Slc12a3 solute carrier family 12, member 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Slc12a3provided by MGI
Official Full Name: solute carrier family 12, member 3provided by MGI
Primary source: MGI:MGI:108114
See related: Ensembl:ENSMUSG00000031766 AllianceGenome:MGI:108114
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: NCC; TSC; NCCT
Summary: Enables sodium ion transmembrane transporter activity. Involved in sodium ion transport. Located in apical plasma membrane and cytosol. Is expressed in metanephros. Used to study Gitelman syndrome. Human ortholog(s) of this gene implicated in Gitelman syndrome and essential hypertension. Orthologous to human SLC12A3 (solute carrier family 12 member 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Restricted expression toward kidney adult (RPKM 195.7) See more
Orthologs: human all
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Genomic context

Location:: 8 C5; 8 46.46 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (95055737..95092850)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (94329109..94366222)

Chromosome 8 - NC_000074.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential IL18 signaling via IL18 receptor and Na-Cl co-transporter discriminating thermogenesis and glucose metabolism regulation.
Title: Differential IL18 signaling via IL18 receptor and Na-Cl co-transporter discriminating thermogenesis and glucose metabolism regulation.
Multiple molecular mechanisms are involved in the activation of the kidney sodium-chloride cotransporter by hypokalemia.
Title: Multiple molecular mechanisms are involved in the activation of the kidney sodium-chloride cotransporter by hypokalemia.
High dietary potassium causes ubiquitin-dependent degradation of the kidney sodium-chloride cotransporter.
Title: High dietary potassium causes ubiquitin-dependent degradation of the kidney sodium-chloride cotransporter.
Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II-Induced Hypertension.
Title: Renal Natriuretic Peptide Receptor-C Deficiency Attenuates NaCl Cotransporter Activity in Angiotensin II-Induced Hypertension.
Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule.
Title: Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule.
Aldosterone acutely activates NCC to modulate renal NaCl excretion.
Title: Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter.
This study reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.
Title: Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC).
Modulation of WNK4 activity by intracellular chloride [Cl(-)]i is not the sole mechanism for regulating NCC. Increased luminal NaCl delivery upregulates NCC via yet unknown mechanism(s) that may override inhibition of WNK4 by high [Cl(-)]i.
Title: Differential roles of WNK4 in regulation of NCC in vivo.
Aldosterone promotes increased interaction of NCC and ENaC.
Title: Aldosterone Modulates the Association between NCC and ENaC.
Kir4.1 plays an essential role in mediating the effect of dietary potassium intake on NCC activity and potassium homeostasis.
Title: Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel.

Submit: New GeneRIF Correction See all GeneRIFs (55)

Variation

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Alleles

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

Targeted (4) 1 citation
Endonuclease-mediated (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI035291 (e-PCR)
- UniSTS:179783

C78859 (e-PCR)
- UniSTS:185768

Slc12a3 (e-PCR), detects polymorphism
- UniSTS:545985

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables chloride:monoatomic cation symporter activity	IEA Inferred from Electronic Annotation more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables sodium:chloride symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:chloride symporter activity	ISO Inferred from Sequence Orthology more info
enables sodium:potassium:chloride symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables symporter activity	IEA Inferred from Electronic Annotation more info
enables transmembrane transporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell volume homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to inorganic substance	IDA Inferred from Direct Assay more info	PubMed
involved_in chloride ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in chloride transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in renal sodium ion absorption	ISO Inferred from Sequence Orthology more info
involved_in response to aldosterone	IDA Inferred from Direct Assay more info	PubMed
involved_in response to dietary excess	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: solute carrier family 12 member 3

Names: Na-Cl symporter; thiazide-sensitive sodium-chloride cotransporter

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_001205311.1 → NP_001192240.1 solute carrier family 12 member 3 isoform 1

See identical proteins and their annotated locations for NP_001192240.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC128663, AK052691

Consensus CDS

CCDS57632.1

UniProtKB/Swiss-Prot

P59158

UniProtKB/TrEMBL

Q543E4, Q62439

Related

ENSMUSP00000034218.4, ENSMUST00000034218.5

Conserved Domains (3) summary

TIGR00930
Location:57 → 1001

2a30; K-Cl cotransporter

pfam03522
Location:653 → 1001

SLC12; Solute carrier family 12

pfam08403
Location:43 → 113

AA_permease_N; Amino acid permease N-terminal
NM_019415.2 → NP_062288.2 solute carrier family 12 member 3 isoform 2

See identical proteins and their annotated locations for NP_062288.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AI647800, AI882166, AK052691

UniProtKB/TrEMBL

Q62439

Conserved Domains (3) summary

TIGR00930
Location:57 → 1000

2a30; K-Cl cotransporter

pfam03522
Location:652 → 1000

SLC12; Solute carrier family 12

pfam08403
Location:43 → 112

AA_permease_N; Amino acid permease N-terminal

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_000074.7 Reference GRCm39 C57BL/6J

Range

95055737..95092850

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017312625.1 → XP_017168114.1 solute carrier family 12 member 3 isoform X1

UniProtKB/TrEMBL

Q62439

Conserved Domains (1) summary

TIGR00930
Location:57 → 1008

2a30; K-Cl cotransporter
XM_017312626.1 → XP_017168115.1 solute carrier family 12 member 3 isoform X2

UniProtKB/TrEMBL

Q62439

Conserved Domains (1) summary

TIGR00930
Location:57 → 1007

2a30; K-Cl cotransporter
XM_017312627.2 → XP_017168116.1 solute carrier family 12 member 3 isoform X3

Conserved Domains (1) summary

TIGR00930
Location:57 → 561

2a30; K-Cl cotransporter