SLC6A7

Summary

SLC6A7 (solute carrier family 6 member 7, HGNC:11054) is a protein-coding gene on chromosome 5q32, encoding Sodium-dependent proline transporter (Q99884). Brain specific sodium (and chloride)-dependent proline transporter.

This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements.

Source: NCBI Gene 6534 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 95 total
• Druggable target: yes
• MANE Select transcript: NM_014228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11054
Approved symbol	SLC6A7
Name	solute carrier family 6 member 7
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	PROT
Ensembl gene	ENSG00000011083
Ensembl biotype	protein_coding
OMIM	606205
Entrez	6534

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000230671, ENST00000513403, ENST00000524041

RefSeq mRNA: 1 — MANE Select: NM_014228 NM_014228

CCDS: CCDS4305

Canonical transcript exons

ENST00000230671 — 14 exons

Exon	Start	End
ENSE00000439588	150197042	150197276
ENSE00000439590	150201089	150201223
ENSE00000439592	150202579	150202703
ENSE00000439593	150203667	150203779
ENSE00000767197	150196716	150196847
ENSE00000767199	150199228	150199366
ENSE00000767201	150202347	150202450
ENSE00000767204	150203907	150204038
ENSE00000767222	150204532	150204631
ENSE00000767224	150204827	150204927
ENSE00000767226	150205456	150205623
ENSE00000841176	150194728	150194911
ENSE00001246868	150209406	150211063
ENSE00001246875	150190062	150190360

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 96.12.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1772 / max 133.2306, expressed in 108 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59413	0.6577	93
59416	0.2476	52
59415	0.2472	59
59414	0.0247	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.12	gold quality
cerebellar hemisphere	UBERON:0002245	95.85	gold quality
cerebellar cortex	UBERON:0002129	95.57	gold quality
cerebellum	UBERON:0002037	91.92	gold quality
right frontal lobe	UBERON:0002810	90.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.80	gold quality
prefrontal cortex	UBERON:0000451	85.08	gold quality
anterior cingulate cortex	UBERON:0009835	84.47	gold quality
cingulate cortex	UBERON:0003027	84.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.21	gold quality
endometrium epithelium	UBERON:0004811	82.59	gold quality
frontal cortex	UBERON:0001870	81.47	gold quality
neocortex	UBERON:0001950	80.65	gold quality
mucosa of transverse colon	UBERON:0004991	79.39	gold quality
Brodmann (1909) area 10	UBERON:0013541	77.95	gold quality
frontal pole	UBERON:0002795	77.21	silver quality
cerebral cortex	UBERON:0000956	75.95	gold quality
middle frontal gyrus	UBERON:0002702	75.44	gold quality
rectum	UBERON:0001052	74.66	gold quality
transverse colon	UBERON:0001157	73.60	gold quality
hypothalamus	UBERON:0001898	69.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.00	gold quality
amygdala	UBERON:0001876	67.72	gold quality
telencephalon	UBERON:0001893	66.81	gold quality
brain	UBERON:0000955	66.53	gold quality
central nervous system	UBERON:0001017	66.27	gold quality
cortical plate	UBERON:0005343	65.75	gold quality
small intestine	UBERON:0002108	65.34	gold quality
cerebellar vermis	UBERON:0004720	64.95	gold quality
Ammon’s horn	UBERON:0001954	64.91	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SPI1

miRNA regulators (miRDB)

39 targeting SLC6A7, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-1913	97.07	66.20	1417

Literature-anchored findings (GeneRIF, showing 1)

• these findings suggest that SLC6A7 could be a susceptible gene for asthma. (PMID:20431603)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc6a7	ENSMUSG00000052026
rattus_norvegicus	Slc6a7	ENSRNOG00000018644

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), 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 proline transporter — Q99884 (reviewed: Q99884)

Alternative names: Solute carrier family 6 member 7

All UniProt accessions (2): Q99884, E5RJL1

UniProt curated annotations — full annotation on UniProt →

Function. Brain specific sodium (and chloride)-dependent proline transporter. Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals.

Subcellular location. Synaptic cell membrane.

Tissue specificity. Brain specific (at protein level). Highly expressed in hippocampus, corpus striatum and temporal cortex. Also expressed in frontal cortex, occipital cortex and, at lower levels, in cerebellum and parietal cortex (at protein level).

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A7 subfamily.

RefSeq proteins (1): NP_055043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 2 shown:

• L-proline(out) + chloride(out) + 2 Na(+)(out) = L-proline(in) + chloride(in) + 2 Na(+)(in) (RHEA:71263)
• L-pipecolate(out) + chloride(out) + 2 Na(+)(out) = L-pipecolate(in) + chloride(in) + 2 Na(+)(in) (RHEA:71267)

UniProt features (27 total): transmembrane region 12, modified residue 8, topological domain 3, chain 1, glycosylation site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9WX7	ELECTRON MICROSCOPY	2.57
9WML	ELECTRON MICROSCOPY	2.79
9WMM	ELECTRON MICROSCOPY	2.8
9WX9	ELECTRON MICROSCOPY	2.84
9WMN	ELECTRON MICROSCOPY	2.91
9WMP	ELECTRON MICROSCOPY	2.91
9WMO	ELECTRON MICROSCOPY	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99884-F1	86.34	0.70

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 (8): 20, 22, 573, 582, 588, 591, 598, 600

Glycosylation sites (1): 182

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-71288	Creatine metabolism
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

MSigDB gene sets: 115 (showing top): MORF_RAGE, MODULE_274, TGCGCANK_UNKNOWN, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_45, MODULE_64, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROTRANSMITTER_TRANSPORT, MODULE_16, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, MODULE_118, MODULE_368, MYOD_01

GO Biological Process (8): neurotransmitter transport (GO:0006836), proline transport (GO:0015824), protein catabolic process (GO:0030163), sodium ion transmembrane transport (GO:0035725), glycine import across plasma membrane (GO:1903804), amino acid transport (GO:0006865), proline transmembrane transport (GO:0035524), transmembrane transport (GO:0055085)

GO Molecular Function (5): proline:sodium symporter activity (GO:0005298), L-proline transmembrane transporter activity (GO:0015193), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
carboxylic acid transmembrane transport	2
neutral amino acid transport	1
L-amino acid transport	1
macromolecule catabolic process	1
protein metabolic process	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
glycine transport	1
amino acid import across plasma membrane	1
amino acid transmembrane transport	1
nitrogen compound transport	1
cellular process	1
amino acid:sodium symporter activity	1
organic acid:sodium symporter activity	1
carboxylic acid transmembrane transporter activity	1
neutral L-amino acid transmembrane transporter activity	1
L-amino acid transmembrane transporter activity	1
proline transmembrane transport	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cell junction	1
synapse	1
plasma membrane region	1

Protein interactions and networks

STRING

1692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A7	HELT	A6NFD8	801
SLC6A7	PTMA	P06454	771
SLC6A7	KIAA1755	Q5JYT7	447
SLC6A7	F5GXR3	F5GXR3	432
SLC6A7	EPB41L4A	Q9HCS5	414
SLC6A7	ARHGAP1	Q07960	398
SLC6A7	SLC36A1	Q7Z2H8	388
SLC6A7	BLOC1S1	P78537	385
SLC6A7	FSIP1	Q8NA03	382
SLC6A7	PPFIBP1	Q86W92	378
SLC6A7	EML6	Q6ZMW3	377
SLC6A7	IL6	P05231	370
SLC6A7	SLC35G2	Q8TBE7	362
SLC6A7	F2	P00734	360
SLC6A7	SLC35F1	Q5T1Q4	356

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC6A13	SPTLC2	psi-mi:“MI:0914”(association)	0.350
SLC6A7	ABCB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): SLC6A7 (Two-hybrid), SLC6A7 (Affinity Capture-MS), SLC6A7 (Affinity Capture-MS), SLC6A7 (Affinity Capture-MS), ABCB1 (Affinity Capture-MS), ABCG2 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), ATP11B (Affinity Capture-MS), ATP11C (Affinity Capture-MS), ATP6AP1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V1A (Affinity Capture-MS), ATP6V1B2 (Affinity Capture-MS)

ESM2 similar proteins: A1A4N1, A2AWR3, A2VE54, B0S5Y3, B2RXV4, B5X4H8, C1BKZ7, D2HSA6, O00400, O54698, O54699, O75387, P28573, Q08B29, Q0VCM6, Q14542, Q28E13, Q4FZU9, Q4HX89, Q5E9R1, Q5RF58, Q60825, Q61672, Q62687, Q6AYY8, Q6BZ39, Q6BZW3, Q6GMG6, Q6PGE7, Q710D3, Q758C3, Q80WK7, Q84XI3, Q86WB7, Q8CGA3, Q8N370, Q8VXY7, Q944P0, Q94AA1, Q99808

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2457 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150190357:CAAGG:C	donor_loss	1.0000
5:150190358:AAGG:A	donor_loss	1.0000
5:150190359:AGG:A	donor_loss	1.0000
5:150194726:A:AG	acceptor_gain	1.0000
5:150194726:AGCCT:A	acceptor_gain	1.0000
5:150194727:G:GG	acceptor_gain	1.0000
5:150194727:GCCT:G	acceptor_gain	1.0000
5:150194727:GCCTG:G	acceptor_gain	1.0000
5:150194908:GGAG:G	donor_gain	1.0000
5:150194909:G:GT	donor_gain	1.0000
5:150194912:GTAT:G	donor_loss	1.0000
5:150194913:T:G	donor_loss	1.0000
5:150196468:A:AG	acceptor_gain	1.0000
5:150196710:CGGCA:C	acceptor_loss	1.0000
5:150196711:GGCA:G	acceptor_loss	1.0000
5:150196712:GCA:G	acceptor_loss	1.0000
5:150196713:CAGGC:C	acceptor_loss	1.0000
5:150196714:A:AG	acceptor_gain	1.0000
5:150196714:A:AT	acceptor_loss	1.0000
5:150196714:AGGC:A	acceptor_gain	1.0000
5:150196715:G:GT	acceptor_gain	1.0000
5:150196715:GGC:G	acceptor_gain	1.0000
5:150196715:GGCG:G	acceptor_gain	1.0000
5:150196715:GGCGC:G	acceptor_gain	1.0000
5:150196845:AAGGT:A	donor_loss	1.0000
5:150196846:AGG:A	donor_loss	1.0000
5:150196847:GGTG:G	donor_loss	1.0000
5:150196848:GTGA:G	donor_loss	1.0000
5:150196849:T:G	donor_loss	1.0000
5:150197212:G:GT	donor_gain	1.0000

AlphaMissense

4136 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150194812:T:A	W40R	1.000
5:150194812:T:C	W40R	1.000
5:150194814:G:C	W40C	1.000
5:150194814:G:T	W40C	1.000
5:150194830:T:C	F46L	1.000
5:150194832:C:A	F46L	1.000
5:150194832:C:G	F46L	1.000
5:150194848:G:C	G52R	1.000
5:150194849:G:A	G52D	1.000
5:150194856:T:G	C54W	1.000
5:150194860:G:C	G56R	1.000
5:150194871:T:A	N59K	1.000
5:150194871:T:G	N59K	1.000
5:150194875:T:A	W61R	1.000
5:150194875:T:C	W61R	1.000
5:150194881:T:C	F63L	1.000
5:150194883:C:A	F63L	1.000
5:150194883:C:G	F63L	1.000
5:150196721:T:C	F75L	1.000
5:150196723:C:A	F75L	1.000
5:150196723:C:G	F75L	1.000
5:150196796:T:C	F100L	1.000
5:150196798:C:A	F100L	1.000
5:150196798:C:G	F100L	1.000
5:150197152:T:A	W154R	1.000
5:150197152:T:C	W154R	1.000
5:150197154:G:C	W154C	1.000
5:150197154:G:T	W154C	1.000
5:150201105:C:A	A247D	1.000
5:150201173:G:C	G270R	1.000

dbSNP variants (sampled 300 via entrez): RS1000294072 (5:150198508 A>G), RS1000402315 (5:150198639 G>A), RS1000803928 (5:150210007 G>A,T), RS1000947919 (5:150191579 C>T), RS1001065708 (5:150191328 C>A), RS1001091323 (5:150208655 C>A), RS1001179314 (5:150193427 A>C), RS1001231679 (5:150193645 G>A,C), RS1001562625 (5:150191264 A>G), RS1001860293 (5:150202932 G>A,C), RS1001896443 (5:150190063 T>C), RS1002062541 (5:150196307 C>T), RS1002081026 (5:150203117 G>A,C), RS1002235830 (5:150192303 C>A,T), RS1002323714 (5:150208028 T>C)

Disease associations

OMIM: gene MIM:606205 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004131_58	Inflammatory bowel disease	5.000000e-09
GCST004133_75	Ulcerative colitis	2.000000e-08
GCST011878_17	Mitochondrial heteroplasmy measurement	1.000000e-08
GCST012303_4	Recurrent major depressive disorder x sex interaction	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0600008	mitochondrial heteroplasmy measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3317335 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Glycine transporter subfamily

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 58 [PMID: 25037917]	Inhibition	7.74	pIC50
LP-403812	Inhibition	7.0	pIC50

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.75	IC50	18	nM	CHEMBL3318586
7.68	IC50	21	nM	CHEMBL3318579
7.62	IC50	24	nM	CHEMBL3318574
7.57	IC50	27	nM	CHEMBL3318585
7.47	IC50	34	nM	CHEMBL3318563
7.47	IC50	34	nM	CHEMBL3318552
7.44	IC50	36	nM	CHEMBL3318548
7.44	IC50	36	nM	CHEMBL3318584
7.28	IC50	52	nM	CHEMBL3317462
7.28	IC50	53	nM	CHEMBL3318573
7.24	IC50	57	nM	CHEMBL3318580
7.21	IC50	61	nM	CHEMBL3318564
7.15	IC50	71	nM	CHEMBL3318549
7.14	IC50	73	nM	CHEMBL3318550
7.12	IC50	76	nM	CHEMBL3318554
7.12	IC50	76	nM	CHEMBL3318576
7.11	IC50	77	nM	CHEMBL3318553
7.05	IC50	89	nM	CHEMBL3318581
6.89	IC50	128	nM	CHEMBL3318577
6.84	IC50	146	nM	CHEMBL3318540
6.82	IC50	150	nM	CHEMBL3318562
6.80	IC50	160	nM	CHEMBL1543754
6.72	IC50	190	nM	CHEMBL3318555
6.72	IC50	190	nM	CHEMBL3318551
6.64	IC50	230	nM	CHEMBL3318556
6.58	IC50	260	nM	CHEMBL3318557
6.57	IC50	270	nM	CHEMBL3318567
6.57	IC50	270	nM	CHEMBL3318543
6.55	IC50	280	nM	CHEMBL1594803
6.41	IC50	392	nM	CHEMBL3318578
6.32	IC50	477	nM	CHEMBL3318575
6.23	IC50	586	nM	CHEMBL3318582
6.18	IC50	653	nM	CHEMBL3318587
6.16	IC50	700	nM	CHEMBL3318572
6.06	IC50	870	nM	CHEMBL3318569
5.99	IC50	1020	nM	CHEMBL3318568
5.90	IC50	1260	nM	CHEMBL3318547
5.89	IC50	1300	nM	CHEMBL3318541
5.87	IC50	1340	nM	CHEMBL3318583
5.83	IC50	1480	nM	CHEMBL1508710
5.73	IC50	1880	nM	CHEMBL3318545
5.71	IC50	1950	nM	CHEMBL3318566
5.66	IC50	2180	nM	CHEMBL3318544
5.65	IC50	2230	nM	CHEMBL3318560
5.57	IC50	2700	nM	CHEMBL3318565
5.46	IC50	3440	nM	CHEMBL1531102
5.30	IC50	5000	nM	CHEMBL3318542
5.22	IC50	6010	nM	CHEMBL3318546
5.15	IC50	7080	nM	CHEMBL3318559
5.15	IC50	7010	nM	CHEMBL3318558

PubChem BioAssay actives

50 with measured affinity, of 56 total; 50 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
[4-(3-chlorophenyl)phenyl]-(3-pyrimidin-2-yl-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0180	uM
[4-(4-chlorophenyl)phenyl]-[(2S)-2-methyl-4-pyrimidin-2-ylpiperazin-1-yl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0210	uM
[4-(3-chlorophenyl)phenyl]-(2,6-dimethyl-4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0240	uM
[4-(3-chlorophenyl)phenyl]-(8-pyrimidin-2-yl-3,8-diazabicyclo[3.2.1]octan-3-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0270	uM
[4-(4-methylthiophen-2-yl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0340	uM
[4-(4-methylphenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0340	uM
[4-(3-chlorophenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0360	uM
[4-(3-chlorophenyl)phenyl]-(2-pyrimidin-2-yl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0360	uM
[4-(4-chlorophenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0520	uM
[4-(3-chlorophenyl)phenyl]-(2,2-dimethyl-4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0530	uM
[4-(4-chlorophenyl)phenyl]-[(2R)-2-methyl-4-pyrimidin-2-ylpiperazin-1-yl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0570	uM
[4-(5-methylthiophen-2-yl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0610	uM
(4-pyrimidin-2-ylpiperazin-1-yl)-[4-[3-(trifluoromethyl)phenyl]phenyl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0710	uM
(4-pyrimidin-2-ylpiperazin-1-yl)-[4-[3-(trifluoromethoxy)phenyl]phenyl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0730	uM
[4-(3-chlorophenyl)phenyl]-[2-(hydroxymethyl)-4-pyrimidin-2-ylpiperazin-1-yl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0760	uM
(4-pyrimidin-2-ylpiperazin-1-yl)-[4-[4-(trifluoromethyl)phenyl]phenyl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0760	uM
[4-(4-ethylphenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0770	uM
[4-(3-chlorophenyl)phenyl]-(4-pyrimidin-2-yl-1,4-diazepan-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.0890	uM
1-[4-(3-chlorophenyl)benzoyl]-4-pyrimidin-2-ylpiperazine-2-carboxylic acid	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.1280	uM
(4-phenylphenyl)-[4-(1,3-thiazol-2-yl)piperazin-1-yl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.1460	uM
[4-(5-chlorothiophen-2-yl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.1500	uM
(4-phenylphenyl)-(4-pyridin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.1600	uM
4-[4-(4-pyrimidin-2-ylpiperazine-1-carbonyl)phenyl]benzonitrile	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.1900	uM
3-[4-(4-pyrimidin-2-ylpiperazine-1-carbonyl)phenyl]benzonitrile	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.1900	uM
[4-(4-methoxyphenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.2300	uM
[4-(4-fluorophenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.2600	uM
[4-(4-methylpyrimidin-2-yl)piperazin-1-yl]-(4-phenylphenyl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.2700	uM
(4-phenylmethoxyphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.2700	uM
(4-phenylphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.2800	uM
1-[4-(3-chlorophenyl)benzoyl]-N,N-dimethyl-4-pyrimidin-2-ylpiperazine-2-carboxamide	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.3920	uM
(3-methyl-4-pyrimidin-2-ylpiperazin-1-yl)-(4-phenylphenyl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.4770	uM
4-(3-chlorophenyl)-N-methyl-N-[2-[methyl(pyrimidin-2-yl)amino]ethyl]benzamide	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.5860	uM
[4-(2-methylphenyl)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.6530	uM
(2-tert-butyl-4-pyrimidin-2-ylpiperazin-1-yl)-[4-(3-chlorophenyl)phenyl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.7000	uM
[4-(benzylamino)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	0.8700	uM
[4-(2-phenylethoxy)phenyl]-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.0200	uM
(4-pyrimidin-2-ylpiperazin-1-yl)-[4-[2-(trifluoromethyl)phenyl]phenyl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.2600	uM
(4-phenylphenyl)-(4-pyrazin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.3000	uM
[4-(3-chlorophenyl)phenyl]-(5-pyrimidin-2-yl-2,5-diazabicyclo[2.2.1]heptan-2-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.3400	uM
(4-phenylphenyl)-(4-phenylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.4800	uM
(3-phenylphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.8800	uM
(4-phenoxyphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	1.9500	uM
(4-phenylphenyl)-[4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	2.1800	uM
(4-pyrimidin-2-ylpiperazin-1-yl)-(4-pyrrol-1-ylphenyl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	2.2300	uM
phenyl-[4-(4-pyrimidin-2-ylpiperazine-1-carbonyl)phenyl]methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	2.7000	uM
[4-(4-fluorophenyl)piperazin-1-yl]-(4-phenylphenyl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	3.4400	uM
(4-phenylphenyl)-(4-pyridazin-3-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	5.0000	uM
(2-phenylphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	6.0100	uM
(4-cyclohexylphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	7.0100	uM
(4-pyridin-2-ylphenyl)-(4-pyrimidin-2-ylpiperazin-1-yl)methanone	1184338: Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	ic50	7.0800	uM

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Lead	affects expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3370229	Binding	Inhibition of human high-affinity L-proline transporter expressed in COS1 cells by [3H]proline uptake assay	Novel inhibitors of the high-affinity L-proline transporter as potential therapeutic agents for the treatment of cognitive disorders. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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