KCNA1 [The Human Chemical-Genetic Interaction Map Project]

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======= KCNA1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: KCNA1
  * **<color #00a2e8>Official Name</color>**: potassium voltage-gated channel subfamily A member 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3736|3736]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q09470|Q09470]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=KCNA1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20KCNA1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176260|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a voltage-gated delayed potassium channel that is phylogenetically related to the Drosophila Shaker channel. The encoded protein has six putative transmembrane segments (S1-S6), and the loop between S5 and S6 forms the pore and contains the conserved selectivity filter motif (GYGD). The functional channel is a homotetramer. The N-terminus of the channel is associated with beta subunits that can modify the inactivation properties of the channel as well as affect expression levels. The C-terminus of the channel is complexed to a PDZ domain protein that is responsible for channel targeting. Mutations in this gene have been associated with myokymia with periodic ataxia (AEMK). [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 kidney (PubMed:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). 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). 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:12077175, PubMed:17156368). 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 (PubMed:12077175, PubMed:17156368). 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 KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (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) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:23903368, PubMed:19307729). {ECO:0000250|UniProtKB:P10499, ECO:0000269|PubMed:11026449, ECO:0000269|PubMed:12077175, ECO:0000269|PubMed:15837928, ECO:0000269|PubMed:17136396, ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:19968958, ECO:0000269|PubMed:21106501, ECO:0000269|PubMed:23903368}.

<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'>
|voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential|
|potassium ion transmembrane transporter activity|
|detection of mechanical stimulus involved in sensory perception of touch|
|voltage-gated ion channel activity involved in regulation of presynaptic membrane potential|
|sensory perception of touch|
|neuronal signal transduction|
|regulation of presynaptic membrane potential|
|cellular response to magnesium ion|
|juxtaparanode region of axon|
|paranode region of axon|
|magnesium ion homeostasis|
|detection of mechanical stimulus involved in sensory perception of pain|
|positive regulation of voltage-gated potassium channel activity|
|cell communication by electrical coupling|
|response to magnesium ion|
|calyx of Held|
|positive regulation of potassium ion transmembrane transporter activity|
|startle response|
|potassium channel activity|
|detection of mechanical stimulus involved in sensory perception|
|neuronal action potential|
|neuroblast proliferation|
|disordered domain specific binding|
|delayed rectifier potassium channel activity|
|positive regulation of potassium ion transmembrane transport|
|detection of mechanical stimulus|
|positive regulation of potassium ion transport|
|integral component of postsynaptic membrane|
|axon terminus|
|stem cell proliferation|
|transmission of nerve impulse|
|regulation of potassium ion transmembrane transporter activity|
|integral component of presynaptic membrane|
|voltage-gated potassium channel activity|
|positive regulation of cation channel activity|
|presynaptic membrane|
|sensory perception of pain|
|neural precursor cell proliferation|
|regulation of potassium ion transmembrane transport|
|hippocampus development|
|voltage-gated potassium channel complex|
|action potential|
|regulation of potassium ion transport|
|regulation of postsynaptic membrane potential|
|positive regulation of ion transmembrane transporter activity|
|neuromuscular process|
|limbic system development|
|positive regulation of transporter activity|
|detection of external stimulus|
|detection of abiotic stimulus|
|perikaryon|
|multicellular organismal signaling|
|positive regulation of cation transmembrane transport|
|positive regulation of ion transmembrane transport|
|potassium ion transmembrane transport|
|regulation of muscle contraction|
|sensory perception of mechanical stimulus|
|potassium ion transport|
|regulation of cation channel activity|
|pallium development|
|cellular response to metal ion|
|positive regulation of transmembrane transport|
|response to mechanical stimulus|
|cellular response to inorganic substance|
|regulation of muscle system process|
|cytoplasmic vesicle|
|regulation of ion transmembrane transporter activity|
|telencephalon development|
|regulation of transmembrane transporter activity|
|synapse|
|positive regulation of ion transport|
|regulation of transporter activity|
|axon|
|apical plasma membrane|
|regulation of cation transmembrane transport|
|protein homooligomerization|
|glutamatergic synapse|
|response to metal ion|
|neuronal cell body|
|forebrain development|
|regulation of metal ion transport|
|monovalent inorganic cation transport|
|anterograde trans-synaptic signaling|
|dendrite|
|chemical synaptic transmission|
|regulation of membrane potential|
|trans-synaptic signaling|
|synaptic signaling|
|regulation of ion transmembrane transport|
|divalent inorganic cation homeostasis|
|protein complex oligomerization|
|response to inorganic substance|
|detection of stimulus involved in sensory perception|
|cell junction|
|cell population proliferation|
|inorganic cation transmembrane transport|
|regulation of transmembrane transport|
|regulation of system process|
|cation transmembrane transport|
|cell surface|
|metal ion homeostasis|
|metal ion transport|
|inorganic ion transmembrane transport|
|detection of stimulus|
|regulation of ion transport|
|cation homeostasis|
|inorganic ion homeostasis|
|brain development|
|head development|
|ion homeostasis|
|cation transport|
|ion transmembrane transport|
|sensory perception|
|central nervous system development|
|positive regulation of transport|
|endoplasmic reticulum|
|chemical homeostasis|
|cell-cell signaling|
|response to abiotic stimulus|
|transmembrane transport|
|ion transport|
|nervous system process|
|integral component of plasma membrane|
|generation of neurons|
|protein-containing complex assembly|
|cellular protein localization|
|cellular macromolecule localization|
|neurogenesis|
|homeostatic process|
|positive regulation of molecular function|
|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:exp306|Rapamycin 2μM R07 exp306]]|1.95|
</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>**: 15295
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -1.57 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='KCNA1 Expression in NALM6 Cells: -1.57'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>