MEGF8: Multiple EGF-like Domains 8
A gene encoding a transmembrane protein involved in cell adhesion, signaling, and left-right axis determination; mutations are associated with Carpenter syndrome and other developmental disorders.
Gene Information Card
| Symbol | MEGF8 |
|---|---|
| Full Name | Multiple EGF-like domains 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 1954 ncbi.nlm.nih.gov/gene/1954 |
| Ensembl ID | ENSG00000105429 |
| UniProt ID | Q96PZ2 |
| OMIM ID | 604267 |
| HGNC ID | 3233 |
| Aliases | EGFL4, MEGF8, SBP1 |
Description
MEGF8 (Multiple EGF-like domains 8) encodes a transmembrane protein containing multiple epidermal growth factor (EGF)-like repeats. It is involved in cell adhesion, migration, and signaling, particularly in the establishment of left-right asymmetry during embryonic development. Mutations in MEGF8 are a cause of Carpenter syndrome (ACPS2), a rare autosomal recessive disorder characterized by craniosynostosis, polysyndactyly, obesity, and cardiac defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Carpenter syndrome 2 (ACPS2) | Loss-of-function mutations in MEGF8 disrupt left-right axis determination and cell adhesion, leading to craniosynostosis, polysyndactyly, and cardiac anomalies. | OMIM #614976; PMID: 22840365 |
| Left-right axis malformations | MEGF8 mutations impair nodal signaling and ciliary function, causing heterotaxy and situs inversus. | OMIM #604267; PMID: 22840365 |
| Obesity (associated with Carpenter syndrome) | MEGF8 deficiency may affect adipogenesis or energy homeostasis, though mechanism is not fully defined. | OMIM #614976; PMID: 22840365 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 3.1 | Low |
| Kidney | 6.7 | Low |
| Testis | 15.2 | Medium |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.1 | Embryonic kidney; moderate expression |
| HeLa | 7.8 | Cervical carcinoma; low expression |
| K562 | 4.2 | Leukemia; low expression |
| HepG2 | 3.5 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3173C>T (p.Pro1058Leu) | Missense | Rare | Likely loss-of-function; associated with Carpenter syndrome |
| c.4321C>T (p.Arg1441*) | Nonsense | Rare | Premature stop; loss-of-function; pathogenic in Carpenter syndrome |
| c.6745C>T (p.Arg2249Trp) | Missense | Rare | Uncertain significance; possibly damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein; missense mutations in conserved EGF domains that disrupt protein folding or ligand binding.
Gain of Function (GOF)
Not reported for MEGF8.
Dominant Negative (DN)
Not reported; all known pathogenic mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACT:147422 – Developmental Biology
• REACT:147424 – Left-Right Axis Determination
• REACT:147425 – Nodal Signaling Pathway
Protein Summary
The MEGF8 protein is a type I transmembrane glycoprotein with multiple EGF-like domains and a single transmembrane helix. It is thought to function as a cell surface receptor or adhesion molecule, interacting with components of the extracellular matrix. It plays a critical role in the establishment of left-right asymmetry by modulating Nodal signaling and ciliary function. The protein is widely expressed, with highest levels in brain and testis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MEGF8 Knockout HEK293 Cell Line | EDJ-KQ908 | Human | 1954 | Details Get a Quote |
| MEGF8 Knockout A-549 Cell Line | EDJ-KQ18414 | Human | 1954 | Details Get a Quote |
| MEGF8 Knockout HCT 116 Cell Line | EDJ-KQ19759 | Human | 1954 | Details Get a Quote |
| MEGF8 Knockout HeLa Cell Line | EDJ-KQ19760 | Human | 1954 | Details Get a Quote |
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