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MEGF8
multiple EGF like domains 8
The MEGF8 gene provides instructions for a protein thought to be involved in cell adhesion and protein interactions, playing a role in embryonic development. The MEGF8 gene encodes the multiple EGF like domains 8 protein, which is believed to contribute to essential cellular processes such as cell-to-cell attachment and protein interactions.
MEGF8 is located on the long (q) arm of chromosome 19, at band 19q13.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The MEGF8 gene, or multiple EGF like domains 8, is responsible for producing a protein whose precise functions are still being investigated. Based on its structural characteristics, the Megf8 protein is hypothesised to be involved in crucial cellular mechanisms like cell adhesion, where cells attach to one another, and in facilitating interactions between different proteins. Furthermore, researchers suggest that the Megf8 protein is important for the normal shaping and development of various body structures during the embryonic stage.
What the gene does
The Megf8 protein, encoded by the MEGF8 gene, is thought to be involved in several fundamental cellular processes. Its structure implies roles in cell adhesion, which is the process by which cells recognise and attach to each other and to the extracellular matrix. This is critical for tissue formation and maintenance. The protein may also facilitate interactions between other proteins, forming complexes essential for various cellular pathways. Evidence suggests that the Megf8 protein contributes significantly to the correct patterning and development of numerous body parts during embryonic growth, influencing how an organism's structure forms. While its exact mechanism remains under investigation, its involvement in cell adhesion and protein interaction points towards a broad role in developmental biology.
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Chromosome location
The MEGF8 gene is located on chromosome 19, specifically at position 19q13.2. Chromosomes are organised structures of DNA and proteins found within cells, containing genetic information. The 'q' indicates the long arm of the chromosome, and '13.2' specifies the precise band location on that arm.
Protein structure
The MEGF8 protein is a large protein composed of 2845 amino acids, characterised by multiple conserved domains and repeats. Key structural elements include the CUB 1 domain (amino acids 30-140), EGF-like 1 (amino acids 138-168), and EGF-like 2 (amino acids 170-203) domains. It also contains several Kelch repeats: Kelch 1 (amino acids 241-287), Kelch 2 (amino acids 290-338), Kelch 3 (amino acids 346-399), Kelch 4 (amino acids 402-453), Kelch 5 (amino acids 459-511), and Kelch 6 (amino acids 525-575). Further domains include PSI 1 (amino acids 561-613), PSI 2 (amino acids 847-899), PSI 3 (amino acids 900-947), an EGF-like 3; calcium-binding domain (amino acids 1074-1115), Laminin EGF-like 1 (amino acids 1163-1210), and Laminin EGF-like 2 (amino acids 1211-1261).
Key variants
Genetic variations within the MEGF8 gene can include a range of changes, such as deletions, insertions, or single nucleotide changes. Pathogenic variants, which impair or eliminate the normal function of the Megf8 protein, can lead to various health implications. The specific effect of a variant often depends on its type and location within the gene, and the resulting alteration to the protein's structure or function.
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.1255C>T | p.Arg419Ter | Pathogenic/Likely pathogenic | ★★☆☆ | MEGF8-related Carpenter syndrome |
c.2971C>T | p.Arg991Ter | Pathogenic/Likely pathogenic | ★★☆☆ | MEGF8-related Carpenter syndrome |
c.116_125del | p.Glu39fs | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.2086C>T | p.Gln696Ter | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.283C>T | p.Arg95Ter | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.4108C>T | p.Arg1370Ter | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.4227del | p.Gly1411fs | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.4885C>T | p.Arg1629Ter | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.5253dup | p.Phe1752fs | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
c.634del | p.Ala212fs | Pathogenic | ★☆☆☆ | MEGF8-related Carpenter syndrome |
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
Variants in the MEGF8 gene have been associated with Carpenter syndrome, an inherited condition characterised by a distinctive set of features. These typically include irregular skull formation (craniosynostosis), abnormalities of the fingers and toes (polydactyly or syndactyly), and a range of other developmental issues. Researchers believe that the severity of Carpenter syndrome symptoms may correlate with the degree to which the Megf8 protein's function is compromised by a particular genetic variant.
No disease links recorded for this gene in our reference set.
UK clinical status
The MEGF8 gene is included in several NHS Genomic Medicine Service national test panels. These include panels for DDG2P, Foetal anomalies (R21), Limb disorders, Rare syndromic craniosynostosis or isolated multisuture synostosis (R100), and Skeletal dysplasia (R104). This indicates its recognised role in these conditions within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the MEGF8 gene?
The MEGF8 gene provides instructions for making the Megf8 protein, which is believed to be involved in cell adhesion, protein-protein interactions, and the normal patterning of body parts during embryonic development.
What condition is associated with MEGF8 gene variants?
Variants in the MEGF8 gene are associated with Carpenter syndrome, a genetic disorder characterised by irregular skull formation and abnormalities of the fingers and toes, among other features.
How many amino acids make up the MEGF8 protein?
The MEGF8 protein is a large protein composed of 2845 amino acids, featuring multiple EGF-like domains, Kelch repeats, and PSI domains.
References
- Twigg SR, Lloyd D, Jenkins D. Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization. American journal of human genetics. 2012. PMID: 23063620
- Zhang Z, Alpert D, Francis R. Massively parallel sequencing identifies the gene Megf8 with ENU-induced mutation causing heterotaxy. Proceedings of the National Academy of Sciences of the United States of America. 2009. PMID: 19218456
- Perlyn CA, Marsh JL. Craniofacial dysmorphology of Carpenter syndrome: lessons from three affected siblings. Plastic and reconstructive surgery. 2008. PMID: 18317146