SLC6A11

Summary

SLC6A11 (solute carrier family 6 member 11, HGNC:11044) is a protein-coding gene on chromosome 3p25.3, encoding Sodium- and chloride-dependent GABA transporter 3 (P48066). Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA).

The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6538 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 90 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11044
Approved symbol	SLC6A11
Name	solute carrier family 6 member 11
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	GAT3
Ensembl gene	ENSG00000132164
Ensembl biotype	protein_coding
OMIM	607952
Entrez	6538

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000254488, ENST00000454147, ENST00000464828, ENST00000861594

RefSeq mRNA: 2 — MANE Select: NM_014229 NM_001317406, NM_014229

CCDS: CCDS2602, CCDS82734

Canonical transcript exons

ENST00000254488 — 14 exons

Exon	Start	End
ENSE00000965777	10929202	10929339
ENSE00000965778	10933151	10933253
ENSE00000965779	10934066	10934166
ENSE00000965780	10935029	10935199
ENSE00001030301	10844214	10844346
ENSE00001030302	10918329	10918453
ENSE00001030305	10819465	10819599
ENSE00001030307	10819712	10819852
ENSE00001030310	10874961	10875095
ENSE00001030311	10823302	10823392
ENSE00001134573	10938250	10940714
ENSE00001134577	10816228	10816521
ENSE00001719085	10912090	10912193
ENSE00001797582	10926004	10926116

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 88.86.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2423 / max 220.8659, expressed in 225 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35310	2.2423	225

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	88.86	gold quality
hypothalamus	UBERON:0001898	88.23	gold quality
nucleus accumbens	UBERON:0001882	85.83	gold quality
globus pallidus	UBERON:0001875	84.95	gold quality
substantia nigra	UBERON:0002038	84.89	gold quality
right frontal lobe	UBERON:0002810	84.19	gold quality
cingulate cortex	UBERON:0003027	83.95	gold quality
anterior cingulate cortex	UBERON:0009835	83.86	gold quality
midbrain	UBERON:0001891	83.23	gold quality
amygdala	UBERON:0001876	81.93	gold quality
cortical plate	UBERON:0005343	81.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.09	gold quality
prefrontal cortex	UBERON:0000451	79.82	gold quality
neocortex	UBERON:0001950	79.65	gold quality
primary visual cortex	UBERON:0002436	79.30	gold quality
esophagus mucosa	UBERON:0002469	78.80	gold quality
frontal cortex	UBERON:0001870	78.71	gold quality
frontal lobe	UBERON:0016525	78.69	gold quality
caudate nucleus	UBERON:0001873	78.43	gold quality
telencephalon	UBERON:0001893	77.86	gold quality
cerebral cortex	UBERON:0000956	77.61	gold quality
secondary oocyte	CL:0000655	77.24	gold quality
temporal lobe	UBERON:0001871	77.07	gold quality
tendon of biceps brachii	UBERON:0008188	77.01	silver quality
forebrain	UBERON:0001890	75.40	gold quality
lower esophagus mucosa	UBERON:0035834	75.17	gold quality
oocyte	CL:0000023	74.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	20.59
E-ANND-3	yes	4.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting SLC6A11, 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-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641

Literature-anchored findings (GeneRIF, showing 10)

• homology models of hGAT-2 and hGAT-3 were built and searched for (i) substrate conformation, (ii) prediction of substrate (inhibitor) interaction, and (iii) distinguishable allosteric Zn2+ inhibition by combining docking and MD calculations. (PMID:19450549)
• The results suggest that GAT3 c.1572T may be one of the contributing factors with a modest effect on antiepileptic drug (AEDs) pharmacoresistance in the epileptic brain. (PMID:21776001)
• Binding assays employing membrane preparations obtained from a stably GAT3 expressing HEK293 cell line and DDPM-1007 as nonlabeled GAT3 marker were performed. In these experiments specific binding of DDPM-1007 at GAT3 could be unambiguously detected. (PMID:23225341)
• results suggest that GABA receptor signaling pathway was associated with the increased susceptibility to TD in Korean schizophrenic patients (PMID:23795861)
• 3p25.3 microdeletion of GABA transporters SLC6A1 and SLC6A11 results in intellectual disability, epilepsy and stereotypic behavior. (PMID:25256099)
• GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (PMID:26212582)
• we performed GATA4 mutation screening for 119 patients with 46, XY DSD without heart anomalies (PMID:29735817)
• GAT-3 expression was selectively decreased in the central amygdala of alcohol-dependent people compared to those who died of unrelated causes. (PMID:29930131)
• GAT-1 (rs2697153) and GAT-3 (rs2272400) polymorphisms are associated with febrile seizures and temporal lobe epilepsy. (PMID:32301730)
• Downregulation of GABA Transporter 3 (GAT3) is Associated with Deficient Oxidative GABA Metabolism in Human Induced Pluripotent Stem Cell-Derived Astrocytes in Alzheimer’s Disease. (PMID:33710537)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc6a11b	ENSDARG00000087981
mus_musculus	Slc6a11	ENSMUSG00000030307
rattus_norvegicus	Slc6a11	ENSRNOG00000005697

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), SLC6A8 (ENSG00000130821), SLC6A6 (ENSG00000131389), 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 GABA transporter 3 — P48066 (reviewed: P48066)

Alternative names: Solute carrier family 6 member 11

All UniProt accessions (1): P48066

UniProt curated annotations — full annotation on UniProt →

Function. Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA). Can also mediate transport of beta-alanine and to a lower extent that of taurine and hypotaurine.

Subcellular location. Cell membrane.

Tissue specificity. Widespread distribution in the brain.

Activity regulation. GABA transport is inhibited by SNAP-5114.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A11 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P48066-1	1	yes
P48066-2	2

RefSeq proteins (2): NP_001304335, NP_055044* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002982	Na/ntran_symport_GABA_GAT3	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 4 shown:

• 4-aminobutanoate(out) + chloride(out) + 2 Na(+)(out) = 4-aminobutanoate(in) + chloride(in) + 2 Na(+)(in) (RHEA:70687)
• taurine(out) + chloride(out) + 2 Na(+)(out) = taurine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71223)
• hypotaurine(out) + chloride(out) + 2 Na(+)(out) = hypotaurine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71243)
• beta-alanine(out) + chloride(out) + 2 Na(+)(out) = beta-alanine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71247)

UniProt features (23 total): transmembrane region 12, topological domain 3, glycosylation site 3, chain 1, region of interest 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9QO8	ELECTRON MICROSCOPY	2.9
9QO9	ELECTRON MICROSCOPY	3.2
9LK8	ELECTRON MICROSCOPY	3.4
9CP4	ELECTRON MICROSCOPY	3.42
9CP5	ELECTRON MICROSCOPY	3.51
9LK9	ELECTRON MICROSCOPY	3.58
9LK7	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48066-F1	87.30	0.76

Antibody-complex structures (SAbDab): 1 — 9CP5

Functional residue map

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

Post-translational modifications (1): 21

Glycosylation sites (3): 187, 190, 198

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-71288	Creatine metabolism
R-HSA-888593	Reuptake of GABA
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-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: 220 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_162, GOBP_NEUROTRANSMITTER_UPTAKE, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_64, MORF_BRCA1, MORF_ATRX, AREB6_01, GOBP_NEUROTRANSMITTER_TRANSPORT, MORF_ESR1, MODULE_16, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GGGTGGRR_PAX4_03

GO Biological Process (9): amino acid transport (GO:0006865), response to xenobiotic stimulus (GO:0009410), monocarboxylic acid transport (GO:0015718), sodium ion transmembrane transport (GO:0035725), gamma-aminobutyric acid reuptake (GO:0051936), neurotransmitter uptake (GO:0001504), amino acid transmembrane transport (GO:0003333), neurotransmitter transport (GO:0006836), taurine transmembrane transport (GO:0015734)

GO Molecular Function (7): gamma-aminobutyric acid:sodium:chloride symporter activity (GO:0005332), taurine:sodium symporter activity (GO:0005369), monocarboxylic acid transmembrane transporter activity (GO:0008028), amino acid binding (GO:0016597), amino acid:sodium symporter activity (GO:0005283), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (7): plasma membrane (GO:0005886), membrane (GO:0016020), presynaptic membrane (GO:0042734), cell projection (GO:0042995), postsynaptic membrane (GO:0045211), GABA-ergic synapse (GO:0098982), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Metabolism of amino acids and derivatives	1
GABA synthesis, release, reuptake and degradation	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	2
transmembrane transport	2
organic acid:sodium symporter activity	2
cellular anatomical structure	2
synaptic membrane	2
response to chemical	1
carboxylic acid transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
gamma-aminobutyric acid transport	1
amino acid neurotransmitter reuptake	1
neurotransmitter transport	1
import into cell	1
amino acid transport	1
alkanesulfonate transmembrane transport	1
nitrogen compound transport	1
amino acid:sodium symporter activity	1
gamma-aminobutyric acid transmembrane transporter activity	1
secondary active monocarboxylate transmembrane transporter activity	1
sodium:chloride symporter activity	1
taurine transmembrane transporter activity	1
monocarboxylic acid transport	1
carboxylic acid transmembrane transporter activity	1
binding	1
amino acid:monoatomic cation symporter activity	1
solute:sodium symporter activity	1
secondary active transmembrane transporter activity	1
transporter activity	1
membrane	1
cell periphery	1
presynapse	1
postsynapse	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A11	CASTOR3P	Q8NAP1	876
SLC6A11	MBNL1	Q9NR56	756
SLC6A11	TTPA	P49638	744
SLC6A11	TWNK	Q96RR1	742
SLC6A11	GABRA5	P31644	736
SLC6A11	GABRD	O14764	735
SLC6A11	CELF1	Q92879	699
SLC6A11	SLC1A2	P43004	639
SLC6A11	SLC32A1	Q9H598	614
SLC6A11	SLC1A3	P43003	602
SLC6A11	GAD1	Q99259	568
SLC6A11	GAD2	Q05329	545
SLC6A11	KCNMA1	Q12791	507
SLC6A11	CALB2	P22676	502
SLC6A11	SLC1A1	P43005	502

IntAct

8 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
SLC6A11	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC6A3	GET1	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): SLC6A11 (Affinity Capture-MS), SLC6A11 (Co-fractionation), ABCD3 (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), AGPAT1 (Affinity Capture-MS), AGPAT2 (Affinity Capture-MS), AGPAT4 (Affinity Capture-MS), ALDH3A2 (Affinity Capture-MS), ALG10 (Affinity Capture-MS), ALG3 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), APMAP (Affinity Capture-MS), ATAD1 (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), ATP2C1 (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	SLC6A11	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2917 predictions. Top by Δscore:

Variant	Effect	Δscore
3:10816518:GGAG:G	donor_gain	1.0000
3:10816519:G:GT	donor_gain	1.0000
3:10816520:AGGT:A	donor_loss	1.0000
3:10816521:GGTG:G	donor_loss	1.0000
3:10816522:G:GC	donor_loss	1.0000
3:10819707:TTCA:T	acceptor_loss	1.0000
3:10819710:A:AG	acceptor_gain	1.0000
3:10819710:A:T	acceptor_loss	1.0000
3:10819710:AG:A	acceptor_gain	1.0000
3:10819711:G:GC	acceptor_gain	1.0000
3:10819711:GG:G	acceptor_gain	1.0000
3:10819711:GGC:G	acceptor_gain	1.0000
3:10819711:GGCAT:G	acceptor_gain	1.0000
3:10819850:CAGG:C	donor_loss	1.0000
3:10819851:AG:A	donor_loss	1.0000
3:10819852:GGTAT:G	donor_loss	1.0000
3:10823295:A:AG	acceptor_gain	1.0000
3:10823300:A:AG	acceptor_gain	1.0000
3:10823301:G:GG	acceptor_gain	1.0000
3:10823301:GA:G	acceptor_gain	1.0000
3:10823389:GGGA:G	donor_gain	1.0000
3:10823390:GGA:G	donor_gain	1.0000
3:10823390:GGAG:G	donor_gain	1.0000
3:10823391:GA:G	donor_gain	1.0000
3:10823391:GAG:G	donor_gain	1.0000
3:10823393:G:GG	donor_gain	1.0000
3:10844212:A:AG	acceptor_gain	1.0000
3:10844213:G:GG	acceptor_gain	1.0000
3:10844345:AGG:A	donor_loss	1.0000
3:10844347:GTA:G	donor_loss	1.0000

AlphaMissense

4153 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:10816422:T:A	W53R	1.000
3:10816422:T:C	W53R	1.000
3:10816424:G:C	W53C	1.000
3:10816424:G:T	W53C	1.000
3:10816440:T:C	F59L	1.000
3:10816442:C:A	F59L	1.000
3:10816442:C:G	F59L	1.000
3:10816476:G:C	G71R	1.000
3:10816481:C:A	N72K	1.000
3:10816481:C:G	N72K	1.000
3:10816485:T:A	W74R	1.000
3:10816485:T:C	W74R	1.000
3:10816491:T:C	F76L	1.000
3:10816493:C:A	F76L	1.000
3:10816493:C:G	F76L	1.000
3:10819470:T:C	F88L	1.000
3:10819472:C:A	F88L	1.000
3:10819472:C:G	F88L	1.000
3:10912093:T:A	W299R	1.000
3:10912093:T:C	W299R	1.000
3:10918378:G:A	G349R	1.000
3:10918378:G:C	G349R	1.000
3:10918378:G:T	G349W	1.000
3:10918379:G:A	G349E	1.000
3:10918390:T:C	F353L	1.000
3:10918392:C:A	F353L	1.000
3:10918392:C:G	F353L	1.000
3:10816423:G:C	W53S	0.999
3:10816441:T:C	F59S	0.999
3:10816449:A:C	S62R	0.999

dbSNP variants (sampled 300 via entrez): RS1000027304 (3:10939785 C>T), RS1000049530 (3:10816642 C>CG), RS1000076021 (3:10894032 C>T), RS1000076839 (3:10932948 C>T), RS1000084600 (3:10939745 A>G), RS1000095835 (3:10933952 G>A), RS1000103518 (3:10851432 A>G), RS1000112396 (3:10854056 T>C), RS1000132077 (3:10898760 A>G,T), RS1000173246 (3:10893648 G>A), RS1000191619 (3:10894273 A>G,T), RS1000196996 (3:10928469 G>A), RS1000241330 (3:10934427 G>A), RS1000270198 (3:10848133 A>G), RS1000301304 (3:10916964 G>A)

Disease associations

OMIM: gene MIM:607952 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001476_4	Response to tocilizumab in rheumatoid arthritis	3.000000e-07
GCST002608_5	Pulmonary function in asthmatics	3.000000e-06
GCST003772_4	Loneliness (linear analysis)	8.000000e-06
GCST006633_5	Initial alcohol sensitivity	6.000000e-06
GCST009391_1407	Metabolite levels	6.000000e-06
GCST90007010_3	Gut microbiota relative abundance (Oscillospira)	4.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0007865	loneliness measurement
EFO:0005132	5-HIAA measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5208 (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)

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — GABA transporter subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
SNAP-5114	Inhibition	5.18	pIC50

ChEMBL bioactivities

27 potent at pChembl≥5 of 45 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	GAMMA-AMINOBUTYRIC ACID
5.95	IC50	1120	nM	CHEMBL75035
5.80	IC50	1590	nM	CHEMBL2403781
5.72	IC50	1900	nM	CHEMBL4458674
5.70	IC50	1995	nM	CHEMBL4458674
5.64	IC50	2300	nM	CHEMBL1788265
5.60	IC50	2512	nM	CHEMBL1788265
5.60	IC50	2512	nM	CHEMBL349005
5.57	IC50	2700	nM	CHEMBL349005
5.56	IC50	2754	nM	CHEMBL4447559
5.53	IC50	2950	nM	CHEMBL4845832
5.50	IC50	3160	nM	CHEMBL4126078
5.48	IC50	3311	nM	CHEMBL75035
5.40	IC50	3981	nM	GAMMA-AMINOBUTYRIC ACID
5.40	IC50	4000	nM	GAMMA-AMINOBUTYRIC ACID
5.30	IC50	5000	nM	CHEMBL432737
5.30	IC50	5000	nM	CHEMBL75035
5.30	IC50	5012	nM	CHEMBL75035
5.21	Ki	6100	nM	CHEMBL1164505
5.16	IC50	7000	nM	GAMMA-AMINOBUTYRIC ACID
5.09	IC50	8128	nM	CHEMBL4566905
5.05	IC50	8920	nM	CHEMBL1446457
5.03	IC50	9333	nM	CHEMBL4548691
5.00	IC50	1e+04	nM	CHEMBL432737

PubChem BioAssay actives

26 with measured affinity, of 170 total; 14 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
.gamma.-aminobutyric acid	1476552: Inhibition of human GAT3 S468Y mutant expresses in tsA201 cells assessed as reduction in [3H]GABA uptake after 3 mins by scintillation counting method	ic50	1.0000	uM
(3S)-1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]piperidine-3-carboxylic acid	1188932: Inhibition of human GAT3 transfected in CHO cells assessed as [3H]GABA uptake after 20 mins by liquid scintillation counting analysis	ic50	1.1200	uM
(3S)-1-[(E)-4,4,4-tris(4-methoxyphenyl)but-2-enyl]piperidine-3-carboxylic acid	1762441: Inhibition of human GAT3 expressed in COS-7 cells assessed as reduction in [2H6]GABA uptake preincubated for 25 mins followed by [2H6]GABA addition and measured after 6 mins by LC-MS/MS analysis	ic50	1.5900	uM
2-(4,5-dihydro-1H-imidazol-5-yl)acetic acid	1599052: Inhibition of human GAT3 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	1.9000	uM
2-[(3R)-pyrrolidin-3-yl]acetic acid	1599052: Inhibition of human GAT3 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	2.3000	uM
2-[(3S)-pyrrolidin-3-yl]acetic acid	1599052: Inhibition of human GAT3 expressed in Flp-In CHO cells assessed as reduction in [3H]GABA uptake incubated for 3 mins by liquid scintillation counting method	ic50	2.5119	uM
(3R,5S)-5-[(2E)-2-[[2-(4-chlorophenyl)-5-fluorophenyl]methylidene]hydrazinyl]piperidine-3-carboxylic acid	1573772: Inhibition of human GAT3 expressed in COS7 cells assessed as reduction in [2H6]GABA uptake preincubated for 25 mins followed by [2H6]GABA addition and measured after 6 mins by LC-MS/MS analysis	ic50	2.7542	uM
N-[(2S,3S)-4-(benzylamino)-3-hydroxy-1-phenylbutan-2-yl]-3,3-diphenylpropanamide	1762441: Inhibition of human GAT3 expressed in COS-7 cells assessed as reduction in [2H6]GABA uptake preincubated for 25 mins followed by [2H6]GABA addition and measured after 6 mins by LC-MS/MS analysis	ic50	2.9500	uM
(3S)-1-[2-[(4-methoxy-2-methylphenyl)-bis(4-methoxyphenyl)methoxy]ethyl]piperidine-3-carboxylic acid	1762441: Inhibition of human GAT3 expressed in COS-7 cells assessed as reduction in [2H6]GABA uptake preincubated for 25 mins followed by [2H6]GABA addition and measured after 6 mins by LC-MS/MS analysis	ic50	3.1600	uM
1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]piperidine-3-carboxylic acid	1859416: Inhibition of human GAT-3 expressed in mouse L-M(TK-) cells assessed as inhibition of [3H]GABA uptake	ic50	5.0000	uM
1-(3-carbazol-9-ylpropyl)-4-(4-methoxyphenyl)piperidin-4-ol	487217: Binding affinity to GAT3	ki	6.1000	uM
5-thiophen-2-yl-1H-indole-2,3-dione	1573772: Inhibition of human GAT3 expressed in COS7 cells assessed as reduction in [2H6]GABA uptake preincubated for 25 mins followed by [2H6]GABA addition and measured after 6 mins by LC-MS/MS analysis	ic50	8.1283	uM
1-(3-carbazol-9-ylpropyl)-4-(2-methoxyphenyl)piperidin-4-ol	1188932: Inhibition of human GAT3 transfected in CHO cells assessed as [3H]GABA uptake after 20 mins by liquid scintillation counting analysis	ic50	8.9200	uM
(3R,5S)-5-[(2E)-2-[[2-(4-phenylphenyl)phenyl]methylidene]hydrazinyl]piperidine-3-carboxylic acid	1573772: Inhibition of human GAT3 expressed in COS7 cells assessed as reduction in [2H6]GABA uptake preincubated for 25 mins followed by [2H6]GABA addition and measured after 6 mins by LC-MS/MS analysis	ic50	9.3325	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Resveratrol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
ethyl-p-hydroxybenzoate	decreases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
gamma-Aminobutyric Acid	increases export	1
Lead	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1
Zidovudine	increases expression	1
Aflatoxin B1	affects methylation, decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

28 unique, capped per target: 27 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1166721	Binding	Binding affinity to GAT3	Azetidine derivatives as novel gamma-aminobutyric acid uptake inhibitors: synthesis, biological evaluation, and structure-activity relationship. — Eur J Med Chem
CHEMBL677769	Functional	Compound was tested for its ability to inhibit uptake of [3H]- GABA by cloned human GAT-3 transporter	On the bioactive conformation of the gaba uptake inhibitor SK&F 89976-A — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4U9	HuH7-SLC6A11-KO-c2	Cancer cell line	Male
CVCL_D4UA	HuH7-SLC6A11-KO-c5	Cancer cell line	Male

Clinical trials (associated diseases)

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