Slc12a4 solute carrier family 12, member 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Slc12a4provided by MGI
Official Full Name: solute carrier family 12, member 4provided by MGI
Primary source: MGI:MGI:1309465
See related: Ensembl:ENSMUSG00000017765 AllianceGenome:MGI:1309465
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: KCC1; RBCKCC1
Summary: Predicted to enable potassium:chloride symporter activity and protein kinase binding activity. Predicted to be involved in several processes, including cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Predicted to act upstream of or within potassium ion transport. Predicted to be located in membrane. Predicted to be integral component of membrane. Is expressed in several structures, including adrenal gland; genitourinary system; liver; retina; and spleen. Orthologous to human SLC12A4 (solute carrier family 12 member 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in ovary adult (RPKM 36.4), lung adult (RPKM 32.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 D3; 8 53.06 cM

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (106670222..106692781, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (105943590..105966149, complement)

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:

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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?

KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria.
Title: KCC1 Activation protects Mice from the Development of Experimental Cerebral Malaria.
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.
data indicate that Zn(2+) acting via ZnR/GPR39 has a direct role in controlling Cl(-) absorption via upregulation of basolateral KCC1 in the colon. Moreover, colonocytic ZnR/GPR39 and KCC1 reduce water loss during diarrhea and may therefore serve as effective drug targets.
Title: The Zn(2+)-sensing receptor, ZnR/GPR39, upregulates colonocytic Cl(-) absorption, via basolateral KCC1, and reduces fluid loss.
We show that a single mutant allele of Kcc1 induces widespread sickling and tissue damage, leading to premature death in a humanized mouse model of sickle cell disease
Title: Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model.
KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 that could result in modulation of KCC activity
Title: K-Cl cotransporter gene expression during human and murine erythroid differentiation.
Treatment of cells expressing mouse K-Cl cotransporter Kcc1 with several chemical cross-linkers shifted Kcc1 polypeptide to higher MW forms. The N-terminal & C-terminal cytoplasmic tails of Kcc1 were not essential for Kcc1 crosslinking.
Title: Chemical crosslinking studies with the mouse Kcc1 K-Cl cotransporter.
Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) with the cotransporters KCC3, NKCC1, and NKCC2 but not KCC1 and KCC4
Title: Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1).

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Variation

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Alleles

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

Targeted (2) 1 citation
Chemically induced (ENU) (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW546649 (e-PCR)
- UniSTS:179806

RH44404 (e-PCR)
- UniSTS:48741

RH125919 (e-PCR)
- UniSTS:142734

Slc12a4 (e-PCR), detects polymorphism
- UniSTS:546993

BB400374 (e-PCR)
- UniSTS:208323

RH124920 (e-PCR)
- UniSTS:161742

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables chloride:monoatomic cation symporter activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation 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 protein kinase binding	ISO Inferred from Sequence Orthology 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 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 transmembrane transport	IBA Inferred from Biological aspect of Ancestor 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 potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: solute carrier family 12 member 4

Names: K-Cl Co-transporter-1; K-Cl cotransporter KCC1; electroneutral potassium-chloride cotransporter 1; erythroid K-Cl cotransporter 1; mKCC1

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_001253804.1 → NP_001240733.1 solute carrier family 12 member 4 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and it encodes the longest protein (isoform 1).

Source sequence(s)

AK149969, AK159274, AK164479, BY740705

Consensus CDS

CCDS57642.1

UniProtKB/TrEMBL

F8WIJ0, Q3UDQ8

Related

ENSMUSP00000034370.10, ENSMUST00000034370.17

Conserved Domains (3) summary

TIGR00930
Location:44 → 1087

2a30; K-Cl cotransporter

pfam03522
Location:711 → 1087

SLC12; Solute carrier family 12

cl00456
Location:144 → 305

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_009195.3 → NP_033221.1 solute carrier family 12 member 4 isoform 2

See identical proteins and their annotated locations for NP_033221.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses a different splice site in the 5' coding region, compared to variant 1. The resulting protein (isoform 2) is shorter than isoform 1 by two amino acids.

Source sequence(s)

AK159274, BY740705

Consensus CDS

CCDS22623.1

UniProtKB/Swiss-Prot

O55069, Q9ET57, Q9JIS8

UniProtKB/TrEMBL

Q3TLV0, Q3TWV2, Q3TWZ6, Q3U9N0, Q6NXV2

Related

ENSMUSP00000112130.3, ENSMUST00000116429.9

Conserved Domains (3) summary

TIGR00930
Location:42 → 1085

2a30; K-Cl cotransporter

pfam03522
Location:709 → 1085

SLC12; Solute carrier family 12

cl00456
Location:142 → 303

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

RNA

NR_045594.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses a different splice site in the 3' end, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK149969, AK159274, AK169044, BY740705

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

106670222..106692781 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006530792.2 → XP_006530855.1 solute carrier family 12 member 4 isoform X1

UniProtKB/TrEMBL

Q3TLV0, Q3TWV2, Q3U689, Q3U9N0, Q6NXV2

Conserved Domains (1) summary

TIGR00930
Location:63 → 1080

2a30; K-Cl cotransporter