DLG5

discs large MAGUK scaffold protein 5, the group of PDZ domain containing|Membrane associated guanylate kinases

Basic information

Region (hg38): 10:77790791-77926755

Links

ENSG00000151208 ∙ NCBI:9231 ∙ OMIM:604090 ∙ HGNC:2904 ∙ Uniprot:Q8TDM6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ciliopathy (Limited), mode of inheritance: AD
• ciliopathy (Limited), mode of inheritance: AR
• congenital anomaly of kidney and urinary tract (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Yuksel-Vogel-Bauser syndrome	AR	Cardiovascular; Renal	Among other findings, individuals have been described with congenital cardiovascular and renal anomalies (such as salt wasting that required supplementation), and awareness may allow early identification and management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	30791088; 32631816

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLG5 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLG5 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				8	9	17
missense			108	12	4	124
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding				1	1	2
Total	1	0	108	21	14

Variants in DLG5

This is a list of pathogenic ClinVar variants found in the DLG5 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-77792491-C-G		not specified	Uncertain significance (Oct 03, 2022)
10-77792515-G-C		not specified	Uncertain significance (Jun 07, 2024)
10-77792526-C-T		not specified	Uncertain significance (Jan 08, 2024)
10-77793998-G-A			Likely benign (May 16, 2018)
10-77794017-A-G		not specified	Uncertain significance (Apr 27, 2024)
10-77794049-G-C		not specified	Uncertain significance (Feb 27, 2023)
10-77794057-C-T			Benign (Dec 31, 2019)
10-77794076-T-A		not specified	Uncertain significance (Dec 20, 2023)
10-77794873-T-C		not specified	Uncertain significance (Mar 31, 2024)
10-77794909-T-G			Uncertain significance (-)
10-77794922-T-C		not specified	Uncertain significance (Jun 04, 2024)
10-77794935-A-G			Likely benign (Sep 19, 2018)
10-77796090-C-T		not specified	Uncertain significance (Oct 03, 2022)
10-77796111-C-T		not specified	Uncertain significance (Apr 23, 2024)
10-77796112-G-A			Likely benign (May 21, 2018)
10-77796120-G-A		not specified	Uncertain significance (Sep 26, 2022)
10-77796146-T-C		not specified	Uncertain significance (Nov 10, 2022)
10-77796486-T-A		not specified	Uncertain significance (Mar 28, 2024)
10-77796543-A-G			Benign (Dec 31, 2019)
10-77796547-C-T			Benign (Dec 31, 2019)
10-77805745-T-C		not specified	Uncertain significance (Apr 01, 2024)
10-77805746-G-C		not specified	Uncertain significance (Jan 31, 2024)
10-77805760-C-T		not specified	Uncertain significance (Apr 13, 2022)
10-77805761-G-A		not specified	Uncertain significance (Apr 08, 2022)
10-77805784-G-A		not specified	Uncertain significance (Sep 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLG5	protein_coding	protein_coding	ENST00000372391	32	135830

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000523	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	919	1.17e+3	0.787	0.0000750	12497
Missense in Polyphen		379	607.02	0.62436		6572
Synonymous	-0.802	524	501	1.05	0.0000332	3859
Loss of Function	7.05	14	83.5	0.168	0.00000421	984

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.000274	0.000217
Finnish	0.000241	0.000231
European (Non-Finnish)	0.0000977	0.0000967
Middle Eastern	0.000274	0.000217
South Asian	0.0000656	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling pathway by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial- mesenchymal transition (EMT), cell migration and invasion (PubMed:28169360). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N- cadherin. Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:E9Q9R9, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360}.

Recessive Scores

• pRec: 0.165

Intolerance Scores

• loftool: 0.124
• rvis_EVS: -2.37
• rvis_percentile_EVS: 1.13

Haploinsufficiency Scores

• pHI: 0.279
• hipred: Y
• hipred_score: 0.685
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.654

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dlg5
• 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system 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); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: epithelial to mesenchymal transition;signal transduction;negative regulation of cell population proliferation;maintenance of cell polarity;negative regulation of cell migration;polarized epithelial cell differentiation;midbrain development;negative regulation of hippo signaling;positive regulation of hippo signaling;intracellular signal transduction;negative regulation of T cell proliferation;regulation of apoptotic process;apical protein localization;zonula adherens assembly;establishment or maintenance of epithelial cell apical/basal polarity;positive regulation of smoothened signaling pathway;positive regulation of synapse assembly;epithelial tube branching involved in lung morphogenesis;positive regulation of dendritic spine development;protein-containing complex assembly;protein localization to adherens junction;metanephric collecting duct development;cell-cell adhesion
• Cellular component: cytoplasm;plasma membrane;cell-cell adherens junction;postsynaptic density;cell junction;ciliary basal body;postsynaptic membrane
• Molecular function: protein binding;beta-catenin binding;cytoskeletal protein binding;receptor signaling complex scaffold activity