KCND2 potassium voltage-gated channel subfamily D member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCND2provided by HGNC
Official Full Name: potassium voltage-gated channel subfamily D member 2provided by HGNC
Primary source: HGNC:HGNC:6238
See related: Ensembl:ENSG00000184408 MIM:605410; AllianceGenome:HGNC:6238
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RK5; KV4.2
Summary: 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, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels. [provided by RefSeq, Jul 2008]
Expression: Biased expression in brain (RPKM 4.5), endometrium (RPKM 1.1) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q31.31

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (120272908..120750337)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (121573495..122065688)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (119913229..120390391)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

KCND2 variants associated with global developmental delay differentially impair Kv4.2 channel gating.
Title: KCND2 variants associated with global developmental delay differentially impair Kv4.2 channel gating.
Structural basis of gating modulation of Kv4 channel complexes.
Title: Structural basis of gating modulation of Kv4 channel complexes.
Potassium voltage-gated channel subfamily D member 2 induces an aggressive phenotype in lung adenocarcinoma.
Title: Potassium voltage-gated channel subfamily D member 2 induces an aggressive phenotype in lung adenocarcinoma.
Modulation of Kv4.2/KChIP3 interaction by the ceroid lipofuscinosis neuronal 3 protein CLN3.
Title: Modulation of Kv4.2/KChIP3 interaction by the ceroid lipofuscinosis neuronal 3 protein CLN3.
The atrial-specific phenotype suggests that targeting Kv4.2 might be effective in the treatment of nocturnal paroxysmal atrial fibrillation, avoiding adverse ventricular effects.
Title: Nocturnal Atrial Fibrillation Caused by Mutation in KCND2, Encoding Pore-Forming (α) Subunit of the Cardiac Kv4.2 Potassium Channel.
KCND2 upregulation is a valuable prognostic biomarker in gastric cancer patients, in terms of overall survival and recurrence-free survival.
Title: KCND2 upregulation might be an independent indicator of poor survival in gastric cancer.
A mutation, V404M, in the Kv4.2 channel subunit is associated with infant-onset epilepsy and autism. V404M enhances inactivation of channels that have not opened but dramatically impairs inactivation after opening. Authors show that increased side-chain volume is largely responsible for these seemingly paradoxical effects.
Title: Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening.
Our results do not support the notion that accessory KChIP2 binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP2 binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes.
Title: Somatodendritic surface expression of epitope-tagged and KChIP binding-deficient Kv4.2 channels in hippocampal neurons.
Ca(2+)/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons.
Title: Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway.
closed-state inactivation in Kv4.2 channels is a multistep process
Title: Intra- and Intersubunit Dynamic Binding in Kv4.2 Channel Closed-State Inactivation.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide search for replicable risk gene regions in alcohol and nicotine co-dependence. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:1317200 (e-PCR)
- UniSTS:5899

SHGC-81435 (e-PCR)
- UniSTS:103191

WI-18408 (e-PCR)
- UniSTS:49713

D7S2892 (e-PCR)
- UniSTS:31801

G63116 (e-PCR)
- UniSTS:140091

RH75415 (e-PCR)
- UniSTS:85566

WI-19785 (e-PCR)
- UniSTS:44874

G49386 (e-PCR)
- UniSTS:109141

D7S1915 (e-PCR)
- UniSTS:22366

RH118760 (e-PCR)
- UniSTS:138094

MDB1071 (e-PCR)
- UniSTS:125044

A004D07 (e-PCR)
- UniSTS:62590

SHGC-112257 (e-PCR)
- UniSTS:168576

D7S2093E (e-PCR)
- UniSTS:69002

UniSTS:498320 (e-PCR)
- UniSTS:498320

Kcnd2 (e-PCR), detects polymorphism
- UniSTS:498320

D7S1436 (e-PCR)
- UniSTS:59536

G31102 (e-PCR)
- UniSTS:83347

KCND2_881 (e-PCR)
- UniSTS:277414

D7S2487 (e-PCR)
- UniSTS:6839

D7S1652 (e-PCR)
- UniSTS:36285

D7S2487 (e-PCR)
- UniSTS:43746

GDB:6028511 (e-PCR)
- UniSTS:64494

GDB:3755049 (e-PCR)
- UniSTS:10738

D7S99 (e-PCR)
- UniSTS:42751

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables A-type (transient outward) potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables A-type (transient outward) potassium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables A-type (transient outward) potassium channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated potassium channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables voltage-gated potassium channel activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in action potential	IDA Inferred from Direct Assay more info	PubMed
involved_in action potential	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
involved_in locomotor rhythm	IEA Inferred from Electronic Annotation more info
involved_in membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle contraction	IDA Inferred from Direct Assay more info	PubMed
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein homooligomerization	IEA Inferred from Electronic Annotation more info
involved_in regulation of heart contraction	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of pain	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in GABA-ergic synapse	IEA Inferred from Electronic Annotation more info
part_of Kv4.2-KChIP2 channel complex	IPI Inferred from Physical Interaction more info	PubMed
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	NAS Non-traceable Author Statement more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in plasma membrane raft	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in postsynaptic specialization membrane	IEA Inferred from Electronic Annotation more info
part_of voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: potassium voltage-gated channel subfamily D member 2

Names: potassium channel, voltage gated Shal related subfamily D, member 2; voltage-gated potassium channel subunit Kv4.2; voltage-sensitive potassium channel

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_034230.1 RefSeqGene

Range

4508..481670

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_012281.3 → NP_036413.1 potassium voltage-gated channel subfamily D member 2

See identical proteins and their annotated locations for NP_036413.1

Status: REVIEWED

Source sequence(s)

AC004888, AC004946, AC092020, BC110449

Consensus CDS

CCDS5776.1

UniProtKB/Swiss-Prot

O95012, O95021, Q2TBD3, Q9NZV8, Q9UBY7, Q9UN98, Q9UNH9

UniProtKB/TrEMBL

A4D0V9

Related

ENSP00000333496.4, ENST00000331113.9

Conserved Domains (3) summary

cl38908
Location:6 → 144

BTB_POZ; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain superfamily

pfam00520
Location:184 → 415

Ion_trans; Ion transport protein

pfam11879
Location:445 → 546

DUF3399; Domain of unknown function (DUF3399)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

120272908..120750337

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047420346.1 → XP_047276302.1 potassium voltage-gated channel subfamily D member 2 isoform X1

UniProtKB/Swiss-Prot

O95012, O95021, Q2TBD3, Q9NZV8, Q9UBY7, Q9UN98, Q9UNH9

UniProtKB/TrEMBL

A4D0V9

Alternate T2T-CHM13v2.0

Genomic

NC_060931.1 Alternate T2T-CHM13v2.0

Range

121573495..122065688

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054358166.1 → XP_054214141.1 potassium voltage-gated channel subfamily D member 2 isoform X1

UniProtKB/Swiss-Prot

O95012, O95021, Q2TBD3, Q9NZV8, Q9UBY7, Q9UN98, Q9UNH9

UniProtKB/TrEMBL

A4D0V9