DLG4

Summary

DLG4 (discs large MAGUK scaffold protein 4, HGNC:2903) is a protein-coding gene on chromosome 17p13.1, encoding Disks large homolog 4 (P78352). Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1742 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 294 total — 58 pathogenic, 23 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001321075

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2903
Approved symbol	DLG4
Name	discs large MAGUK scaffold protein 4
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	PSD-95, PSD95, SAP90, SAP-90
Ensembl gene	ENSG00000132535
Ensembl biotype	protein_coding
OMIM	602887
Entrez	1742

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000302955, ENST00000399506, ENST00000399510, ENST00000447163, ENST00000451807, ENST00000485100, ENST00000486626, ENST00000489885, ENST00000491753, ENST00000493294, ENST00000647975, ENST00000648103, ENST00000648172, ENST00000648263, ENST00000648658, ENST00000648707, ENST00000648760, ENST00000648896, ENST00000649186, ENST00000649514, ENST00000649520, ENST00000649971, ENST00000650120, ENST00000650301

RefSeq mRNA: 7 — MANE Select: NM_001321075 NM_001128827, NM_001321074, NM_001321075, NM_001321076, NM_001321077, NM_001365, NM_001369566

CCDS: CCDS45599, CCDS45600, CCDS82050, CCDS92243, CCDS92244, CCDS92245

Canonical transcript exons

ENST00000399506 — 20 exons

Exon	Start	End
ENSE00000905431	7191893	7192002
ENSE00000905437	7194319	7194495
ENSE00000905439	7196473	7196575
ENSE00000905440	7196757	7197052
ENSE00001061565	7193844	7193871
ENSE00001061566	7193964	7194000
ENSE00001061571	7202903	7203047
ENSE00001061572	7193667	7193714
ENSE00001151000	7196220	7196334
ENSE00001770579	7193483	7193584
ENSE00002402016	7208174	7208239
ENSE00002746247	7192945	7193117
ENSE00002885439	7203424	7203593
ENSE00002885830	7203193	7203329
ENSE00002889704	7203692	7203816
ENSE00003611188	7204199	7204252
ENSE00003617786	7204008	7204067
ENSE00003621363	7191267	7191358
ENSE00003841025	7217118	7217627
ENSE00003898185	7187187	7190814

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6805 / max 75.6900, expressed in 177 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164144	54.2257	1742
164133	0.6612	203
164145	0.3904	121
164128	0.2497	77
164146	0.1977	83
164134	0.1552	62
164127	0.1216	39
164129	0.1040	24
164147	0.1032	50
164142	0.0501	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.14	gold quality
cerebellar hemisphere	UBERON:0002245	98.92	gold quality
cerebellar cortex	UBERON:0002129	98.87	gold quality
right frontal lobe	UBERON:0002810	98.86	gold quality
cortical plate	UBERON:0005343	98.69	gold quality
nucleus accumbens	UBERON:0001882	97.63	gold quality
cingulate cortex	UBERON:0003027	97.61	gold quality
anterior cingulate cortex	UBERON:0009835	97.50	gold quality
prefrontal cortex	UBERON:0000451	97.42	gold quality
adenohypophysis	UBERON:0002196	97.27	gold quality
amygdala	UBERON:0001876	96.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.87	gold quality
caudate nucleus	UBERON:0001873	96.72	gold quality
cerebellum	UBERON:0002037	96.72	gold quality
ganglionic eminence	UBERON:0004023	96.71	gold quality
putamen	UBERON:0001874	96.60	gold quality
pituitary gland	UBERON:0000007	95.78	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.91	gold quality
neocortex	UBERON:0001950	94.74	gold quality
right ovary	UBERON:0002118	94.68	gold quality
frontal cortex	UBERON:0001870	94.44	gold quality
frontal lobe	UBERON:0016525	94.42	gold quality
ventricular zone	UBERON:0003053	93.75	gold quality
forebrain	UBERON:0001890	93.62	gold quality
left ovary	UBERON:0002119	93.61	gold quality
telencephalon	UBERON:0001893	93.56	gold quality
brain	UBERON:0000955	93.48	gold quality
body of uterus	UBERON:0009853	93.40	gold quality
central nervous system	UBERON:0001017	93.35	gold quality
type B pancreatic cell	CL:0000169	93.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX2, ESR2, EZH2, IKZF4, LMO4, ZNF354C

miRNA regulators (miRDB)

92 targeting DLG4, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• PSD-95 has a role in regulating the functional activity and intracellular trafficking of 5-HT2A receptors and possibly other GPCRs (PMID:12682061)
• A single nucleotide polymorphism was identified as not significantly associated with schizophrenia. (PMID:12950712)
• PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current (PMID:15317815)
• ApoEr2 can form a multiprotein complex with NMDA receptor subunits and PSD95 (PMID:16332682)
• it is unlikely that the PSD-95 polymorphisms investigated play a substantial role in conferring susceptibility to schizophrenia in the Chinese population (PMID:17093888)
• GABARAP and DLG4 genes are involved in the etiology of nicotine dependence in European-American smokers. (PMID:17164261)
• thermodynamic parameters associated with the binding of several series of linear peptides to the third PDZ domain of PSD-9 have been measured using isothermal titration calorimetry (PMID:17474715)
• The results clearly indicate that D1R-modulated NR1a/NR2B receptor function depends on PSD-95 and is subjected to the regulation of PKA and PKC. (PMID:17506933)
• validated occurrence of an unusual TG 3’ splice site in intron 5 (PMID:17672918)
• PSD-95, the Kv1.3 potassium channel, and insulin receptor serine kinase co-localize to regulate membrane excitability and synaptic transmission at critical locations in the olfactory bulb. (PMID:17854350)
• PSD-95 levels increased postnatally to reach a stable plateau by early childhood with a slight reduction in late adolescence and early adulthood (PMID:17916412)
• These results suggest that NR2A and NR2B may associate with PSD-95 but with different affinities. This may be important in the determination of the lateral mobility of NMDA receptor subtypes in post-synaptic membranes. (PMID:18308477)
• Increase in postsynaptic density protein PSD-95 expression positively correlates with beta amyloid and phosphorylated Tau proteins in Alzheimer’s disease cases. (PMID:18424056)
• This study found that the PSD-95 protein level significationalty elevated in pateint with deression. (PMID:18570704)
• Muscarinic-induced recruitment of plasma membrane Ca2+-ATPase involves PSD-95/Dlg/Zo-1-mediated interactions. (PMID:19017653)
• The DLG4 protein enhances the resensitization of the D1 DA receptor by accelerating D1 receptor recycling to the cell membrane. (PMID:19274064)
• These data suggest that NMDA receptor complex formation, localization, and downstream signaling may be abnormal in schizophrenia as PSD95, SynGAP and MUPP1 expression is altered. (PMID:19483657)
• An altered association between membrane-associated guanylate kinases (such as PSD-95) and NMDA receptors in mutant huntingtin-expressing cells contributes to increased susceptibility to excitotoxicity. (PMID:19726651)
• Our current findings, suggesting decreased levels of PSD95, NR2A, and LRP-1, with elevated levels of caspase-3 and Bcl2 proteins, may reflect or contribute to neuronal and synaptic loss in the amnestic mild cognitive impairment hippocampus (PMID:19774677)
• Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia (PMID:21151988)
• tetrad complex shows the close association of the Kir2.1 cytoplasmic domains and the influence of PSD-95 mediated self-assembly on the clustering of these channels (PMID:21756874)
• In developing visual cortex TrkB and protein kinase M zeta, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses (PMID:21849550)
• Phosphorylation of a PDZ domain extension modulates binding affinity and interdomain interactions in postsynaptic density-95 (PSD-95) protein, a membrane-associated guanylate kinase (MAGUK). (PMID:21965656)
• study adds new components to the multi-dentate membrane targeting mechanism and highlights the role of N- and C-terminal PDZ extensions of PSD-95/ZO-1 in the regulation of syntenin-1 plasma membrane localization (PMID:22673509)
• Fyn mediates postsynaptic density protein- 95Y523 phosphorylation, which may be responsible for the excitotoxic signal cascades and neuronal apoptosis in brain ischemia and amyloid-beta peptide neurotoxicity. (PMID:22709448)
• a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95. (PMID:22807451)
• CAR and ASIC3 co-immunoprecipitate only when co-expressed with PSD-95. (PMID:22809504)
• Calcyon forms a novel ternary complex with dopamine D1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization (PMID:22843680)
• Polymorphisms of DRD1, DLG4 and HOMER1 are associated with opiate abuse. (PMID:23044706)
• The PDZ1 domain of PSD-95 has a shallow binding pocket that accommodates a peptide ligand involving far fewer interactions and a micromolar affinity (PMID:23394112)
• interactions of G protein-coupled receptors with postsynaptic density protein 95 (PMID:23691031)
• No association was found between the seven single nucleotide polymorphisms in DLG4 and schizophrenia. (PMID:23921260)
• A putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, has been described. (PMID:23936182)
• The crystal structures of the Dlg4 GK domain in complex with two phosphor-Lgl2 peptides reveal the molecular mechanism underlying the specific and phosphorylation-dependent Dlg/Lgl complex formation. (PMID:24513855)
• An association was found between reduced PSD95 in the prefrontal cortex and cognitive impairment in patients with either dementia with Lewy bodies or Parkinson’s disease dementia. (PMID:25104558)
• PSD-95 mRNA G-rich region folds into alternate G quadruplex conformations that coexist in equilibrium and miR-125a forms a stable complex with PSD-95 mRNA. (PMID:25406362)
• Docosahexaenoic acid-containing phosphatidylcholines and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer’s disease. (PMID:25410733)
• The postsynaptic membrane protein PSD95 was increased in schizophrenia in CA3 tissue, but not in CA1 tissue. (PMID:25585032)
• Data indicate the very high affinities of the trimeric ligands to postsynaptic density protein 95 (PSD-95) PDZ domains. (PMID:25658767)
• Data demonstrate a role for SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels may contribute to the pathology through an effect on postsynaptic function and plasticity. (PMID:25678324)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	DLG4	ENSDARG00000039385
danio_rerio	dlg4a	ENSDARG00000041926
mus_musculus	Dlg4	ENSMUSG00000020886
rattus_norvegicus	Dlg4	ENSRNOG00000018526

Paralogs (3): DLG1 (ENSG00000075711), DLG3 (ENSG00000082458), DLG2 (ENSG00000150672)

Protein

Protein identifiers

Disks large homolog 4 — P78352 (reviewed: P78352)

Alternative names: Postsynaptic density protein 95, Synapse-associated protein 90

All UniProt accessions (17): P78352, A0A3B3IRP2, A0A3B3IS17, A0A3B3ISL1, A0A3B3ISQ5, A0A3B3ISR0, A0A3B3ITD1, A0A3B3ITI9, A0A3B3IU19, B7Z3U2, B7Z647, B9EGL1, C9JWP9, C9JYG3, K7EKP9, K7EKU8, O14909

UniProt curated annotations — full annotation on UniProt →

Function. Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression. Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins.

Subunit / interactions. Interacts through its PDZ domains with ANO2 and NETO1. Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D. Interacts with ASIC3. Interacts with SEMA4C. Interacts with CXADR. Interacts with KCND2. Interacts with SYNGAP1. Interacts with LRRC4 and LRRC4B. Interacts with ERBB4. Interacts with KCNA1, KCNA2, KCNA3 and KCNA4. Interacts through its first PDZ domain with GRIK2, KCNA4 and CRIPT. Interacts through its second PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON. Interacts through its third PDZ domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3. Interacts through its guanylate kinase-like domain with KIF13B. Interacts through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN and SIPA1L1. Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK. Interacts with ADR1B and ANKS1B. May interact with HTR2A. Interacts with ADAM22. Interacts with KLHL17 and LGI1. Interacts with FRMPD4 (via C-terminus). Interacts with LRFN1, LRFN2 and LRFN4. Interacts (via N-terminal tandem pair of PDZ domains) with GPER1 (via C-terminus tail motif); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner. Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-terminal domain). Interacts with SHANK3. Interacts with KCNJ4. Interacts with GPR85. Interacts with CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-module). Interacts with ADGRB1. Found in a complex with PRR7 and GRIN1. Interacts (via PDZ3 domain and to lesser degree via PDZ2 domain) with PRR7. Component of the postsynaptic hippocampal AMPA-type glutamate receptor (AMPAR) complex, at least composed of pore forming AMPAR subunits GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and SHISA7. Interacts (via its first two PDZ domains) with SHISA6 and SHISA7 (via PDZ-binding motif); the interaction is direct. Interacts with RPH3A and GRIN2A; this ternary complex regulates NMDA receptor composition at postsynaptic membranes. Interacts with ABR and BCR. Interacts with DGKI (via PDZ-binding motif); controls the localization of DGKI to the synapse. Interacts with C9orf72, SMCR8 and RAB39B. Interacts with ZDHHC5. Interacts with PTEN (via PDZ domain-binding motif); the interaction is induced by NMDA and is required for PTEN location at postsynaptic density. Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CACNG8 and CNIH2. Interacts with FAM81A; the interaction facilitates condensate formation via liquid-liquid phase separation. Interacts with ADGRL3. Interacts with SORCS3. Interacts with ABTB3; the interaction stabilizes DLG4 at glutamatergic synapses.

Subcellular location. Cell membrane. Postsynaptic density. Synapse. Cytoplasm. Cell projection. Axon. Dendritic spine. Dendrite. Presynapse.

Tissue specificity. Brain.

Post-translational modifications. Palmitoylated. Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses. Palmitoylation by ZDHHC2 occurs when the synaptic activity decreases and induces DLG4 synaptic clustering. Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic density and function in synaptogenesis. Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering. Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2. Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during neuronal development which slow down in mature neurons. Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.

Disease relevance. Intellectual developmental disorder, autosomal dominant 62 (MRD62) [MIM:618793] An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PDZ domain 3 mediates interaction with ADR1B. The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to postsynaptic density.

Similarity. Belongs to the MAGUK family.

Isoforms (3)

UniProt ID	Names	Canonical?
P78352-1	1, PSD95-alpha	yes
P78352-2	2, PSD95-beta
P78352-3	3

RefSeq proteins (7): NP_001122299, NP_001308003, NP_001308004, NP_001308005, NP_001308006, NP_001356, NP_001356495 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR001478	PDZ	Domain
IPR008144	Guanylate_kin-like_dom	Domain
IPR008145	GK/Ca_channel_bsu	Domain
IPR016313	DLG1-like	Family
IPR019583	DLG1-4_PDZ_assoc	Domain
IPR019590	DLG1_PEST_dom	Domain
IPR020590	Guanylate_kinase_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR050614	Synaptic_Scaffolding_LAP-MAGUK	Family

Pfam: PF00018, PF00595, PF00625, PF10600, PF10608

UniProt features (59 total): strand 21, modified residue 15, helix 8, domain 5, lipid moiety-binding region 2, splice variant 2, sequence variant 2, chain 1, turn 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
9TNG	X-RAY DIFFRACTION	0.95
6QJL	X-RAY DIFFRACTION	1.04
6QJK	X-RAY DIFFRACTION	1.05
8AH5	X-RAY DIFFRACTION	1.25
8AH7	X-RAY DIFFRACTION	1.25
3I4W	X-RAY DIFFRACTION	1.35
3K82	X-RAY DIFFRACTION	1.4
9TNF	X-RAY DIFFRACTION	1.45
8AH4	X-RAY DIFFRACTION	1.48
6QJF	X-RAY DIFFRACTION	1.5
6QJI	X-RAY DIFFRACTION	1.5
8AH8	X-RAY DIFFRACTION	1.5
6QJD	X-RAY DIFFRACTION	1.55
8AH6	X-RAY DIFFRACTION	1.63
6QJJ	X-RAY DIFFRACTION	1.7
6QJN	X-RAY DIFFRACTION	1.8
6QJG	X-RAY DIFFRACTION	2
6SPV	X-RAY DIFFRACTION	2.04
6SPZ	X-RAY DIFFRACTION	2.08
5JXB	X-RAY DIFFRACTION	2.9
3ZRT	X-RAY DIFFRACTION	3.4
1KEF	SOLUTION NMR
2MES	SOLUTION NMR
5J7J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78352-F1	78.00	0.52

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 (17): 295, 415, 418, 420, 422, 425, 449, 480, 580, 606, 654, 715, 3, 5, 73, 142, 240

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1236394	Signaling by ERBB4
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-447038	NrCAM interactions
R-HSA-451308	Activation of Ca-permeable Kainate Receptor
R-HSA-5625900	RHO GTPases activate CIT
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5682910	LGI-ADAM interactions
R-HSA-6794361	Neurexins and neuroligins
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9617324	Negative regulation of NMDA receptor-mediated neuronal transmission
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 359 (showing top): GOBP_DENDRITE_DEVELOPMENT, REACTOME_IONOTROPIC_ACTIVITY_OF_KAINATE_RECEPTORS, GOBP_COGNITION, MODULE_274, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, PEREZ_TP63_TARGETS, GOBP_VESICLE_ORGANIZATION, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_RESPONSE_TO_POTASSIUM_ION, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (28): negative regulation of receptor internalization (GO:0002091), signal transduction (GO:0007165), positive regulation of cytosolic calcium ion concentration (GO:0007204), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), learning (GO:0007612), synaptic vesicle maturation (GO:0016188), social behavior (GO:0035176), protein localization to synapse (GO:0035418), locomotory exploration behavior (GO:0035641), cellular response to potassium ion (GO:0035865), establishment of protein localization (GO:0045184), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), regulation of long-term neuronal synaptic plasticity (GO:0048169), positive regulation of synaptic transmission (GO:0050806), neuromuscular process controlling balance (GO:0050885), dendritic spine morphogenesis (GO:0060997), protein-containing complex assembly (GO:0065003), vocalization behavior (GO:0071625), AMPA glutamate receptor clustering (GO:0097113), receptor localization to synapse (GO:0097120), cell-cell adhesion (GO:0098609), NMDA selective glutamate receptor signaling pathway (GO:0098989), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645), positive regulation of neuron projection arborization (GO:0150012), positive regulation of excitatory postsynaptic potential (GO:2000463), regulation of grooming behavior (GO:2000821)

GO Molecular Function (14): kinase binding (GO:0019900), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), PDZ domain binding (GO:0030165), protein-macromolecule adaptor activity (GO:0030674), beta-1 adrenergic receptor binding (GO:0031697), D1 dopamine receptor binding (GO:0031748), P2Y1 nucleotide receptor binding (GO:0031812), acetylcholine receptor binding (GO:0033130), ionotropic glutamate receptor binding (GO:0035255), protein-containing complex binding (GO:0044877), neuroligin family protein binding (GO:0097109), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (34): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), synaptic vesicle (GO:0008021), postsynaptic density (GO:0014069), cell junction (GO:0030054), endocytic vesicle membrane (GO:0030666), cortical cytoskeleton (GO:0030863), neuromuscular junction (GO:0031594), AMPA glutamate receptor complex (GO:0032281), dendrite cytoplasm (GO:0032839), neuron projection (GO:0043005), dendritic spine (GO:0043197), juxtaparanode region of axon (GO:0044224), cerebellar mossy fiber (GO:0044300), neuron projection terminus (GO:0044306), neuron spine (GO:0044309), synapse (GO:0045202), postsynaptic membrane (GO:0045211), excitatory synapse (GO:0060076), synaptic membrane (GO:0097060), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), cell projection (GO:0042995), organelle (GO:0043226), cell periphery (GO:0071944), presynapse (GO:0098793), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
Protein-protein interactions at synapses	2
Signaling by Receptor Tyrosine Kinases	1
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
L1CAM interactions	1
Ionotropic activity of kainate receptors	1
RHO GTPase Effectors	1
MAPK1/MAPK3 signaling	1
Developmental Biology	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
behavior	2
protein binding	2
signaling receptor binding	2
binding	2
cytoplasm	2
dendrite	2
neuron projection	2
regulation of receptor internalization	1
receptor internalization	1
negative regulation of receptor-mediated endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of biological quality	1
anterograde trans-synaptic signaling	1
system development	1
learning or memory	1
vesicle organization	1
developmental maturation	1
biological process involved in intraspecies interaction between organisms	1
protein localization to cell junction	1
locomotory behavior	1
exploration behavior	1
response to potassium ion	1
cellular response to metal ion	1
establishment of localization	1
establishment or maintenance of apical/basal cell polarity	1
regulation of neuronal synaptic plasticity	1
chemical synaptic transmission	1
positive regulation of cell communication	1
positive regulation of signaling	1
modulation of chemical synaptic transmission	1
musculoskeletal movement	1
neuromuscular process	1
neuron projection development	1
neuron projection morphogenesis	1
dendrite morphogenesis	1

Protein interactions and networks

STRING

5288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLG4	GRIN2B	Q13224	999
DLG4	CACNG2	Q9Y698	998
DLG4	DLGAP1	P78335	998
DLG4	GRIN2A	Q12879	998
DLG4	NLGN1	Q8N2Q7	996
DLG4	NLGN2	Q8NFZ4	995
DLG4	SYNGAP1	Q96PV0	995
DLG4	NOS1	P29475	993
DLG4	SHANK3	Q9BYB0	993
DLG4	FYN	P06241	992
DLG4	GRIK2	Q13002	991
DLG4	CRIPT	Q9P021	989
DLG4	TJP1	Q07157	988
DLG4	NLGN3	Q9NZ94	988
DLG4	NLGN4X	Q8N0W4	987

IntAct

1291 interactions, top by confidence:

A	B	Type	Score
DLG4	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.820
DLG4	GRIN2B	psi-mi:“MI:0915”(physical association)	0.820
DLG4	GRIN2A	psi-mi:“MI:0915”(physical association)	0.810
GRIN2A	DLG4	psi-mi:“MI:0915”(physical association)	0.810
DLG4	GRIN2A	psi-mi:“MI:0407”(direct interaction)	0.810
DLG4	RALBP1	psi-mi:“MI:0407”(direct interaction)	0.780
RALBP1	DLG4	psi-mi:“MI:0915”(physical association)	0.780
DLG4	RALBP1	psi-mi:“MI:0915”(physical association)	0.780
RALBP1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.780
DLG4	CRIPT	psi-mi:“MI:0407”(direct interaction)	0.770
CRIPT	DLG4	psi-mi:“MI:0407”(direct interaction)	0.770
ERBB4	DLG4	psi-mi:“MI:0915”(physical association)	0.740
DLG4	ERBB4	psi-mi:“MI:0915”(physical association)	0.740
DLG4	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.720
DLG4	NET1	psi-mi:“MI:0407”(direct interaction)	0.720
DLG4	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.720
DLG4	FRMPD4	psi-mi:“MI:0915”(physical association)	0.720
NET1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.720
FRMPD4	DLG4	psi-mi:“MI:0407”(direct interaction)	0.720
CYSLTR2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.720
MDM2	EEF1A1	psi-mi:“MI:0914”(association)	0.710
GRIN2C	DLG4	psi-mi:“MI:0407”(direct interaction)	0.680
KCNA4	DLG4	psi-mi:“MI:0407”(direct interaction)	0.680

BioGRID (326): SPRR2A (Reconstituted Complex), KCNJ4 (Two-hybrid), DLG4 (Two-hybrid), KCNJ2 (Two-hybrid), PTPN5 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG4 (Biochemical Activity), DLG4 (Biochemical Activity), SIPA1L1 (Affinity Capture-Western), SIPA1L1 (Two-hybrid), SIPA1L1 (Reconstituted Complex), DLGAP1 (Affinity Capture-Western), DLG3 (Affinity Capture-Western)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A2AWA9, A6QQZ7, A8KBF6, O55047, O88506, O95747, P20936, P23727, P26450, P27986, P31016, P78352, Q08CW1, Q08E27, Q12959, Q15139, Q15700, Q1ECX4, Q28C55, Q5PYH5, Q5PYH6, Q5PYH7, Q5R372, Q5R495, Q5R685, Q5R6Y5, Q5RAN1, Q5RCW6, Q5SRX1, Q5T2T1, Q5U2Y3, Q5ZIL4, Q5ZMW5, Q62101, Q62108, Q62696, Q63622, Q68FK8

Diamond homologs: A0A140LI67, A5PKA5, A7UA95, E1JIT7, O14910, O15018, O19132, O35274, O35867, O35889, O62666, O62674, O62675, O62676, O62677, O62678, O88951, O88952, P11434, P29475, P29476, P31016, P51140, P55196, P57105, P78352, Q07436, Q0P5F3, Q12923, Q14005, Q29498, Q2KIB6, Q32LM6, Q3T0C9, Q3UHD6, Q4KL35, Q5F425, Q5RAA5, Q62108, Q64512

SIGNOR signaling

55 interactions.

A	Effect	B	Mechanism
FYN	up-regulates	DLG4	phosphorylation
SRC	up-regulates	DLG4	phosphorylation
ZDHHC2	“up-regulates activity”	DLG4	palmitoylation
LRRC4C	“up-regulates activity”	DLG4	binding
LRRC4	“up-regulates activity”	DLG4	binding
LRRC4B	“up-regulates activity”	DLG4	binding
DLG4	up-regulates	Synaptic_plasticity
KIF5A	“up-regulates activity”	DLG4	binding
DLG4	“up-regulates activity”	LRFN2	binding
DLG4	“up-regulates activity”	LRFN1	binding
LRFN4	“up-regulates activity”	DLG4	binding
NLGN3	“up-regulates activity”	DLG4	relocalization
NLGN4Y	“up-regulates activity”	DLG4	relocalization
NLGN1	“up-regulates activity”	DLG4	relocalization
NLGN4X	“up-regulates activity”	DLG4	relocalization
NLGN2	“up-regulates activity”	DLG4	relocalization
DLG4	“up-regulates activity”	GRIN2A	relocalization
DLG4	“up-regulates activity”	GRIN2B	relocalization
DLG4	“up-regulates activity”	DLGAP1	relocalization
DLGAP1	“up-regulates activity”	DLG4	binding
DLGAP2	“up-regulates activity”	DLG4	binding
DLGAP3	“up-regulates activity”	DLG4	binding
DLGAP4	“up-regulates activity”	DLG4	binding
DLGAP5	“up-regulates activity”	DLG4	binding
“NMDA receptor_2A”	“up-regulates activity”	DLG4	binding
“NMDA receptor_2B”	“up-regulates activity”	DLG4	binding
“NMDA receptor_2C”	“up-regulates activity”	DLG4	binding
“NMDA receptor_2D”	“up-regulates activity”	DLG4	binding
DLG4	“up-regulates activity”	NOS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Long-term potentiation	7	47.6×	1e-08
Unblocking of NMDA receptors, glutamate binding and activation	6	46.6×	2e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	6	46.6×	2e-07
Neurexins and neuroligins	12	33.8×	4e-13
Assembly and cell surface presentation of NMDA receptors	9	32.6×	1e-09
Activation of NMDA receptors and postsynaptic events	5	13.2×	2e-03
Neurotransmitter receptors and postsynaptic signal transmission	6	8.6×	3e-03
RAF/MAP kinase cascade	8	7.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
long-term synaptic potentiation	6	18.3×	4e-04
regulation of synaptic plasticity	5	14.1×	2e-03
modulation of chemical synaptic transmission	6	11.9×	1e-03
sodium ion transmembrane transport	5	11.0×	4e-03
chemical synaptic transmission	9	7.6×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	58
Likely pathogenic	23
Uncertain significance	126
Likely benign	32
Benign	6

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012889	NM_001321075.3(DLG4):c.193del (p.Glu65fs)	Pathogenic
1070455	NM_001321075.3(DLG4):c.1977-2A>G	Pathogenic
1076973	NC_000017.10:g.(?6589506)(7128436_?)del	Pathogenic
1300623	NM_001321075.3(DLG4):c.1072C>T (p.Gln358Ter)	Pathogenic
1325828	NM_001321075.3(DLG4):c.1849C>T (p.Arg617Ter)	Pathogenic
1328479	NM_001321075.3(DLG4):c.1412G>A (p.Trp471Ter)	Pathogenic
1329878	NM_001321075.3(DLG4):c.193G>T (p.Glu65Ter)	Pathogenic
1329880	NM_001321075.3(DLG4):c.218C>G (p.Ser73Ter)	Pathogenic
1329881	NM_001321075.3(DLG4):c.243dup (p.Gly82fs)	Pathogenic
1329882	NM_001321075.3(DLG4):c.319C>T (p.Gln107Ter)	Pathogenic
1329883	NM_001321075.3(DLG4):c.339del (p.Asn114fs)	Pathogenic
1329884	NM_001321075.3(DLG4):c.478G>T (p.Glu160Ter)	Pathogenic
1329889	NM_001321075.3(DLG4):c.792T>A (p.Tyr264Ter)	Pathogenic
1329892	NM_001321075.3(DLG4):c.1195C>T (p.Arg399Ter)	Pathogenic
1329893	NM_001321075.3(DLG4):c.1458del (p.Phe487fs)	Pathogenic
1329897	NM_001321075.3(DLG4):c.1497G>A (p.Trp499Ter)	Pathogenic
1329898	NM_001321075.3(DLG4):c.1496G>A (p.Trp499Ter)	Pathogenic
1329900	NM_001321075.3(DLG4):c.1672A>T (p.Lys558Ter)	Pathogenic
1329902	NM_001321075.3(DLG4):c.1757G>A (p.Arg586Gln)	Pathogenic
1329905	NM_001321075.3(DLG4):c.1855del (p.Val619fs)	Pathogenic
1329907	NM_001321075.3(DLG4):c.2074_2078delinsT (p.Val692fs)	Pathogenic
1335243	NM_001321075.3(DLG4):c.1184_1186+7del	Pathogenic
1455262	NM_001321075.3(DLG4):c.413_414del (p.Lys138fs)	Pathogenic
1699291	NM_001321075.3(DLG4):c.410_411del (p.Leu137fs)	Pathogenic
1700174	NM_001321075.3(DLG4):c.1697del (p.Thr566fs)	Pathogenic
1803960	NM_001321075.3(DLG4):c.981_982dup (p.Val328fs)	Pathogenic
1805263	NM_001321075.3(DLG4):c.1512dup (p.Lys505fs)	Pathogenic
2264869	NM_001321075.3(DLG4):c.1240del (p.Ser414fs)	Pathogenic
2498082	NM_001321075.3(DLG4):c.94C>T (p.Gln32Ter)	Pathogenic
2498086	NM_001321075.3(DLG4):c.143dup (p.Gly49fs)	Pathogenic

SpliceAI

3232 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7191261:CCTCA:C	donor_loss	1.0000
17:7191262:CTCAC:C	donor_loss	1.0000
17:7191263:TCAC:T	donor_loss	1.0000
17:7191264:CA:C	donor_loss	1.0000
17:7191265:A:AC	donor_gain	1.0000
17:7191266:C:CC	donor_gain	1.0000
17:7191355:CTCT:C	acceptor_gain	1.0000
17:7191357:CT:C	acceptor_gain	1.0000
17:7191358:TC:T	acceptor_loss	1.0000
17:7191359:C:CC	acceptor_gain	1.0000
17:7191361:G:C	acceptor_gain	1.0000
17:7191361:G:GC	acceptor_gain	1.0000
17:7191748:T:TA	donor_gain	1.0000
17:7191887:A:AC	donor_gain	1.0000
17:7191888:C:CC	donor_gain	1.0000
17:7191889:TCA:T	donor_loss	1.0000
17:7191890:CA:C	donor_loss	1.0000
17:7191891:A:AC	donor_gain	1.0000
17:7191891:AC:A	donor_loss	1.0000
17:7191891:ACAG:A	donor_gain	1.0000
17:7191892:C:CT	donor_gain	1.0000
17:7191892:CAG:C	donor_gain	1.0000
17:7191892:CAGC:C	donor_gain	1.0000
17:7191892:CAGCA:C	donor_gain	1.0000
17:7192000:CCC:C	acceptor_gain	1.0000
17:7192001:CCC:C	acceptor_gain	1.0000
17:7192941:CTAC:C	donor_loss	1.0000
17:7192942:TA:T	donor_loss	1.0000
17:7192943:A:T	donor_loss	1.0000
17:7192944:C:CT	donor_loss	1.0000

AlphaMissense

4763 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7190734:A:G	W717R	1.000
17:7190734:A:T	W717R	1.000
17:7191272:A:G	F688S	1.000
17:7191283:G:C	F684L	1.000
17:7191283:G:T	F684L	1.000
17:7191285:A:G	F684L	1.000
17:7191296:A:G	L680P	1.000
17:7191929:G:T	A647D	1.000
17:7191935:G:C	P645R	1.000
17:7191935:G:T	P645H	1.000
17:7191956:A:G	L638P	1.000
17:7191956:A:T	L638Q	1.000
17:7191968:G:T	A634D	1.000
17:7191980:A:T	V630D	1.000
17:7191982:A:C	D629E	1.000
17:7191982:A:T	D629E	1.000
17:7191983:T:A	D629V	1.000
17:7191983:T:C	D629G	1.000
17:7191983:T:G	D629A	1.000
17:7191984:C:G	D629H	1.000
17:7191986:A:G	L628P	1.000
17:7191986:A:T	L628H	1.000
17:7191991:G:C	C626W	1.000
17:7191992:C:T	C626Y	1.000
17:7191993:A:G	C626R	1.000
17:7192953:C:G	A620P	1.000
17:7192964:A:T	V616E	1.000
17:7192982:C:A	G610V	1.000
17:7192982:C:T	G610E	1.000
17:7192983:C:A	G610W	1.000

dbSNP variants (sampled 300 via entrez): RS1000051015 (17:7206355 C>G), RS1000112994 (17:7201520 C>G,T), RS1000123891 (17:7205085 G>C), RS1000136380 (17:7199878 G>A), RS1000321560 (17:7194151 A>T), RS1000403680 (17:7206027 G>A,T), RS1000404312 (17:7188324 C>T), RS1000495978 (17:7221016 A>C,G), RS1000582364 (17:7195280 C>T), RS1000682524 (17:7195372 C>T), RS1000710148 (17:7189285 T>A,C), RS1000764604 (17:7207726 A>G,T), RS1001019087 (17:7217766 AGGCAAACATGGAGACCT>A), RS1001027299 (17:7219801 G>A,C), RS1001057866 (17:7195515 G>A)

Disease associations

OMIM: gene MIM:602887 | disease phenotypes: MIM:201475, MIM:618793

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder 62	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (3): very long chain acyl-CoA dehydrogenase deficiency (MONDO:0008723), intellectual developmental disorder 62 (MONDO:0032919), intellectual disability (MONDO:0001071)

Orphanet (2): Very long chain acyl-CoA dehydrogenase deficiency (Orphanet:26793), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001276_5	Liver enzyme levels (alkaline phosphatase)	8.000000e-12
GCST002221_71	Cholesterol, total	3.000000e-10
GCST002222_51	LDL cholesterol	3.000000e-10
GCST002896_31	Cholesterol, total	7.000000e-12
GCST002898_30	LDL cholesterol	9.000000e-12
GCST004233_19	LDL cholesterol levels	4.000000e-10
GCST006016_37	Serum alkaline phosphatase levels	4.000000e-33
GCST90002383_59	Hematocrit	3.000000e-14
GCST90002384_401	Hemoglobin	1.000000e-14
GCST90011900_152	Serum alkaline phosphatase levels	3.000000e-192
GCST90013406_7	Liver enzyme levels (alkaline phosphatase)	1.000000e-300

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin 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): CHEMBL5666 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 164 (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
CHEMBL502630	NERINETIDE	3	164

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(S)-2-[(S)-2-((2S,3R)-2-{(S)-2-[(Adamantan-1-ylmethyl)-amino]-4-carboxy-butyrylamino}-3-hydroxy-butyrylamino)-propionylamino]-3-methyl-butyric acid	KI	2100 nM

ChEMBL bioactivities

61 potent at pChembl≥5 of 121 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.35	Ki	450	nM	CHEMBL1688601
6.20	Ki	630	nM	CHEMBL1688601
6.20	Ki	630	nM	CHEMBL1688631
6.12	Ki	750	nM	CHEMBL1688606
6.03	Ki	940	nM	CHEMBL1688601
6.02	Ki	950	nM	CHEMBL1688637
6.01	Ki	980	nM	CHEMBL2372220
6.00	Ki	1000	nM	CHEMBL1688637
6.00	Ki	1000	nM	CHEMBL2372223
6.00	Ki	1000	nM	CHEMBL2372220
6.00	Ki	1000	nM	CHEMBL1688633
5.96	Ki	1100	nM	CHEMBL1688638
5.96	Ki	1100	nM	CHEMBL1688632
5.92	Kd	1200	nM	NERINETIDE
5.92	Ki	1200	nM	CHEMBL1688612
5.92	Ki	1200	nM	CHEMBL1688619
5.89	Ki	1300	nM	CHEMBL2372223
5.89	Ki	1300	nM	CHEMBL1688616
5.85	Ki	1400	nM	CHEMBL1688618
5.82	Ki	1500	nM	CHEMBL1688617
5.80	Ki	1600	nM	CHEMBL2372217
5.75	Kd	1800	nM	CHEMBL6165528
5.75	Ki	1800	nM	CHEMBL1688611
5.75	Ki	1800	nM	CHEMBL1688620
5.68	Ki	2100	nM	CHEMBL2372219
5.68	Ki	2100	nM	CHEMBL505051
5.68	Ki	2100	nM	CHEMBL1688615
5.64	Ki	2300	nM	CHEMBL2372215
5.62	Ki	2400	nM	CHEMBL1688638
5.51	Ki	3100	nM	CHEMBL2372219
5.44	Ki	3600	nM	CHEMBL1688610
5.40	Ki	4000	nM	CHEMBL2372222
5.39	Ki	4100	nM	CHEMBL445253
5.38	Ki	4200	nM	CHEMBL2372221
5.38	Ki	4200	nM	CHEMBL1688621
5.36	Ki	4400	nM	CHEMBL2372217
5.36	Ki	4400	nM	NERINETIDE
5.36	Ki	4400	nM	CHEMBL1688608
5.30	Ki	5000	nM	CHEMBL1688622
5.28	Ki	5200	nM	CHEMBL2372216
5.20	Ki	6300	nM	CHEMBL2372215
5.17	Ki	6700	nM	CHEMBL1688638
5.17	Ki	6700	nM	CHEMBL1688615
5.16	Ki	7000	nM	CHEMBL2372221
5.16	Ki	7000	nM	CHEMBL445253
5.14	Ki	7200	nM	CHEMBL2372216
5.11	Ki	7800	nM	CHEMBL2372220
5.09	Ki	8100	nM	CHEMBL1688609
5.08	Ki	8400	nM	CHEMBL2372222
5.08	Ki	8300	nM	CHEMBL1688633

PubChem BioAssay actives

59 with measured affinity, of 212 total; 35 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
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-cyclohexylethylamino)-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	0.4500	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-sulfanylidenepropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-cyclohexylethylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	0.6300	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-cyclohexylethylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	0.7500	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-naphthalen-2-ylethylamino)-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	0.9500	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[2-(3,4-difluorophenyl)ethylamino]-5-oxopentanoic acid	391156: Binding affinity to human PSD95 domain PDZ1 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	0.9800	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(cyclohexylmethylamino)-5-oxopentanoic acid	391156: Binding affinity to human PSD95 domain PDZ1 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	1.0000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-sulfanylidenepropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[2-(3,4-dichlorophenyl)ethylamino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.0000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[2-(3,4-dichlorophenyl)ethylamino]-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	1.1000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-sulfanylidenepropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-naphthalen-2-ylethylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.1000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[2-(3,4-dichlorophenyl)ethylamino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.2000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-cycloheptylethylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.2000	uM
(4S)-4-(2-bicyclo[2.2.1]heptanylmethylamino)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.3000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(cycloheptylmethylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.4000	uM
(4S)-4-[2-(2-bicyclo[2.2.1]heptanyl)ethylamino]-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.5000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxo-4-(2-phenylethylamino)pentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	1.6000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(2-naphthalen-2-ylethylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.8000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxo-4-[2-(2,3,4-trifluorophenyl)ethylamino]pentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	1.8000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxo-4-(3-phenylpropylamino)pentanoic acid	391156: Binding affinity to human PSD95 domain PDZ1 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	2.1000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylbutanoic acid	391158: Binding affinity to human PSD95 domain PDZ3 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	2.1000	uM
(4S)-4-(1-adamantylmethylamino)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	2.1000	uM
(4S)-4-[[(2S)-2-amino-3-phenylpropanoyl]amino]-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	2.3000	uM
(2S)-2-[[(2S)-3-carboxy-2-[[(2S,3R)-2-[[(2S)-2-(2-cyclohexylethylamino)propanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-3-methylbutanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	3.6000	uM
(4S)-4-(butylamino)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	4.0000	uM
(4S)-5-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-carboxy-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	4.1000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxo-4-(propylamino)pentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	4.2000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxo-4-[3-(2,3,4-trifluorophenyl)propylamino]pentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	4.2000	uM
(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	4.4000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-(2-cyclohexylethylamino)-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	4.4000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(3-naphthalen-2-ylpropylamino)-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	5.0000	uM
(4S)-4-(benzylamino)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	5.2000	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-(2-cyclohexylethylamino)propanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-3-methylbutanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	8.1000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(methylamino)-5-oxopentanoic acid	391157: Binding affinity to human PSD95 domain PDZ2 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	8.9000	uM
(4S)-4-(3-anthracen-9-ylpropylamino)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	9.0000	uM
(4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-(ethylamino)-5-oxopentanoic acid	391156: Binding affinity to human PSD95 domain PDZ1 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	ki	9.3000	uM
(4S)-4-(2-anthracen-9-ylethylamino)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	588167: Inhibition of PSD-95 PDZ2 domain by competitive fluorescence polarization assay	ki	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
Acetylcysteine	decreases expression, decreases reaction	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	2
Glutathione	decreases expression, decreases reaction	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
Particulate Matter	decreases reaction, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
fisetin	decreases expression, decreases reaction	1
ferrous chloride	increases expression	1
beta-methylcholine	affects expression	1
amyloid beta-protein (1-42)	decreases expression, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases expression, decreases reaction	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects reaction, affects expression	1
bisphenol S	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Aripiprazole	decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Sunitinib	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024689	Binding	Binding affinity to human PSD95 domain PDZ1 expressed in Escherichia coli BL21-DE3 by fluorescence polarization assay	Modified peptides as potent inhibitors of the postsynaptic density-95/N-methyl-D-aspartate receptor interaction. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0YJ	Abcam SH-SY5Y DLG4 KO	Cancer cell line	Female
CVCL_D1S5	Abcam U-87MG DLG4 KO	Cancer cell line	Male
CVCL_D7NR	Ubigene A-549 DLG4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

207 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
NCT00983788	PHASE2	COMPLETED	Effect of Bezafibrate on Muscle Metabolism in Patients With Fatty Acid Oxidation Defects
NCT01886378	PHASE2	COMPLETED	A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
NCT02214160	PHASE2	COMPLETED	Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
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)
NCT01494051	PHASE1/PHASE2	COMPLETED	High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders
NCT05411835	EARLY_PHASE1	COMPLETED	Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders
NCT02517307	Not specified	COMPLETED	Fatty Acid Oxidation Defects and Insulin Sensitivity
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT03531554	Not specified	COMPLETED	Acute Nutritional Ketosis in VLCAD Deficiency
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
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
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome