SLC6A15

Summary

SLC6A15 (solute carrier family 6 member 15, HGNC:13621) is a protein-coding gene on chromosome 12q21.31, encoding Sodium-dependent neutral amino acid transporter B(0)AT2 (Q9H2J7). Functions as a sodium-dependent neutral amino acid transporter.

This gene encodes a member of the solute carrier family 6 protein family which transports neutral amino acids. The encoded protein is thought to play a role in neuronal amino acid transport (PMID: 16185194) and may be associated with major depression (PMID: 21521612). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55117 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 92 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_182767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13621
Approved symbol	SLC6A15
Name	solute carrier family 6 member 15
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Aliases	hv7-3, NTT73, FLJ10316, V7-3, SBAT1
Ensembl gene	ENSG00000072041
Ensembl biotype	protein_coding
OMIM	607971
Entrez	55117

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 20 protein_coding, 11 retained_intron, 9 nonsense_mediated_decay, 7 protein_coding_CDS_not_defined

ENST00000266682, ENST00000309283, ENST00000450363, ENST00000547240, ENST00000548267, ENST00000549540, ENST00000551010, ENST00000551388, ENST00000551612, ENST00000551818, ENST00000552192, ENST00000679363, ENST00000679414, ENST00000679430, ENST00000679453, ENST00000679652, ENST00000679679, ENST00000679681, ENST00000679920, ENST00000679933, ENST00000679956, ENST00000679989, ENST00000680067, ENST00000680187, ENST00000680207, ENST00000680260, ENST00000680379, ENST00000680469, ENST00000680676, ENST00000680714, ENST00000680780, ENST00000680892, ENST00000680901, ENST00000680963, ENST00000681106, ENST00000681220, ENST00000681281, ENST00000681418, ENST00000681453, ENST00000681582, ENST00000681628, ENST00000681688, ENST00000681721, ENST00000681939, ENST00000681953, ENST00000918073, ENST00000970189

RefSeq mRNA: 3 — MANE Select: NM_182767 NM_001146335, NM_018057, NM_182767

CCDS: CCDS53816, CCDS9026, CCDS9027

Canonical transcript exons

ENST00000266682 — 12 exons

Exon	Start	End
ENSE00000909329	84870478	84870670
ENSE00000993525	84867034	84867193
ENSE00001700389	84883859	84884040
ENSE00002206643	84891832	84892308
ENSE00002334409	84912523	84912799
ENSE00002381970	84859491	84862006
ENSE00003471638	84872602	84872794
ENSE00003502484	84876497	84876607
ENSE00003511441	84873087	84873328
ENSE00003519049	84885911	84886068
ENSE00003538635	84863439	84863601
ENSE00003557356	84885435	84885561

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 93.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1269 / max 411.1186, expressed in 1124 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132349	8.3536	993
132350	5.9906	980
132344	2.3239	716
132351	1.2453	582
132346	0.1391	59
132347	0.0407	12
132348	0.0337	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.89	gold quality
pigmented layer of retina	UBERON:0001782	89.20	gold quality
retina	UBERON:0000966	89.17	gold quality
prefrontal cortex	UBERON:0000451	87.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.45	gold quality
cerebellar hemisphere	UBERON:0002245	86.20	gold quality
cerebellar cortex	UBERON:0002129	86.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.59	gold quality
cerebellum	UBERON:0002037	85.38	gold quality
middle temporal gyrus	UBERON:0002771	85.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.84	gold quality
ganglionic eminence	UBERON:0004023	84.51	gold quality
primary visual cortex	UBERON:0002436	84.19	gold quality
neocortex	UBERON:0001950	83.97	gold quality
frontal cortex	UBERON:0001870	83.91	gold quality
frontal lobe	UBERON:0016525	83.91	gold quality
hypothalamus	UBERON:0001898	83.58	gold quality
endothelial cell	CL:0000115	83.27	gold quality
cingulate cortex	UBERON:0003027	83.27	gold quality
anterior cingulate cortex	UBERON:0009835	83.19	gold quality
cerebral cortex	UBERON:0000956	83.01	gold quality
ventricular zone	UBERON:0003053	82.96	gold quality
right frontal lobe	UBERON:0002810	82.48	gold quality
telencephalon	UBERON:0001893	81.03	gold quality
brain	UBERON:0000955	80.76	gold quality
orbitofrontal cortex	UBERON:0004167	80.73	gold quality
frontal pole	UBERON:0002795	80.63	gold quality
forebrain	UBERON:0001890	80.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	9.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

252 targeting SLC6A15, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170

Literature-anchored findings (GeneRIF, showing 10)

• SBAT1-mediated transport of BCAA, particularly leucine, may be an important source of amino nitrogen for neurotransmitter synthesis in glutamatergic and GABAergic neurons. (PMID:16226721)
• The substrate profile of the NTT4/XT1-dependent activity is similar to that of the closely related B(0)AT2/SBAT1 (SLC6A15), including a submillimolar apparent affinity for proline and leucine and a low millimolar apparent affinity for glutamine. (PMID:19147495)
• The data from human genetics(SLC6A15), expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting. (PMID:21521612)
• The SLC6A15 gene plays a role in adrenocorticotropic hormone (ACTH) and cortisol secretion during cognitive impairments in unipolar depression. (PMID:22475622)
• SNP rs1545843 associated with with local gray matter volume in median cingulate gyrus (PMID:23820837)
• an association between the risk allele of the SLC6A15 gene rs1545843 and the White Matter Tracts integrity of the PHC in Major Depressive Disorder patients, which is known to play an important role in the neural circuit involved in emotion processing. (PMID:27723767)
• This study provides the first evidence that, at least among Han Chinese patients with PD, AA genotype at rs1545843 in the SLC6A15 gene. (PMID:28320136)
• We observed an association between the SLC6A15 rs1545843 and resting-state brain function of the corpus callosum, cingulum and the frontal, parietal, and temporal lobes in MDD patients, which may be involved in the pathogenesis of Major Depressive Disorder. There was no interaction between rs1545843 genotypes and disease status. (PMID:28915082)
• Fine-scale haplotype mapping of MUT, AACS, SLC6A15 and PRKCA genes indicates association with insulin resistance of metabolic syndrome and relationship with branched chain amino acid metabolism or regulation. (PMID:30913280)
• SLC6A15 acts as a tumor suppressor to inhibit migration and invasion in human papillary thyroid cancer. (PMID:33690923)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc6a15	ENSDARG00000062821
mus_musculus	Slc6a15	ENSMUSG00000019894
rattus_norvegicus	Slc6a15	ENSRNOG00000027468

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), 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-dependent neutral amino acid transporter B(0)AT2 — Q9H2J7 (reviewed: Q9H2J7)

Alternative names: Sodium- and chloride-dependent neurotransmitter transporter NTT73, Sodium-coupled branched-chain amino-acid transporter 1, Solute carrier family 6 member 15, Transporter v7-3

All UniProt accessions (17): Q9H2J7, A0A7P0T826, A0A7P0T8B7, A0A7P0T8I1, A0A7P0T9G8, A0A7P0T9P8, A0A7P0T9Z9, A0A7P0TA72, A0A7P0TAT1, A0A7P0TAZ8, A0A7P0TB05, A0A7P0TB74, A0A7P0TBL2, A0A7P0Z4F0, A0A7P0Z4M4, F8VSG1, F8WJN6

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a sodium-dependent neutral amino acid transporter. Exhibits preference for the branched-chain amino acids, particularly leucine, valine and isoleucine and methionine. Can also transport low-affinity substrates such as alanine, phenylalanine, glutamine and pipecolic acid. Mediates the saturable, pH-sensitive and electrogenic cotransport of proline and sodium ions with a stoichiometry of 1:1. May have a role as transporter for neurotransmitter precursors into neurons. In contrast to other members of the neurotransmitter transporter family, does not appear to be chloride-dependent.

Subcellular location. Membrane.

Tissue specificity. Almost exclusively expressed in the brain.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A15 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H2J7-1	1	yes
Q9H2J7-2	2
Q9H2J7-3	3

RefSeq proteins (3): NP_001139807, NP_060527, NP_877499* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002438	Neutral_aa_SLC6	Family
IPR037272	SNS_sf	Homologous_superfamily
IPR042934	B(0)AT2	Domain

Pfam: PF00209

Catalyzed reactions (Rhea), 12 shown:

• L-proline(in) + Na(+)(in) = L-proline(out) + Na(+)(out) (RHEA:28967)
• L-leucine(in) + Na(+)(in) = L-leucine(out) + Na(+)(out) (RHEA:29263)
• L-valine(in) + Na(+)(in) = L-valine(out) + Na(+)(out) (RHEA:29267)
• L-isoleucine(in) + Na(+)(in) = L-isoleucine(out) + Na(+)(out) (RHEA:29275)
• L-alanine(in) + Na(+)(in) = L-alanine(out) + Na(+)(out) (RHEA:29283)
• L-serine(in) + Na(+)(in) = L-serine(out) + Na(+)(out) (RHEA:29575)
• L-cysteine(in) + Na(+)(in) = L-cysteine(out) + Na(+)(out) (RHEA:68232)
• L-glutamine(in) + Na(+)(in) = L-glutamine(out) + Na(+)(out) (RHEA:68236)
• L-methionine(in) + Na(+)(in) = L-methionine(out) + Na(+)(out) (RHEA:68240)
• L-phenylalanine(in) + Na(+)(in) = L-phenylalanine(out) + Na(+)(out) (RHEA:68244)
• L-threonine(in) + Na(+)(in) = L-threonine(out) + Na(+)(out) (RHEA:69999)
• L-asparagine(in) + Na(+)(in) = L-asparagine(out) + Na(+)(out) (RHEA:71383)

UniProt features (33 total): transmembrane region 12, modified residue 5, topological domain 4, glycosylation site 4, splice variant 3, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2J7-F1	80.15	0.57

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 (5): 25, 55, 687, 699, 701

Glycosylation sites (4): 187, 213, 383, 394

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 221 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, NKX25_02, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, USF_C, GOBP_MONOATOMIC_CATION_TRANSPORT, AGGCACT_MIR5153P, GOBP_ORGANIC_ACID_TRANSPORT, NKX61_01, BILD_HRAS_ONCOGENIC_SIGNATURE, MYCMAX_01, chr12q21, BROWNE_HCMV_INFECTION_14HR_DN, ATTACAT_MIR3803P

GO Biological Process (11): neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), neutral amino acid transport (GO:0015804), L-leucine transport (GO:0015820), proline transport (GO:0015824), sodium ion transmembrane transport (GO:0035725), amino acid transmembrane transport (GO:0003333), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), transmembrane transport (GO:0055085), carboxylic acid transmembrane transport (GO:1905039)

GO Molecular Function (9): neutral L-amino acid:sodium symporter activity (GO:0005295), proline:sodium symporter activity (GO:0005298), neurotransmitter transmembrane transporter activity (GO:0005326), amino acid transmembrane transporter activity (GO:0015171), branched-chain amino acid:sodium symporter activity (GO:0015657), protein binding (GO:0005515), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SLC-mediated transport of amino acids	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	4
transmembrane transport	3
amino acid transport	2
neutral amino acid transport	2
L-amino acid transport	2
amino acid:sodium symporter activity	2
organic acid:sodium symporter activity	2
transmembrane transporter activity	2
branched-chain amino acid transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
cellular process	1
carboxylic acid transport	1
neutral L-amino acid transmembrane transporter activity	1
carboxylic acid transmembrane transporter activity	1
neurotransmitter transport	1
amino acid transmembrane transport	1
branched-chain amino acid transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A15	SLC43A1	O75387	489
SLC6A15	METTL25	Q8N6Q8	475
SLC6A15	SLC1A4	P43007	457
SLC6A15	SLC7A6	Q92536	454
SLC6A15	SLC43A2	Q8N370	448
SLC6A15	SLC7A8	Q9UHI5	447
SLC6A15	SLC3A1	Q07837	426
SLC6A15	SLC38A2	Q96QD8	415
SLC6A15	SLC1A1	P43005	411
SLC6A15	SLC38A5	Q8WUX1	409
SLC6A15	SLC38A1	Q9H2H9	407
SLC6A15	SLC7A7	Q9UM01	392
SLC6A15	SLC1A3	P43003	390
SLC6A15	SLC38A8	A6NNN8	383
SLC6A15	SLC38A11	Q08AI6	381
SLC6A15	SLC38A6	Q8IZM9	381

IntAct

87 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SFXN5	CTSA	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
TMEM60	SLC6A15	psi-mi:“MI:0915”(physical association)	0.560
FZD7	SLC6A15	psi-mi:“MI:0915”(physical association)	0.560
SLC38A7	SLC6A15	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	SLC6A15	psi-mi:“MI:0915”(physical association)	0.560
NRM	SLC6A15	psi-mi:“MI:0915”(physical association)	0.560
SLC6A15	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
SLC6A15	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
TEX29	TOR1A	psi-mi:“MI:0914”(association)	0.530
SLC6A15	CLGN	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
EEA1	IGF2R	psi-mi:“MI:2364”(proximity)	0.450
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420

BioGRID (283): SLC6A15 (Affinity Capture-MS), SLC6A15 (Affinity Capture-MS), SLC6A15 (Proximity Label-MS), SLC6A15 (Proximity Label-MS), SLC6A15 (Proximity Label-MS), TEX2 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), TLCD1 (Affinity Capture-MS), SLC6A15 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), GOLGA5 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT9 (Affinity Capture-MS), CAV1 (Affinity Capture-MS), SLC6A15 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IDX9, A0A2C9VBV6, A2ARJ3, A7T1N0, A7Y2X0, A8Y2U2, O12977, O17386, O35119, O70131, O76689, O80739, P31662, P52166, P70617, P79100, Q05005, Q08469, Q0WMJ8, Q3UP23, Q57UM0, Q5JK32, Q5R9C2, Q5W0B7, Q69RI8, Q6H4R6, Q6NPT7, Q6ZUK4, Q75G84, Q84MS3, Q84MS4, Q8BG16, Q8BJI1, Q8MPP0, Q90X07, Q92982, Q94KB1, Q94KB9, Q9FI00, Q9FY75

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
Loratadine	“down-regulates activity”	SLC6A15	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Retrograde transport at the Trans-Golgi-Network	5	21.1×	6e-05
RAB geranylgeranylation	5	16.6×	1e-04
Constitutive Signaling by Aberrant PI3K in Cancer	5	12.2×	5e-04
Cargo recognition for clathrin-mediated endocytosis	6	12.1×	1e-04
RAB GEFs exchange GTP for GDP on RABs	5	11.9×	5e-04
Clathrin-mediated endocytosis	6	9.8×	3e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	9.3×	1e-03
RAF/MAP kinase cascade	6	7.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	5	44.9×	5e-05
exocytosis	5	11.3×	5e-03
positive regulation of neuron projection development	5	10.2×	6e-03
endocytosis	6	8.5×	5e-03
positive regulation of MAPK cascade	6	7.2×	7e-03
intracellular protein transport	7	6.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2332 predictions. Top by Δscore:

Variant	Effect	Δscore
12:84862003:ATGCC:A	acceptor_loss	1.0000
12:84862004:TGCCT:T	acceptor_loss	1.0000
12:84862005:GCC:G	acceptor_loss	1.0000
12:84862007:C:A	acceptor_loss	1.0000
12:84862008:T:A	acceptor_loss	1.0000
12:84863434:TTTA:T	donor_loss	1.0000
12:84863435:TTAC:T	donor_loss	1.0000
12:84863436:TA:T	donor_loss	1.0000
12:84863437:ACCT:A	donor_loss	1.0000
12:84863438:CCT:C	donor_loss	1.0000
12:84863597:TAAAC:T	acceptor_gain	1.0000
12:84863598:AAACC:A	acceptor_loss	1.0000
12:84863599:AACCT:A	acceptor_loss	1.0000
12:84863602:C:A	acceptor_loss	1.0000
12:84863603:T:A	acceptor_loss	1.0000
12:84867032:A:AC	donor_gain	1.0000
12:84867033:C:CT	donor_gain	1.0000
12:84867033:CTTAT:C	donor_gain	1.0000
12:84867189:GATAA:G	acceptor_gain	1.0000
12:84867191:TAA:T	acceptor_gain	1.0000
12:84867194:C:CC	acceptor_gain	1.0000
12:84870473:CTCA:C	donor_loss	1.0000
12:84870475:CA:C	donor_loss	1.0000
12:84870476:A:AC	donor_gain	1.0000
12:84870476:ACCAG:A	donor_loss	1.0000
12:84870477:C:CC	donor_gain	1.0000
12:84870493:T:A	donor_gain	1.0000
12:84872596:A:AC	donor_gain	1.0000
12:84872597:C:CC	donor_gain	1.0000
12:84872597:CTAA:C	donor_gain	1.0000

AlphaMissense

4830 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:84873137:A:C	F353L	1.000
12:84873137:A:T	F353L	1.000
12:84873139:A:G	F353L	1.000
12:84873301:A:G	W299R	1.000
12:84873301:A:T	W299R	1.000
12:84885961:A:G	W133R	1.000
12:84885961:A:T	W133R	1.000
12:84885993:C:A	G122V	1.000
12:84885993:C:T	G122D	1.000
12:84885994:C:G	G122R	1.000
12:84886002:A:G	L119P	1.000
12:84891868:A:G	W85R	1.000
12:84891868:A:T	W85R	1.000
12:84891929:C:A	W64C	1.000
12:84891929:C:G	W64C	1.000
12:84891931:A:G	W64R	1.000
12:84891931:A:T	W64R	1.000
12:84863451:C:A	W602C	0.999
12:84863451:C:G	W602C	0.999
12:84863540:A:G	W573R	0.999
12:84863540:A:T	W573R	0.999
12:84867091:A:G	L533P	0.999
12:84867139:C:A	G517V	0.999
12:84867139:C:T	G517E	0.999
12:84870644:A:C	F443L	0.999
12:84870644:A:T	F443L	0.999
12:84870646:A:G	F443L	0.999
12:84870648:G:T	A442D	0.999
12:84870651:A:G	L441S	0.999
12:84870661:C:A	G438W	0.999

dbSNP variants (sampled 300 via entrez): RS1000016480 (12:84869972 C>T), RS1000043655 (12:84910795 C>A), RS1000114250 (12:84893229 A>T), RS1000300995 (12:84888535 C>T), RS1000443035 (12:84870275 T>C), RS1000483297 (12:84897717 A>G), RS1000659421 (12:84890213 G>T), RS1000660221 (12:84860895 C>T), RS1000721299 (12:84901839 T>C,G), RS1000782746 (12:84903270 G>A), RS1000817728 (12:84881005 A>C), RS1000820223 (12:84896338 A>G), RS1000845031 (12:84907223 C>G), RS1000883533 (12:84882438 T>C,G), RS1000895899 (12:84907572 C>T)

Disease associations

OMIM: gene MIM:607971 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002131_6	Behavioural disinhibition (generation interaction)	2.000000e-06
GCST003075_142	Cognitive decline rate in late mild cognitive impairment	6.000000e-07
GCST003075_42	Cognitive decline rate in late mild cognitive impairment	5.000000e-07
GCST003180_1	Atopic march	5.000000e-09
GCST006041_15	Major depressive disorder	3.000000e-08
GCST006065_40	Glaucoma (primary open-angle)	2.000000e-09
GCST009391_857	Metabolite levels	3.000000e-06
GCST009724_96	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-75
GCST009724_97	Vertical cup-disc ratio (multi-trait analysis)	4.000000e-36
GCST009724_98	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-32
GCST010320_130	PR interval	7.000000e-13
GCST010321_75	PR interval	1.000000e-12
GCST90011770_62	Glaucoma (primary open-angle)	2.000000e-32

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0005430	nicotine use
EFO:0005431	illegal drug consumption
EFO:0005432	non-substance related disinhibited behaviour
EFO:0008364	generational effect measurement
EFO:0007710	cognitive decline measurement
EFO:0007755	atopic march
EFO:0010533	sorbitol measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3351189 (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: 42,161 (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
CHEMBL998	LORATADINE	4	42,161

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Neutral amino acid transporter subfamily

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

Ligand	Action	Affinity	Parameter
loratadine	Inhibition	5.4	pIC50

ChEMBL bioactivities

12 potent at pChembl≥5 of 28 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.47	IC50	3400	nM	CHEMBL3357043
5.40	IC50	4000	nM	LORATADINE
5.35	IC50	4500	nM	CHEMBL3357024
5.34	IC50	4600	nM	CHEMBL3357033
5.31	IC50	4900	nM	CHEMBL3357037
5.31	IC50	4900	nM	CHEMBL331603
5.30	IC50	5000	nM	CHEMBL3357041
5.28	IC50	5200	nM	CHEMBL3357044
5.28	IC50	5300	nM	CHEMBL3357029
5.24	IC50	5700	nM	CHEMBL3357045
5.11	IC50	7700	nM	CHEMBL3357049
5.11	IC50	7800	nM	CHEMBL3357035

PubChem BioAssay actives

12 with measured affinity, of 42 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
1-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]pentan-1-one	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	3.4000	uM
Loratadine	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	4.0000	uM
ethyl 4-(13-chloro-6-methoxy-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	4.5000	uM
propyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	4.6000	uM
prop-2-enyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	4.9000	uM
1-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]butan-1-one	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	4.9000	uM
(E)-1-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]but-2-en-1-one	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	5.0000	uM
1-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]hexan-1-one	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	5.2000	uM
S-ethyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carbothioate	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	5.3000	uM
1-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]-2-cyclohexylethanone	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	5.7000	uM
(2R)-2-amino-1-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]-4-methylpentan-1-one	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	7.7000	uM
2-methylpropyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate	1169507: Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	ic50	7.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	5
Valproic Acid	affects expression, decreases expression, increases expression	5
methylmercuric chloride	decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cisplatin	decreases expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	increases expression	1
pentanal	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, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1
ormosil	affects binding, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
licochalcone B	decreases expression	1
(+)-JQ1 compound	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3386947	Binding	Inhibition of eGFP-tagged human B0AT2 expressed in HEK293 cells measured within 10 mins by [3H]proline uptake assay	Loratadine and analogues: discovery and preliminary structure-activity relationship of inhibitors of the amino acid transporter B(0)AT2. — J Med Chem

Clinical trials (associated diseases)

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