DLG3

discs large MAGUK scaffold protein 3, the group of PDZ domain containing|Membrane associated guanylate kinases|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): X:70444834-70505490

Links

ENSG00000082458 ∙ NCBI:1741 ∙ OMIM:300189 ∙ HGNC:2902 ∙ Uniprot:Q92796 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 90 (Definitive), mode of inheritance: XLR
• intellectual disability, X-linked 90 (Strong), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 90 (Definitive), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 90	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	15185169; 24721225

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLG3 gene.

• not provided (97 variants)
• Inborn genetic diseases (40 variants)
• not specified (23 variants)
• Intellectual disability, X-linked 90 (22 variants)
• Intellectual disability (2 variants)
• DLG3-related condition (2 variants)
• DLG3-Related Disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLG3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	23	1	28
missense			71	3	2	76
nonsense	6	4				10
start loss						0
frameshift	3	2				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			5	2		7
non coding	1		3	3	17	24
Total	10	9	79	29	20

Variants in DLG3

This is a list of pathogenic ClinVar variants found in the DLG3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-70445188-C-CG		Intellectual disability, X-linked 90	Pathogenic (May 25, 2016)
X-70445206-A-C		Intellectual disability, X-linked 90 • Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
X-70445243-T-G			Likely pathogenic (Jun 11, 2019)
X-70445249-G-C		Inborn genetic diseases	Likely benign (Jun 20, 2018)
X-70445266-T-C			Uncertain significance (Jun 24, 2022)
X-70445283-C-A		not specified • Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
X-70445292-G-A		Inborn genetic diseases	Likely benign (Oct 29, 2021)
X-70445294-C-T			Benign (Dec 31, 2019)
X-70445295-G-A		not specified	Uncertain significance (Aug 25, 2017)
X-70445297-C-T			Likely benign (Aug 01, 2022)
X-70445301-C-T			Pathogenic (Feb 22, 2023)
X-70445309-C-T			Likely benign (Jun 01, 2022)
X-70445316-T-TA		Intellectual disability, X-linked 90	Likely pathogenic (Aug 23, 2023)
X-70445325-G-A			Uncertain significance (May 21, 2019)
X-70445326-G-GT			not provided (-)
X-70445327-T-A		not specified	Likely benign (Apr 09, 2018)
X-70445328-G-A		Intellectual disability, X-linked 90	Uncertain significance (Jul 02, 2020)
X-70445329-G-T		Inborn genetic diseases	Uncertain significance (Mar 30, 2020)
X-70445350-G-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
X-70445353-A-C		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
X-70445359-GC-G		Intellectual disability, X-linked 90	Pathogenic/Likely pathogenic (Dec 16, 2022)
X-70445359-G-GA		Inborn genetic diseases	Likely pathogenic (Aug 20, 2021)
X-70445367-T-A			Uncertain significance (Sep 27, 2022)
X-70445394-G-A		Inborn genetic diseases	Likely benign (Mar 12, 2024)
X-70445397-A-C		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLG3	protein_coding	protein_coding	ENST00000374360	19	60627

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000703	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.88	186	334	0.557	0.0000262	5330
Missense in Polyphen		21	44.716	0.46963		713
Synonymous	0.697	124	134	0.924	0.0000109	1591
Loss of Function	5.35	0	33.3	0.00	0.00000283	484

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for learning most likely through its role in synaptic plasticity following NMDA receptor signaling.
• Disease: DISEASE: Mental retardation, X-linked 90 (MRX90) [MIM:300850]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:15185169}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Developmental Biology;Activation of Ca-permeable Kainate Receptor;Ionotropic activity of kainate receptors;Activation of kainate receptors upon glutamate binding;Fibroblast growth factor-1;NrCAM interactions;Neuronal System;Synaptic adhesion-like molecules;EGFR1;Neurexins and neuroligins;L1CAM interactions;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Axon guidance;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.342

Intolerance Scores

• loftool: 0.0977
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.999
• hipred: Y
• hipred_score: 0.853
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.704

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dlg3
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• Biological process: MAPK cascade;establishment of planar polarity;chemical synaptic transmission;negative regulation of cell population proliferation;negative regulation of phosphatase activity;receptor clustering;establishment or maintenance of epithelial cell apical/basal polarity;positive regulation of protein tyrosine kinase activity;receptor localization to synapse;cell-cell adhesion;regulation of postsynaptic membrane neurotransmitter receptor levels;maintenance of postsynaptic density structure
• Cellular component: extracellular space;cytosol;plasma membrane;bicellular tight junction;ionotropic glutamate receptor complex;basolateral plasma membrane;cell junction;growth cone;neuromuscular junction;AMPA glutamate receptor complex;neuron projection;neuronal cell body;dendritic shaft;postsynaptic density membrane;glutamatergic synapse;postsynaptic density, intracellular component
• Molecular function: Ras guanyl-nucleotide exchange factor activity;protein binding;protein C-terminus binding;kinase binding;phosphatase binding;protein phosphatase binding;PDZ domain binding;ubiquitin protein ligase binding;ionotropic glutamate receptor binding;structural constituent of postsynaptic density