ADAM22 Gene: A Disintegrin and Metalloproteinase Domain 22
Key regulator in synaptic transmission and epilepsy pathogenesis
Gene Information Card
| Symbol | ADAM22 |
|---|---|
| Full Name | ADAM metallopeptidase domain 22 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q21.12 |
| NCBI Gene ID | 53616 ncbi.nlm.nih.gov/gene/53616 |
| Ensembl ID | ENSG00000106333 |
| UniProt ID | Q9P0K1 |
| OMIM ID | 607075 |
| HGNC ID | 201 |
| Aliases | MDC2, ADAM 22, ADAM metallopeptidase domain 22 |
Description
ADAM22 (ADAM metallopeptidase domain 22) is a member of the ADAM (a disintegrin and metalloprotease) family. Unlike many ADAM family members, ADAM22 lacks catalytic metalloprotease activity due to critical amino acid substitutions in the active site. It functions primarily as a receptor for the secreted synaptic organizer LGI1 and is essential for synaptic transmission, particularly in the central nervous system. Mutations in ADAM22 are associated with epilepsy and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 1 | Loss-of-function mutations impair LGI1-ADAM22 signaling, disrupting synaptic AMPA receptor clustering | ClinVar, OMIM |
| Epilepsy, familial temporal lobe, 5 | Missense variants alter protein conformation and reduce binding to LGI1 | ClinVar, OMIM |
| Intellectual disability, autosomal recessive | Homozygous truncating mutations lead to complete loss of protein function | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.2 | High |
| Cerebellum | 10.8 | High |
| Testis | 3.4 | Low |
| Heart | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | Neuronal model |
| U-87 MG (glioblastoma) | 6.2 | Glial model |
| HEK 293 (embryonic kidney) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1972C>T (p.Arg658Ter) | Nonsense | Rare | Loss of function; truncation of extracellular domain |
| c.1118G>A (p.Arg373His) | Missense | Rare | Reduced LGI1 binding affinity |
| c.2440G>A (p.Gly814Arg) | Missense | Rare | Impaired trafficking to cell surface |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature stop codons or protein truncation; missense mutations that disrupt LGI1 binding or surface expression.
Gain of Function (GOF)
Not reported for ADAM22.
Dominant Negative (DN)
Not reported for ADAM22.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005886 - plasma membrane | • GO:0007155 - cell adhesion |
| • GO:0007268 - chemical synaptic transmission | • GO:0030054 - cell junction |
| • GO:0043235 - receptor complex | • GO:0005515 - protein binding |
Pathways
• LGI1-ADAM22 signaling in synaptic transmission
• AMPA receptor clustering and stabilization
Protein Summary
ADAM22 is a transmembrane protein predominantly expressed in the brain. It lacks protease activity but serves as a receptor for LGI1, a secreted protein that regulates synaptic AMPA receptor clustering. The LGI1-ADAM22 complex is critical for excitatory synaptic transmission and neuronal network stability. Loss-of-function mutations cause early infantile epileptic encephalopathy and familial temporal lobe epilepsy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM22 Knockout HEK293 Cell Line | EDJ-KQ11347 | Human | 53616 | Details Get a Quote |
| ADAM22 Knockout HCT 116 Cell Line | EDJ-KQ39516 | Human | 53616 | Details Get a Quote |
| ADAM22 Knockout HeLa Cell Line | EDJ-KQ39517 | Human | 53616 | Details Get a Quote |
| ADAM22 Knockout A-549 Cell Line | EDJ-KQ64867 | Human | 53616 | Details Get a Quote |
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