DLG2

Summary

DLG2 (discs large MAGUK scaffold protein 2, HGNC:2901) is a protein-coding gene on chromosome 11q14.1, encoding Disks large homolog 2 (Q15700). Required for perception of chronic pain through NMDA receptor signaling.

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. The encoded protein forms a heterodimer with a related family member that 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. Additional transcript variants have been described, but their full-length nature is not known.

Source: NCBI Gene 1740 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability (Moderate, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 147 total — 3 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001142699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2901
Approved symbol	DLG2
Name	discs large MAGUK scaffold protein 2
Location	11q14.1
Locus type	gene with protein product
Status	Approved
Aliases	PSD-93, PSD93, chapsyn-110, PPP1R58
Ensembl gene	ENSG00000150672
Ensembl biotype	protein_coding
OMIM	603583
Entrez	1740

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 32 protein_coding, 10 protein_coding_CDS_not_defined, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000280241, ENST00000330014, ENST00000376104, ENST00000398299, ENST00000398301, ENST00000398304, ENST00000398309, ENST00000404783, ENST00000418306, ENST00000420775, ENST00000426717, ENST00000434967, ENST00000456295, ENST00000457267, ENST00000472545, ENST00000524601, ENST00000524941, ENST00000524982, ENST00000526147, ENST00000527088, ENST00000527466, ENST00000529111, ENST00000529159, ENST00000529399, ENST00000529401, ENST00000530260, ENST00000530589, ENST00000530800, ENST00000531015, ENST00000532653, ENST00000648622, ENST00000650630, ENST00000705960, ENST00000706006, ENST00000706007, ENST00000706203, ENST00000706204, ENST00000706205, ENST00000706206, ENST00000706207, ENST00000706208, ENST00000706209, ENST00000706210, ENST00000706226, ENST00000706232, ENST00000706233, ENST00000706243, ENST00000706244, ENST00000706266, ENST00000706267

RefSeq mRNA: 25 — MANE Select: NM_001142699 NM_001142699, NM_001142700, NM_001142702, NM_001206769, NM_001300983, NM_001351274, NM_001351275, NM_001351276, NM_001364, NM_001377966, NM_001377967, NM_001377968, NM_001377970, NM_001377971, NM_001377972, NM_001377973, NM_001377974, NM_001377975, NM_001377976, NM_001377977, NM_001377978, NM_001377979, NM_001377980, NM_001377981, NM_001377982

CCDS: CCDS41696, CCDS44690, CCDS44691, CCDS44692, CCDS55782, CCDS73357, CCDS91555, CCDS91556, CCDS91557, CCDS91558, CCDS91559, CCDS91563, CCDS91565, CCDS91566

Canonical transcript exons

ENST00000376104 — 28 exons

Exon	Start	End
ENSE00001157190	83484129	83484228
ENSE00001157212	83541682	83541858
ENSE00001469378	85111661	85111735
ENSE00001532710	85626587	85626753
ENSE00001680261	83462002	83462093
ENSE00001749092	83469201	83469373
ENSE00001775400	83472727	83472777
ENSE00002198604	83471626	83471727
ENSE00002198764	83532708	83532783
ENSE00002454945	83466708	83466817
ENSE00003471737	84251238	84251291
ENSE00003483868	83965324	83965468
ENSE00003484205	84059315	84059484
ENSE00003487678	84534570	84534731
ENSE00003542004	83786690	83786792
ENSE00003544320	83833614	83833770
ENSE00003586389	84098923	84099047
ENSE00003590811	83874420	83874488
ENSE00003591235	83930328	83930483
ENSE00003595386	83980506	83980642
ENSE00003607494	83962885	83963023
ENSE00003616457	84163461	84163511
ENSE00003659102	85598657	85598788
ENSE00003672135	83633211	83633325
ENSE00003913216	85627218	85627344
ENSE00003995067	83455173	83459924
ENSE00003995156	85154556	85154651
ENSE00003995158	85285220	85285365

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 97.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8521 / max 2659.4335, expressed in 1173 samples.

FANTOM5 promoters (46 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121637	3.5936	142
121680	2.3300	955
121633	2.2632	90
121607	1.6698	152
121638	1.0230	117
121681	0.8415	413
121664	0.7014	79
121642	0.6756	104
121616	0.6029	129
121606	0.4645	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.00	gold quality
endothelial cell	CL:0000115	96.44	gold quality
corpus callosum	UBERON:0002336	95.66	gold quality
inferior vagus X ganglion	UBERON:0005363	94.18	gold quality
prefrontal cortex	UBERON:0000451	93.52	gold quality
entorhinal cortex	UBERON:0002728	93.34	gold quality
right frontal lobe	UBERON:0002810	93.34	gold quality
middle temporal gyrus	UBERON:0002771	93.10	gold quality
nucleus accumbens	UBERON:0001882	92.70	gold quality
Ammon’s horn	UBERON:0001954	92.65	gold quality
temporal lobe	UBERON:0001871	92.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.52	gold quality
amygdala	UBERON:0001876	92.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.07	gold quality
superior vestibular nucleus	UBERON:0007227	91.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.90	gold quality
parietal lobe	UBERON:0001872	91.72	gold quality
substantia nigra pars compacta	UBERON:0001965	91.64	gold quality
frontal cortex	UBERON:0001870	91.33	gold quality
superior frontal gyrus	UBERON:0002661	91.31	gold quality
frontal lobe	UBERON:0016525	91.30	gold quality
telencephalon	UBERON:0001893	91.29	gold quality
lateral globus pallidus	UBERON:0002476	91.29	gold quality
cerebral cortex	UBERON:0000956	91.28	gold quality
neocortex	UBERON:0001950	91.14	gold quality
subthalamic nucleus	UBERON:0001906	91.08	gold quality
postcentral gyrus	UBERON:0002581	91.07	gold quality
cingulate cortex	UBERON:0003027	90.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.97	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	63.55
E-MTAB-7316	yes	32.59
E-GEOD-137537	yes	14.44
E-ANND-3	yes	8.72
E-MTAB-11268	no	3106.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

288 targeting DLG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458

Literature-anchored findings (GeneRIF, showing 24)

• Coexpression of Kir2.1 and PSD-93delta had no discernible effect upon channel kinetics but resulted in cell surface Kir2.1 clustering and suppression of channel internalization. (PMID:15304517)
• identifies new isoform of DLG2 gene, which contains 3’-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266; new isoform is specifically upregulated in renal oncocytoma (PMID:16640776)
• postsynaptic density-93 and N-methyl-D-aspartate receptors subunits 2B mRNA are upregulated in temporal lobe tissue of epilepsy (PMID:17506987)
• Variation at the DLG2 locus contributes to maintenance of glucose homeostasis through regulation of insulin sensitivity and beta-cell function. (PMID:19931931)
• Comparison of the structures of the binding cleft of PSD-93 PDZ1 with the previously reported structures of PSD-93 PDZ2 and PDZ3 as well as of the closely related human PSD-95 PDZ1 shows that they are very similar in terms of amino-acid composition (PMID:20054121)
• This study showed that DLG2 is related the complex learning. (PMID:23201973)
• The PDZ1 domain of PSD-93 might accept peptides with larger residues at the C-terminus than that of PSD-95, for example the GluD2 C-terminal Ile versus the Val found at the C-terminus of NMDA receptors. (PMID:23519667)
• DLG2 - novel candidate genes validated in a large case-control sample of schizophrenia. (PMID:26460480)
• Two novel promoters and coding first exons in the DLG2 gene were identified. These novel isoforms are expressed in the fetal brain. Deletions of these new elements were found associated with neurodevelopmental disorders. The work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases. (PMID:28724449)
• We identified a novel susceptibility locus (rs655484 in DLG2) that reached significance level for migraine risk in Han Chinese (PMID:28952330)
• DLG2 influenced the risk of Parkinson disease in Taiwan. (PMID:29290481)
• our findings suggested that the inhibition of miR-23a results in the suppression of OC progression by releasing DLG2, which provides new understanding on the potential therapeutic effect of miR-23a inhibition in OC patients. (PMID:30862230)
• Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival. (PMID:32312269)
• DLG2 variants in patients with pubertal disorders. (PMID:32341572)
• SNPs in SNCA, MCCC1, DLG2, GBF1 and MBNL2 are associated with Parkinson’s disease in southern Chinese population. (PMID:32652860)
• 11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma. (PMID:32966799)
• Circ0106714 inhibits tumorigenesis of colorectal cancer by sponging miR-942-5p and releasing DLG2 via Hippo-YAP signaling. (PMID:33128289)
• DLG2 Mutations in the Etiology of Pubertal Delay and Idiopathic Hypogonadotropic Hypogonadism. (PMID:34695822)
• Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants. (PMID:35031607)
• DLG2 impairs dsDNA break repair and maintains genome integrity in neuroblastoma. (PMID:35217496)
• Region-based analysis of rare genomic variants in whole-genome sequencing datasets reveal two novel Alzheimer’s disease-associated genes: DTNB and DLG2. (PMID:35246634)
• Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances. (PMID:35627244)
• DLG2 intragenic exonic deletions reinforce the link to neurodevelopmental disorders and suggest a potential association with congenital anomalies and dysmorphism. (PMID:37860969)
• Glioma stem cell-derived exosomes induce the transformation of astrocytes via the miR-3065-5p/DLG2 signaling axis. (PMID:38234042)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dlg2	ENSDARG00000099323
mus_musculus	Dlg2	ENSMUSG00000052572
rattus_norvegicus	Dlg2	ENSRNOG00000022635

Paralogs (3): DLG1 (ENSG00000075711), DLG3 (ENSG00000082458), DLG4 (ENSG00000132535)

Protein

Protein identifiers

Disks large homolog 2 — Q15700 (reviewed: Q15700)

Alternative names: Channel-associated protein of synapse-110, Postsynaptic density protein PSD-93

All UniProt accessions (31): Q15700, A0A3B3ISW2, A0A3B3ITF1, A0A3B3ITF4, A0A5F9ZH92, A0A994J570, A0A994J587, A0A994J5A4, A0A994J5G4, A0A994J5T6, A0A994J7N9, A0A994J7P1, A0A994J7Q5, A0A994J7X6, A0A994J819, A0A994J822, A8MUT9, A8MVA8, B5MCC5, B7Z2T4, C9JFF9, E9PIJ9, E9PIW2, E9PN83, E9PPV7, E9PQT9, E9PRL2, E9PRX3, F8VYC1, F8W750, H7C325

UniProt curated annotations — full annotation on UniProt →

Function. Required for perception of chronic pain through NMDA receptor signaling. Regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord. Interacts with the cytoplasmic tail of NMDA receptor subunits as well as inward rectifying potassium channels. Involved in regulation of synaptic stability at cholinergic synapses. Part of the postsynaptic protein scaffold of excitatory synapses.

Subunit / interactions. Interacts through its PDZ domains with NETO1. Interacts with NOS1/nNOS through second PDZ domain. Interacts with KCNJ2/Kir2.1 (via C-terminus) through one of its PDZ domains. Interacts with KCNJ4, Interacts with FRMPD4 (via C-terminus). Interacts with LRFN1, LRFN2 and LRFN4. Interacts with FASLG. Interacts with KCNJ4. Interacts with ADAM22. Interacts with DGKI (via PDZ-binding motif).

Subcellular location. Cell membrane. Postsynaptic density. Synapse. Membrane. Cell projection. Axon. Perikaryon.

Post-translational modifications. Palmitoylation of isoform 1 is not required for targeting to postsynaptic density.

Domain organisation. An N-terminally truncated L27 domain is predicted in isoform 2 at positions 1 through 27.

Similarity. Belongs to the MAGUK family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q15700-1	1, PSD93-alpha	yes
Q15700-2	2, PSD93-beta
Q15700-3	3
Q15700-4	4, PSD93-delta
Q15700-5	5

RefSeq proteins (25): NP_001136171, NP_001136172, NP_001136174, NP_001193698, NP_001287912, NP_001338203, NP_001338204, NP_001338205, NP_001355, NP_001364895, NP_001364896, NP_001364897, NP_001364899, NP_001364900, NP_001364901, NP_001364902, NP_001364903, NP_001364904, NP_001364905, NP_001364906, NP_001364907, NP_001364908, NP_001364909, NP_001364910, NP_001364911 (=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
IPR035759	DLG2_SH3	Domain
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 (53 total): modified residue 17, strand 10, splice variant 7, sequence conflict 6, domain 5, helix 5, lipid moiety-binding region 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2HE2	X-RAY DIFFRACTION	1.5
2BYG	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15700-F1	69.93	0.40

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 (19): 328, 360, 365, 406, 414, 505, 528, 530, 553, 627, 635, 750, 755, 5, 7, 28, 58, 65, 307

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6794361	Neurexins and neuroligins
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: 416 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, RNGTGGGC_UNKNOWN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_AXO_DENDRITIC_TRANSPORT, WWTAAGGC_UNKNOWN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, AAGTCCA_MIR422B_MIR422A, GCANCTGNY_MYOD_Q6, AREB6_03, AAGCCAT_MIR135A_MIR135B, GOBP_RESPONSE_TO_POTASSIUM_ION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2

GO Biological Process (13): chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), protein localization to synapse (GO:0035418), cellular response to potassium ion (GO:0035865), receptor clustering (GO:0043113), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), receptor localization to synapse (GO:0097120), cell-cell adhesion (GO:0098609), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), anterograde axonal protein transport (GO:0099641), retrograde axonal protein transport (GO:0099642), GMP metabolic process (GO:0046037), GDP metabolic process (GO:0046710)

GO Molecular Function (6): GMP kinase activity (GO:0004385), kinase binding (GO:0019900), protein kinase binding (GO:0019901), ionotropic glutamate receptor binding (GO:0035255), protein binding (GO:0005515), enzyme binding (GO:0019899)

GO Cellular Component (16): cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), postsynaptic density (GO:0014069), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), neuromuscular junction (GO:0031594), neuron projection (GO:0043005), perikaryon (GO:0043204), juxtaparanode region of axon (GO:0044224), postsynaptic density membrane (GO:0098839), axon cytoplasm (GO:1904115), voltage-gated potassium channel complex (GO:0008076), axon (GO:0030424), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
MAPK1/MAPK3 signaling	1
Protein-protein interactions at synapses	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
axo-dendritic protein transport	2
purine ribonucleotide metabolic process	2
anterograde trans-synaptic signaling	1
system development	1
protein localization to cell junction	1
response to potassium ion	1
cellular response to metal ion	1
plasma membrane	1
protein localization to membrane	1
establishment or maintenance of apical/basal cell polarity	1
localization	1
cell adhesion	1
regulation of biological quality	1
anterograde axonal transport	1
protein localization to presynapse	1
retrograde axonal transport	1
purine ribonucleoside monophosphate metabolic process	1
purine ribonucleoside diphosphate metabolic process	1
GMP metabolic process	1
GDP metabolic process	1
nucleoside monophosphate kinase activity	1
enzyme binding	1
kinase binding	1
glutamate receptor binding	1
binding	1
protein binding	1
cytoplasm	1
membrane	1
cell periphery	1
cell-cell junction	1
asymmetric synapse	1
postsynaptic specialization	1
basal plasma membrane	1
plasma membrane region	1
synapse	1
plasma membrane bounded cell projection	1
neuronal cell body	1
main axon	1
postsynaptic density	1

Protein interactions and networks

STRING

3322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLG2	GRIN2A	Q12879	992
DLG2	GRIN2B	Q13224	988
DLG2	DLG4	P78352	918
DLG2	ADAM22	Q9P0K1	899
DLG2	SYNGAP1	Q96PV0	869
DLG2	KCNA4	P22459	853
DLG2	SHANK3	Q9BYB0	826
DLG2	DLG3	Q92796	815
DLG2	TJAP1	Q5JTD0	796
DLG2	BEGAIN	Q9BUH8	789
DLG2	CACNG2	Q9Y698	772
DLG2	ERBB4	Q15303	767
DLG2	FYN	P06241	754
DLG2	GRIA1	P42261	745
DLG2	CNTNAP2	Q9UHC6	734

IntAct

758 interactions, top by confidence:

A	B	Type	Score
DLG2	PLEKHA2	psi-mi:“MI:0915”(physical association)	0.680
ABCA1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.610
DLG2	GRIN2B	psi-mi:“MI:0915”(physical association)	0.590
ERBB4	DLG2	psi-mi:“MI:0407”(direct interaction)	0.590
GRIN2B	DLG2	psi-mi:“MI:0407”(direct interaction)	0.590
DLG2	SERPINB13	psi-mi:“MI:0915”(physical association)	0.560
RPS8	DLG2	psi-mi:“MI:0915”(physical association)	0.560
DLGAP3	DLG2	psi-mi:“MI:0915”(physical association)	0.560
DLG2	PPIL4	psi-mi:“MI:0915”(physical association)	0.560
DLG2	RPF2	psi-mi:“MI:0915”(physical association)	0.560
DLG2	DLGAP2	psi-mi:“MI:0915”(physical association)	0.560
DLG2	FA2H	psi-mi:“MI:0915”(physical association)	0.560
DLG2	DLGAP1	psi-mi:“MI:0915”(physical association)	0.560
VTN	DLG2	psi-mi:“MI:0915”(physical association)	0.560
KDELR1	DLG2	psi-mi:“MI:0915”(physical association)	0.560
AOAH	DLG2	psi-mi:“MI:0915”(physical association)	0.560
RNASE2	DLG2	psi-mi:“MI:0915”(physical association)	0.560
E6	DLG2	psi-mi:“MI:0407”(direct interaction)	0.540
E6	DLG2	psi-mi:“MI:0915”(physical association)	0.540
DLG2	PTEN	psi-mi:“MI:0407”(direct interaction)	0.540
PTEN	DLG2	psi-mi:“MI:0915”(physical association)	0.540
Tax	DLG2	psi-mi:“MI:0407”(direct interaction)	0.540
NET1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.540
Tax	DLG2	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (67): DLG2 (Two-hybrid), DLG2 (Two-hybrid), DLG2 (Affinity Capture-MS), DLG2 (Affinity Capture-Western), DLG2 (Synthetic Lethality), DLG2 (Synthetic Lethality), DLG2 (Affinity Capture-MS), DLG2 (Two-hybrid), DLG2 (Two-hybrid), DLG2 (Two-hybrid), DLG2 (Two-hybrid), DLG2 (Two-hybrid), DLG2 (Two-hybrid), DLG2 (Two-hybrid), RNASE2 (Two-hybrid)

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: A0A8C0TYJ0, A0A8P0N4K0, B4F7E7, D3ZAA9, E2QY99, E2QYC9, E7FDW2, F1MAD2, G5ECY0, O14910, O15018, O55164, O75970, O84033, O88382, O88951, O88952, P15454, P31006, P31007, P31016, P46195, P57105, P68907, P70175, P78352, P93757, Q0P5F3, Q0SS73, Q0TPK6, Q12959, Q13425, Q13884, Q14160, Q15700, Q16774, Q24210, Q255A8, Q28C55, Q2KIB6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DLG2	“form complex”	Scribble_complex_DLG2-LLGL2_variant	binding
DLG2	“form complex”	Scribble_complex_DLG2-LLGL1_variant	binding
FYN	“up-regulates activity”	DLG2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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	48.3×	3e-08
Unblocking of NMDA receptors, glutamate binding and activation	6	47.3×	1e-07
Synaptic adhesion-like molecules	6	47.3×	1e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	6	47.3×	1e-07
Trafficking of AMPA receptors	5	39.4×	7e-06
Neurexins and neuroligins	8	22.8×	1e-07
Assembly and cell surface presentation of NMDA receptors	6	22.1×	1e-05
Class B/2 (Secretin family receptors)	5	13.8×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of synaptic transmission, glutamatergic	7	46.5×	9e-08
positive regulation of excitatory postsynaptic potential	5	28.0×	2e-04
learning or memory	5	12.8×	2e-03
modulation of chemical synaptic transmission	6	11.7×	1e-03
chemical synaptic transmission	9	7.4×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	101
Likely benign	14
Benign	8

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
545150	NC_000011.10:g.(?84405313)(84547789_?)del	Likely pathogenic
545151	NC_000011.10:g.(?84809995)(84986152_?)del	Likely pathogenic
545152	NC_000011.10:g.(?84877230)(84963429_?)del	Likely pathogenic

SpliceAI

6355 predictions. Top by Δscore:

Variant	Effect	Δscore
11:83459828:T:A	donor_gain	1.0000
11:83461997:CTTA:C	donor_loss	1.0000
11:83462000:A:AC	donor_gain	1.0000
11:83462000:A:AT	donor_loss	1.0000
11:83462000:AC:A	donor_gain	1.0000
11:83462001:C:CT	donor_gain	1.0000
11:83462001:CC:C	donor_gain	1.0000
11:83462001:CCT:C	donor_gain	1.0000
11:83462001:CCTG:C	donor_gain	1.0000
11:83462001:CCTGT:C	donor_gain	1.0000
11:83462090:CTCC:C	acceptor_gain	1.0000
11:83462091:TCC:T	acceptor_gain	1.0000
11:83462092:CC:C	acceptor_gain	1.0000
11:83462092:CCC:C	acceptor_gain	1.0000
11:83462093:CC:C	acceptor_gain	1.0000
11:83462094:C:CC	acceptor_gain	1.0000
11:83462094:CTGGG:C	acceptor_loss	1.0000
11:83462095:T:A	acceptor_loss	1.0000
11:83466706:A:AC	donor_gain	1.0000
11:83466707:C:CC	donor_gain	1.0000
11:83466817:CCTGG:C	acceptor_gain	1.0000
11:83469199:A:AC	donor_gain	1.0000
11:83469200:C:CC	donor_gain	1.0000
11:83469200:CT:C	donor_gain	1.0000
11:83469221:CAGA:C	donor_gain	1.0000
11:83469224:A:AC	donor_gain	1.0000
11:83469225:C:CC	donor_gain	1.0000
11:83469376:T:TC	acceptor_gain	1.0000
11:83471619:CACTT:C	donor_loss	1.0000
11:83471620:ACTT:A	donor_loss	1.0000

AlphaMissense

6422 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:83459844:A:G	W863R	1.000
11:83459844:A:T	W863R	1.000
11:83459918:A:T	V838D	1.000
11:83462031:A:G	L826P	1.000
11:83462043:C:G	R822P	1.000
11:83466771:A:G	L784S	1.000
11:83466774:C:G	R783P	1.000
11:83466783:G:T	A780D	1.000
11:83466789:C:T	G778E	1.000
11:83466795:A:T	V776E	1.000
11:83466797:A:C	D775E	1.000
11:83466797:A:T	D775E	1.000
11:83466798:T:A	D775V	1.000
11:83466798:T:C	D775G	1.000
11:83466798:T:G	D775A	1.000
11:83466799:C:G	D775H	1.000
11:83466801:A:G	L774P	1.000
11:83466801:A:T	L774H	1.000
11:83466804:A:C	I773R	1.000
11:83466804:A:T	I773K	1.000
11:83466806:A:C	C772W	1.000
11:83466807:C:A	C772F	1.000
11:83466807:C:T	C772Y	1.000
11:83466808:A:G	C772R	1.000
11:83469209:C:G	A766P	1.000
11:83469231:A:C	S758R	1.000
11:83469231:A:T	S758R	1.000
11:83469233:T:G	S758R	1.000
11:83469238:C:A	G756V	1.000
11:83469238:C:T	G756E	1.000

dbSNP variants (sampled 300 via entrez): RS1000001999 (11:84891218 T>C), RS1000002687 (11:85532623 A>G), RS1000003294 (11:83547834 G>A), RS1000006483 (11:83978318 G>A,T), RS1000006833 (11:85500306 C>A,G,T), RS1000007063 (11:84607968 C>T), RS1000008685 (11:85469227 C>G,T), RS1000010290 (11:84338699 G>A), RS1000011412 (11:84601564 A>G), RS1000013099 (11:85578020 A>G), RS1000013683 (11:84153024 G>A), RS1000017723 (11:85592270 A>G), RS1000018257 (11:84034754 C>A,G), RS1000019019 (11:83588646 C>T), RS1000019611 (11:83913218 T>C)

Disease associations

OMIM: gene MIM:603583 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Moderate	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant
delayed puberty, self-limited	Limited	Autosomal dominant

Mondo (4): schizophrenia (MONDO:0005090), neurodevelopmental disorder (MONDO:0700092), delayed puberty, self-limited (MONDO:0859205), intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Aflatoxin B1	decreases expression, decreases methylation	3
Nickel	decreases expression	2
Valproic Acid	affects expression, increases expression	2
methyleugenol	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment, increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	affects methylation	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	decreases methylation	1
prothioconazole	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Gemcitabine	increases expression	1
Air Pollutants	decreases expression	1
Atrazine	increases expression	1
Benztropine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cannabidiol	increases expression	1
Cannabinoids	affects methylation, increases abundance	1
Clozapine	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dichlorvos	affects response to substance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1679	SBC-5	Cancer cell line	Male
CVCL_SK92	HAP1 DLG2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine