She found that NPAS4 helps to regulate plasticity by orchestrating a redistribution of inhibitory synapses, wherein they are lost from proximal apical dendrites of CA1 pyramidal neurons and increased on the somata.
NPAS4 is a transcription factor expressed in neurons of the brain that plays a crucial role in regulating the balance between excitatory and inhibitory signals within neural circuits. This balance is essential for various brain functions, including contextual memory, which is the ability to remember specific details of an event or experience. NPAS4 contributes to neuronal plasticity, both structural and functional, enabling neurons to adapt and change in response to stimuli. As an early-response transcription factor, NPAS4 activates distinct sets of genes in both excitatory and inhibitory neurons, allowing synapses to be modified based on their role in the circuit. This fine-tuning of synaptic function ensures appropriate responses to sensory experiences. In excitatory neurons, NPAS4 activates the transcription of brain-derived neurotrophic factor (BDNF), which promotes the formation of inhibitory synapses on excitatory neurons. In inhibitory neurons, NPAS4 regulates a set of target genes that increase excitatory input onto somatostatin neurons, enhancing feedback inhibition within cortical circuits. The proper balance of excitation and inhibition impacts various cognitive processes, including short-term and long-term memory, learning, fear memory, stress response, and social behavior. NPAS4 also regulates dendritic spine development in olfactory bulb granule cells, a process that is influenced by sensory experiences. For effective DNA binding, NPAS4 requires dimerization with another bHLH protein, such as ARNT, ARNT2, or BMAL1. NPAS4 can also activate the CME (CNS midline enhancer) element.
NPAS4 is also known as Le-PAS, NXF, PASD10, bHLHe79.
Associated Diseases
- substance abuse
- developmental and epileptic encephalopathy, 9
- intellectual disability, autosomal dominant 50
- developmental and epileptic encephalopathy 104
- autosomal dominant epilepsy with auditory features
- intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies
- developmental and epileptic encephalopathy, 43
- schizophrenia 15
- intellectual developmental disorder, X-linked, syndromic, Pilorge type
