SLC12A2 solute carrier family 12 member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC12A2provided by HGNC
Official Full Name: solute carrier family 12 member 2provided by HGNC
Primary source: HGNC:HGNC:10911
See related: Ensembl:ENSG00000064651 MIM:600840; AllianceGenome:HGNC:10911
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: BSC; BSC2; CCC1; BSC-2; KILQS; NKCC1; PPP1R141
Summary: The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
Expression: Broad expression in colon (RPKM 25.6), stomach (RPKM 18.8) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q23.3

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (128083766..128189677)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (128602602..128708515)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (127419458..127525369)

Chromosome 5 - NC_000005.10 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: 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?

Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.
Title: Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.
NKCC1: Newly Found as a Human Disease-Causing Ion Transporter.
Title: NKCC1: Newly Found as a Human Disease-Causing Ion Transporter.
Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.
Title: Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.
[Expression of cation chloride cotransporter (NKCC1/KCC2) in brain tissue of children with focal cortical dysplasia type ].
Title: [Expression of cation chloride cotransporter (NKCC1/KCC2) in brain tissue of children with focal cortical dysplasia type Ⅱ].
Loss of NKCC1 function increases epithelial tight junction permeability by upregulating claudin-2 expression.
Title: Loss of NKCC1 function increases epithelial tight junction permeability by upregulating claudin-2 expression.
NKCC1 to KCC2 mRNA Ratio in Schizophrenia and Its Psychopathology: a Case-Control Study.
Title: NKCC1 to KCC2 mRNA Ratio in Schizophrenia and Its Psychopathology: a Case-Control Study.
Further confirmation of the association of SLC12A2 with non-syndromic autosomal-dominant hearing impairment.
Title: Further confirmation of the association of SLC12A2 with non-syndromic autosomal-dominant hearing impairment.
PNPT1, MYO15A, PTPRQ, and SLC12A2-associated genetic and phenotypic heterogeneity among hearing impaired assortative mating families in Southern India.
Title: PNPT1, MYO15A, PTPRQ, and SLC12A2-associated genetic and phenotypic heterogeneity among hearing impaired assortative mating families in Southern India.
GWAS Identifies LINC01184/SLC12A2 as a Risk Locus for Skin and Soft Tissue Infections.
Title: GWAS Identifies LINC01184/SLC12A2 as a Risk Locus for Skin and Soft Tissue Infections.
Clinical characterization and further confirmation of the autosomal recessive SLC12A2 disease.
Title: Clinical characterization and further confirmation of the autosomal recessive SLC12A2 disease.

Submit: New GeneRIF Correction See all GeneRIFs (78)

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
Delpire-McNeill syndrome MedGen: C5436771 OMIM: 619083 GeneReviews: Not available	Compare labs
Hearing loss, autosomal dominant 78 MedGen: C5436768 OMIM: 619081 GeneReviews: Not available	Compare labs
Kilquist syndrome MedGen: C5436756 OMIM: 619080 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. EBI GWAS Catalog EBI GWAS CatalogPubMed
A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D10S275 (e-PCR)
- UniSTS:147992

016YB7 (e-PCR)
- UniSTS:29480

D8S2279 (e-PCR)
- UniSTS:473907

A006Y26 (e-PCR)
- UniSTS:36168

STS-N22107 (e-PCR)
- UniSTS:25949

SGC35509 (e-PCR)
- UniSTS:43113

bac5341T (e-PCR)
- UniSTS:181617

D1S1423 (e-PCR)
- UniSTS:149619

SLC12A2_2056 (e-PCR)
- UniSTS:281000

bac51423S (e-PCR)
- UniSTS:181460

bac51488T (e-PCR)
- UniSTS:181469

SGC32885 (e-PCR)
- UniSTS:22497

SHGC-79547 (e-PCR)
- UniSTS:103671

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Hsp90 protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ammonium transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables ammonium transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables chloride:monoatomic cation symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium ion transmembrane transporter 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-folding chaperone binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:potassium:chloride symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium:potassium:chloride symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:potassium:chloride symporter activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in T cell chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ammonium transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in ammonium transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in cell volume homeostasis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cell volume homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell volume homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of cell volume homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to chemokine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to potassium ion	ISS Inferred from Sequence or Structural Similarity 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
involved_in chloride transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in chloride transmembrane transport	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within gamma-aminobutyric acid signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in hyperosmotic response	IEA Inferred from Electronic Annotation more info
involved_in inorganic anion import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in inorganic cation import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within intracellular chloride ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within intracellular chloride ion homeostasis	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within intracellular potassium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within intracellular sodium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within maintenance of blood-brain barrier	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of maintenance of blood-brain barrier	TAS Traceable Author Statement more info	PubMed
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
acts_upstream_of_or_within negative regulation of vascular wound healing	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of aspartate secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell volume	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 import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of matrix metallopeptidase secretion	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of spontaneous synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in sodium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in transepithelial ammonium transport	IDA Inferred from Direct Assay more info	PubMed
involved_in transepithelial chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

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 basal plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in basolateral plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in cell body membrane	TAS Traceable Author Statement more info	PubMed
located_in cell periphery	IDA Inferred from Direct Assay more info	PubMed
located_in cell periphery	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cell projection	ISS Inferred from Sequence or Structural Similarity more info
located_in cell projection membrane	TAS Traceable Author Statement more info	PubMed
located_in cytoplasmic vesicle membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular vesicle	HDA more info	PubMed
located_in lateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	RCA inferred from Reviewed Computational Analysis more info	PubMed
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: solute carrier family 12 member 2

Names: basolateral Na-K-Cl symporter; bumetanide-sensitive cotransporter type 2; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2; protein phosphatase 1, regulatory subunit 141; solute carrier family 12 (sodium/potassium/chloride transporter), member 2; solute carrier family 12 (sodium/potassium/chloride transporters), member 2

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_042286.1 RefSeqGene

Range

4976..110887

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001046.3 → NP_001037.1 solute carrier family 12 member 2 isoform 1

See identical proteins and their annotated locations for NP_001037.1

Status: REVIEWED

Description

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

Source sequence(s)

AA425438, AA425619, AA843086, AC011332, AK025062, AV708692, AY280459, BC033003, BM978607, U30246

Consensus CDS

CCDS4144.1

UniProtKB/Swiss-Prot

P55011, Q8N713, Q8WWH7

UniProtKB/TrEMBL

B7ZM24, Q53ZR1

Related

ENSP00000262461.2, ENST00000262461.7

Conserved Domains (1) summary

TIGR00930
Location:216 → 1212

2a30; K-Cl cotransporter
NM_001256461.2 → NP_001243390.1 solute carrier family 12 member 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC008577, AC011332, AI493213, AY280459, BC144221

Consensus CDS

CCDS58965.1

UniProtKB/TrEMBL

B7ZM24

Related

ENSP00000340878.4, ENST00000343225.4

Conserved Domains (3) summary

TIGR00930
Location:216 → 1196

2a30; K-Cl cotransporter

pfam03522
Location:801 → 1196

SLC12; Solute carrier family 12

pfam08403
Location:202 → 263

AA_permease_N; Amino acid permease N-terminal

RNA

NR_046207.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice junction in the 3' end that truncates the coding sequence compared to variant 1. The resulting transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is therefore thought not to be proten-coding.

Source sequence(s)

AC008577, AC011332, AI493213, AY280459, BC033003

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

128083766..128189677

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417591.1 → XP_047273547.1 solute carrier family 12 member 2 isoform X1

Related

ENSP00000486323.1, ENST00000628403.2
XM_011543588.3 → XP_011541890.1 solute carrier family 12 member 2 isoform X2

Conserved Domains (1) summary

pfam08403
Location:202 → 263

AA_permease_N; Amino acid permease N-terminal
XM_047417592.1 → XP_047273548.1 solute carrier family 12 member 2 isoform X3