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FLASH GENE

Symbol

SLC12A6

contributors: mct/npt - updated : 09-06-2021

HGNC name	solute carrier family 12 (potassium/chloride transporters), member 6
HGNC id	10914

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ACCPN corpus callosum, agenesis of, with neuronopathy
Location	15q14      Physical location : 34.522.197 - 34.630.265
Synonym name	potassium chloride cotransporter 3
	potassium chloride cotransporter KCC3a-S3
	electroneutral potassium-chloride cotransporter 3
	K-Cl cotransporter 3
Synonym symbol(s)	KCC3, KCC3A, KCC3B, ACCPN, DKFZp434D2135

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head
STRUCTURE	108.70 kb     25 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001365088 26 - 8072 NP_001352017 - 1150 - 2016 27485015 NM_133647 25 - 7502 NP_598408 - 1150 - 2016 27485015 NM_005135 25 - 7327 NP_005126 - 1099 - 2016 27485015 NM_001042494 23 - 7688 NP_001035959 - 1091 - 2016 27485015 NM_001042495 26 - 7363 NP_001035960 - 1091 - 2016 27485015 NM_001042496 25 - 7754 NP_001035961 - 1141 - 2016 27485015 NM_001042497 23 - 7457 NP_001035962 - 1135 - 2016 27485015

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Hearing/Equilibrium ear inner       Nervous plexus choroid       highly   spinal cord         Homo sapiens Respiratory lung       highly Urinary kidney tubule Henles loop   highly Homo sapiens Visual eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly Nervous central white matter     Homo sapiens Nervous peripherous       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a variable N-terminal region
	twelve transmembrane segments (12TM)
	a large extracellular loop with five N-glycosylation sites
	a large C-terminal domain (CTD) within the cytoplasm, critical for function, possibly due to defective protein–protein interactions

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to C.Elegans k02a2.3

Homologene

FAMILY	KCC family
	SLC12A transporter family

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm

basic FUNCTION	playing a role in the development and maintenance of the nervous system
	down-regulating E-cadherin/beta-catenin complex formation by inhibiting transcription of E-cadherin gene and accelerating proteosome-dependent degradation of beta-catenin protein, promoting epithelial-mesenchymal transition, thereby stimulating tumor progression
	play an important role in the maintenance of cellular homeostasis (Adragna 2007)
	role for SLC12A6 in the proximal tubule glucose reabsorption mechanism and for SLC12A7 in salt reabsorption of the thick ascending loop of Henle's loop and acid secretion of the collecting duct
	function of the peripheral nervous system depends likely on finely tuned, kinase-regulated SLC12A6 activity, implicating abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration
	is responsible for the efflux of K+ and Cl- in neurons to help maintain cell volume and intracellular chloride levels
	releases chloride with potassium ions at the basolateral membrane

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	amino-acid transporter

PATHWAY

metabolism

signaling

novel pathway modulating the cell surface expression of SLC12A1 and SLC12A6 and this same pathway has opposite functional outcomes for these two cotransporters

a component

INTERACTION

DNA

RNA

small molecule

protein	potent negative regulator for E-cadherin gene expression
	interaction with CKB has a major impact on the activity of the co-transporter, similar to the functional defect of ACCPN truncated variant
	STK39 plays a role in regulating many biological activities, and interacts with SLC12A6

cell & other

REGULATION

activated by

IGF1 (plays an important role in IGF1 receptor signaling to promote growth and spread of breast cancer cells) (Hsu 2007)

repressed by

decreased by TNF

Other

upregulated in vascular endothelial cells by VEGF

ASSOCIATED DISORDERS

corresponding disease(s)

ACCPN

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   contribute to IGF1-enhanced KCC activity (Hsu 2007)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS