KCNB1 Gene (Protein Coding)

Potassium Voltage-Gated Channel Subfamily B Member 1

GC20M049293
GIFtS:
47
Voltage-gated potassium (Kv) 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 potassi... See more...

Aliases for KCNB1 Gene

Aliases for KCNB1 Gene

  • Potassium Voltage-Gated Channel Subfamily B Member 1 2 3 4 5
  • Potassium Voltage-Gated Channel, Shab-Related Subfamily, Member 1 2 3
  • Voltage-Gated Potassium Channel Subunit Kv2.1 3 4
  • Delayed Rectifier Potassium Channel 1 3 4
  • Kv2.1 2 3
  • DRK1 3 4
  • H-DRK1 4
  • KCNB1 5

External Ids for KCNB1 Gene

Previous GeneCards Identifiers for KCNB1 Gene

  • GC20M047717
  • GC20M048626
  • GC20M048673
  • GC20M047421
  • GC20M047984
  • GC20M044737
  • GC20M049363

Summaries for KCNB1 Gene

Entrez Gene Summary for KCNB1 Gene

  • Voltage-gated potassium (Kv) 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, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

GeneCards Summary for KCNB1 Gene

KCNB1 (Potassium Voltage-Gated Channel Subfamily B Member 1) is a Protein Coding gene. Diseases associated with KCNB1 include Epileptic Encephalopathy, Early Infantile, 26 and Undetermined Early-Onset Epileptic Encephalopathy. Among its related pathways are Integration of energy metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include ion channel activity and voltage-gated potassium channel activity. An important paralog of this gene is KCNB2.

UniProtKB/Swiss-Prot Summary for KCNB1 Gene

  • Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). 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. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340, PubMed:19074135, PubMed:19717558, PubMed:24901643). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (By similarity). 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. Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity).

Tocris Summary for KCNB1 Gene

  • Voltage-gated potassium channels (KV) belong to the 6-TM family of potassium channel that also comprises the Ca2+-activated Slo (actually 7-TM) and the Ca2+-activated SK subfamilies. The alpha-subunits contain a single pore-forming region and combine to form tetramers.

Gene Wiki entry for KCNB1 Gene

Additional gene information for KCNB1 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KCNB1 Gene

Genomics for KCNB1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for KCNB1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KCNB1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KCNB1

Top Transcription factor binding sites by QIAGEN in the KCNB1 gene promoter:
  • c-Myc
  • Chx10
  • Ik-2
  • LCR-F1
  • Max1
  • NF-1
  • NRSF form 1
  • NRSF form 2
  • Pax-4a
  • Spz1

Genomic Locations for KCNB1 Gene

Genomic Locations for KCNB1 Gene
chr20:49,293,394-49,484,297
(GRCh38/hg38)
Size:
190,904 bases
Orientation:
Minus strand
chr20:47,980,414-48,099,184
(GRCh37/hg19)
Size:
118,771 bases
Orientation:
Minus strand

Genomic View for KCNB1 Gene

Genes around KCNB1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KCNB1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KCNB1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for KCNB1 Gene

Proteins for KCNB1 Gene

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  • Protein details for KCNB1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14721-KCNB1_HUMAN
    Recommended name:
    Potassium voltage-gated channel subfamily B member 1
    Protein Accession:
    Q14721
    Secondary Accessions:
    • Q14193

    Protein attributes for KCNB1 Gene

    Size:
    858 amino acids
    Molecular mass:
    95878 Da
    Quaternary structure:
    • Homotetramer or heterotetramer with KCNB2 (PubMed:8081723, PubMed:1283219). Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19357235, PubMed:19074135, PubMed:19717558, PubMed:24901643). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (By similarity). Self-associates (via N-terminus and C-terminus) (PubMed:12560340, PubMed:24901643); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (By similarity). Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons. Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner. Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate. Interacts with CREB1; this promotes channel acetylation in response to stimulation of incretin hormones. Interacts (via N-terminus and C-terminus) with MYL12B. Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface (By similarity). Interacts with SUMO1 (PubMed:19223394). Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells (By similarity).
    SequenceCaution:
    • Sequence=AAA36156.1; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for KCNB1 Gene

Protein Expression for KCNB1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for KCNB1 Gene

  • Phosphorylated. Differential C-terminal phosphorylation on a subset of serines allows graded activity-dependent regulation of channel gating in hippocampal neurons. Ser-607 and Tyr-128 are significant sites of voltage-gated regulation through phosphorylation/dephosphorylation activities. Tyr-128 can be phosphorylated by Src and dephosphorylated by cytoplasmic form of the phosphatase PTPRE. CDK5-induced Ser-607 phosphorylation increases in response to acute blockade of neuronal activity. Phosphorylated on Tyr-128 by Src and on Ser-805 by MAPK14/P38MAPK; phosphorylations are necessary and sufficient for an increase in plasma membrane insertion, apoptotic potassium current surge and completion of the neuronal cell death program. Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation. The Ser-607 phosphorylation state differs between KCNB1-containing clusters on the proximal and distal portions of the axon initial segment (AIS). Highly phosphorylated on serine residues in the C-terminal cytoplasmic tail in resting neurons. Phosphorylated in pancreatic beta cells in response to incretin hormones stimulation in a PKA- and RPS6KA5/MSK1-dependent signaling pathway, promoting beta cell survival. Phosphorylation on Ser-567 is reduced during postnatal development with low levels at P2 and P5; levels then increase to reach adult levels by P14. Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties. Dephosphorylation by phosphatase PTPRE confers neuroprotection by its inhibitory influence on the neuronal apoptotic potassium current surge in a Zn(2+)-dependent manner. Dephosphorylated at Ser-607 by protein phosphatase PPP1CA. Hypoxia-, seizure- or glutamate-induced neuronal activity promote calcium/calcineurin-dependent dephosphorylation resulting in a loss of KCNB1-containing clustering and enhanced channel activity. In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-720 are less dephosphorylated. In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced. Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic nerve tissue (By similarity).
  • Acetylated. Acetylation occurs in pancreatic beta cells in response to stimulation by incretin hormones in a histone acetyltransferase (HAT)/histone deacetylase (HDAC)-dependent signaling pathway, promoting beta cell survival.
  • Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity (PubMed:19223394). Sumoylation increases the frequency of repetitive action potential firing at the cell surface of hippocampal neurons and decreases its frequency in pancreatic beta cells (PubMed:19223394). Desumoylated by SENP1 (PubMed:19223394).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for KCNB1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for KCNB1 Gene

Domains & Families for KCNB1 Gene

Gene Families for KCNB1 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • FDA approved drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Transporters
  • Voltage-gated ion channels

Protein Domains for KCNB1 Gene

InterPro:
Blocks:
  • BTB/POZ domain
  • Potassium channel signature
  • Kv2.1 voltage-gated K+ channel signature
ProtoNet:

Suggested Antigen Peptide Sequences for KCNB1 Gene

GenScript: Design optimal peptide antigens:
  • Voltage-gated potassium channel subunit Kv2.1 (KCNB1_HUMAN)
  • KCNB1 protein (Q2NLD5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14721

UniProtKB/Swiss-Prot:

KCNB1_HUMAN :
  • The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
  • Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.
Domain:
  • The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
  • The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (PubMed:11852086, PubMed:12060745, PubMed:12560340, PubMed:19074135, PubMed:24901643). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits (PubMed:24901643). The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells. The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons (By similarity).
Family:
  • Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.
genes like me logo Genes that share domains with KCNB1: view

Function for KCNB1 Gene

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Molecular function for KCNB1 Gene

UniProtKB/Swiss-Prot Function:
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). 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. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340, PubMed:19074135, PubMed:19717558, PubMed:24901643). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (By similarity). 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. Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity).
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: Note=Homotetrameric channels expressed in xenopus oocytes or in mammalian non-neuronal cells display delayed-rectifier voltage-dependent potassium currents which are activated during membrane depolarization, i.e within a risetime of about 20 msec (PubMed:8081723, PubMed:1283219). After that, inactivate very slowly, i.e within more than 5 sec (PubMed:8081723, PubMed:1283219). Their activation requires low threshold potentials of about -20 to -30 mV, with a midpoint activation at about 10 mV. For inactivation, the voltage at half-maximal amplitude is about -20 mV (PubMed:11852086). The time constant for recovery after inactivation is about 1.6 sec. Channels have an unitary conductance of about 8 pS (PubMed:10484328). The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, the presence or absence of ancillary subunits and post-translational modifications. {ECO:0000269|PubMed:10484328, ECO:0000269|PubMed:11852086, ECO:0000269|PubMed:1283219, ECO:0000269|PubMed:8081723, ECO:0000305|PubMed:10414301, ECO:0000305|PubMed:15858231};
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (PubMed:14565763). Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata (PubMed:14565763). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) (PubMed:8081723, PubMed:1283219). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).
GENATLAS Biochemistry:
potassium voltage-gated channel,Drosophila Shab-related subfamily

Phenotypes From GWAS Catalog for KCNB1 Gene

Gene Ontology (GO) - Molecular Function for KCNB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IEA --
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005249 voltage-gated potassium channel activity IBA 21873635
GO:0005251 delayed rectifier potassium channel activity ISS --
GO:0005267 potassium channel activity IEA --
genes like me logo Genes that share ontologies with KCNB1: view
genes like me logo Genes that share phenotypes with KCNB1: view

Human Phenotype Ontology for KCNB1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KCNB1 Gene

MGI Knock Outs for KCNB1:
  • Kcnb1 Kcnb1<tm1Dgen>
  • Kcnb1 Kcnb1<tm1b(EUCOMM)Hmgu>

Animal Model Products

  • Taconic Biosciences Mouse Models for KCNB1

CRISPR Products

miRNA for KCNB1 Gene

miRTarBase miRNAs that target KCNB1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNB1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for KCNB1 Gene

Localization for KCNB1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KCNB1 Gene

Cell membrane. Perikaryon. Cell projection, axon. Cell projection, dendrite. Membrane. Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane. Cell junction, synapse. Cell junction, synapse, synaptosome. Lateral cell membrane. Cell membrane, sarcolemma. Note=Localizes to high-density somatodendritic clusters and non-clustered sites on the surface of neocortical and hippocampal pyramidal neurons in a cortical actin cytoskeleton-dependent manner (PubMed:24477962). Localizes also to high-density clusters in the axon initial segment (AIS), at ankyrin-G-deficient sites, on the surface of neocortical and hippocampal pyramidal neurons (PubMed:24477962). KCNB1-containing AIS clusters localize either in close apposition to smooth endoplasmic reticulum cisternal organelles or with GABA-A receptor-containing synapses of hippocampal and cortical pyramidal neurons, respectively (PubMed:24477962). Localizes to high-density clusters on the cell surface of atrial and ventricular myocytes and at the lateral plasma membrane in epithelial cells. Localizes both to the axial and transverse tubules (T tubule) and sarcolemma in ventricular myocytes. Associated with lipid raft domains. In cortical neurons, apoptotic injuries induce de novo plasma membrane insertion in a SNARE-dependent manner causing an apoptotic potassium current surge. {ECO:0000250 UniProtKB:P15387, ECO:0000250 UniProtKB:Q03717, ECO:0000269 PubMed:12060745, ECO:0000269 PubMed:19074135, ECO:0000269 PubMed:24477962, ECO:0000269 PubMed:24901643}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KCNB1 gene
Compartment Confidence
plasma membrane 5
extracellular 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for KCNB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005886 plasma membrane TAS --
GO:0008076 voltage-gated potassium channel complex ISS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IBA 21873635
genes like me logo Genes that share ontologies with KCNB1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KCNB1 Gene

Pathways & Interactions for KCNB1 Gene

genes like me logo Genes that share pathways with KCNB1: view

Pathways by source for KCNB1 Gene

1 BioSystems pathway for KCNB1 Gene
1 Qiagen pathway for KCNB1 Gene
  • Dopamine-DARPP32 Feedback onto cAMP Pathway

SIGNOR curated interactions for KCNB1 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for KCNB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001508 action potential IDA 19223394
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport IEA --
GO:0006887 exocytosis IEA --
GO:0006904 vesicle docking involved in exocytosis ISS --
genes like me logo Genes that share ontologies with KCNB1: view

Drugs & Compounds for KCNB1 Gene

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(15) Drugs for KCNB1 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
linoleic acid Approved, Experimental Pharma Agonist, Full agonist, Activator, Pore Blocker, Channel blocker 0
4-Aminopyridine Approved Pharma Pore Blocker, Inhibitor, Antagonist, Target, antagonist potassium channel-blocking agent 60
Enflurane Approved, Investigational, Vet_approved Pharma Target, inhibitor, activator 2
Promethazine Approved, Investigational Pharma Target, inducer 470
Gliquidone Approved, Investigational Pharma 5

(1) Additional Compounds for KCNB1 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Kaliotoxin
145199-73-1

(4) Tocris Compounds for KCNB1 Gene

Compound Action Cas Number
Chromanol 293B IKs blocker. Also blocks ICFTR 163163-23-3
Flupirtine maleate KV7 channel activator 75507-68-5
Kaliotoxin KV and KCa blocker 145199-73-1
MaxiPost Potassium channel modulator; exerts subtype-specific effects 187523-35-9

(2) ApexBio Compounds for KCNB1 Gene

Compound Action Cas Number
Gliquidone 33342-05-1
Tolbutamide CAMP inhibitor 64-77-7
genes like me logo Genes that share compounds with KCNB1: view

Drug Products

Transcripts for KCNB1 Gene

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mRNA/cDNA for KCNB1 Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNB1

Alternative Splicing Database (ASD) splice patterns (SP) for KCNB1 Gene

No ASD Table

Relevant External Links for KCNB1 Gene

GeneLoc Exon Structure for
KCNB1

Expression for KCNB1 Gene

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  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KCNB1 Gene

mRNA expression in normal human tissues for KCNB1 Gene
mRNA expression by BioGPS for KCNB1 GenemRNA expression by GTEx for KCNB1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KCNB1 Gene

This gene is overexpressed in Brain - Frontal Cortex (BA9) (x5.4), Brain - Cortex (x5.0), and Brain - Anterior cingulate cortex (BA24) (x4.0).

Protein differential expression in normal tissues from HIPED for KCNB1 Gene

This gene is overexpressed in Retina (60.7) and Frontal cortex (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KCNB1 Gene



Protein tissue co-expression partners for KCNB1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KCNB1

SOURCE GeneReport for Unigene cluster for KCNB1 Gene:

Hs.84244

mRNA Expression by UniProt/SwissProt for KCNB1 Gene:

Q14721-KCNB1_HUMAN
Tissue specificity: Expressed in neocortical pyramidal cells (PubMed:24477962). Expressed in pancreatic beta cells (at protein level) (PubMed:12403834, PubMed:14988243). Expressed in brain, heart, lung, liver, colon, kidney and adrenal gland (PubMed:19074135). Expressed in the cortex, amygdala, cerebellum, pons, thalamus, hypothalamus, hippocampus and substantia nigra (PubMed:19074135).

Evidence on tissue expression from TISSUES for KCNB1 Gene

  • Nervous system(4.7)
  • Eye(4.5)
  • Muscle(2.8)
  • Heart(2.4)
  • Kidney(2.2)
  • Pancreas(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for KCNB1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • eye
  • face
  • forehead
  • head
  • lip
  • mouth
  • nose
  • pharynx
  • skull
Thorax:
  • chest wall
  • diaphragm
  • esophagus
  • lung
  • rib
  • rib cage
Abdomen:
  • abdominal wall
  • intestine
  • large intestine
  • stomach
Pelvis:
  • pelvis
  • rectum
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • upper limb
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with KCNB1: view

Orthologs for KCNB1 Gene

This gene was present in the common ancestor of animals.

Orthologs for KCNB1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia KCNB1 30 31
  • 99.73 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia KCNB1 30 31
  • 93.32 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia KCNB1 30 31
  • 91.96 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia KCNB1 31
  • 88 (a)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Kcnb1 30
  • 86.91 (n)
Mouse
(Mus musculus)
 Mammalia Kcnb1 30 17 31
  • 86.62 (n)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia KCNB1 31
  • 75 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves KCNB1 30 31
  • 75.44 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia -- 31
  • 83 (a)
 ManyToMany
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia kcnb1 30
  • 70.22 (n)
African clawed frog
(Xenopus laevis)
 Amphibia kcnb1-A 30
Zebrafish
(Danio rerio)
 Actinopterygii kcnb1 30 31
  • 67.81 (n)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta Shab 31 32
  • 25 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea Y48A6B.6 32
  • 37 (a)
exp-2 32
  • 37 (a)
C32C4.1 32
  • 36 (a)
F44A2.2 32
  • 33 (a)
Y55F3C.3 32
  • 30 (a)
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 70 (a)
 OneToMany
Species where no ortholog for KCNB1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for KCNB1 Gene

ENSEMBL:
Gene Tree for KCNB1 (if available)
TreeFam:
Gene Tree for KCNB1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KCNB1: view image

Paralogs for KCNB1 Gene

Paralogs for KCNB1 Gene

(25) SIMAP similar genes for KCNB1 Gene using alignment to 2 proteins:

  • KCNB1_HUMAN
  • Q2NLD5_HUMAN
genes like me logo Genes that share paralogs with KCNB1: view

Variants for KCNB1 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KCNB1 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
639890 Uncertain Significance: Epileptic encephalopathy, early infantile, 26 49,373,597(-) C/T MISSENSE_VARIANT
645917 Uncertain Significance: Epileptic encephalopathy, early infantile, 26 49,373,497(-) A/G MISSENSE_VARIANT
646121 Benign: Epileptic encephalopathy, early infantile, 26 49,373,905(-) G/A MISSENSE_VARIANT
647049 Uncertain Significance: Epileptic encephalopathy, early infantile, 26 49,374,823(-) A/C MISSENSE_VARIANT
647767 Uncertain Significance: Epileptic encephalopathy, early infantile, 26 49,373,417(-) C/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for KCNB1 Gene

Structural Variations from Database of Genomic Variants (DGV) for KCNB1 Gene

Variant ID Type Subtype PubMed ID
esv2661866 CNV deletion 23128226
esv3568004 CNV loss 25503493
esv3646013 CNV loss 21293372
esv3646014 CNV loss 21293372
nsv1064443 CNV gain 25217958
nsv1067146 CNV loss 25217958
nsv459001 CNV loss 19166990
nsv473424 CNV novel sequence insertion 20440878
nsv509775 CNV insertion 20534489
nsv527882 CNV loss 19592680
nsv586171 CNV loss 21841781
nsv586172 CNV loss 21841781

Variation tolerance for KCNB1 Gene

Residual Variation Intolerance Score: 33.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.42; 42.72% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KCNB1 Gene

Human Gene Mutation Database (HGMD)
KCNB1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KCNB1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KCNB1 Gene

Disorders for KCNB1 Gene

MalaCards: The human disease database

(16) MalaCards diseases for KCNB1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search KCNB1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

KCNB1_HUMAN
  • Epileptic encephalopathy, early infantile, 26 (EIEE26) [MIM:616056]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE26 patients manifest multiple types of seizures, delayed psychomotor development, poor or absent speech, hypotonia, hypsarrhythmia. {ECO:0000269 PubMed:25164438, ECO:0000269 PubMed:26477325, ECO:0000269 PubMed:26503721}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for KCNB1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with KCNB1: view

No data available for Genatlas for KCNB1 Gene

Publications for KCNB1 Gene

  1. Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus. (PMID: 12403834) MacDonald PE … Gaisano HY (Molecular endocrinology (Baltimore, Md.) 2002) 3 4 23
  2. De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing. (PMID: 26477325) Saitsu H … Matsumoto N (Scientific reports 2015) 3 4
  3. A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion selectivity, expression, and localization. (PMID: 26503721) Thiffault I … Sack JT (The Journal of general physiology 2015) 3 4
  4. De novo KCNB1 mutations in epileptic encephalopathy. (PMID: 25164438) Torkamani A … Kearney JA (Annals of neurology 2014) 3 4
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41

ExternalLinks

View latest publications for KCNB1 gene in Mastermind

Products for KCNB1 Gene

  • Addgene plasmids for KCNB1

Sources for KCNB1 Gene