KCNC3 potassium voltage-gated channel subfamily C member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNC3provided by HGNC
Official Full Name: potassium voltage-gated channel subfamily C member 3provided by HGNC
Primary source: HGNC:HGNC:6235
See related: Ensembl:ENSG00000131398 MIM:176264; AllianceGenome:HGNC:6235
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: KV3.3; SCA13; KSHIIID
Summary: The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Alternate splicing results in several transcript variants. [provided by RefSeq, Mar 2014]
Expression: Broad expression in brain (RPKM 4.9), kidney (RPKM 2.9) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.33

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (50311937..50333536, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (53399467..53421072, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (50815194..50836793, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Study expanded the genotype-phenotype-pathophysiology repertoire of SCA13 by addition of a causative KCNC3 mutation, p.Pro583_Pro585del, its associated phenotype of profound spasticity, and the decreased inactivation rate of the mutant channel.
Title: C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity.
results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology
Title: A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.
This review covers the localization and physiological function of Kv3.3 in the central nervous system and how the normal function of the channel is altered by the disease-causing mutations
Title: Kv3.3 potassium channels and spinocerebellar ataxia.
Kv3.3 regulates Arp2/3-dependent cortical actin nucleation mediated by Hax-1; resulting cortical actin structures interact with the channel's gating machinery to slow its inactivation rate during sustained membrane depolarizations; a mutation that leads to late-onset spinocerebellar ataxia type 13.
Title: Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.
The Kv channels, or at least Kv3.3, appear to be associated with cell differentiation
Title: Voltage-Gated K+ Channel, Kv3.3 Is Involved in Hemin-Induced K562 Differentiation.
Functional and in silico analysis identified at least one novel pathogenic mutation in KCNC3 that cause Spinocerebellar ataxia type 13 (SCA13) and two additionally potential ones.
Title: Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia cases.
investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2
Title: De novo point mutations in patients diagnosed with ataxic cerebral palsy.
These results are specific to the KCNC3(R420H) allele and provide new insight into the molecular basis of disease manifestation in SCA13.
Title: KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking.
Data indicate that an autosomal dominant mutation in the gene encoding Kv3.3 has been identified in a large Filipino kindred manifesting as spinocerebellar ataxia type 13 (SCA13).
Title: Mutation in the kv3.3 voltage-gated potassium channel causing spinocerebellar ataxia 13 disrupts sound-localization mechanisms.
no disease-related KCNC3 mutation was identified, suggesting that spinocerebellar ataxia type 13 is a rare form of SCA in mainland China
Title: Spinocerebellar ataxia type 13 is an uncommon SCA subtype in the Chinese Han population.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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

Associated conditions

Description	Tests
Spinocerebellar ataxia type 13 MedGen: C1854488 OMIM: 605259 GeneReviews: Hereditary Ataxia Overview, Spinocerebellar Ataxia Type 13	Compare labs

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

D19S553 (e-PCR)
- UniSTS:149250

RH27338 (e-PCR)
- UniSTS:85691

D19S219 (e-PCR), detects polymorphism
- UniSTS:57818

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables delayed rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated potassium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein homooligomerization	IEA Inferred from Electronic Annotation more info
involved_in protein tetramerization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in axon terminus	IBA Inferred from Biological aspect of Ancestor more info
located_in cell cortex	IEA Inferred from Electronic Annotation more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in dendrite membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine membrane	IEA Inferred from Electronic Annotation more info
is_active_in neuronal cell body membrane	IBA Inferred from Biological aspect of Ancestor 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	TAS Traceable Author Statement more info
is_active_in postsynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in presynaptic membrane	IBA Inferred from Biological aspect of Ancestor 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 C member 3

Names: Shaw-related voltage-gated potassium channel protein 3; potassium channel, voltage gated Shaw related subfamily C, member 3; potassium voltage-gated channel, Shaw-related subfamily, member 3; voltage-gated potassium channel protein KV3.3; voltage-gated potassium channel subunit Kv3.3

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_008134.2 RefSeqGene

Range

5001..22441

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_668

mRNA and Protein(s)

NM_001372305.1 → NP_001359234.1 potassium voltage-gated channel subfamily C member 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding region, compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AC008655

UniProtKB/TrEMBL

E7ETH1

Conserved Domains (3) summary

PHA03247
Location:561 → 676

PHA03247; large tegument protein UL36; Provisional

cd18414
Location:13 → 126

BTB_KCNC1_3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily C members KCNC1 and KCNC3

pfam00520
Location:213 → 474

Ion_trans; Ion transport protein
NM_004977.3 → NP_004968.2 potassium voltage-gated channel subfamily C member 3 isoform 1

See identical proteins and their annotated locations for NP_004968.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AC008655, AF055989

Consensus CDS

CCDS12793.1

UniProtKB/Swiss-Prot

Q14003

UniProtKB/TrEMBL

E7ETH1

Related

ENSP00000434241.1, ENST00000477616.2

Conserved Domains (4) summary

PHA03247
Location:637 → 752

PHA03247; large tegument protein UL36; Provisional

pfam11404
Location:1 → 18

Potassium_chann; Potassium voltage-gated channel

cd18414
Location:89 → 202

BTB_KCNC1_3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily C members KCNC1 and KCNC3

pfam00520
Location:289 → 550

Ion_trans; Ion transport protein

RNA

NR_110912.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AC008655, AK127492

Related

ENST00000474951.1