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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC6A12
solute carrier family 6 member 12
Chromosome 12 · 12p13.33
NCBI Gene: 6539Ensembl: ENSG00000111181.14HGNC: HGNC:11045UniProt: P48065
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
gamma-aminobutyric acid:sodium:chloride symporter activityprotein bindingmonocarboxylic acid transmembrane transporter activitymonocarboxylic acid transportAbnormality of the skeletal systemIGA glomerulonephritisvascular diseaserenal carcinoma
✦AI Summary

SLC6A12 encodes a sodium- and chloride-dependent transporter that mediates cellular uptake of GABA and betaine 1. The transporter plays critical roles in GABAergic neurotransmission through GABA reuptake into presynaptic terminals and in osmotic regulation 1. In cancer biology, SLC6A12 demonstrates significant pathological relevance. In hepatocellular carcinoma, SLC6A12 transports GABA, which directly stabilizes β-catenin and activates Wnt/β-catenin signaling, promoting metastasis 2. In ovarian cancer, aberrant hypomethylation of the SLC6A12 promoter increases expression 8.1-14.0-fold in metastases, enhancing cell migration and invasion 3. Downregulated lncRNAs regulate SLC6A12 expression in cholangiocarcinoma through transcription factor recruitment 4. SLC6A12 also contributes to neuroinflammatory and autoimmune diseases. In rheumatoid arthritis, high salt promotes macrophage pyroptosis through SLC6A12-mediated sodium transport and SGK1/p38 MAPK/NF-κB signaling activation 5. In Parkinson's disease, elevated SLC6A12 expression promotes neuronal injury via MAPK signaling 6. A genetic polymorphism (rs216250) associates with negative symptoms in schizophrenia 7, and SLC6A12 variants are implicated in aspirin-exacerbated respiratory disease 8. These findings position SLC6A12 as a multifunctional transporter with therapeutic potential across cancer, neurological, and inflammatory diseases.

Sources cited
1
SLC6A12 mediates sodium- and chloride-dependent cellular uptake of betaine and GABA; involved in GABAergic transmission and osmotic regulation
PMID: 7589472
2
SLC6A12 transports GABA in hepatocellular carcinoma; GABA stabilizes β-catenin to activate Wnt/β-catenin signaling and promote metastasis
PMID: 39740661
3
SLC6A12 expression is 8.1-14.0-fold upregulated in ovarian cancer metastases with promoter hypomethylation; overexpression increases migration and invasion
PMID: 27873492
4
lncRNAs lnc-SLC6A12-1:3 and lnc-SLC6A12-7:5 regulate SLC6A12 and GAD1 expression in cholangiocarcinoma through transcription factor recruitment
PMID: 40578094
5
High salt promotes macrophage pyroptosis through SLC6A12-mediated sodium transport activating SGK1 and p38 MAPK/NF-κB signaling in rheumatoid arthritis
PMID: 38904021
6
SLC6A12 expression is elevated in Parkinson's disease; overexpression promotes neuronal injury via MAPK signaling pathway
PMID: 38871234
7
SLC6A12 polymorphism rs216250 correlates with negative symptoms in schizophrenia
PMID: 21367462
8
SLC6A12 polymorphisms are associated with aspirin-exacerbated respiratory disease
PMID: 37011853
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.11Weak
IGA glomerulonephritisOpen Targets
0.07Suggestive
vascular diseaseOpen Targets
0.07Suggestive
renal carcinomaOpen Targets
0.06Suggestive
chronic kidney diseaseOpen Targets
0.06Suggestive
respiratory tract infectious disorderOpen Targets
0.06Suggestive
sleep apneaOpen Targets
0.06Suggestive
Barrett's esophagusOpen Targets
0.06Suggestive
Cognitive impairmentOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
Parkinson diseaseOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
placenta praeviaOpen Targets
0.04Suggestive
cholangiocarcinomaOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
juvenile idiopathic arthritisOpen Targets
0.03Suggestive
epilepsyOpen Targets
0.03Suggestive
gastroesophageal reflux diseaseOpen Targets
0.03Suggestive
acute liver failureOpen Targets
0.03Suggestive
restless legs syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
AKR1B1Protein interaction84%SLC5A3Protein interaction84%NFAT5Protein interaction79%SLC6A11Shared pathway63%SLC6A16Shared pathway60%SLC6A8Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Brain
12%
Lung
2%
Ovary
1%
Bone Marrow
1%
Heart
1%
Gene Interaction Network
Click a node to explore
SLC6A12AKR1B1SLC5A3NFAT5SLC6A11SLC6A16SLC6A8
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P48065
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.52–0.86]
RankingsWhere SLC6A12 stands among ~20K protein-coding genes
  • #11,802of 20,598
    Most Researched31
  • #7,598of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedSLC6A12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The de novo synthesis of GABA and its gene regulatory function control hepatocellular carcinoma metastasis.
PMID: 39740661
Dev Cell · 2025
1.00
2
Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12.
PMID: 38904021
Int J Biol Sci · 2024
0.90
3
Association between the SLC6A12 gene and negative symptoms of schizophrenia in a Korean population.
PMID: 21367462
Psychiatry Res · 2011
0.80
4
Aberrant Hypomethylation of Solute Carrier Family 6 Member 12 Promoter Induces Metastasis of Ovarian Cancer.
PMID: 27873492
Yonsei Med J · 2017
0.70
5
Decoding the role of novel long noncoding RNAs lnc-SLC6A12-1:3 and lnc-SLC6A12-7:5 in regulating the expression of GAD1 and SLC6A12 in cholangiocarcinoma.
PMID: 40578094
Comput Biol Chem · 2025
0.60