ADAM10 Gene (A Disintegrin And Metalloproteinase Domain 10): Function, Mutations, and Disease Relevance
Comprehensive biomedical resource on ADAM10, a key sheddase in Notch signaling and Alzheimer's disease, with genomic annotations, expression data, and clinical implications.
Gene Information Card
| Symbol | ADAM10 |
|---|---|
| Full Name | ADAM metallopeptidase domain 10 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q21.3 (GRCh38) |
| NCBI Gene ID | 102 ncbi.nlm.nih.gov/gene/102 |
| Ensembl ID | ENSG00000137845 |
| UniProt ID | O14672 |
| OMIM ID | 602537 |
| HGNC ID | 195 |
| Aliases | CD156c, Kuzbanian, MADM, RAK |
Description
ADAM10 (A Disintegrin And Metalloproteinase Domain 10) encodes a type I transmembrane metalloproteinase that functions as a major alpha-secretase in the cleavage of amyloid precursor protein (APP), preventing amyloid-beta plaque formation. It also mediates the proteolytic processing of Notch receptors, cadherins, and other membrane proteins, playing critical roles in neurodevelopment, cell adhesion, and immune responses. Mutations in ADAM10 are associated with Alzheimer's disease and certain cancers, highlighting its dual role in neurodegeneration and tumor biology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease | Loss-of-function mutations reduce alpha-secretase activity, leading to increased amyloid-beta production and plaque deposition. | ClinVar: Pathogenic variants (e.g., Q170H, R181G) associated with late-onset AD; PMID: 19667186 |
| Hereditary spastic paraplegia | Biallelic mutations impair ADAM10 function, affecting axonal outgrowth and myelination. | OMIM: 602537; PMID: 27545674 |
| Colorectal cancer | Overexpression of ADAM10 promotes tumor invasion and metastasis via Notch and EGFR signaling. | COSMIC: Amplifications and overexpression; PMID: 28712811 |
| Inflammatory skin disease | ADAM10 regulates desmoglein processing; dysregulation contributes to acantholysis. | PMID: 19667186 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.2 | High |
| Lung | 18.5 | Medium |
| Liver | 12.3 | Medium |
| Kidney | 15.8 | Medium |
| Heart | 9.4 | Low |
| Skeletal Muscle | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 22.1 | High expression; involved in cell migration |
| A549 (lung cancer) | 19.4 | Moderate; associated with invasion |
| HepG2 (liver cancer) | 14.7 | Moderate; regulates Notch signaling |
| SH-SY5Y (neuroblastoma) | 28.3 | High; relevant to neuronal function |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Q170H | Missense | Rare (0.1% in AD cohorts) | Reduced alpha-secretase activity; increased Abeta42/40 ratio |
| R181G | Missense | Rare (0.05%) | Impaired APP cleavage; associated with familial AD |
| L43P | Missense | Very rare | Loss of protein stability; dominant-negative effect |
| S230L | Missense | Somatic in cancer | Altered substrate specificity; promotes tumor invasion |
Mutation functional classification
Loss of Function (LOF)
Most AD-associated mutations (e.g., Q170H, R181G) reduce catalytic activity or protein stability, leading to decreased APP cleavage and increased amyloid-beta accumulation.
Gain of Function (GOF)
In certain cancers, somatic mutations or overexpression enhance ADAM10 activity, promoting Notch and EGFR signaling, thereby increasing cell proliferation and metastasis.
Dominant Negative (DN)
Some missense mutations (e.g., L43P) may exert dominant-negative effects by forming inactive dimers with wild-type ADAM10, reducing overall sheddase activity.
View complete mutation data：
Gene Ontology (GO)
| • metallopeptidase activity | • protein binding |
| • zinc ion binding | • integrin binding |
| • amyloid-beta precursor protein binding | • Notch binding |
| • plasma membrane | • extracellular exosome |
| • proteolysis | • cell adhesion |
| • Notch signaling pathway | • amyloid precursor protein catabolic process |
Pathways
• Notch signaling pathway
• Amyloid-beta formation (Alzheimer's disease)
• Cell adhesion and migration (ECM-receptor interaction)
• EGFR signaling (cancer)
• Regulation of actin cytoskeleton
Protein Summary
ADAM10 is a 748-amino acid type I transmembrane protein with a prodomain, metalloproteinase domain, disintegrin domain, cysteine-rich region, and cytoplasmic tail. It is synthesized as a zymogen and activated by furin cleavage. The mature protein localizes to the plasma membrane and cleaves extracellular domains of various substrates, including APP, Notch, and cadherins. Its catalytic activity is zinc-dependent. ADAM10 is widely expressed, with high levels in the brain, and is essential for embryonic development. Dysregulation of ADAM10 is implicated in neurodegeneration and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAM10 Knockout HEK293 Cell Line | EDJ-KQ12280 | Human | 102 | Details Get a Quote |
| ADAM10 Knockout A-549 Cell Line | EDJ-KQ18056 | Human | 102 | Details Get a Quote |
| ADAM10 Knockout HeLa Cell Line | EDJ-KQ41086 | Human | 102 | Details Get a Quote |
| ADAM10 Knockout HCT 116 Cell Line | EDJ-KQ39837 | Human | 102 | Details Get a Quote |
