On this page
DLG3
discs large MAGUK scaffold protein 3
The DLG3 gene provides instructions for making a protein critical to brain development and normal cognitive function, with alterations potentially linked to X-linked intellectual disability. The DLG3 gene encodes a protein known as discs large MAGUK scaffold protein 3.
DLG3 is located on the long (q) arm of chromosome X, at band Xq13.1. Arm ratio per GRCh38 - banding schematic.
Explore chromosome X in the library →Available at Jeen Health
Clinical tests that include this
Overview
The DLG3 gene, also known as discs large MAGUK scaffold protein 3, is located on the X chromosome. It plays a significant role in the development and proper functioning of the brain, particularly in the formation and maintenance of synapses. Synapses are specialised junctions between nerve cells crucial for transmitting signals throughout the nervous system.
Changes within the DLG3 gene can affect its protein product, leading to impaired neuronal communication. Such alterations are primarily linked to X-linked intellectual disability, affecting cognitive abilities.
What the gene does
The DLG3 gene produces the DLG3 protein, which acts as a scaffold protein within neurons. Scaffold proteins are vital for organising molecular components at specific cellular locations, ensuring that signalling pathways function correctly. The DLG3 protein is highly expressed in the brain, especially in regions involved in learning and memory, such as the hippocampus and cerebral cortex.
Its primary function involves anchoring and organising various proteins at the postsynaptic density, a specialised area of the neuron that receives signals. By forming complexes with neurotransmitter receptors and other signalling molecules, DLG3 helps modulate synaptic strength and plasticity. These processes are fundamental for signal transmission, neural circuit formation, and cognitive functions like learning and memory.
Video: Genetics 101
Chromosome location
The DLG3 gene is situated on the long (q) arm of the X chromosome at position 13.1, a region designated as Xq13.1. This chromosomal location indicates that the gene's inheritance pattern is X-linked. The DLG3 gene spans approximately 188,000 base pairs of DNA.
Protein structure
The DLG3 protein is composed of 817 amino acids and features several distinct domains critical for its scaffolding and signalling functions. These include an N-terminal Disordered region from amino acids 33-101, which typically mediates protein-protein interactions. Following this are three PDZ domains: PDZ 1 (amino acids 130-217), PDZ 2 (amino acids 226-311), and PDZ 3 (amino acids 379-465). These PDZ domains are known for binding to specific motifs on other proteins. The protein also contains an SH3 domain (amino acids 501-571), involved in protein-protein interactions and signal transduction. Finally, a Guanylate kinase-like domain, spanning amino acids 627-802, is also present.
Key variants
Variations within the DLG3 gene can include changes to the DNA sequence that affect the structure or function of the DLG3 protein. These can range from small alterations, such as single nucleotide changes, to larger deletions or insertions. Such genetic variations can disrupt the protein's ability to maintain proper neuronal connections and signalling pathways.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.159del | p.Tyr54fs | Pathogenic/Likely pathogenic | ★★☆☆ | Intellectual disability, X-linked 90 |
c.2035C>T | p.Arg679Ter | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.2266C>T | p.Arg756Ter | Pathogenic | ★★☆☆ | Intellectual disability, X-linked 90 |
c.631C>T | p.Arg211Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.649C>T | p.Arg217Ter | Pathogenic | ★★☆☆ | Intellectual disability, X-linked 90 |
c.100C>T | p.Gln34Ter | Pathogenic | ★☆☆☆ | not provided |
c.1513_1519del | p.Tyr505fs | Pathogenic | ★☆☆☆ | not provided |
c.158del | p.Gly53fs | Pathogenic | ★☆☆☆ | Inborn genetic diseases |
c.1669C>T | p.Gln557Ter | Pathogenic | ★☆☆☆ | Intellectual disability, X-linked 90 |
c.791del | p.Gly264fs | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variations in the DLG3 gene are primarily associated with X-linked intellectual disability. This condition is characterised by impairments in cognitive function, affecting intelligence and adaptive behaviour. Because the DLG3 gene is located on the X chromosome, conditions associated with it often show a distinct inheritance pattern, typically affecting males more severely than females.
No disease links recorded for this gene in our reference set.
UK clinical status
The DLG3 gene is recognised within the UK's genomic healthcare framework. It is listed on the 'DDG2P' and 'Intellectual disability (R29)' panels in PanelApp, indicating its relevance to developmental disorders and intellectual disability in a clinical diagnostic setting.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is X-linked intellectual disability?
X-linked intellectual disability refers to forms of intellectual disability caused by gene variations on the X chromosome. Because males have only one X chromosome, they are often more severely affected than females, who have two X chromosomes.
How does the DLG3 protein contribute to brain function?
The DLG3 protein acts as a scaffold at synapses, which are the connections between nerve cells. It helps organise other proteins and receptors, which is crucial for transmitting signals effectively and for processes like learning and memory.
Can DLG3 variations be inherited?
Yes, variations in the DLG3 gene can be inherited in an X-linked manner. This means that mothers who carry a variant on one of their X chromosomes can pass it on to their children.