SLC12A6 solute carrier family 12 member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC12A6provided by HGNC
Official Full Name: solute carrier family 12 member 6provided by HGNC
Primary source: HGNC:HGNC:10914
See related: Ensembl:ENSG00000140199 MIM:604878; AllianceGenome:HGNC:10914
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: KCC3; ACCPN; KCC3A; KCC3B; CMT2II
Summary: This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]
Expression: Broad expression in testis (RPKM 15.1), bone marrow (RPKM 10.0) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q14

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (34229784..34338057, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (32028044..32136362, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (34521985..34630258, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype.
Title: Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype.
Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.
Title: Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.
ZnR/GPR39 controls cell migration by orchestrating recruitment of KCC3 into protrusions, re-organization of actin and activation of MMP.
Title: ZnR/GPR39 controls cell migration by orchestrating recruitment of KCC3 into protrusions, re-organization of actin and activation of MMP.
De novo variants in SLC12A6 cause sporadic early-onset progressive sensorimotor neuropathy.
Title: De novo variants in SLC12A6 cause sporadic early-onset progressive sensorimotor neuropathy.
SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus.
Title: SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus.
AS may also occur in the Roma population with a new mutation being found: frameshift mutation c.2604delT in the exon 20 of the SLC12A6 gene. Roma patients with probable AS should be primarily tested for this mutation.
Title: First case of Roma ethnic origin with Andermann syndrome: A novel frameshift mutation in exon 20 of SLC12A6 gene.
we present the first Mexican patients with hereditary motor and sensory neuropathy with agenesis of the corpus callosum and a novel heterozygous frameshift variant, c.2097du p or p.(Trp700Leufs*19) of the SLC12A6 gene
Title: Identification of a novel SLC12A6 pathogenic variant associated with hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) in a non-French-Canadian family.
Neurodegenerative deficits in hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.
Title: KCC3 axonopathy: neuropathological features in the central and 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.
These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.
Title: The K-Cl cotransporter KCC3 as an independent prognostic factor in human esophageal squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (29)

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
Agenesis of the corpus callosum with peripheral neuropathy MedGen: C0795950 OMIM: 218000 GeneReviews: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum	Compare labs
Charcot-Marie-Tooth disease, axonal, IIa 2II MedGen: C5774227 OMIM: 620068 GeneReviews: Not available	Compare labs

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

D8S2279 (e-PCR)
- UniSTS:473907

sY3084 (e-PCR)
- UniSTS:515126

SHGC-53908 (e-PCR)
- UniSTS:7259

D15S1477 (e-PCR)
- UniSTS:474482

SHGC-57948 (e-PCR)
- UniSTS:42866

D11S3114 (e-PCR)
- UniSTS:152207

STS-M55683 (e-PCR)
- UniSTS:24479

RH46282 (e-PCR)
- UniSTS:90576

GDB:631802 (e-PCR)
- UniSTS:158429

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ammonium transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion 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	TAS Traceable Author Statement more info
enables protein kinase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in ammonium import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in angiogenesis	NAS Non-traceable Author Statement more info	PubMed
involved_in cell volume homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell volume homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular hypotonic salinity response	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation 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 ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in chloride transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic ion transport	TAS Traceable Author Statement more info
involved_in potassium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion homeostasis	ISS Inferred from Sequence or Structural Similarity 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

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation 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; potassium chloride cotransporter 3; potassium chloride cotransporter KCC3a-S3; potassium-chloride transporter-3a; potassium-chloride transporter-3b; solute carrier family 12 (potassium/chloride transporter), member 6; solute carrier family 12 (potassium/chloride transporters), member 6

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_007951.1 RefSeqGene

Range

5001..113069

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_270

mRNA and Protein(s)

NM_001042494.2 → NP_001035959.1 solute carrier family 12 member 6 isoform c

See identical proteins and their annotated locations for NP_001035959.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an additional exon in its 5' UTR and uses an alternate in-frame splice site in the first protein coding exon, compared to variant 1. The encoded protein (isoform c) uses a downstream start codon, compared to isoform a.

Source sequence(s)

AC021822, AC079203, AF531259

Consensus CDS

CCDS42012.1

UniProtKB/TrEMBL

Q6NSI7

Related

ENSP00000387725.2, ENST00000458406.6

Conserved Domains (3) summary

TIGR00930
Location:50 → 1091

2a30; K-Cl cotransporter

pfam03522
Location:715 → 1091

SLC12; Solute carrier family 12

cl00456
Location:150 → 301

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_001042495.2 → NP_001035960.1 solute carrier family 12 member 6 isoform c

See identical proteins and their annotated locations for NP_001035960.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an additional exon in its 5' UTR and uses an alternate in-frame splice site in the first protein coding exon, compared to variant 1. The encoded protein (isoform c) uses a downstream start codon, compared to isoform a.

Source sequence(s)

AC079203, BC070107

Consensus CDS

CCDS42012.1

UniProtKB/TrEMBL

Q6NSI7

Related

ENSP00000380814.2, ENST00000397702.6

Conserved Domains (3) summary

TIGR00930
Location:50 → 1091

2a30; K-Cl cotransporter

pfam03522
Location:715 → 1091

SLC12; Solute carrier family 12

cl00456
Location:150 → 301

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_001042496.2 → NP_001035961.1 solute carrier family 12 member 6 isoform d

See identical proteins and their annotated locations for NP_001035961.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) has an additional exon in its 5' UTR and uses an alternate in-frame splice site in the first protein coding exon, compared to variant 1. The encoded protein (isoform d) uses a downstream start codon, compared to isoform a.

Source sequence(s)

AC021822, AC079203, DQ138323

Consensus CDS

CCDS42011.1

UniProtKB/TrEMBL

A8K935

Related

ENSP00000452776.1, ENST00000558589.5

Conserved Domains (3) summary

TIGR00930
Location:100 → 1141

2a30; K-Cl cotransporter

pfam03522
Location:765 → 1141

SLC12; Solute carrier family 12

cl00456
Location:200 → 351

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
NM_001042497.2 → NP_001035962.1 solute carrier family 12 member 6 isoform e

See identical proteins and their annotated locations for NP_001035962.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an alternate in-frame exon in the coding region, compared to variant 1. The encoded protein (isoform e) is shorter, compared to isoform a.

Source sequence(s)

AC021822, AC079203, AF531258

Consensus CDS

CCDS42010.1

UniProtKB/TrEMBL

A8K935

Related

ENSP00000380819.2, ENST00000397707.6

Conserved Domains (1) summary

TIGR00930
Location:94 → 1135

2a30; K-Cl cotransporter
NM_001365088.1 → NP_001352017.1 solute carrier family 12 member 6 isoform a

Status: REVIEWED

Source sequence(s)

AC079203, AF116242, AF477977, BC033894, BC051744, BX648195

Consensus CDS

CCDS58352.1

UniProtKB/Swiss-Prot

A0AV76, Q2VI00, Q7Z2E7, Q7Z4G5, Q8TDD4, Q9UFR2, Q9UHW9, Q9Y642, Q9Y665

UniProtKB/TrEMBL

A8K935

Related

ENSP00000346112.3, ENST00000354181.8

Conserved Domains (1) summary

TIGR00930
Location:109 → 1150

2a30; K-Cl cotransporter
NM_005135.2 → NP_005126.1 solute carrier family 12 member 6 isoform b

See identical proteins and their annotated locations for NP_005126.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon for the 5' UTR and 5' coding region, compared to variant 1. The encoded protein (isoform b) is shorter and has a distinct N-terminus, compared to isoform a.

Source sequence(s)

AC021822, AC079203, AF108831

Consensus CDS

CCDS10036.1

UniProtKB/TrEMBL

Q6NSI7

Related

ENSP00000290209.5, ENST00000290209.9

Conserved Domains (1) summary

TIGR00930
Location:58 → 1099

2a30; K-Cl cotransporter
NM_133647.2 → NP_598408.1 solute carrier family 12 member 6 isoform a

See identical proteins and their annotated locations for NP_598408.1

Status: REVIEWED

Description

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

Source sequence(s)

AC021822, AC079203, AF105366

Consensus CDS

CCDS58352.1

UniProtKB/Swiss-Prot

A0AV76, Q2VI00, Q7Z2E7, Q7Z4G5, Q8TDD4, Q9UFR2, Q9UHW9, Q9Y642, Q9Y665

UniProtKB/TrEMBL

A8K935

Related

ENSP00000454168.1, ENST00000560611.5

Conserved Domains (1) summary

TIGR00930
Location:109 → 1150

2a30; K-Cl cotransporter

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_000015.10 Reference GRCh38.p14 Primary Assembly

Range

34229784..34338057 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006720793.5 → XP_006720856.1 solute carrier family 12 member 6 isoform X1

UniProtKB/TrEMBL

A8K935

Conserved Domains (3) summary

TIGR00930
Location:109 → 1101

2a30; K-Cl cotransporter

pfam03522
Location:725 → 1101

SLC12; Solute carrier family 12

cl00456
Location:184 → 311

SLC5-6-like_sbd; Solute carrier families 5 and 6-like; solute binding domain
XM_047433396.1 → XP_047289352.1 solute carrier family 12 member 6 isoform X2

Related

ENSP00000452705.1, ENST00000560164.5
XM_011522269.4 → XP_011520571.1 solute carrier family 12 member 6 isoform X3

Conserved Domains (2) summary

TIGR00930
Location:109 → 680

2a30; K-Cl cotransporter

cl00456
Location:209 → 360

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