NAALAD2

Summary

NAALAD2 (N-acetylated alpha-linked acidic dipeptidase 2, HGNC:14526) is a protein-coding gene on chromosome 11q14.3, encoding N-acetylated-alpha-linked acidic dipeptidase 2 (Q9Y3Q0). Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity.

This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a neuropeptide expressed both in the central nervous systems and in the periphery and is thought to function as a neurotransmitter. The product of this gene is a type II integral membrane protein. Transient transfection of this gene confers both NAALADase and dipetidyl peptidase IV activities to mammalian cells. This gene is highly expressed in ovary and testis as well as within discrete brain areas. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10003 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 117 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_005467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14526
Approved symbol	NAALAD2
Name	N-acetylated alpha-linked acidic dipeptidase 2
Location	11q14.3
Locus type	gene with protein product
Status	Approved
Aliases	NAALADASE2, GCPIII
Ensembl gene	ENSG00000077616
Ensembl biotype	protein_coding
OMIM	611636
Entrez	10003

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000321955, ENST00000375944, ENST00000524501, ENST00000525171, ENST00000525497, ENST00000526637, ENST00000527493, ENST00000529090, ENST00000532691, ENST00000534061

RefSeq mRNA: 2 — MANE Select: NM_005467 NM_001300930, NM_005467

CCDS: CCDS73364, CCDS8288

Canonical transcript exons

ENST00000534061 — 19 exons

Exon	Start	End
ENSE00000989327	90158145	90158238
ENSE00001242551	90182916	90183008
ENSE00001242557	90181620	90181701
ENSE00001242564	90177853	90178117
ENSE00001242570	90175972	90176062
ENSE00001242577	90173824	90173915
ENSE00001242584	90170069	90170136
ENSE00001242587	90168929	90168992
ENSE00002166955	90191558	90192894
ENSE00002175281	90134663	90134840
ENSE00003464443	90159239	90159337
ENSE00003471532	90152298	90152484
ENSE00003547511	90163535	90163617
ENSE00003573748	90135559	90135670
ENSE00003608228	90150482	90150607
ENSE00003616842	90147330	90147516
ENSE00003618803	90162949	90163034
ENSE00003649105	90163310	90163429
ENSE00003785016	90149006	90149107

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 90.87.

FANTOM5 (CAGE): breadth broad, TPM avg 6.5801 / max 374.1229, expressed in 622 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116165	6.3983	617
116164	0.1295	61
116166	0.0523	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	90.87	gold quality
pituitary gland	UBERON:0000007	89.24	gold quality
endometrium	UBERON:0001295	87.56	gold quality
adenohypophysis	UBERON:0002196	86.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.35	gold quality
left testis	UBERON:0004533	85.45	gold quality
right testis	UBERON:0004534	85.31	gold quality
testis	UBERON:0000473	85.25	gold quality
right adrenal gland cortex	UBERON:0035827	84.65	gold quality
right adrenal gland	UBERON:0001233	84.30	gold quality
left adrenal gland cortex	UBERON:0035825	83.54	gold quality
adrenal gland	UBERON:0002369	83.20	gold quality
left adrenal gland	UBERON:0001234	83.00	gold quality
putamen	UBERON:0001874	82.01	gold quality
hypothalamus	UBERON:0001898	81.47	gold quality
primary visual cortex	UBERON:0002436	81.18	gold quality
caudate nucleus	UBERON:0001873	80.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.70	gold quality
nucleus accumbens	UBERON:0001882	80.29	gold quality
right ovary	UBERON:0002118	80.27	gold quality
substantia nigra	UBERON:0002038	80.22	gold quality
left ovary	UBERON:0002119	80.03	gold quality
right frontal lobe	UBERON:0002810	79.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.71	gold quality
ovary	UBERON:0000992	79.63	gold quality
superior frontal gyrus	UBERON:0002661	79.60	gold quality
placenta	UBERON:0001987	79.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.39	gold quality
corpus callosum	UBERON:0002336	78.96	gold quality
endocervix	UBERON:0000458	78.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	10.57
E-ANND-3	no	2.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting NAALAD2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 5)

• four novel compounds, Ac-Glu-Met, Ac-Asp-Met and, surprisingly, Ac-Ala-Glu and Ac-Ala-Met were identified as substrates for GCPII (PMID:11905994)
• GCPII polymorphism may affect the predisposition to cardiovascular diseases. (PMID:12204797)
• GCPII has been recognized as a neuropeptidase in the central nervous system, as a folate hydrolase participating in absorption of folates in the jejunum and, most importantly, as a prostate-specific membrane antigen that is highly expressed in prostate adenocarcinoma; GCPIII has not been associated with any specific physiolological functions [review] (PMID:30844704)
• Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to Prostate Cancer and Predicts Biochemical Disease Recurrence. (PMID:34198725)
• Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus. (PMID:34850884)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	naalad2	ENSDARG00000021383
mus_musculus	Naalad2	ENSMUSG00000043943
rattus_norvegicus	Naalad2	ENSRNOG00000005955
caenorhabditis_elegans		WBGENE00007954
caenorhabditis_elegans		WBGENE00020082

Paralogs (5): TFRC (ENSG00000072274), FOLH1 (ENSG00000086205), TFR2 (ENSG00000106327), NAALADL1 (ENSG00000168060), NAALADL2 (ENSG00000177694)

Protein

Protein identifiers

N-acetylated-alpha-linked acidic dipeptidase 2 — Q9Y3Q0 (reviewed: Q9Y3Q0)

Alternative names: Glutamate carboxypeptidase III, N-acetylated-alpha-linked acidic dipeptidase II

All UniProt accessions (6): Q9Y3Q0, E9PII2, E9PJ53, E9PJV2, E9PKX5, J3KNJ3

UniProt curated annotations — full annotation on UniProt →

Function. Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivates the peptide neurotransmitter N-acetylaspartylglutamate.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Tissue specificity. Highest expression in the testis. Also found in ovary and spleen. Weak expression in prostate, heart and placenta. In brain, expressed in striatum, parietal cortex and ventral striatum with lower levels in hippocampus, brain stem, putamen and superior colliculus.

Activity regulation. Inhibited by quisqualate.

Cofactor. Binds 2 Zn(2+) ions per subunit. Required for NAALADase activity.

Domain organisation. The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.

Similarity. Belongs to the peptidase M28 family. M28B subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y3Q0-1	1	yes
Q9Y3Q0-2	2

RefSeq proteins (2): NP_001287859, NP_005458* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003137	PA_domain	Domain
IPR007365	TFR-like_dimer_dom	Domain
IPR007484	Peptidase_M28	Domain
IPR036757	TFR-like_dimer_dom_sf	Homologous_superfamily
IPR039373	Peptidase_M28B	Family
IPR046450	PA_dom_sf	Homologous_superfamily

Pfam: PF02225, PF04253, PF04389

UniProt features (94 total): helix 26, strand 26, binding site 18, glycosylation site 7, active site 4, turn 4, topological domain 2, splice variant 2, sequence variant 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3FED	X-RAY DIFFRACTION	1.29
3FF3	X-RAY DIFFRACTION	1.37
3FEC	X-RAY DIFFRACTION	1.49
3FEE	X-RAY DIFFRACTION	1.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3Q0-F1	95.13	0.91

Functional residue map

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

Catalytic / active sites (4): 414 (nucleophile; for naaladase activity); 618 (charge relay system); 656 (charge relay system); 679 (charge relay system)

Ligand- & substrate-binding residues (18): 247; 259; 262; 367; 377; 377; 414; 415; 423; 426; 443; 507–508 …

Glycosylation sites (7): 111, 143, 185, 314, 449, 603, 628

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8963693	Aspartate and asparagine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 81 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOMF_METALLOPEPTIDASE_ACTIVITY, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, BENPORATH_NOS_TARGETS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, BENPORATH_OCT4_TARGETS, GOBP_PROTEOLYSIS, GOMF_CARBOXYPEPTIDASE_ACTIVITY, GOMF_METALLOEXOPEPTIDASE_ACTIVITY, GOMF_METALLOCARBOXYPEPTIDASE_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, GOMF_DIPEPTIDASE_ACTIVITY, GOMF_DIPEPTIDYL_PEPTIDASE_ACTIVITY, GOMF_EXOPEPTIDASE_ACTIVITY

GO Biological Process (2): proteolysis (GO:0006508), carboxylic acid catabolic process (GO:0046395)

GO Molecular Function (12): carboxypeptidase activity (GO:0004180), metallocarboxypeptidase activity (GO:0004181), serine-type peptidase activity (GO:0008236), dipeptidyl-peptidase activity (GO:0008239), dipeptidase activity (GO:0016805), metal ion binding (GO:0046872), N-formylglutamate deformylase activity (GO:0050129), catalytic activity (GO:0003824), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exopeptidase activity	3
peptidase activity	2
protein metabolic process	1
carboxylic acid metabolic process	1
small molecule catabolic process	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
serine hydrolase activity	1
cation binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
molecular_function	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAALAD2	DPP4	P27487	810
NAALAD2	TRIM49B	A6NDI0	540
NAALAD2	TRIM49	P0CI25	538
NAALAD2	TRIM64B	A6NI03	509
NAALAD2	GRM3	Q14832	493
NAALAD2	TRIM64	A6NGJ6	485
NAALAD2	ALS2CL	Q60I27	483
NAALAD2	TMEM225	Q6GV28	456
NAALAD2	SNX16	P57768	454
NAALAD2	ADGB	Q8N7X0	441
NAALAD2	DHRS12	A0PJE2	405
NAALAD2	GRM5	P41594	404
NAALAD2	TMCO5A	Q8N6Q1	401
NAALAD2	RGS20	O76081	396
NAALAD2	ACVRL1	P37023	382

IntAct

31 interactions, top by confidence:

A	B	Type	Score
SMIM1	NAALAD2	psi-mi:“MI:0915”(physical association)	0.560
	NAALAD2	psi-mi:“MI:0915”(physical association)	0.560
RHBDD2	NAALAD2	psi-mi:“MI:0915”(physical association)	0.560
CIDEB	NAALAD2	psi-mi:“MI:0915”(physical association)	0.560
NAALAD2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
NAALADL2	IGSF3	psi-mi:“MI:0914”(association)	0.350
GGT7	ENTPD6	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
SPCS1	DHX16	psi-mi:“MI:0914”(association)	0.350
FOLH1	GLG1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC15A2	LGALS8	psi-mi:“MI:0914”(association)	0.350
SMIM1	NAALAD2	psi-mi:“MI:0915”(physical association)	0.000
NAALAD2	CIDEB	psi-mi:“MI:0915”(physical association)	0.000
NAALAD2		psi-mi:“MI:0915”(physical association)	0.000
NAALAD2	RHBDD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Two-hybrid), SPCS1 (Two-hybrid), CIDEB (Two-hybrid), SMIM1 (Two-hybrid), NAALAD2 (Proximity Label-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS), NAALAD2 (Affinity Capture-MS)

ESM2 similar proteins: B6EWW8, F8S0Z7, J3SBP3, O00462, O14638, O35409, O65355, O77564, P02786, P15396, P21588, P22413, P49614, P70627, P70665, P82450, P97675, Q04609, Q07891, Q17QK3, Q29444, Q29548, Q2V905, Q5R5M5, Q5RDH6, Q5RDN7, Q5RFI5, Q5RFU0, Q61503, Q62351, Q6DYE8, Q6GQ29, Q6IRK9, Q6P9A2, Q8HZV3, Q95327, Q99376, Q9BTY2, Q9CZR2, Q9FNA3

Diamond homologs: A0A1D6L709, B2GUY2, D4B1R0, O35409, O43023, O54697, O77564, P70627, P91406, Q04609, Q5RDH6, Q5WN23, Q7M758, Q7Y228, Q852M4, Q9CZR2, Q9HBA9, Q9JKX3, Q9M1S8, Q9UP52, Q9UQQ1, Q9Y3Q0, A4R017, A6REE0, B2W3C7, B2W572, B6K327, C4JHZ6, C5FP82, C9SPU8, D4AM42, D4D8N9, E3RJ99, E3S5D4, E4URG0, E5A6Z0, E5R501, Q01693, Q0UNS4, Q2U1F3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NAALAD2	“down-regulates quantity”	Ac-Asp-Glu(3-)	“chemical modification”
NAALAD2	“up-regulates quantity”	L-glutamate(1-)	“chemical modification”
NAALAD2	“up-regulates quantity”	N-acetyl-L-aspartate(2-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	98
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
590793	GRCh37/hg19 11q14.1-14.3(chr11:81771852-90851187)	Pathogenic

SpliceAI

2885 predictions. Top by Δscore:

Variant	Effect	Δscore
11:90134837:GTGG:G	donor_gain	1.0000
11:90134839:GG:G	donor_gain	1.0000
11:90134840:GG:G	donor_gain	1.0000
11:90134840:GGT:G	donor_loss	1.0000
11:90134841:G:GG	donor_gain	1.0000
11:90134841:G:T	donor_loss	1.0000
11:90134842:T:TC	donor_loss	1.0000
11:90134843:AAGT:A	donor_loss	1.0000
11:90135554:CTTA:C	acceptor_loss	1.0000
11:90135555:TTAG:T	acceptor_loss	1.0000
11:90135557:A:AG	acceptor_gain	1.0000
11:90135557:AG:A	acceptor_gain	1.0000
11:90135557:AGGCT:A	acceptor_gain	1.0000
11:90135558:G:GA	acceptor_gain	1.0000
11:90135558:GG:G	acceptor_gain	1.0000
11:90135558:GGC:G	acceptor_gain	1.0000
11:90135558:GGCT:G	acceptor_gain	1.0000
11:90135558:GGCTG:G	acceptor_gain	1.0000
11:90135666:CTTCG:C	donor_gain	1.0000
11:90135667:TTCG:T	donor_gain	1.0000
11:90135667:TTCGG:T	donor_loss	1.0000
11:90135668:TCG:T	donor_gain	1.0000
11:90135669:CG:C	donor_gain	1.0000
11:90135669:CGG:C	donor_loss	1.0000
11:90135670:GG:G	donor_gain	1.0000
11:90135670:GGTA:G	donor_loss	1.0000
11:90135671:G:GG	donor_gain	1.0000
11:90135671:GT:G	donor_loss	1.0000
11:90135672:T:A	donor_loss	1.0000
11:90147325:TTTA:T	acceptor_loss	1.0000

AlphaMissense

4849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:90163345:T:A	W371R	0.997
11:90163345:T:C	W371R	0.997
11:90163567:A:C	S410R	0.996
11:90163569:C:A	S410R	0.996
11:90163569:C:G	S410R	0.996
11:90163570:T:A	W411R	0.996
11:90163570:T:C	W411R	0.996
11:90150593:T:C	F199L	0.995
11:90150595:C:A	F199L	0.995
11:90150595:C:G	F199L	0.995
11:90163576:G:C	A413P	0.994
11:90168973:C:A	N441K	0.994
11:90168973:C:G	N441K	0.994
11:90147403:T:A	W90R	0.993
11:90147403:T:C	W90R	0.993
11:90152307:G:C	A207P	0.993
11:90163339:G:C	D369H	0.993
11:90163340:A:T	D369V	0.991
11:90175994:A:C	S509R	0.991
11:90175996:T:A	S509R	0.991
11:90175996:T:G	S509R	0.991
11:90163337:G:C	R368P	0.990
11:90177886:C:G	H543D	0.990
11:90177899:A:T	E547V	0.990
11:90163340:A:C	D369A	0.989
11:90163583:A:T	E415V	0.989
11:90163347:G:C	W371C	0.988
11:90163347:G:T	W371C	0.988
11:90163572:G:C	W411C	0.988
11:90163572:G:T	W411C	0.988

dbSNP variants (sampled 300 via entrez): RS1000023553 (11:90153149 T>A), RS1000077237 (11:90153507 C>G,T), RS1000088064 (11:90180808 A>G), RS1000125896 (11:90158549 A>G), RS1000166742 (11:90192411 G>A), RS1000168489 (11:90176145 G>A), RS1000212127 (11:90153865 C>T), RS1000216452 (11:90154292 A>G), RS1000218443 (11:90135125 G>A,T), RS1000299915 (11:90174974 T>C,G), RS1000338234 (11:90160818 G>A), RS1000481815 (11:90138175 G>C,T), RS1000498977 (11:90192506 G>A), RS1000520957 (11:90170493 T>C,G), RS1000531361 (11:90169309 T>C,G)

Disease associations

OMIM: gene MIM:611636 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001134_7	White blood cell types	2.000000e-09
GCST005316_359	Intelligence (MTAG)	8.000000e-09
GCST005976_19	White blood cell count (basophil)	2.000000e-16
GCST009391_752	Metabolite levels	3.000000e-06
GCST009733_122	Urinary metabolite levels in chronic kidney disease	3.000000e-25
GCST009735_13	Urinary metabolite modules (eigenmetabolites) in chronic kidney disease	2.000000e-14
GCST010988_424	Adult body size	7.000000e-13
GCST012020_223	Serum metabolite levels	2.000000e-29
GCST012020_224	Serum metabolite levels	2.000000e-47

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0004337	intelligence
EFO:0010390	sphingomyelin 14:0 measurement
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2609 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M28: Aminopeptidase Y

ChEMBL bioactivities

49 potent at pChembl≥5 of 51 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.05	Ki	0.9	nM	CHEMBL49669
8.85	Ki	1.4	nM	CHEMBL47009
8.82	Kd	1.5	nM	CHEMBL5559973
8.77	Kd	1.7	nM	CHEMBL5560474
8.68	Ki	2.1	nM	CHEMBL298530
8.52	Ki	3	nM	CHEMBL297489
8.37	Kd	4.3	nM	CHEMBL5557579
8.35	Kd	4.5	nM	CHEMBL5565532
8.32	Kd	4.8	nM	CHEMBL5561626
8.28	Ki	5.3	nM	CHEMBL47058
8.23	Ki	5.9	nM	CHEMBL50489
8.20	Kd	6.3	nM	CHEMBL5561704
8.19	Kd	6.4	nM	CHEMBL5561251
8.15	Kd	7	nM	CHEMBL5558611
8.10	Kd	8	nM	CHEMBL5532306
8.10	Ki	8	nM	CHEMBL46005
7.92	Kd	12	nM	CHEMBL5557217
7.92	Kd	12	nM	CHEMBL5559378
7.92	Kd	12	nM	CHEMBL5567644
7.92	Ki	12	nM	CHEMBL415916
7.85	Kd	14	nM	CHEMBL5557349
7.84	Ki	14.4	nM	CHEMBL416650
7.83	Ki	14.9	nM	CHEMBL49271
7.82	Kd	15	nM	CHEMBL5555029
7.64	Kd	23	nM	CHEMBL5556760
7.62	Kd	24	nM	CHEMBL5558512
7.52	Kd	30	nM	CHEMBL5555028
7.39	Kd	41	nM	CHEMBL5556591
7.28	Kd	53	nM	CHEMBL5527868
7.17	Kd	67	nM	CHEMBL5557505
7.06	Kd	87	nM	CHEMBL5561889
7.02	Ki	95.3	nM	CHEMBL47416
6.97	Kd	106	nM	CHEMBL5532072
6.77	Kd	169	nM	CHEMBL5562614
6.52	Kd	300	nM	CHEMBL5558291
6.47	Kd	338	nM	CHEMBL5567083
6.47	Ki	335	nM	CHEMBL3348570
6.41	Ki	392	nM	CHEMBL295457
6.30	Kd	505	nM	CHEMBL5567951
6.03	Ki	939	nM	CHEMBL45640
5.96	Ki	1109	nM	CHEMBL2114987
5.89	Ki	1285	nM	CHEMBL2115435
5.70	Kd	2000	nM	CHEMBL5560669
5.57	Ki	2711	nM	CHEMBL301575
5.50	Kd	3200	nM	CHEMBL5512586
5.36	Ki	4388	nM	CHEMBL47477
5.35	Ki	4434	nM	CHEMBL46660
5.19	Kd	6400	nM	CHEMBL5558312
5.00	Kd	1e+04	nM	CHEMBL5556671

PubChem BioAssay actives

49 with measured affinity, of 68 total; 49 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
(2S)-2-[[(1S)-1-carboxy-3-(2H-tetrazol-5-yl)propyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0009	uM
2-(phosphonomethyl)pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0014	uM
(2S)-3-(2H-triazole-4-carbonylamino)-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]propanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0015	uM
(2S)-3-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]propanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0017	uM
(2S)-2-[[(S)-carboxy(phenyl)methyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0021	uM
(2S)-2-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0030	uM
(2S)-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]-2-[[(2S,4R)-1-(5-propan-2-yl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0043	uM
2-(3-amino-6-imino-4,5-disulfoxanthen-9-yl)-5-[[(5S)-5-carboxy-5-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]pentyl]carbamoyl]benzoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0045	uM
(2S)-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0048	uM
(2S)-2-[[(1S)-1-carboxy-3-[1-(2-cyanoethyl)tetrazol-5-yl]propyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0053	uM
(2S)-2-[[(S)-carboxy-(4-hydroxyphenyl)methyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0059	uM
(2S)-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-3-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]propanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0063	uM
(2S)-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]-2-[[(2S,4R)-1-(5-phenyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0064	uM
N-[(3R,5S)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-5-[6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]hexylcarbamoyl]pyrrolidin-3-yl]-2H-triazole-4-carboxamide	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0070	uM
(2S)-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-3-(2H-triazole-4-carbonylamino)propanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0080	uM
(2S)-2-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0080	uM
(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0120	uM
methyl (2S)-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]hexanoate	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0120	uM
(2S)-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-(2H-triazole-4-carbonylamino)hexanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0120	uM
(2S)-6-(2H-triazole-4-carbonylamino)-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0120	uM
2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0140	uM
(2S,4S)-2-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]-4-methylpentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0144	uM
(2S)-2-[[(1S)-1-carboxy-3-(2H-tetrazol-5-yl)propyl]carbamoylamino]-4-(2H-tetrazol-5-yl)butanoic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0149	uM
(2S)-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-[3-[2,2-difluoro-12-(4-methoxyphenyl)-4,6-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-5-yl]propanoylamino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0150	uM
(2R)-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0230	uM
N-[(3R,5S)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-5-[2-[2-[2-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]ethoxy]ethoxy]ethylcarbamoyl]pyrrolidin-3-yl]-2H-triazole-4-carboxamide	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0240	uM
(2S)-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]-2-[[(2S,4R)-1-(3-propan-2-yl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0300	uM
(2S)-6-acetamido-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0410	uM
(2S)-6-[4-[[(5S)-5-carboxy-5-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]pentyl]carbamoylamino]butylcarbamoylamino]-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0530	uM
(2S)-3-acetamido-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]propanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0670	uM
(2S)-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]-2-(2H-triazole-4-carbonylamino)hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.0870	uM
(2R,4S)-2-benzyl-4-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.0953	uM
(2S)-2-[[(2S,4S)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazol-4-ylmethyl)pyrrolidine-2-carbonyl]amino]-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.1060	uM
(2S)-2-[[(2S,4R)-1-acetyl-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-yl)carbamothioylamino]hexanoic acid	2071329: Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.1690	uM
(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carboxylic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.3000	uM
(2S)-2-[[(1S)-3-carboxy-1-(5H-tetrazol-5-yl)propyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.3350	uM
N-[(5S)-6-oxo-5-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]-6-(2H-triazol-4-ylamino)hexyl]-2H-triazole-4-carboxamide	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.3380	uM
(2R,4S)-2-benzyl-4-[[(1S,3S)-1,3-dicarboxy-4-phenylbutyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.3920	uM
(2S)-6-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[3-[[(5S)-5-carboxy-5-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]pentyl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	0.5050	uM
(2S)-2-[[(2S)-2,4-dicarboxybutan-2-yl]carbamoylamino]-2-methylpentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	0.9390	uM
(2S,4S)-2-[[(1S,3S)-1,3-dicarboxybutyl]carbamoylamino]-4-methylpentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	1.1090	uM
(2S,4R)-2-[[(1S,3R)-1,3-dicarboxybutyl]carbamoylamino]-4-methylpentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	1.2850	uM
(2S)-3-acetamido-2-[[(2S,4R)-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]propanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	2.0000	uM
(2S)-2-[[(1S)-3-carboxy-1-[1-(2-cyanoethyl)tetrazol-5-yl]propyl]carbamoylamino]pentanedioic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	2.7110	uM
N-[(3R,5S)-5-[[(2S)-6-acetamido-1-oxo-1-(2H-triazol-4-ylamino)hexan-2-yl]carbamoyl]-1-(5-cyclopropyl-1,2-oxazole-4-carbonyl)pyrrolidin-3-yl]-2H-triazole-4-carboxamide	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	3.2000	uM
(4S)-4-[[(1S)-3-carboxy-1-(2H-tetrazol-5-yl)propyl]carbamoylamino]-4-(2H-tetrazol-5-yl)butanoic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	4.3880	uM
(2S)-2-[[(1S)-1-carboxy-3-[1-(2-cyanoethyl)tetrazol-5-yl]propyl]carbamoylamino]-4-[1-(2-cyanoethyl)tetrazol-5-yl]butanoic acid	74534: In vitro inhibitory activity against human Glutamate carboxypeptidase II by using fluorescent assay	ki	4.4340	uM
(2S)-6-acetamido-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]hexanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	6.4000	uM
(2S)-3-amino-2-[[(2S,4R)-1-(2H-triazole-4-carbonyl)-4-(2H-triazole-4-carbonylamino)pyrrolidine-2-carbonyl]amino]propanoic acid	2071346: Displacement of [177Lu]LU-PSMA-617 from human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	kd	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	6
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, decreases expression, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
perfluorooctanoic acid	decreases expression	1
4-nonylphenol	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
mono-benzyl phthalate	decreases methylation	1
4-tert-octylphenol	affects cotreatment, decreases 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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases activity, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1
Mercuric Chloride	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5510484	Binding	Binding affinity to human recombinant GCPIII assessed as dissociation constant by fluorescence polarization assay	Discovery of Glutamate Carboxypeptidase III Ligands to Compete the Uptake of [177Lu]Lu-PSMA-617 in Healthy Organs. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
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