KCNN3 potassium calcium-activated channel subfamily N member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNN3provided by HGNC
Official Full Name: potassium calcium-activated channel subfamily N member 3provided by HGNC
Primary source: HGNC:HGNC:6292
See related: Ensembl:ENSG00000143603 MIM:602983; AllianceGenome:HGNC:6292
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: SK3; ZLS3; hSK3; SKCA3; KCa2.3
Summary: Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
Expression: Broad expression in brain (RPKM 8.1), endometrium (RPKM 1.9) and 16 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (154697455..154870281, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (153834568..154009637, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (154669931..154842757, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

Preferential formation of human heteromeric SK2:SK3 channels limits homomeric SK channel assembly and function.
Title: Preferential formation of human heteromeric SK2:SK3 channels limits homomeric SK channel assembly and function.
The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction.
Title: The role of SK3 in progesterone-induced inhibition of human fallopian tubal contraction.
Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
Title: Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
Hypoxia Promotes Prostate Cancer Aggressiveness by Upregulating EMT-Activator Zeb1 and SK3 Channel Expression.
Title: Hypoxia Promotes Prostate Cancer Aggressiveness by Upregulating EMT-Activator Zeb1 and SK3 Channel Expression.
HDAC2-dependent remodeling of KCa2.2 (KCNN2) and KCa2.3 (KCNN3) K(+) channels in atrial fibrillation with concomitant heart failure.
Title: HDAC2-dependent remodeling of K(Ca)2.2 (KCNN2) and K(Ca)2.3 (KCNN3) K(+) channels in atrial fibrillation with concomitant heart failure.
Liability of the voltage-gated potassium channel KCNN3 repeat polymorphism to acute oxaliplatin-induced peripheral neurotoxicity.
Title: Liability of the voltage-gated potassium channel KCNN3 repeat polymorphism to acute oxaliplatin-induced peripheral neurotoxicity.
Immuno-visualization of the subcellular localization of SK2 and SK3 subunits showed a high degree of colocalization, consistent with the formation of heteromeric SK2/SK3 channels.
Title: Role of SK channel activation in determining the action potential configuration in freshly isolated human atrial myocytes from the SKArF study.
Gain-of-Function Mutations in KCNN3 gene Causes Zimmermann-Laband Syndrome.
Title: Gain-of-Function Mutations in KCNN3 Encoding the Small-Conductance Ca(2+)-Activated K(+) Channel SK3 Cause Zimmermann-Laband Syndrome.
he clinical implication of these findings is that KCNN3 polymorphism may increase patient susceptibility to taxane neurotoxicity and that the use of SK3 blockers during taxanes' administration may represent an interesting approach for the prevention of this neurotoxicity.
Title: SK3 Gene Polymorphism Is Associated with Taxane Neurotoxicity and Cell Calcium Homeostasis.
Authors observed a slight association between OIN and CAG repeat polymorphisms of the KCNN3 gene in a preclinical model, but not a clinical study.
Title: Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity.

Submit: New GeneRIF Correction See all GeneRIFs (68)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Zimmermann-laband syndrome 3 MedGen: C5231447 OMIM: 618658 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common variants in KCNN3 are associated with lone atrial fibrillation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies six new susceptibility loci for atrial fibrillation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AL033640 (e-PCR)
- UniSTS:93475

AF021127 (e-PCR)
- UniSTS:5427

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-148977 (e-PCR)
- UniSTS:176716

L18426 (e-PCR)
- UniSTS:34648

SHGC-145644 (e-PCR)
- UniSTS:174701

SHGC-145645 (e-PCR)
- UniSTS:174702

D1S1423 (e-PCR)
- UniSTS:149619

G35510 (e-PCR)
- UniSTS:44150

G16005 (e-PCR)
- UniSTS:43402

D16S325 (e-PCR)
- UniSTS:147089

KCNN3_897 (e-PCR)
- UniSTS:277433

SHGC-147087 (e-PCR)
- UniSTS:172747

D5S1597E (e-PCR)
- UniSTS:151019

SHGC-81767 (e-PCR)
- UniSTS:103926

STS-Y08263 (e-PCR)
- UniSTS:23544

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IDA Inferred from Direct Assay more info	PubMed
enables inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small conductance calcium-activated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables small conductance calcium-activated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
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

Component	Evidence Code	Pubs
located_in Z disc	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: small conductance calcium-activated potassium channel protein 3

Names: SKCa 3; potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 3; potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3; small conductance calcium-activated potassium channel 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_016807.2 RefSeqGene

Range

4998..177824

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204087.2 → NP_001191016.1 small conductance calcium-activated potassium channel protein 3 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (c, also known as SK3-ex4) containing a 15 aa protein segment that is not found in isoform a. This variant does not have independent transcript support; it was based on a publication (PMID:14978258) that reports that this variant is widely expressed in different tissues, and the encoded isoform is active, but exhibits different pharmacological properties compared to isoform a.

Source sequence(s)

AJ251016, AL390204, AL606500, AW135188, BC042147

Consensus CDS

CCDS72928.1

UniProtKB/TrEMBL

A0A087WYJ0, Q6JXY2

Related

ENSP00000481848.1, ENST00000618040.4

Conserved Domains (4) summary

pfam02888
Location:576 → 648

CaMBD; Calmodulin binding domain

pfam03530
Location:273 → 380

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:508 → 562

Ion_trans_2; Ion channel

cl09111
Location:610 → 688

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...
NM_001365837.1 → NP_001352766.1 small conductance calcium-activated potassium channel protein 3 isoform d

Status: REVIEWED

Source sequence(s)

AL390204, AL606500, AL954342

Conserved Domains (4) summary

pfam02888
Location:263 → 335

CaMBD; Calmodulin binding domain

pfam03530
Location:1 → 67

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:195 → 249

Ion_trans_2; Ion channel

cl09111
Location:297 → 375

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...
NM_001365838.1 → NP_001352767.1 small conductance calcium-activated potassium channel protein 3 isoform e

Status: REVIEWED

Source sequence(s)

AL390204, AL606500, AL954342

Consensus CDS

CCDS91063.1

Related

ENSP00000351295.2, ENST00000358505.2

Conserved Domains (4) summary

smart01053
Location:248 → 323

CaMBD; Calmodulin binding domain

pfam03530
Location:1 → 67

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:155 → 234

Ion_trans_2; Ion channel

cl09111
Location:288 → 360

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...
NM_002249.6 → NP_002240.3 small conductance calcium-activated potassium channel protein 3 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform a (also known as SK3).

Source sequence(s)

AJ251016, AL390204, AL606500, AW135188, BC042147

Consensus CDS

CCDS30880.1

UniProtKB/Swiss-Prot

B1ANX0, O43517, Q86VF9, Q8WXG7, Q9UGI6

UniProtKB/TrEMBL

Q6JXY2

Related

ENSP00000271915.3, ENST00000271915.9

Conserved Domains (4) summary

pfam02888
Location:561 → 633

CaMBD; Calmodulin binding domain

pfam03530
Location:273 → 380

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:468 → 547

Ion_trans_2; Ion channel

cl09111
Location:595 → 673

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...
NM_170782.3 → NP_740752.1 small conductance calcium-activated potassium channel protein 3 isoform b

See identical proteins and their annotated locations for NP_740752.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1, resulting in translation initiation from a different start codon, and a shorter isoform (b) with a distinct N-terminus compared to isoform a. This isoform lacks the two CAG repeat regions.

Source sequence(s)

AA284005, AL390204, AL606500, AW135188, BC042147

Consensus CDS

CCDS1072.1

UniProtKB/Swiss-Prot

Q9UGI6

Related

ENSP00000354764.4, ENST00000361147.8

Conserved Domains (4) summary

pfam02888
Location:256 → 328

CaMBD; Calmodulin binding domain

pfam03530
Location:6 → 75

SK_channel; Calcium-activated SK potassium channel

pfam07885
Location:163 → 242

Ion_trans_2; Ion channel

cl09111
Location:290 → 368

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...