KCNA2 [The Human Chemical-Genetic Interaction Map Project]

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======= KCNA2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: KCNA2
  * **<color #00a2e8>Official Name</color>**: potassium voltage-gated channel subfamily A member 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3737|3737]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P16389|P16389]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=KCNA2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20KCNA2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176262|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559, PubMed:11211111, PubMed:23769686). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559, PubMed:20220134). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2- containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2- containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity). {ECO:0000250|UniProtKB:P63141, ECO:0000250|UniProtKB:P63142, ECO:0000269|PubMed:11211111, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:20220134, ECO:0000269|PubMed:23769686, ECO:0000269|PubMed:8495559, ECO:0000305}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Ion trans 2|
|Ion trans|
|K tetra|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|optic nerve structural organization|
|optic nerve morphogenesis|
|paranodal junction|
|regulation of circadian sleep/wake cycle, non-REM sleep|
|juxtaparanode region of axon|
|cranial nerve structural organization|
|outward rectifier potassium channel activity|
|optic nerve development|
|regulation of circadian sleep/wake cycle, sleep|
|anatomical structure arrangement|
|regulation of circadian sleep/wake cycle|
|lamellipodium membrane|
|calyx of Held|
|neuronal cell body membrane|
|potassium channel activity|
|neuronal action potential|
|cranial nerve morphogenesis|
|delayed rectifier potassium channel activity|
|regulation of dopamine secretion|
|kinesin binding|
|cranial nerve development|
|axon terminus|
|transmission of nerve impulse|
|integral component of presynaptic membrane|
|voltage-gated potassium channel activity|
|regulation of catecholamine secretion|
|regulation of behavior|
|sensory perception of pain|
|nerve development|
|voltage-gated potassium channel complex|
|regulation of amine transport|
|action potential|
|regulation of response to drug|
|regulation of circadian rhythm|
|perikaryon|
|multicellular organismal signaling|
|potassium ion transmembrane transport|
|potassium ion transport|
|lamellipodium|
|axon|
|protein homooligomerization|
|monovalent inorganic cation transport|
|dendrite|
|regulation of membrane potential|
|regulation of ion transmembrane transport|
|protein complex oligomerization|
|inorganic cation transmembrane transport|
|regulation of transmembrane transport|
|cation transmembrane transport|
|metal ion transport|
|inorganic ion transmembrane transport|
|regulation of ion transport|
|regulation of secretion by cell|
|regulation of secretion|
|cation transport|
|endoplasmic reticulum membrane|
|ion transmembrane transport|
|sensory perception|
|transmembrane transport|
|ion transport|
|nervous system process|
|integral component of plasma membrane|
|protein-containing complex assembly|
|protein-containing complex subunit organization|
|regulation of transport|
|system process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|-1.86|
|[[:results:exp41|BI-2536 0.001μM R01 exp41]]|1.76|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 4559
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -0.25 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='KCNA2 Expression in NALM6 Cells: -0.25'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>