SLC6A9

Summary

SLC6A9 (solute carrier family 6 member 9, HGNC:11056) is a protein-coding gene on chromosome 1p34.1, encoding Sodium- and chloride-dependent glycine transporter 1 (P48067). Sodium- and chloride-dependent glycine transporter.

The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft.

Source: NCBI Gene 6536 — RefSeq curated summary.

At a glance

• Gene–disease (curated): atypical glycine encephalopathy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 381 total — 6 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001024845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11056
Approved symbol	SLC6A9
Name	solute carrier family 6 member 9
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	GLYT1, GlyT-1
Ensembl gene	ENSG00000196517
Ensembl biotype	protein_coding
OMIM	601019
Entrez	6536

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000357730, ENST00000360584, ENST00000372306, ENST00000372307, ENST00000372310, ENST00000466926, ENST00000475075, ENST00000489764, ENST00000492434, ENST00000528803, ENST00000533007, ENST00000673836, ENST00000857497, ENST00000857498, ENST00000857499, ENST00000857500, ENST00000857501, ENST00000857502, ENST00000857503, ENST00000857504, ENST00000912216

RefSeq mRNA: 9 — MANE Select: NM_001024845 NM_001024845, NM_001261380, NM_001328626, NM_001328627, NM_001328628, NM_001328629, NM_001328630, NM_006934, NM_201649

CCDS: CCDS30695, CCDS41316, CCDS41317, CCDS85966

Canonical transcript exons

ENST00000372310 — 14 exons

Exon	Start	End
ENSE00000770792	43997855	43998025
ENSE00000770799	44000956	44001055
ENSE00000861424	44002853	44002985
ENSE00000861427	44002512	44002646
ENSE00000861433	44001164	44001298
ENSE00000861437	43996483	43997739
ENSE00000905909	44002313	44002416
ENSE00000905911	44001390	44001627
ENSE00000905921	44000767	44000867
ENSE00003477352	44024248	44024362
ENSE00003485500	44008353	44008623
ENSE00003522021	44009965	44010096
ENSE00003785193	44010726	44010882
ENSE00003903618	44031306	44031462

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 95.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7995 / max 166.0870, expressed in 1270 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12066	3.9843	1094
12064	1.9648	759
12067	0.9980	577
12058	0.7572	98
12061	0.4246	69
12065	0.3152	168
12063	0.2488	107
12059	0.0842	46
12060	0.0224	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	95.71	gold quality
spinal cord	UBERON:0002240	91.99	gold quality
skin of leg	UBERON:0001511	91.51	gold quality
skin of abdomen	UBERON:0001416	90.08	gold quality
right adrenal gland	UBERON:0001233	88.75	gold quality
stromal cell of endometrium	CL:0002255	88.26	gold quality
left adrenal gland	UBERON:0001234	88.11	gold quality
right adrenal gland cortex	UBERON:0035827	87.96	gold quality
left adrenal gland cortex	UBERON:0035825	87.63	gold quality
zone of skin	UBERON:0000014	86.42	gold quality
adrenal gland	UBERON:0002369	86.05	gold quality
mucosa of transverse colon	UBERON:0004991	85.74	gold quality
esophagus mucosa	UBERON:0002469	84.44	gold quality
adrenal cortex	UBERON:0001235	84.41	gold quality
adrenal tissue	UBERON:0018303	83.00	gold quality
lower esophagus mucosa	UBERON:0035834	82.18	gold quality
hypothalamus	UBERON:0001898	81.82	gold quality
transverse colon	UBERON:0001157	81.49	gold quality
upper lobe of left lung	UBERON:0008952	81.35	gold quality
esophagus	UBERON:0001043	80.82	gold quality
right uterine tube	UBERON:0001302	80.38	gold quality
ectocervix	UBERON:0012249	79.91	gold quality
ventricular zone	UBERON:0003053	79.50	gold quality
substantia nigra	UBERON:0002038	79.21	gold quality
upper lobe of lung	UBERON:0008948	79.17	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.00	gold quality
medial globus pallidus	UBERON:0002477	78.87	silver quality
vagina	UBERON:0000996	78.74	gold quality
prefrontal cortex	UBERON:0000451	78.63	gold quality
amygdala	UBERON:0001876	78.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	3.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting SLC6A9, 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-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-4668-3P	100.00	68.74	2635
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699

Literature-anchored findings (GeneRIF, showing 21)

• The mechanism of allosteric interaction of cytoplasmic and extracellular Cl- in the glial glycine transporter (hGlyTlb). (PMID:16121932)
• Genetic variation of the glycine transporter 1 gene may contribute to individual vulnerability to methamphetamine dependence and psychosis. (PMID:17582620)
• Single nucleotide polymorphism or haplotype of the gene produce risks for susceptibility to drug dependence. (PMID:18411704)
• SLC6A9 gene is associated with schizophrenia. (PMID:18638388)
• the results suggest that GLYT1 and membrane rafts are co-localized in the membrane, and that this influences the rate of glycine transport. (PMID:19427831)
• association between SLC6A9 SNPs and essential hypertension in a Japanese population, suggesting that SLC6A9 is a susceptibility locus for essential hypertension. (PMID:19556729)
• metabolic functions of GLYT1 in intestine: metabolism/regulation of glycine/glutathione; role in response to physiological stress (e.g., oxidative stress); possible role in pathophysiology/therapy of inflammatory bowel diseases [REVIEW] (PMID:21628872)
• Human positron-emission tomography studies determine the test-retest reproducibility of [11C]GSK931145, a ligand which readily enters the brain, displaying a heterogeneous uptake which corresponds well with the known distribution of GlyT-1. (PMID:21688322)
• Synaptic and extrasynaptic concentrations of glycine are regulated by its type-1 glycine transporter, which is primarily expressed in astroglial and glutamatergic cell membranes. (PMID:22425803)
• The increased sensitivity of human GlyT1c to sanguinarine is abolished by the mutation of only cysteine 475. (PMID:22705056)
• Following biopterin administration, glycine transporter type I occupancy correlates with biopterin plasma concentration. (PMID:23132267)
• Study found that temporal lobe epilepsy is associated with increased levels of GlyT1 (PMID:26302655)
• Whole-exome sequencing revealed a novel homozygous missense variant in exon 9 of SLC6A9 NM_201649.3: c.1219 A>G (p.Ser407Gly) that segregates with the disease within the family. In murine model, knockout of Slc6a9 is associated with equivalent phenotype of non-ketotic hyperglycinemia (NKH), namely respiratory distress and hypotonia. (PMID:27481395)
• This study demonstrates that lack of GLYT1 leads to a distinct human neurological syndrome hallmarked by mildly elevated cerebrospinal fluid glycine and normal serum glycine. (PMID:27773429)
• GlyT1 encephalopathy: Characterization of presumably disease causing GlyT1 mutations. (PMID:32712301)
• Do damaging variants of SLC6A9, the gene for the glycine transporter 1 (GlyT-1), protect against schizophrenia? (PMID:32796235)
• GLYT1 encephalopathy: Further delineation of disease phenotype and discussion of pathophysiological mechanisms. (PMID:33269555)
• Chloride-dependent conformational changes in the GlyT1 glycine transporter. (PMID:33658361)
• Structural insights into the inhibition of glycine reuptake. (PMID:33658720)
• Functional crosstalk of the glycine transporter GlyT1 and NMDA receptors. (PMID:37003571)
• Transport mechanism and pharmacology of the human GlyT1. (PMID:38513663)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc6a9	ENSDARG00000018534
mus_musculus	Slc6a9	ENSMUSG00000028542
rattus_norvegicus	Slc6a9	ENSRNOG00000019484

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), 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), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Sodium- and chloride-dependent glycine transporter 1 — P48067 (reviewed: P48067)

Alternative names: Solute carrier family 6 member 9

All UniProt accessions (6): B7Z3A9, B7Z589, E9PJ65, E9PLM5, P48067, J3KPA5

UniProt curated annotations — full annotation on UniProt →

Function. Sodium- and chloride-dependent glycine transporter. Essential for regulating glycine concentrations at inhibitory glycinergic synapses. Sodium- and chloride-dependent glycine transporter. Sodium- and chloride-dependent glycine transporter.

Subunit / interactions. Interacts with EXOC1; interaction increases the transporter capacity of SLC6A9 probably by promoting its insertion into the cell membrane. Interacts with EXOC3 and EXOC4.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the brain, kidney, pancreas, lung, placenta and liver. Expressed in the brain, kidney, pancreas, lung, placenta and liver. Expressed only in the brain.

Disease relevance. Glycine encephalopathy with normal serum glycine (GCENSG) [MIM:617301] An autosomal recessive, severe metabolic disorder characterized by arthrogryposis multiplex congenita, joint hyperlaxity, lack of neonatal respiratory effort, axial hypotonia, hypertonia with pronounced clonus, and delayed psychomotor development. Some patients may have dysmorphic facial features and/or brain imaging abnormalities. Laboratory studies show increased CSF glycine and normal or only mildly increased serum glycine. Most patients die in infancy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by sarcosine. Inhibited by sarcosine.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A9 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P48067-1	GlyT-1C	yes
P48067-2	GlyT-1A
P48067-3	GlyT-1B

RefSeq proteins (9): NP_001020016, NP_001248309, NP_001315555, NP_001315556, NP_001315557, NP_001315558, NP_001315559, NP_008865, NP_964012 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR003028	Na/ntran_symport_glycine_GLY1	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 1 shown:

• glycine(out) + chloride(out) + 2 Na(+)(out) = glycine(in) + chloride(in) + 2 Na(+)(in) (RHEA:70691)

UniProt features (75 total): helix 31, transmembrane region 12, strand 11, turn 7, topological domain 3, region of interest 2, modified residue 2, splice variant 2, sequence conflict 2, chain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8WFI	ELECTRON MICROSCOPY	2.58
9J8C	ELECTRON MICROSCOPY	2.9
9J8D	ELECTRON MICROSCOPY	3
8WFL	ELECTRON MICROSCOPY	3.03
8WFK	ELECTRON MICROSCOPY	3.22
8WFJ	ELECTRON MICROSCOPY	3.35
6ZBV	X-RAY DIFFRACTION	3.4
9J8B	ELECTRON MICROSCOPY	3.9
6ZPL	X-RAY DIFFRACTION	3.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48067-F1	81.95	0.63

Antibody-complex structures (SAbDab): 2 — 6ZBV, 6ZPL

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 (2): 673, 698

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 331 (showing top): MORF_RAGE, GOBP_HEMOGLOBIN_METABOLIC_PROCESS, CAR_TNFRSF25, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, GOCC_SECRETORY_GRANULE, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEUROTRANSMITTER_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT

GO Biological Process (13): neurotransmitter uptake (GO:0001504), glycine transport (GO:0015816), sodium ion transmembrane transport (GO:0035725), positive regulation of hemoglobin biosynthetic process (GO:0046985), regulation of synaptic transmission, glycinergic (GO:0060092), glycine secretion, neurotransmission (GO:0061537), positive regulation of heme biosynthetic process (GO:0070455), transport across blood-brain barrier (GO:0150104), glycine import across plasma membrane (GO:1903804), amino acid transmembrane transport (GO:0003333), neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), transmembrane transport (GO:0055085)

GO Molecular Function (6): amino acid:sodium symporter activity (GO:0005283), glycine transmembrane transporter activity (GO:0015187), glycine:sodium symporter activity (GO:0015375), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

GO Cellular Component (15): endosome (GO:0005768), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), postsynaptic density (GO:0014069), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), synaptic vesicle membrane (GO:0030672), dense core granule (GO:0031045), presynaptic membrane (GO:0042734), postsynaptic membrane (GO:0045211), hippocampal mossy fiber to CA3 synapse (GO:0098686), parallel fiber to Purkinje cell synapse (GO:0098688), asymmetric synapse (GO:0032279)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
plasma membrane region	3
synaptic transmission, glycinergic	2
glycine transport	2
transmembrane transport	2
cellular anatomical structure	2
synaptic membrane	2
neuron to neuron synapse	2
neurotransmitter transport	1
import into cell	1
neutral amino acid transport	1
carboxylic acid transport	1
nitrogen compound transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
positive regulation of macromolecule biosynthetic process	1
hemoglobin biosynthetic process	1
regulation of hemoglobin biosynthetic process	1
positive regulation of protein metabolic process	1
modulation of chemical synaptic transmission	1
neurotransmitter secretion	1
glycine secretion	1
heme biosynthetic process	1
regulation of heme biosynthetic process	1
positive regulation of tetrapyrrole biosynthetic process	1
vascular transport	1
amino acid import across plasma membrane	1
carboxylic acid transmembrane transport	1
amino acid transport	1
cellular process	1
amino acid:monoatomic cation symporter activity	1
solute:sodium symporter activity	1
neutral L-amino acid transmembrane transporter activity	1
carboxylic acid transmembrane transporter activity	1
neutral L-amino acid:sodium symporter activity	1
organic acid:sodium symporter activity	1
glycine transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
transporter activity	1
cation binding	1

Protein interactions and networks

STRING

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A9	HMGN3	Q15651	894
SLC6A9	SLC1A4	P43007	565
SLC6A9	SLC7A1	P30825	565
SLC6A9	HMGN2	P05204	544
SLC6A9	THRB	P10828	496
SLC6A9	SLC1A5	Q15758	496
SLC6A9	SLC7A5	Q01650	446
SLC6A9	SLC3A2	P08195	445
SLC6A9	SLC22A14	Q9Y267	428
SLC6A9	RXRA	P19793	428
SLC6A9	HMGN1	P05114	424
SLC6A9	SLC7A10	Q9NS82	423
SLC6A9	SLC32A1	Q9H598	409
SLC6A9	GLRA3	O75311	407
SLC6A9	GCLM	P48507	407

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SLC6A9	H1-5	psi-mi:“MI:0915”(physical association)	0.400
SLC4A9	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC6A9	CLGN	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	GPR89A	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (40): SLC6A9 (Proximity Label-MS), SLC6A9 (Proximity Label-MS), SLC6A9 (Affinity Capture-MS), SLC6A9 (Affinity Capture-MS), SLC6A9 (Proximity Label-MS), SLC6A9 (Proximity Label-MS), SLC6A9 (Proximity Label-MS), SLC6A9 (Proximity Label-MS), SLC6A9 (Proximity Label-MS), SLC6A9 (Negative Genetic), SLC6A9 (Proximity Label-MS), STX1A (Affinity Capture-Western), SLC6A9 (Affinity Capture-MS), SLC6A9 (Affinity Capture-MS), SLC3A2 (Affinity Capture-Western)

ESM2 similar proteins: A7Y2W8, A7Y2X0, B3MRS1, B3NV41, B4GVM9, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBM5, O35316, O35899, O55192, O76689, O88575, P23975, P28571, P31641, P31643, P31645, P31652, P31662, P48066, P48067, P51143, P51905, P58295, Q00589, Q01959, Q03614, Q08469, Q29GB8, Q5R9C2, Q60857, Q61327, Q761V0, Q7K4Y6, Q8BG16, Q8BJI1

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

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	6
Uncertain significance	150
Likely benign	162
Benign	39

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
2581302	NM_001024845.3(SLC6A9):c.31-764_31-763del	Pathogenic
3659467	NM_001024845.3(SLC6A9):c.941dup (p.Phe315fs)	Pathogenic
374986	NM_001024845.3(SLC6A9):c.1000A>G (p.Ser334Gly)	Pathogenic
374987	NM_001024845.3(SLC6A9):c.1498C>T (p.Gln500Ter)	Pathogenic
374988	NM_001024845.3(SLC6A9):c.709_713del (p.Lys237fs)	Pathogenic
4536025	NM_001024845.3(SLC6A9):c.31-6242G>T	Pathogenic
1236206	NM_001024845.3(SLC6A9):c.235C>T (p.Pro79Ser)	Likely pathogenic
1472818	NM_001024845.3(SLC6A9):c.31-6164G>C	Likely pathogenic
2573356	NM_001024845.3(SLC6A9):c.1536+1G>A	Likely pathogenic
446106	NM_001024845.3(SLC6A9):c.1492_1493del (p.Phe498fs)	Likely pathogenic
4697810	NM_001024845.3(SLC6A9):c.31-678G>A	Likely pathogenic
4849494	NM_001024845.3(SLC6A9):c.671C>T (p.Ser224Phe)	Likely pathogenic

SpliceAI

4075 predictions. Top by Δscore:

Variant	Effect	Δscore
1:43997738:CG:C	acceptor_gain	1.0000
1:43997849:CCTCA:C	donor_loss	1.0000
1:43997850:CTCA:C	donor_loss	1.0000
1:43997851:TCACC:T	donor_loss	1.0000
1:43997852:CACC:C	donor_loss	1.0000
1:43997853:A:AT	donor_loss	1.0000
1:43997854:C:A	donor_loss	1.0000
1:43997999:C:CC	acceptor_gain	1.0000
1:44000765:A:AC	donor_gain	1.0000
1:44000766:C:CC	donor_gain	1.0000
1:44000766:CGAAG:C	donor_gain	1.0000
1:44000950:GCTCA:G	donor_loss	1.0000
1:44000951:CTCA:C	donor_loss	1.0000
1:44000952:TCA:T	donor_loss	1.0000
1:44000953:CAC:C	donor_loss	1.0000
1:44000954:A:AC	donor_gain	1.0000
1:44000954:A:C	donor_loss	1.0000
1:44000955:C:CA	donor_loss	1.0000
1:44000955:C:CC	donor_gain	1.0000
1:44001051:CCTGC:C	acceptor_loss	1.0000
1:44001052:CTGC:C	acceptor_gain	1.0000
1:44001053:TGC:T	acceptor_gain	1.0000
1:44001053:TGCCT:T	acceptor_loss	1.0000
1:44001056:C:CA	acceptor_loss	1.0000
1:44001056:C:CC	acceptor_gain	1.0000
1:44001057:T:C	acceptor_loss	1.0000
1:44001159:CTTA:C	donor_loss	1.0000
1:44001162:A:AC	donor_gain	1.0000
1:44001162:A:AG	donor_loss	1.0000
1:44001163:C:CC	donor_gain	1.0000

AlphaMissense

4151 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44001394:G:A	T472I	1.000
1:44001403:C:T	G469E	1.000
1:44001404:C:A	G469W	1.000
1:44001404:C:G	G469R	1.000
1:44001404:C:T	G469R	1.000
1:44001417:C:A	M464I	1.000
1:44001417:C:G	M464I	1.000
1:44001417:C:T	M464I	1.000
1:44001486:G:C	F441L	1.000
1:44001486:G:T	F441L	1.000
1:44001488:A:G	F441L	1.000
1:44001545:C:G	A422P	1.000
1:44001553:C:A	G419V	1.000
1:44001553:C:T	G419D	1.000
1:44001554:C:A	G419C	1.000
1:44001554:C:G	G419R	1.000
1:44001564:G:C	F415L	1.000
1:44001564:G:T	F415L	1.000
1:44001566:A:G	F415L	1.000
1:44001566:A:T	F415I	1.000
1:44001577:C:T	G411D	1.000
1:44001578:C:G	G411R	1.000
1:44001580:G:T	A410D	1.000
1:44001581:C:G	A410P	1.000
1:44001588:G:C	S407R	1.000
1:44001588:G:T	S407R	1.000
1:44001589:C:A	S407I	1.000
1:44001590:T:G	S407R	1.000
1:44001599:A:G	C404R	1.000
1:44001600:G:C	N403K	1.000

dbSNP variants (sampled 300 via entrez): RS1000009132 (1:43998975 C>A,G,T), RS1000080661 (1:43999885 C>G), RS1000110896 (1:44028474 G>C), RS1000198267 (1:44023480 T>C), RS1000313129 (1:44023697 C>G), RS1000328240 (1:44018320 C>T), RS1000356543 (1:44005322 G>A), RS1000385214 (1:44021740 A>G), RS1000528807 (1:44014897 C>G,T), RS1000704250 (1:44026959 A>T), RS1000725794 (1:44016017 C>T), RS1000784166 (1:44017965 T>C), RS1000843326 (1:44013485 C>A,G,T), RS1001092886 (1:44020753 G>A), RS1001135947 (1:44006397 G>A)

Disease associations

OMIM: gene MIM:601019 | disease phenotypes: MIM:617301, MIM:621428

GenCC curated gene-disease

Disease	Classification	Inheritance
atypical glycine encephalopathy	Strong	Autosomal recessive
infantile glycine encephalopathy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
atypical glycine encephalopathy	Definitive	AR

Mondo (4): atypical glycine encephalopathy (MONDO:0015010), scoliosis, isolated, susceptibility to, 6 (MONDO:0980986), prostate cancer (MONDO:0008315), infantile glycine encephalopathy (MONDO:0017354)

Orphanet (2): Atypical glycine encephalopathy (Orphanet:289863), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000278	Retrognathia
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000648	Optic atrophy
HP:0001188	Hand clenching
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001298	Encephalopathy
HP:0001371	Flexion contracture
HP:0001382	Joint hypermobility
HP:0001762	Talipes equinovarus
HP:0001845	Overlapping toe
HP:0002015	Dysphagia
HP:0002058	Myopathic facies
HP:0002079	Hypoplasia of the corpus callosum
HP:0002104	Apnea
HP:0002119	Ventriculomegaly
HP:0002154	Hyperglycinemia
HP:0002169	Clonus
HP:0002267	Exaggerated startle response
HP:0002650	Scoliosis
HP:0002804	Arthrogryposis multiplex congenita
HP:0002816	Genu recurvatum

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004521_235	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST006011_20	Mean corpuscular volume	2.000000e-08
GCST006983_3	Attention deficit hyperactivity disorder or cannabis use	5.000000e-10
GCST010002_357	Refractive error	3.000000e-13
GCST90002390_596	Mean corpuscular hemoglobin	6.000000e-19
GCST90002392_162	Mean corpuscular volume	3.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007585	Cannabis use
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2337 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,314,109 (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
CHEMBL773	GLYCINE	4	1,220,071
CHEMBL1171829	BITOPERTIN	3	334
CHEMBL5314576	ICLEPERTIN	3	14
CHEMBL304383	SARCOSINE	2	93,566
CHEMBL4228124	ORG-25935	2	81
CHEMBL563251	PF-03463275	2	43

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2248829	SLC6A9		0.00	0
rs2486001	SLC6A9		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Glycine transporter subfamily

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
GlyT1 inhibitor 27a	Inhibition	9.1	pKi
(R)-NFPS	Inhibition	9.1	pIC50
3H-NPTS	Binding	9.0	pKd
[3H]GSK931145	Binding	8.8	pKd
[3H]SB-733993	Binding	8.7	pKd
[35S]ACPPB	Binding	8.7	pKd
SSR-103800	Inhibition	8.7	pIC50
N-methyl-SSR504734	Inhibition	8.6	pIC50
[3H]N-methyl-SSR504734		8.5	pKd
iclepertin	Inhibition	8.3	pIC50
[3H]NFPS		8.2	pKd
Org 24598	Inhibition	8.2	pIC50
PF-03463275	Inhibition	7.94	pKi
LY2365109	Inhibition	7.8	pIC50
GlyT1 inhibitor 51b	Inhibition	7.74	pKi
GSK931145	Inhibition	7.6	pIC50
bitopertin	Inhibition	7.33	pKi
ASP2535	Inhibition	7.04	pIC50

Binding affinities (BindingDB)

160 measured of 754 human assays (754 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1,1-dioxothian-4-yl)-[(2R)-2-(4-fluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]methanone	IC50	1 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-phenyl-4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methanone	IC50	1 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[(2S)-2-(5-chlorothiophen-2-yl)-4-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	1 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[(2R)-2-(4-fluorophenyl)-4-[5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]methanone	IC50	2 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(2-fluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]methanone	IC50	3 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-fluorothiophen-2-yl)-4-[5-(trifluoromethyl)pyrazin-2-yl]piperazin-1-yl]methanone	IC50	3 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-fluorothiophen-2-yl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	3 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[(2S)-2-(5-chlorothiophen-2-yl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	3 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(4-chlorophenyl)-2-phenylpiperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	3 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(2,3-difluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[(2R)-2-(2-fluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(2,3-difluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(2,4-difluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(3,4-difluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(5-chlorothiophen-2-yl)-4-[5-(difluoromethyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[(2R)-2-(4-fluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(5-cyclopropylpyrimidin-2-yl)-2-(5-fluorothiophen-2-yl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-phenyl-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]methanone	IC50	4 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[(2R)-2-(2,3-difluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	5 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[(2R)-2-(3-fluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	5 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(2,4-difluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	5 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[(2R)-2-(2,4-difluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	5 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(2,3-difluorophenyl)-4-[5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	5 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[(2R)-2-(3,4-difluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[(2R)-2-(4-fluorophenyl)-4-[5-(trifluoromethyl)pyrazin-2-yl]piperazin-1-yl]methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-fluorothiophen-2-yl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(5-chlorothiophen-2-yl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(5-cyclopropylpyrimidin-2-yl)-2-(2-fluorophenyl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(5-cyclopropylpyrimidin-2-yl)-2-(4-fluorophenyl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(4-chlorophenyl)-2-thiophen-2-ylpiperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-methylthiophen-2-yl)-4-[5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]methanone	IC50	6 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-fluorothiophen-2-yl)-4-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]piperazin-1-yl]methanone	IC50	7 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-fluorothiophen-2-yl)-4-(5-methylpyrimidin-2-yl)piperazin-1-yl]methanone	IC50	7 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(5-chlorothiophen-2-yl)-4-[5-(trifluoromethyl)pyrazin-2-yl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	7 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(3-fluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]methanone	IC50	7 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(4-fluorophenyl)-4-[5-(trifluoromethyl)-1,2-oxazol-3-yl]piperazin-1-yl]methanone	IC50	8 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(5-cyclopropylpyrazin-2-yl)-2-(2-fluorophenyl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	8 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(5-chlorothiophen-2-yl)-4-(5-cyclopropylpyrimidin-2-yl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	8 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(2-fluorophenyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl]methanone	IC50	8 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-methylthiophen-2-yl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	8 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(3-fluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(2-fluorophenyl)-4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(2,4-difluorophenyl)-4-[5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-(5-cyclopropylpyrimidin-2-yl)-2-(3-fluorophenyl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[2-(5-chlorothiophen-2-yl)-4-(5-methylpyrimidin-2-yl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(4-fluorophenyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl]methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(3-fluorophenyl)-4-[5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]methanone	IC50	9 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[2-(5-fluorothiophen-2-yl)-4-(5-methylpyrazin-2-yl)piperazin-1-yl]methanone	IC50	10 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
[4-[5-(difluoromethyl)-1,2,4-oxadiazol-3-yl]-2-(4-fluorophenyl)piperazin-1-yl]-(1,1-dioxothian-4-yl)methanone	IC50	10 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1
(1,1-dioxothian-4-yl)-[4-[4-methoxy-3-(trifluoromethyl)phenyl]-2-phenylpiperazin-1-yl]methanone	IC50	10 nM	US-9233953: Derivatives of 4-(piperazinylcarbonyl)thiane-1, 1-dione which inhibit GlyT1

ChEMBL bioactivities

1094 potent at pChembl≥5 of 1140 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL485356
9.51	IC50	0.31	nM	CHEMBL483938
9.41	IC50	0.39	nM	CHEMBL180966
9.33	IC50	0.47	nM	CHEMBL379668
9.19	IC50	0.65	nM	CHEMBL521463
9.17	IC50	0.671	nM	CHEMBL4593786
9.14	IC50	0.726	nM	CHEMBL4526580
9.13	IC50	0.733	nM	CHEMBL4468117
9.10	Ki	0.8	nM	CHEMBL4161906
9.10	Ki	0.8	nM	CHEMBL4169829
9.10	Kd	0.8	nM	CHEMBL26512
9.05	Ki	0.9	nM	CHEMBL4171521
9.03	IC50	0.934	nM	CHEMBL5871489
9.02	IC50	0.95	nM	CHEMBL206851
9.01	IC50	0.98	nM	CHEMBL6040522
9.00	IC50	1	nM	CHEMBL3913494
9.00	IC50	1	nM	CHEMBL3923537
9.00	IC50	1	nM	CHEMBL3912223
9.00	Ki	1	nM	CHEMBL4165362
9.00	IC50	1	nM	CHEMBL4228975
9.00	IC50	1	nM	CHEMBL4225587
9.00	IC50	1	nM	CHEMBL4224734
9.00	IC50	1	nM	CHEMBL4226364
9.00	IC50	1	nM	CHEMBL4228859
9.00	IC50	1	nM	CHEMBL4226039
9.00	EC50	1	nM	CHEMBL496333
9.00	Kd	1	nM	CHEMBL26512
8.99	IC50	1.03	nM	CHEMBL4448986
8.97	IC50	1.06	nM	CHEMBL4448986
8.96	Ki	1.1	nM	CHEMBL4173657
8.94	IC50	1.14	nM	CHEMBL4456392
8.92	Ki	1.2	nM	CHEMBL4166406
8.92	Ki	1.2	nM	CHEMBL4165340
8.92	Ki	1.2	nM	CHEMBL4159998
8.92	Ki	1.2	nM	CHEMBL4161781
8.91	IC50	1.24	nM	CHEMBL4582587
8.90	IC50	1.27	nM	CHEMBL4516089
8.83	IC50	1.49	nM	CHEMBL4572086
8.82	Ki	1.5	nM	CHEMBL4163697
8.82	IC50	1.5	nM	CHEMBL5858677
8.82	IC50	1.51	nM	CHEMBL5951595
8.81	IC50	1.54	nM	CHEMBL4579165
8.80	Kd	1.6	nM	CHEMBL23390
8.77	Ki	1.71	nM	CHEMBL596699
8.76	IC50	1.74	nM	CHEMBL482764
8.75	Ki	1.79	nM	CHEMBL563761
8.75	Ki	1.79	nM	CHEMBL3217125
8.72	IC50	1.9	nM	CHEMBL482960
8.72	IC50	1.9	nM	CHEMBL540967
8.72	IC50	1.89	nM	CHEMBL482960

PubChem BioAssay actives

911 with measured affinity, of 1134 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
2,4-dichloro-N-[[3-(cyclopropylmethyl)-1-(1-methyltriazol-4-yl)sulfonylazetidin-3-yl]methyl]benzamide	353605: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in human JAR cells after 3 hrs by scintillation counting	ic50	0.0001	uM
2,4-dichloro-N-[[3-(3-fluoro-2-pyridinyl)-1-(1-methyltriazol-4-yl)sulfonylazetidin-3-yl]methyl]benzamide	353605: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in human JAR cells after 3 hrs by scintillation counting	ic50	0.0003	uM
2-[[(3R)-3-(4-fluorophenyl)-3-(4-phenylphenoxy)propyl]-methylamino]acetic acid	639652: Inhibition of GlyT1 in human JAR cells assessed as inhibition of [3H]glycine uptake preincubated for 1 mins measured after 2 hrs by liquid scintillation counting	ic50	0.0004	uM
(2S)-2-[2-(4,5-dichloro-6-methoxy-1,3-dioxo-2-phenylinden-2-yl)ethyl-methylamino]propanoic acid	262007: Inhibition of uptake of [14C]glycine into human JAR cells expressing human GlyT1	ic50	0.0005	uM
2,4-dichloro-N-[[4-(3-fluoro-2-pyridinyl)-1-(1-methyltriazol-4-yl)sulfonylpiperidin-4-yl]methyl]benzamide	353605: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in human JAR cells after 3 hrs by scintillation counting	ic50	0.0006	uM
2-chloro-N-[[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]-6-(trifluoromethoxy)benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0007	uM
2-chloro-N-[[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]-4-(trifluoromethyl)benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0007	uM
N-[[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]-2,4-bis(trifluoromethyl)benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0007	uM
N-[2-[[(7S,8R)-7-amino-8-[[3-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylimidazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0008	uM
2-[[3-(4-fluorophenyl)-3-(4-phenylphenoxy)propyl]-methylamino]acetic acid	73803: Binding affinity towards rat hippocampus GlyT1 transporter expressed in HEK 293 cells	kd	0.0008	uM
N-[2-[[(7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylimidazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0008	uM
N-[1-[(7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]azetidin-3-yl]-1-cyclopropylmethanesulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0009	uM
2-[2-[4,5-dichloro-2-(4-fluorophenyl)-6-methoxy-1,3-dioxoinden-2-yl]ethyl-methylamino]acetic acid	262007: Inhibition of uptake of [14C]glycine into human JAR cells expressing human GlyT1	ic50	0.0009	uM
1-[3-fluoro-4-[4-(5-nitro-2-piperidin-1-ylbenzoyl)piperazin-1-yl]phenyl]ethanone	348436: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in CHO cells by scintillation counter	ec50	0.0010	uM
2-chloro-N-[1-[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]ethyl]-4-(trifluoromethyl)benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0010	uM
(3R,4S)-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-4-(4-fluorophenyl)-1-(1-methylimidazol-4-yl)sulfonylpyrrolidin-3-amine	1355822: Inhibition of [3H]N-Methyl-SSR504734 binding to human recombinant GlyT1c expressed in CHO cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0010	uM
2,6-dimethyl-N-[(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)-pyridin-4-ylmethyl]benzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0010	uM
N-[[4-(cyclopropylmethylsulfonyl)phenyl]-(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)methyl]-2,6-dimethylbenzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0010	uM
2,6-dimethyl-N-[(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)-(5-methylfuran-2-yl)methyl]benzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0010	uM
2,6-dimethyl-N-[phenyl-(7-propan-2-yl-7-azabicyclo[2.2.1]heptan-1-yl)methyl]benzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0010	uM
2,6-dimethyl-N-[(R)-(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)-phenylmethyl]benzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0010	uM
2,3-dichloro-N-[(R)-(2-methyl-2-azabicyclo[2.2.2]octan-1-yl)-phenylmethyl]benzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0010	uM
2-chloro-N-[[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]-4-fluorobenzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0011	uM
N-[2-[[(7S,8R)-7-amino-8-[(4-chlorophenyl)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylimidazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0011	uM
2,4-dichloro-N-[[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0012	uM
N-[2-[[(7S,8R)-7-amino-8-[(3-chloro-5-fluorophenyl)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylimidazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0012	uM
N-[2-[[(7S,8R)-8-benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-cyclopropylmethanesulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0012	uM
N-[2-[[(7S,8R)-7-amino-8-[(3,4-dichlorophenyl)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylpyrazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0012	uM
N-[2-[[(7S,8R)-8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylimidazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0012	uM
2,6-dichloro-N-[[4,4-difluoro-1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0013	uM
2-chloro-N-[[4,4-difluoro-1-[4-(1-methylimidazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]-6-(trifluoromethoxy)benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0015	uM
N-[2-[[(7S,8R)-7-amino-8-[(3-chlorophenyl)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]ethyl]-1-methylimidazole-4-sulfonamide	1356787: Displacement of [3H]N-Methyl-SSR504734 from human GlyT1c expressed in cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0015	uM
2,4-dichloro-N-[[1-[4-(1-methyltriazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0015	uM
2-[methyl-[3-[4-(4-methylbenzoyl)phenoxy]-3-phenylpropyl]amino]acetic acid	73803: Binding affinity towards rat hippocampus GlyT1 transporter expressed in HEK 293 cells	kd	0.0016	uM
2,4-dichloro-N-[[4-(3-fluoro-2-pyridinyl)-1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]methyl]benzamide	353605: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in human JAR cells after 3 hrs by scintillation counting	ic50	0.0017	uM
N-[(3aR,6aS)-1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-5-yl]-N-[[4-fluoro-3-(trifluoromethyl)phenyl]methyl]-1-methylimidazole-4-carboxamide	461120: Displacement of tritiated NPTS from human glycine transporter 1 expressed in HEK293 cells	ki	0.0017	uM
N-(4-aminocyclohexyl)-N-[(3-chlorophenyl)methyl]-1-methylimidazole-4-carboxamide	419479: Binding affinity to GlyT1	ki	0.0018	uM
N-(4-aminocyclohexyl)-N-[(3-chlorophenyl)methyl]-1-methylimidazole-4-carboxamide;trihydrochloride	461120: Displacement of tritiated NPTS from human glycine transporter 1 expressed in HEK293 cells	ki	0.0018	uM
2,4-dichloro-N-[[1-(cyclopropylmethyl)-4-(1-methyltriazol-4-yl)sulfonylcyclohexyl]methyl]benzamide	353605: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in human JAR cells after 3 hrs by scintillation counting	ic50	0.0019	uM
2-[2-(4,5-dichloro-6-methoxy-1,3-dioxo-2-phenylinden-2-yl)ethyl-methylamino]acetic acid	262007: Inhibition of uptake of [14C]glycine into human JAR cells expressing human GlyT1	ic50	0.0019	uM
2,4-dichloro-N-[[1-(cyclopropylmethylsulfonyl)-4-(3-fluoro-2-pyridinyl)piperidin-4-yl]methyl]benzamide	353605: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in human JAR cells after 3 hrs by scintillation counting	ic50	0.0020	uM
1-[3-fluoro-4-[4-[5-nitro-2-(propan-2-ylamino)benzoyl]piperazin-1-yl]phenyl]ethanone	348436: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in CHO cells by scintillation counter	ec50	0.0020	uM
1-[4-[4-[2-(cyclohexylamino)-5-nitrobenzoyl]piperazin-1-yl]-3-fluorophenyl]ethanone	348436: Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in CHO cells by scintillation counter	ec50	0.0020	uM
N-[(3aR,6aS)-1,2,3,3a,4,5,6,6a-octahydrocyclopenta[c]pyrrol-5-yl]-1-methyl-N-[[3-(trifluoromethoxy)phenyl]methyl]imidazole-4-carboxamide	461120: Displacement of tritiated NPTS from human glycine transporter 1 expressed in HEK293 cells	ki	0.0020	uM
N-[(7-cyclopropyl-7-azabicyclo[2.2.1]heptan-1-yl)-phenylmethyl]-2,6-dimethylbenzamide	1389926: Inhibition of recombinant human GlyT1 expressed in CHO cells assessed as reduction in [3H]glycine uptake pretreated for 15 mins followed by [3H]glycine addition measured after 2 hrs by Topcount method	ic50	0.0020	uM
(3R,4S)-4-(4-fluorophenyl)-1-(1-methylimidazol-4-yl)sulfonyl-N-[3-(trifluoromethyl)phenyl]pyrrolidin-3-amine	1355822: Inhibition of [3H]N-Methyl-SSR504734 binding to human recombinant GlyT1c expressed in CHO cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0020	uM
(3R,4S)-4-(4-fluorophenyl)-N-[4-fluoro-3-(trifluoromethoxy)phenyl]-1-(1-methylimidazol-4-yl)sulfonylpyrrolidin-3-amine	1355822: Inhibition of [3H]N-Methyl-SSR504734 binding to human recombinant GlyT1c expressed in CHO cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0020	uM
(3R,4S)-4-(1,3-dioxan-2-yl)-1-(1-methylimidazol-4-yl)sulfonyl-N-[3-(trifluoromethoxy)phenyl]pyrrolidin-3-amine	1355822: Inhibition of [3H]N-Methyl-SSR504734 binding to human recombinant GlyT1c expressed in CHO cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0020	uM
(3R,4S)-4-(1,3-dioxepan-2-yl)-1-(1-methylimidazol-4-yl)sulfonyl-N-[3-(trifluoromethoxy)phenyl]pyrrolidin-3-amine	1355822: Inhibition of [3H]N-Methyl-SSR504734 binding to human recombinant GlyT1c expressed in CHO cell membranes incubated for 1 hr by liquid scintillation spectrometry	ki	0.0020	uM
2,4-dichloro-N-[[1-[4-(1-methylimidazol-4-yl)sulfonylpiperazin-1-yl]cyclohexyl]methyl]benzamide;hydrochloride	1629818: Inhibition of glycine transporter-1B in human JAR cells assessed as reduction in [14C]glycine uptake preincubated for 10 mins followed by [14C]glycine addition measured after 3 hrs by scintillation proximity assay	ic50	0.0021	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression, decreases expression	3
Particulate Matter	increases expression, affects cotreatment, increases abundance	3
perfluorooctane sulfonic acid	increases expression	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Endosulfan	increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
chloroacetaldehyde	decreases expression	1
bisphenol A	increases expression	1
nobiletin	increases expression	1
titanium dioxide	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1

ChEMBL screening assays

88 unique, capped per target: 83 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1007112	Binding	Inhibition of [3H]glycine uptake at human glycine transporter 1 expressed in CHO cells by scintillation counter	Discovery of benzoylpiperazines as a novel class of potent and selective GlyT1 inhibitors. — Bioorg Med Chem Lett
CHEMBL5209610	Functional	Substrate uptake and inhibition of the Glycine Transporter-1 (GlyT1, SLC6A9) as assessed by the fluorescent FLIPR membrane potential dye in HEK-293 JumpIN-SLC6A9 cells (PubChem AID: 1794809)	Membrane potential based assay for SLC6A9 using HEK-293 SLC6A9 OE cells

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4FE	1321N1-SLC6A9-KO-c3	Cancer cell line	Male
CVCL_D4FF	1321N1-SLC6A9-KO-c5	Cancer cell line	Male
CVCL_TP07	HAP1 SLC6A9 (-) 1	Cancer cell line	Male
CVCL_XT34	HAP1 SLC6A9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer