JAM3: Junctional Adhesion Molecule 3
A key tight junction protein involved in cell adhesion, angiogenesis, and genetic disorders including hemorrhagic destruction of the brain.
Gene Information Card
| Symbol | JAM3 |
|---|---|
| Full Name | junctional adhesion molecule 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q25 |
| NCBI Gene ID | 83700 ncbi.nlm.nih.gov/gene/83700 |
| Ensembl ID | ENSG00000168229 |
| UniProt ID | Q9BX67 |
| OMIM ID | 613730 |
| HGNC ID | 15532 |
| Aliases | JAM-C, JAM-2, JAM3, Jcam3, UNQ524/PRO1058 |
Description
JAM3 (junctional adhesion molecule 3) encodes a member of the immunoglobulin superfamily that localizes to tight junctions of endothelial and epithelial cells. The protein functions as a homophilic adhesion molecule and also interacts with JAM2. It plays critical roles in leukocyte transmigration, angiogenesis, and platelet activation. Mutations in JAM3 cause hemorrhagic destruction of the brain, subependymal calcification, and cataracts (HDBSCC).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hemorrhagic destruction of the brain, subependymal calcification, and cataracts (HDBSCC) | Loss-of-function mutations in JAM3 disrupt tight junction integrity in brain endothelium, leading to microhemorrhages and calcification. | OMIM #613730; ClinVar |
| Congenital cataract | JAM3 mutations impair lens epithelial cell adhesion, causing cataract formation. | OMIM #613730 |
| Leukocyte adhesion deficiency type III (LAD-III) | JAM3 deficiency impairs leukocyte transmigration across endothelium. | PubMed; functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Heart | 6.1 | Low |
| Kidney | 5.4 | Low |
| Placenta | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 15.2 | High expression; consistent with role in tight junctions |
| HEK293 | 2.1 | Low |
| HeLa | 1.8 | Low |
| K562 | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.428G>A (p.Trp143*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no translation initiation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations in JAM3 lead to truncated or absent protein, causing HDBSCC.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cell junction organization (Reactome R-HSA-446728)
• Tight junction interactions (Reactome R-HSA-420029)
• Leukocyte transendothelial migration (KEGG hsa04670)
Protein Summary
JAM3 (JAM-C) is a 310-amino-acid transmembrane glycoprotein with two extracellular Ig-like domains, a single transmembrane segment, and a short cytoplasmic tail. It forms homodimers and heterodimers with JAM2. The protein is highly expressed in endothelial cells, platelets, and some epithelial cells. It regulates tight junction assembly, vascular permeability, and immune cell trafficking. Loss of JAM3 function leads to severe cerebral hemorrhage and cataracts in humans.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| JAM3 Knockout HEK293 Cell Line | EDJ-KQ9891 | Human | 83700 | Details Get a Quote |
| JAM3 Knockout A-549 Cell Line | EDJ-KQ36772 | Human | 83700 | Details Get a Quote |
| JAM3 Knockout HeLa Cell Line | EDJ-KQ57469 | Human | 83700 | Details Get a Quote |
| JAM3 Knockout HCT 116 Cell Line | EDJ-KQ74396 | Human | 83700 | Details Get a Quote |
