SLC6A12

Summary

SLC6A12 (solute carrier family 6 member 12, HGNC:11045) is a protein-coding gene on chromosome 12p13.33, encoding Sodium- and chloride-dependent betaine transporter (P48065). Transporter that mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process.

Enables gamma-aminobutyric acid:sodium:chloride symporter activity. Involved in gamma-aminobutyric acid transport and monocarboxylic acid transport. Predicted to be located in basolateral plasma membrane. Predicted to be active in cell projection and plasma membrane.

Source: NCBI Gene 6539 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 93 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001122848

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11045
Approved symbol	SLC6A12
Name	solute carrier family 6 member 12
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Aliases	BGT-1
Ensembl gene	ENSG00000111181
Ensembl biotype	protein_coding
OMIM	603080
Entrez	6539

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 23 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000359674, ENST00000397296, ENST00000424061, ENST00000535347, ENST00000535498, ENST00000536116, ENST00000536824, ENST00000537793, ENST00000537826, ENST00000538272, ENST00000538424, ENST00000538580, ENST00000540094, ENST00000542825, ENST00000544782, ENST00000545058, ENST00000684302, ENST00000855745, ENST00000855746, ENST00000855747, ENST00000855748, ENST00000855749, ENST00000855750, ENST00000855751, ENST00000855752, ENST00000855753, ENST00000855754, ENST00000855755, ENST00000855756, ENST00000855757, ENST00000965394, ENST00000965395, ENST00000965396

RefSeq mRNA: 4 — MANE Select: NM_001122848 NM_001122847, NM_001122848, NM_001206931, NM_003044

CCDS: CCDS8501

Canonical transcript exons

ENST00000684302 — 16 exons

Exon	Start	End
ENSE00000816743	209773	210043
ENSE00001347449	212026	212110
ENSE00003510482	198797	198931
ENSE00003520333	195225	195327
ENSE00003536839	196770	196882
ENSE00003560996	196124	196261
ENSE00003576982	202740	202880
ENSE00003591350	193277	193377
ENSE00003610185	197900	198003
ENSE00003627330	192478	192648
ENSE00003647810	197377	197501
ENSE00003667279	204564	204698
ENSE00003676156	200651	200783
ENSE00003684467	201762	201849
ENSE00003921175	190081	191211
ENSE00003922144	213922	214157

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 97.73.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9800 / max 74.4604, expressed in 252 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128876	0.2230	73
128872	0.1952	133
128871	0.1624	90
128873	0.1220	80
128874	0.1160	60
128870	0.0921	25
128867	0.0247	7
128875	0.0195	8
128869	0.0187	4
128868	0.0064	3

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	97.73	gold quality
right lobe of liver	UBERON:0001114	92.65	gold quality
putamen	UBERON:0001874	88.99	gold quality
right frontal lobe	UBERON:0002810	88.97	gold quality
adult mammalian kidney	UBERON:0000082	88.46	gold quality
caudate nucleus	UBERON:0001873	87.57	gold quality
cingulate cortex	UBERON:0003027	87.38	gold quality
anterior cingulate cortex	UBERON:0009835	87.31	gold quality
amygdala	UBERON:0001876	85.56	gold quality
liver	UBERON:0002107	85.20	gold quality
prefrontal cortex	UBERON:0000451	84.57	gold quality
nucleus accumbens	UBERON:0001882	83.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.47	gold quality
right uterine tube	UBERON:0001302	82.19	gold quality
right lobe of thyroid gland	UBERON:0001119	81.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.56	gold quality
monocyte	CL:0000576	81.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.37	gold quality
left lobe of thyroid gland	UBERON:0001120	81.21	gold quality
mononuclear cell	CL:0000842	80.97	gold quality
leukocyte	CL:0000738	80.59	gold quality
hypothalamus	UBERON:0001898	80.50	gold quality
neocortex	UBERON:0001950	80.28	gold quality
frontal cortex	UBERON:0001870	80.27	gold quality
cerebellar hemisphere	UBERON:0002245	80.00	gold quality
cerebellar cortex	UBERON:0002129	79.79	gold quality
telencephalon	UBERON:0001893	79.60	gold quality
kidney	UBERON:0002113	79.40	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	7.25
E-CURD-10	no	116.83
E-ANND-3	no	2.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFAT5

miRNA regulators (miRDB)

34 targeting SLC6A12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-6072	98.00	66.47	804

Literature-anchored findings (GeneRIF, showing 10)

• The primary structure of BGT-1 predicts two putative phosphorylation sites for the Ca2+/diacylglycerol-dependent protein kinase (PKC), which regulates BGT-1 function by phosphorylation events in a transport system expressed in cultured astrocytoma cells. (PMID:12111824)
• BGT-1 is expressed from mRNA and transports GABA in platelets. (PMID:16198020)
• Results showed that two polymorphisms and a haplotype in SLC6A12, were significantly associated with AIA after multiple testing corrections. (PMID:20597903)
• This study found that rs216250 of SLC6A12 was correlated with the Scale for the Assessment of Negative Symptoms (SANS) scores. (PMID:21367462)
• JAK2 is a novel regulator of the GABA transporter BGT1. (PMID:22405821)
• T40 may be important for the trafficking and insertion of BGT1 in the plasma membrane (PMID:24829506)
• The SLC6A12 expression levels in peripheral blood mononuclear cells were significantly higher in TLE patients. (PMID:26690518)
• This review gathers the current structural and functional knowledge on BGT1 with emphasis on brain relevance, discusses all available compounds, and tries to shed light on the molecular determinants driving BGT1 selectivity–{REVIEW} (PMID:31108110)
• Protein kinases as regulators of osmolyte accumulation under stress conditions: An overview. (PMID:32114438)
• Overexpression of solute carrier family 6 member 12 promotes cell injury in Parkinson’s disease via MAPK signaling pathway. (PMID:38871234)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc6a12	ENSMUSG00000030109
rattus_norvegicus	Slc6a12	ENSRNOG00000013547

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A8 (ENSG00000130821), SLC6A6 (ENSG00000131389), SLC6A11 (ENSG00000132164), SLC6A3 (ENSG00000142319), SLC6A1 (ENSG00000157103), SLC6A20 (ENSG00000163817), SLC6A18 (ENSG00000164363), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Sodium- and chloride-dependent betaine transporter — P48065 (reviewed: P48065)

Alternative names: BGT-1, Na(+)/Cl(-) betaine/GABA transporter, Solute carrier family 6 member 12

All UniProt accessions (3): P48065, F5H2T6, F5H4L6

UniProt curated annotations — full annotation on UniProt →

Function. Transporter that mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation. Probably also involved in renal and hepatic osmotic regulation.

Subunit / interactions. Interacts with LIN7C.

Subcellular location. Basolateral cell membrane. Cell membrane.

Tissue specificity. Expressed in kidney, liver, heart, skeletal muscle, placenta, and a widespread distribution in the brain.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A12 subfamily.

RefSeq proteins (4): NP_001116319, NP_001116320, NP_001193860, NP_003035 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002983	Na/ntran_symport_betaine	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 2 shown:

• 4-aminobutanoate(out) + chloride(out) + 3 Na(+)(out) = 4-aminobutanoate(in) + chloride(in) + 3 Na(+)(in) (RHEA:70731)
• glycine betaine(out) + 2 chloride(out) + 3 Na(+)(out) = glycine betaine(in) + 2 chloride(in) + 3 Na(+)(in) (RHEA:71175)

UniProt features (24 total): transmembrane region 12, topological domain 3, sequence conflict 3, glycosylation site 2, chain 1, region of interest 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9LNN	ELECTRON MICROSCOPY	2.6
9LNM	ELECTRON MICROSCOPY	2.67
9LNO	ELECTRON MICROSCOPY	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48065-F1	88.03	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 157–166

Glycosylation sites (2): 171, 183

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-71288	Creatine metabolism
R-HSA-888593	Reuptake of GABA
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1430728	Metabolism
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-888590	GABA synthesis, release, reuptake and degradation

MSigDB gene sets: 219 (showing top): CREL_01, GOBP_NEUROTRANSMITTER_UPTAKE, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_AMINO_ACID_BETAINE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, NFKB_Q6, NFKB_C, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT

GO Biological Process (9): amino acid transport (GO:0006865), monocarboxylic acid transport (GO:0015718), gamma-aminobutyric acid transport (GO:0015812), glycine betaine transport (GO:0031460), sodium ion transmembrane transport (GO:0035725), gamma-aminobutyric acid reuptake (GO:0051936), amino acid transmembrane transport (GO:0003333), neurotransmitter transport (GO:0006836), transmembrane transport (GO:0055085)

GO Molecular Function (7): gamma-aminobutyric acid:sodium:chloride symporter activity (GO:0005332), monocarboxylic acid transmembrane transporter activity (GO:0008028), amino acid transmembrane transporter activity (GO:0015171), protein binding (GO:0005515), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), cell projection (GO:0042995), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
SLC-mediated transport of amino acids	1
Metabolism of amino acids and derivatives	1
GABA synthesis, release, reuptake and degradation	1
SLC-mediated transmembrane transport	1
Transmission across Chemical Synapses	1
Neuronal System	1
Transport of small molecules	1
Metabolism	1
Neurotransmitter release cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
cellular anatomical structure	3
carboxylic acid transport	2
amino acid transport	2
transmembrane transport	2
nitrogen compound transport	1
amino-acid betaine transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
gamma-aminobutyric acid transport	1
amino acid neurotransmitter reuptake	1
cellular process	1
amino acid:sodium symporter activity	1
organic acid:sodium symporter activity	1
gamma-aminobutyric acid transmembrane transporter activity	1
secondary active monocarboxylate transmembrane transporter activity	1
sodium:chloride symporter activity	1
monocarboxylic acid transport	1
carboxylic acid transmembrane transporter activity	1
amino acid transmembrane transport	1
transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
cation binding	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
synapse	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A12	SLC5A3	P53794	877
SLC6A12	CASTOR3P	Q8NAP1	843
SLC6A12	AKR1B1	P15121	840
SLC6A12	NFAT5	O94916	817
SLC6A12	LIN7A	O14910	567
SLC6A12	BHMT	Q93088	538
SLC6A12	GAD1	Q99259	523
SLC6A12	LIN7B	Q9HAP6	520
SLC6A12	SLC32A1	Q9H598	517
SLC6A12	GABRD	O14764	512
SLC6A12	GAD2	Q05329	508
SLC6A12	GABRA5	P31644	506
SLC6A12	LIN7C	Q9NUP9	498
SLC6A12	SLC47A1	Q96FL8	491
SLC6A12	NFATC1	O95644	485

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SCRIB	SLC6A12	psi-mi:“MI:0915”(physical association)	0.570
SLC6A12	SCRIB	psi-mi:“MI:0915”(physical association)	0.570
SLC6A12	REL	psi-mi:“MI:0915”(physical association)	0.560
CD79A	SLC6A12	psi-mi:“MI:0915”(physical association)	0.560
RHCG	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC6A12	CD79A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (194): SLC6A12 (Two-hybrid), SLC6A12 (Two-hybrid), SLC6A12 (Affinity Capture-MS), ABHD12 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), LPHN2 (Affinity Capture-MS), ADPGK (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT4 (Affinity Capture-MS), AIG1 (Affinity Capture-MS), ALDH3A2 (Affinity Capture-MS), ALG10 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), APH1B (Affinity Capture-MS)

ESM2 similar proteins: A5PJX7, A7Y2W8, O18875, O35316, O35899, O55192, O88576, P23975, P23977, P23978, P27799, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651, P31652, P31661, P48029, P48055, P48056, P48057, P48065, P48066, P51143, P51905, Q00589, Q01959, Q28039, Q2PG55, Q60857

Diamond homologs: A5PJX7, A7Y2W8, A7Y2X0, B3MRS1, B3NV41, B4GVM9, B4JMC1, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBN9, O18875, O35316, O35899, O45813, O55192, O76689, O88575, O88576, P23975, P23977, P23978, P27799, P27922, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
85375-15-1	down-regulates	SLC6A12	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

93 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	13
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2453 predictions. Top by Δscore:

Variant	Effect	Δscore
12:191210:CG:C	acceptor_gain	1.0000
12:192480:T:A	donor_gain	1.0000
12:193388:A:C	acceptor_gain	1.0000
12:193392:C:CT	acceptor_gain	1.0000
12:195235:G:C	donor_gain	1.0000
12:196118:GCTCA:G	donor_loss	1.0000
12:196119:CTCA:C	donor_loss	1.0000
12:196120:TCA:T	donor_loss	1.0000
12:196121:CA:C	donor_loss	1.0000
12:196123:C:CT	donor_loss	1.0000
12:196258:CAAA:C	acceptor_gain	1.0000
12:196260:AA:A	acceptor_gain	1.0000
12:196262:C:CC	acceptor_gain	1.0000
12:197372:CCTA:C	donor_loss	1.0000
12:197373:CTAC:C	donor_loss	1.0000
12:197374:TACCT:T	donor_loss	1.0000
12:197375:A:AC	donor_gain	1.0000
12:197375:A:AT	donor_loss	1.0000
12:197376:C:CC	donor_gain	1.0000
12:197376:CCTGA:C	donor_gain	1.0000
12:197499:TCC:T	acceptor_gain	1.0000
12:197500:CC:C	acceptor_gain	1.0000
12:197500:CCC:C	acceptor_gain	1.0000
12:197501:CC:C	acceptor_gain	1.0000
12:197502:C:CC	acceptor_gain	1.0000
12:197532:C:CT	acceptor_gain	1.0000
12:197896:TCAC:T	donor_loss	1.0000
12:197898:A:AC	donor_gain	1.0000
12:197898:A:T	donor_loss	1.0000
12:197899:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000060618 (12:207691 T>C), RS1000120998 (12:213003 A>G), RS1000211201 (12:205415 T>C), RS1000415090 (12:207953 C>T), RS1000435189 (12:197140 T>C), RS1000451702 (12:211829 C>G), RS1000478755 (12:188699 G>A), RS1000481869 (12:210132 G>A), RS1000505359 (12:211526 G>A), RS1000546931 (12:204141 G>A), RS1000557440 (12:200646 C>G,T), RS1000727714 (12:209314 T>C), RS1000869786 (12:192896 G>A,C), RS1000896375 (12:184566 C>A,T), RS1000929911 (12:192750 A>G)

Disease associations

OMIM: gene MIM:603080 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000649_10	Chronic kidney disease	1.000000e-09
GCST001852_6	Metabolite levels	2.000000e-10
GCST002875_57	Diisocyanate-induced asthma	1.000000e-06
GCST009391_1914	Metabolite levels	2.000000e-12
GCST012020_445	Serum metabolite levels	8.000000e-23

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0006995	response to diisocyanate
EFO:0010464	beta-aminoisobutyric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3715 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 160,188 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1	160,188

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs557881	Toxicity	3	aspirin	Asthma

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs499368	SLC6A12		0.00	0
rs557881	SLC6A12	3	2.50	1	aspirin

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — GABA transporter subfamily

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
NNC052090	Inhibition	5.9	pKi
(R/S) EF-1500	Inhibition	4.9	pIC50
(R)-EF-1520	Inhibition	4.66	pIC50
(S)-EF-1520	Inhibition	4.47	pIC50
LU32-176B	Inhibition	4.0	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Dimethyl-[2-(1,7,7-trimethyl-2-phenyl-bicyclo[2.2.1]hept-2-yloxy)-ethyl]-amine	IC50	39000 nM

ChEMBL bioactivities

82 potent at pChembl≥5 of 146 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.23	IC50	590	nM	CHEMBL3326391
6.07	IC50	851.1	nM	GAMMA-AMINOBUTYRIC ACID
6.00	IC50	1000	nM	GAMMA-AMINOBUTYRIC ACID
5.81	IC50	1549	nM	GAMMA-AMINOBUTYRIC ACID
5.80	Ki	1600	nM	CHEMBL1164505
5.79	IC50	1622	nM	CHEMBL1882801
5.78	IC50	1660	nM	CHEMBL1882801
5.70	IC50	2000	nM	CHEMBL1882801
5.70	IC50	2000	nM	GAMMA-AMINOBUTYRIC ACID
5.66	IC50	2188	nM	GAMMA-AMINOBUTYRIC ACID
5.54	IC50	2884	nM	CHEMBL1882801
5.52	IC50	3000	nM	CHEMBL1882801
5.52	IC50	3000	nM	GAMMA-AMINOBUTYRIC ACID
5.52	IC50	3000	nM	CHEMBL4526098
5.50	IC50	3162	nM	CHEMBL4526098
5.48	IC50	3311	nM	GAMMA-AMINOBUTYRIC ACID
5.44	IC50	3631	nM	GAMMA-AMINOBUTYRIC ACID
5.41	IC50	3890	nM	GAMMA-AMINOBUTYRIC ACID
5.40	IC50	3981	nM	GAMMA-AMINOBUTYRIC ACID
5.40	IC50	4000	nM	GAMMA-AMINOBUTYRIC ACID
5.40	IC50	3981	nM	CHEMBL349005
5.39	IC50	4074	nM	CHEMBL1882801
5.38	IC50	4169	nM	GAMMA-AMINOBUTYRIC ACID
5.31	IC50	4898	nM	CHEMBL1882801
5.30	IC50	5000	nM	CHEMBL1882801
5.30	IC50	5000	nM	GAMMA-AMINOBUTYRIC ACID
5.30	IC50	5000	nM	CHEMBL349005
5.29	IC50	5100	nM	CHEMBL1446457
5.29	IC50	5129	nM	CHEMBL1882801
5.29	IC50	5129	nM	GAMMA-AMINOBUTYRIC ACID
5.27	IC50	5370	nM	GAMMA-AMINOBUTYRIC ACID
5.26	IC50	5480	nM	CHEMBL2415009
5.26	IC50	5480	nM	CHEMBL3040189
5.26	IC50	5495	nM	CHEMBL1882801
5.26	IC50	5495	nM	GAMMA-AMINOBUTYRIC ACID
5.23	IC50	5888	nM	CHEMBL1882801
5.22	IC50	6026	nM	CHEMBL1882801
5.22	IC50	6000	nM	CHEMBL1882801
5.22	IC50	6000	nM	GAMMA-AMINOBUTYRIC ACID
5.18	IC50	6607	nM	CHEMBL1882801
5.18	IC50	6607	nM	GAMMA-AMINOBUTYRIC ACID
5.16	IC50	7000	nM	CHEMBL1882801
5.16	IC50	7000	nM	GAMMA-AMINOBUTYRIC ACID
5.15	IC50	7079	nM	CHEMBL1882801
5.14	IC50	7300	nM	CHEMBL4458674
5.13	IC50	7413	nM	GAMMA-AMINOBUTYRIC ACID
5.12	IC50	7586	nM	GAMMA-AMINOBUTYRIC ACID
5.10	IC50	7943	nM	CHEMBL1882801
5.10	IC50	8000	nM	CHEMBL1882801
5.10	IC50	7943	nM	CHEMBL4060376

PubChem BioAssay actives

82 with measured affinity, of 268 total; 12 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,2S,5R)-5-aminobicyclo[3.1.0]hexane-2-carboxylic acid	1188933: Inhibition of human BGT1 transfected in CHO cells assessed as [3H]GABA uptake after 20 mins by liquid scintillation counting analysis	ic50	0.5900	uM
.gamma.-aminobutyric acid	1476530: Inhibition of human BGT1 Q299L mutant expressed in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method	ic50	0.8511	uM
1-(3-carbazol-9-ylpropyl)-4-(4-methoxyphenyl)piperidin-4-ol	487221: Binding affinity to BGT-1	ki	1.6000	uM
N-(1-benzylpiperidin-4-yl)-2,4-dichlorobenzamide	1476555: Inhibition of human BGT1/human GAT3 chimera D expresses in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method	ic50	1.6218	uM
2-(2-amino-4,5-dihydro-1H-imidazol-5-yl)acetic acid	1599053: Inhibition of human BGT1 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	3.0000	uM
2-[(3S)-pyrrolidin-3-yl]acetic acid	1599053: Inhibition of human BGT1 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	3.9811	uM
1-(3-carbazol-9-ylpropyl)-4-(2-methoxyphenyl)piperidin-4-ol	1188933: Inhibition of human BGT1 transfected in CHO cells assessed as [3H]GABA uptake after 20 mins by liquid scintillation counting analysis	ic50	5.1000	uM
2-[(1S,2S)-2-aminocyclopropyl]acetic acid	1188933: Inhibition of human BGT1 transfected in CHO cells assessed as [3H]GABA uptake after 20 mins by liquid scintillation counting analysis	ic50	5.4800	uM
2-[(1S,2R)-2-aminocyclopropyl]acetic acid;hydrochloride	764975: Inhibition of human BGT1 transfected in CHO cells assessed as [3H]GABA uptake after 20 mins by liquid scintillation counting analysis	ic50	5.4800	uM
2-(4,5-dihydro-1H-imidazol-5-yl)acetic acid	1599053: Inhibition of human BGT1 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	7.3000	uM
N-(1-benzylpiperidin-4-yl)-2,6-dichloropyridine-3-carboxamide	1476530: Inhibition of human BGT1 Q299L mutant expressed in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method	ic50	7.9433	uM
2-[(3R)-pyrrolidin-3-yl]acetic acid	1599053: Inhibition of human BGT1 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	7.9433	uM

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	4
Cisplatin	affects cotreatment, decreases expression, affects response to substance	2
Diethylhexyl Phthalate	decreases expression, increases expression	2
Estradiol	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression, affects expression	2
aristolochic acid I	increases expression	1
Esketamine	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation, affects cotreatment	1
sodium arsenate	increases abundance, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
myxothiazol	decreases reaction, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Aspirin	affects response to substance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1

ChEMBL screening assays

50 unique, capped per target: 48 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1166725	Binding	Binding affinity to BGT-1	Azetidine derivatives as novel gamma-aminobutyric acid uptake inhibitors: synthesis, biological evaluation, and structure-activity relationship. — Eur J Med Chem
CHEMBL5209603	Functional	Substrate uptake by the Sodium- and Chloride-Dependent BetaineTransporter (BGT-1, SLC6A12) as assessed by the fluorescent FLIPR membrane potential dye in HEK-293 JumpIN-SLC6A12 cells (PubChem AID: 1794822)	Membrane potential based assay for SLC6A12 using HEK-293 SLC6A12 OE cells

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4UB	HuH7-SLC6A12-KO-c3	Cancer cell line	Male
CVCL_D4UC	HuH7-SLC6A12-KO-c8	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.