Slc12a6 solute carrier family 12, member 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Slc12a6provided by MGI
Official Full Name: solute carrier family 12, member 6provided by MGI
Primary source: MGI:MGI:2135960
See related: Ensembl:ENSMUSG00000027130 Ensembl:ENSMUSG00000096764 AllianceGenome:MGI:2135960
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: KCC3; gaxp; 9530023I19Rik
Summary: Enables potassium:chloride symporter activity and protein kinase binding activity. Involved in cellular response to glucose stimulus; chloride ion homeostasis; and potassium ion homeostasis. Located in axon and basolateral plasma membrane. Is expressed in nervous system and sensory organ. Used to study agenesis of the corpus callosum with peripheral neuropathy and motor peripheral neuropathy. Human ortholog(s) of this gene implicated in Charcot-Marie-Tooth disease and agenesis of the corpus callosum with peripheral neuropathy. Orthologous to human SLC12A6 (solute carrier family 12 member 6). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in bladder adult (RPKM 21.4), thymus adult (RPKM 18.0) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 E3; 2 56.99 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (112096659..112193508)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (112266314..112363163)

Chromosome 2 - NC_000068.8 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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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Erythroid-specific inactivation of Slc12a6/Kcc3 by EpoR promoter-driven Cre expression reduces K-Cl cotransport activity in mouse erythrocytes.
Title: Erythroid-specific inactivation of Slc12a6/Kcc3 by EpoR promoter-driven Cre expression reduces K-Cl cotransport activity in mouse erythrocytes.
Temporal manipulation of KCC3 expression in juvenile or adult mice suggests irreversible developmental deficit in hereditary motor sensory neuropathy with agenesis of the corpus callosum.
Title: Temporal manipulation of KCC3 expression in juvenile or adult mice suggests irreversible developmental deficit in hereditary motor sensory neuropathy with agenesis of the corpus callosum.
Osmotic Response of Dorsal Root Ganglion Neurons Expressing Wild-Type and Mutant KCC3 Transporters.
Title: Osmotic Response of Dorsal Root Ganglion Neurons Expressing Wild-Type and Mutant KCC3 Transporters.
the effect of genetic inactivation of K-Cl cotransporters KCC1 and KCC3 in a mouse model of beta-thalassemia intermedia; conclude that genetic inactivation of K-Cl cotransport can reverse red cell dehydration and partially attenuate the hematologic phenotype in a mouse model of beta-thalassemia.
Title: Genetic disruption of KCC cotransporters in a mouse model of thalassemia intermedia.
effect of genetic inactivation of KCC3 and KCC1 in the SAD mouse model of sickle red cell dehydration, finding decreased red cell density and improved hematological indices.
Title: Combined genetic disruption of K-Cl cotransporters and Gardos channel KCNN4 rescues erythrocyte dehydration in the SAD mouse model of sickle cell disease.
Results reveal the role of electrical activity in the process of neuromuscular junction (NMJ) denervation and subsequent neurodegeneration in Andermann syndrome. Study found that loss of KCC3 function is associated with an abnormal intrinsic neuronal electrical activity. Notably, we show that pharmacologically decreasing the firing frequency of Slc12a6-/- motoneurons partially rescues innervation at the NMJ.
Title: KCC3 loss-of-function contributes to Andermann syndrome by inducing activity-dependent neuromuscular junction defects.
electrophysiological studies using the threshold tracking technique indicated a reduced stimulus-response curve slope with an elevated rheobase, a decreased strength-duration time constant, diminished persistent Na(+) currents, and an outward deviation of threshold electrotonus in KCC3(-/-) nerves compared to wild-type nerves
Title: KCC3 deficiency-induced disruption of paranodal loops and impairment of axonal excitability in the peripheral nervous system.
These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration.
Title: Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter.
Kcc3 inactivation caused systemic vascular resistance and ventricular mass to increase while preventing extracellular fluid volume to accumulate.
Title: Ablation of Potassium-Chloride Cotransporter Type 3 (Kcc3) in Mouse Causes Multiple Cardiovascular Defects and Isosmotic Polyuria.
The results establish that the parvalbumin-positive neuronal population is an important player in the pathogenic development of peripheral neuropathy associated with agenesis of the corpus callosum.
Title: Deletion of KCC3 in parvalbumin neurons leads to locomotor deficit in a conditional mouse model of peripheral neuropathy associated with agenesis of the corpus callosum.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4) 1 citation
Gene trapped (1)
Spontaneous (1)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Slc12a6 (e-PCR), detects polymorphism
- UniSTS:546994

D2Dcr58 (e-PCR), detects polymorphism
- UniSTS:507617

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ammonium channel activity	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables potassium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables potassium:chloride symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium:chloride symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium:chloride symporter activity	ISO Inferred from Sequence Orthology more info
enables potassium:chloride symporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in ammonium import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in cell volume homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell volume homeostasis	IEA Inferred from Electronic Annotation more info
involved_in cell volume homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cellular hypotonic response	ISO Inferred from Sequence Orthology more info
involved_in cellular hypotonic salinity response	ISO Inferred from Sequence Orthology more info
involved_in cellular hypotonic salinity response	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucose stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	ISO Inferred from Sequence Orthology more info
involved_in potassium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion import across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in potassium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in potassium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
NOT located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: solute carrier family 12 member 6

Names: K-Cl cotransporter 3; electroneutral potassium-chloride cotransporter 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.

mRNA and Protein(s)

NM_001362700.1 → NP_001349629.1 solute carrier family 12 member 6 isoform 3

Status: VALIDATED

Source sequence(s)

AL683897, AL713853

UniProtKB/TrEMBL

Q6P6P5

Related

ENSMUSP00000124314.2, ENSMUST00000141047.2

Conserved Domains (1) summary

TIGR00930
Location:94 → 1135

2a30; K-Cl cotransporter
NM_133648.2 → NP_598409.2 solute carrier family 12 member 6 isoform 1

See identical proteins and their annotated locations for NP_598409.2

Status: VALIDATED

Source sequence(s)

AK133006, AL683897, BC036323, BC051061

Consensus CDS

CCDS16552.1

UniProtKB/TrEMBL

Q6P6P5

Related

ENSMUSP00000051490.8, ENSMUST00000053666.8

Conserved Domains (3) summary

TIGR00930
Location:58 → 1099

2a30; K-Cl cotransporter

pfam03522
Location:723 → 1099

SLC12; Solute carrier family 12

cl00456
Location:158 → 309

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_133649.2 → NP_598410.2 solute carrier family 12 member 6 isoform 2

See identical proteins and their annotated locations for NP_598410.2

Status: VALIDATED

Source sequence(s)

AK133006, BC036323, BC051061

Consensus CDS

CCDS16551.1

UniProtKB/Swiss-Prot

A2AGK1, Q924N3, Q924N4

UniProtKB/TrEMBL

Q3V0N8

Related

ENSMUSP00000028549.8, ENSMUST00000028549.14

Conserved Domains (3) summary

TIGR00930
Location:109 → 1150

2a30; K-Cl cotransporter

pfam03522
Location:774 → 1150

SLC12; Solute carrier family 12

cl00456
Location:209 → 360

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

112096659..112193508

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006498546.5 → XP_006498609.1 solute carrier family 12 member 6 isoform X1

UniProtKB/TrEMBL

Q6P6P5

Conserved Domains (1) summary

TIGR00930
Location:43 → 1084

2a30; K-Cl cotransporter