DLG1

discs large MAGUK scaffold protein 1, the group of PDZ domain containing|Scribble complex|Membrane associated guanylate kinases|MicroRNA protein coding host genes

Basic information

Region (hg38): 3:197042559-197299330

Links

ENSG00000075711 ∙ NCBI:1739 ∙ OMIM:601014 ∙ HGNC:2900 ∙ Uniprot:Q12959 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome (Limited), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLG1 gene.

• Inborn genetic diseases (28 variants)
• not provided (6 variants)
• DLG1-related condition (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLG1 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					3	3
missense			31		1	32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	1	2
Total	0	0	31	1	5

Variants in DLG1

This is a list of pathogenic ClinVar variants found in the DLG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-197044635-T-G		not specified	Uncertain significance (Sep 20, 2023)
3-197044642-G-A		DLG1-related disorder	Benign (Sep 25, 2019)
3-197044676-T-G		DLG1-related disorder	Uncertain significance (Mar 08, 2023)
3-197044683-T-C		DLG1-related disorder	Benign (Sep 25, 2019)
3-197044715-C-T		not specified	Uncertain significance (Dec 28, 2022)
3-197051568-G-A			Likely benign (Apr 13, 2018)
3-197051604-C-T		not specified	Uncertain significance (Jan 04, 2024)
3-197051621-T-C		not specified	Uncertain significance (Dec 15, 2022)
3-197051654-C-T		not specified	Uncertain significance (Mar 02, 2023)
3-197059893-T-C		not specified	Uncertain significance (Feb 22, 2023)
3-197065290-C-T		not specified	Uncertain significance (Apr 10, 2023)
3-197065292-C-T		DLG1-related disorder	Benign (Aug 08, 2019)
3-197065325-T-C		not specified	Uncertain significance (Jun 22, 2021)
3-197065325-T-G		not specified	Uncertain significance (Mar 14, 2023)
3-197065333-C-A		not specified	Uncertain significance (Aug 30, 2022)
3-197066757-ATTAGAAAGTGAAGGCACAG-A		Mendelian syndromes with cleft lip/palate	Uncertain significance (-)
3-197069219-G-A		DLG1-related disorder	Likely benign (Feb 07, 2022)
3-197069252-T-C		not specified	Uncertain significance (Nov 30, 2021)
3-197069259-C-G		DLG1-related disorder	Uncertain significance (Jan 31, 2023)
3-197081057-A-C			Benign (Dec 01, 2022)
3-197081058-T-C		not specified	Uncertain significance (Jan 18, 2022)
3-197081061-C-G		not specified	Uncertain significance (Oct 26, 2022)
3-197085586-T-A		DLG1-related disorder	Uncertain significance (Jun 07, 2023)
3-197085721-C-A		not specified	Uncertain significance (Dec 08, 2023)
3-197090942-C-T		not specified	Uncertain significance (Jul 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLG1	protein_coding	protein_coding	ENST00000346964	25	256741

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00607	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.50	403	497	0.811	0.0000254	6076
Missense in Polyphen		118	198.41	0.59471		2313
Synonymous	1.54	139	164	0.847	0.00000806	1729
Loss of Function	5.93	10	59.3	0.169	0.00000382	648

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000253	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. {ECO:0000250, ECO:0000269|PubMed:10656683, ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15263016, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:20605917}.
• Pathway: T cell receptor signaling pathway - Homo sapiens (human);Tight junction - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Developmental Biology;Activation of Ca-permeable Kainate Receptor;Ionotropic activity of kainate receptors;Activation of kainate receptors upon glutamate binding;NrCAM interactions;Neuronal System;Synaptic adhesion-like molecules;Trafficking of AMPA receptors;L1CAM interactions;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Axon guidance;Protein-protein interactions at synapses;CDC42 signaling events;E-cadherin signaling in the nascent adherens junction (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• loftool: 0.621
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.41

Haploinsufficiency Scores

• pHI: 0.991
• hipred: Y
• hipred_score: 0.651
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dlg1
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail phenotype; 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); vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system 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); reproductive system phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;MAPK cascade;branching involved in ureteric bud morphogenesis;immunological synapse formation;endothelial cell proliferation;lens development in camera-type eye;T cell cytokine production;protein dephosphorylation;actin filament organization;mitotic cell cycle checkpoint;establishment or maintenance of cell polarity;chemical synaptic transmission;positive regulation of cell population proliferation;regulation of cell shape;viral process;peristalsis;positive regulation of actin filament polymerization;cortical actin cytoskeleton organization;astral microtubule organization;membrane raft organization;regulation of myelination;activation of protein kinase activity;cellular protein-containing complex localization;T cell activation;negative regulation of T cell proliferation;regulation of membrane potential;amyloid precursor protein metabolic process;receptor clustering;positive regulation of potassium ion transport;cortical microtubule organization;establishment or maintenance of epithelial cell apical/basal polarity;negative regulation of mitotic cell cycle;GMP metabolic process;GDP metabolic process;reproductive structure development;embryonic skeletal system morphogenesis;smooth muscle tissue development;negative regulation of epithelial cell proliferation;establishment of centrosome localization;negative regulation of protein kinase B signaling;hard palate development;negative regulation of ERK1 and ERK2 cascade;bicellular tight junction assembly;protein localization to plasma membrane;receptor localization to synapse;cell-cell adhesion;regulation of ventricular cardiac muscle cell action potential;maintenance of postsynaptic density structure;neurotransmitter receptor localization to postsynaptic specialization membrane;regulation of NIK/NF-kappaB signaling;regulation of sodium ion transmembrane transport;positive regulation of protein localization to plasma membrane;regulation of potassium ion import;negative regulation of p38MAPK cascade;regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization;regulation of potassium ion export across plasma membrane
• Cellular component: immunological synapse;basement membrane;nucleus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;cytosol;microtubule;plasma membrane;cell-cell junction;bicellular tight junction;ionotropic glutamate receptor complex;cytoplasmic side of plasma membrane;intercalated disc;basolateral plasma membrane;apical plasma membrane;lateral plasma membrane;cell junction;cell projection membrane;neuromuscular junction;node of Ranvier;myelin sheath abaxonal region;sarcolemma;neuron projection;lateral loop;membrane raft;perinuclear region of cytoplasm;extracellular exosome;MPP7-DLG1-LIN7 complex;postsynaptic density membrane;glutamatergic synapse
• Molecular function: guanylate kinase activity;phosphoprotein phosphatase activity;Ras guanyl-nucleotide exchange factor activity;protein binding;protein C-terminus binding;cytoskeletal protein binding;potassium channel regulator activity;protein kinase binding;phosphatase binding;mitogen-activated protein kinase kinase binding;protein-containing complex scaffold activity;ionotropic glutamate receptor binding;ion channel binding;cadherin binding;L27 domain binding;structural constituent of postsynaptic density