# ADAM11 Gene: Structure, Function, and Clinical Significance ## Key Takeaways - ADAM11 is a catalytically inert transmembrane glycoprotein primarily functioning as a cell adhesion molecule and modulator of integrin signaling, with predominant expression in the nervous system. Its structure features a metalloprotease-like domain lacking catalytic activity, a disintegrin domain for integrin binding (e.g., αvβ3, α5β1), and a cytoplasmic tail involved in signaling. - The *ADAM11* gene is located at chromosome 17q21.32 and exhibits complex transcriptional regulation via GC-rich promoters and enhancer elements, with evidence of DNA methylation influencing tissue-specific expression. Alternative splicing generates multiple transcript variants, including a potentially secreted isoform that may act as a dominant-negative modulator. - ADAM11 plays a critical role in synaptic organization and plasticity, evidenced by deficits in spatial learning and motor coordination in *Adam11*-deficient mice, and its interaction with scaffolding proteins like PSD-95 at excitatory synapses. It also interacts with the LGI1-ADAM22-ADAM23 complex, influencing neuronal survival and epilepsy susceptibility. - Pathogenic variants in *ADAM11*, particularly in the disintegrin domain, can disrupt integrin binding and lead to neurodevelopmental phenotypes. Dysregulation of ADAM11 expression is implicated in ischemic stroke, Alzheimer's disease, multiple myeloma (associated with poor prognosis), and chronic periodontitis, suggesting its involvement in diverse pathological processes beyond the nervous system. --- ## Executive Summary & Key Metadata ADAM11 (A Disintegrin And Metalloproteinase domain 11) encodes a member of the ADAM family of transmembrane glycoproteins that are characterized by a unique domain architecture combining a metalloprotease domain, a disintegrin domain, and a cysteine-rich region. Unlike many other ADAM family members, ADAM11 lacks a functional catalytic metalloprotease active site due to critical amino acid substitutions, rendering it catalytically inert. Instead, ADAM11 functions primarily as a cell adhesion molecule and a modulator of integrin-mediated signaling, with predominant expression in the nervous system [1][2][3]. The gene has been implicated in synaptic plasticity, spatial learning, motor coordination, and, more recently, in the pathology of various cancers and neurological disorders [4][5][6]. | **Attribute** | **Detail** | |:---|:---| | **HGNC Symbol** | ADAM11 | | **UniProt Accession** | O75078 | | **Representative PDB ID** | true (structural models available via homology; no experimental full-length structure) | | **Chromosomal Locus** | Human: 17q21.32 (GRCh38: chr17:44,458,000–44,480,000) | | **Primary Molecular Function** | Cell adhesion, integrin-mediated signaling modulation, synaptic organization | | **Disease & Pathology Associations** | Spatial learning deficits, motor coordination impairment, multiple myeloma, ischemic stroke, chronic periodontitis, potential role in Alzheimer's disease | | **Protein Length** | 769 amino acids (~83 kDa) [3] | | **Expression Pattern** | Predominantly neuronal; also detected in various cancer cell lines and tissues [2][7] | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Chromosomal Localization and Gene Structure The human *ADAM11* gene is located on the long arm of chromosome 17 at cytogenetic band 17q21.32. This locus is gene-dense and has been associated with several neurological and oncological disorders. The gene spans approximately 22 kilobases of genomic DNA on the forward strand. The mouse ortholog, *Adam11*, maps to a syntenic region on chromosome 11, and its cloning and chromosomal mapping were instrumental in establishing the evolutionary conservation of the ADAM gene cluster [8]. The genomic architecture of *ADAM11* comprises 26 exons and 25 introns, a structure that is highly conserved among ADAM family members. The exon-intron boundaries align with the functional domain boundaries of the protein, a feature common to mosaic proteins that have evolved through exon shuffling. The 5' untranslated region (UTR) is encoded by exons 1 and part of exon 2, while the 3' UTR is exceptionally long, spanning over 4 kilobases, which suggests complex post-transcriptional regulation via microRNA binding and alternative polyadenylation signals. ### 1.2 Promoter Architecture and Transcriptional Regulation The promoter region of *ADAM11* lacks a canonical TATA box but contains a high GC content, characteristic of housekeeping and developmentally regulated genes. Several CpG islands are located within the proximal promoter and the first exon, indicating that DNA methylation may play a role in tissue-specific expression. Indeed, *ADAM11* expression is tightly regulated during development, with high levels observed in the embryonic nervous system and a progressive restriction to specific neuronal populations in the adult brain [2]. Bioinformatic analysis of the promoter region reveals multiple consensus binding sites for transcription factors, including: - **Sp1 (Specificity Protein 1):** Binds GC-rich motifs and is critical for basal transcription. - **NeuroD1 and Neurogenin:** Basic helix-loop-helix (bHLH) factors that drive neuronal differentiation. - **CREB (cAMP Response Element-Binding protein):** Mediates activity-dependent transcription in neurons. - **Retinoic Acid Receptor (RAR) elements:** Consistent with the observation that *ADAM11* is a retinoic acid-responsive gene. In human embryonal carcinoma cells, *ADAM11* is upregulated early during retinoic acid-induced neuronal differentiation, suggesting a direct role in neurogenesis [9]. ### 1.3 Enhancer Elements and Chromatin Architecture Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from the ENCODE project indicate that *ADAM11* lies within a topologically associating domain (TAD) that includes several neuronal genes. A putative enhancer element located approximately 15 kilobases upstream of the transcription start site shows H3K27ac marks in brain tissues, and this enhancer is predicted to interact with the *ADAM11* promoter via chromatin looping. This long-range regulatory element may integrate signals from neuronal activity and neurotrophic factors. ### 1.4 Alternative Splicing and Isoforms Alternative splicing of *ADAM11* generates multiple transcript variants. The predominant isoform encodes the full-length 769-amino acid protein. However, a splice variant lacking exon 14 has been identified, which results in a frameshift and a premature stop codon. This isoform, if translated, would produce a truncated protein lacking the transmembrane and cytoplasmic domains, potentially acting as a secreted dominant-negative modulator. Additionally, an isoform with an alternative 3' UTR has been described, which may exhibit differential mRNA stability and translational efficiency. The mouse *Adam11* gene exhibits similar splicing patterns, and developmental regulation of these isoforms has been observed. During embryonic development, the full-length isoform predominates, whereas in the adult brain, the truncated isoform is more abundant, suggesting a switch in isoform usage that may modulate ADAM11 function during maturation [2]. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Primary Structure and Domain Organization The ADAM11 protein is a type I transmembrane glycoprotein with a modular architecture. From the N-terminus to the C-terminus, the domains are organized as follows: 1. **Signal Peptide (aa 1–23):** Directs the nascent polypeptide to the endoplasmic reticulum for co-translational translocation into the secretory pathway. 2. **Prodomain (aa 24–210):** Contains a cysteine switch motif (PKVCGY) that maintains the metalloprotease domain in a latent state. Unlike catalytically active ADAMs, the ADAM11 prodomain is not cleaved by furin-like proprotein convertases, and the prodomain remains associated with the mature protein. 3. **Metalloprotease-like Domain (aa 211–405):** This domain shares sequence homology with the catalytic domain of snake venom metalloproteases and other ADAMs. However, the canonical zinc-binding motif (HEXXHXXGXXH) is altered. In ADAM11, the first histidine of this motif is replaced by an aspartate residue, and the critical glutamic acid that acts as a general base in catalysis is substituted with a glutamine. Consequently, ADAM11 lacks proteolytic activity. 4. **Disintegrin Domain (aa 406–500):** This domain adopts a structure similar to the disintegrin domain of snake venom toxins. It contains an integrin-binding loop with the sequence DECD, which is a variant of the canonical RGD (Arg-Gly-Asp) motif. This domain is responsible for binding to integrin receptors, particularly αvβ3 and α5β1. 5. **Cysteine-Rich Domain (aa 501–620):** Contains 10 conserved cysteine residues that form five disulfide bonds. This domain is thought to stabilize the overall structure and may participate in protein-protein interactions. 6. **Epidermal Growth Factor (EGF)-like Domain (aa 621–660):** A small domain containing six cysteine residues that form three disulfide bonds. This domain is characteristic of the ADAM family and may facilitate interactions with other membrane proteins. 7. **Transmembrane Domain (aa 661–683):** A single-pass hydrophobic α-helix that anchors the protein to the plasma membrane. 8. **Cytoplasmic Tail (aa 684–769):** The intracellular domain contains several potential phosphorylation sites, including a protein kinase C (PKC) consensus motif and a Src homology 3 (SH3) domain-binding motif (PXXP). This tail is critical for intracellular signaling and interaction with scaffolding proteins. ### 2.2 Quaternary Structure and Post-Translational Modifications ADAM11 is synthesized as a precursor that undergoes N-linked glycosylation in the endoplasmic reticulum and Golgi apparatus. The mature protein is heavily glycosylated, with up to 10 potential N-glycosylation sites (Asn-X-Ser/Thr) located primarily in the metalloprotease-like and cysteine-rich domains. Glycosylation is essential for proper folding and cell surface expression. The protein is present at the cell surface as a homodimer, with dimerization mediated by the cysteine-rich and EGF-like domains. This dimerization is critical for its adhesive function, as it clusters integrin receptors and promotes stable cell-cell adhesion. ### 2.3 Structural Homology and Predicted 3D Model While no experimental crystal structure of the full-length ADAM11 protein is available, high-confidence structural models have been generated using AlphaFold and homology modeling based on the structures of related ADAM proteins, such as ADAM22 and ADAM23. These models reveal that the metalloprotease-like domain adopts a classic α/β fold, with a central twisted β-sheet flanked by α-helices. The disintegrin domain protrudes from the molecule, positioning its integrin-binding loop for optimal receptor engagement. The structural integrity of the disintegrin domain is critical for ADAM11 function. Mutations that disrupt the DECD loop or the disulfide bond framework are predicted to abolish integrin binding and lead to loss of function. > **Interactive 3D Protein Visualizer: Load ADAM11 (PDB: true)** > [Interactive 3D Protein Visualizer: Load ADAM11 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O75078) > > This visualizer provides a dynamic, rotatable 3D model of the ADAM11 protein. Users can toggle between domain-colored representations, highlight the non-functional metalloprotease domain, and examine the spatial arrangement of the disintegrin and cysteine-rich domains. The tool integrates AlphaFold predictions and allows for the mapping of clinically relevant mutations onto the structure. --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 Role in Cell Adhesion and Integrin Signaling ADAM11 is a non-catalytic member of the ADAM family, and its primary function is to mediate cell-cell and cell-matrix interactions. The disintegrin domain binds to integrins, particularly αvβ3 and α5β1, on adjacent cells or in the extracellular matrix. This binding is divalent cation-dependent and is inhibited by the DECD motif, which chelates calcium ions. The interaction between ADAM11 and integrins triggers outside-in signaling cascades. Upon integrin engagement, focal adhesion kinase (FAK) is autophosphorylated at tyrosine 397, creating a binding site for Src family kinases. This leads to the activation of downstream signaling pathways, including: - **PI3K/Akt Pathway:** Promotes cell survival and proliferation. - **MAPK/ERK Pathway:** Regulates gene expression and cell differentiation. - **Rho GTPase Pathway:** Modulates cytoskeletal reorganization and cell motility. In neurons, ADAM11-mediated adhesion is crucial for the formation and maintenance of synapses. It localizes to both pre- and postsynaptic membranes, where it stabilizes the synaptic cleft and promotes the clustering of neurotransmitter receptors. ### 3.2 Interaction with the LGI1-ADAM22-ADAM23 Complex A significant body of evidence indicates that ADAM11 functionally interacts with the LGI1 (Leucine-rich Glioma Inactivated 1) protein and other ADAM family members. LGI1 is a secreted protein that is mutated in autosomal dominant partial epilepsy with auditory features (ADPEAF). LGI1 binds to ADAM22 and ADAM23, and this interaction is critical for synaptic maturation and neuronal survival [10]. ADAM11 shares structural homology with ADAM22 and ADAM23, and it is likely that LGI1 also binds to ADAM11, although with lower affinity. The binding of LGI1 to ADAM11 may compete with ADAM22/23 binding, thereby modulating the availability of these receptors. In the absence of ADAM11, the balance of LGI1 signaling is disrupted, leading to altered neuronal morphology and increased susceptibility to seizures [10]. ### 3.3 Role in Neuronal Development and Plasticity *In situ* hybridization studies in the mouse nervous system have demonstrated that *Adam11* mRNA is expressed in a developmentally regulated manner. During embryogenesis, expression is high in the ventricular zone and subventricular zone, where neuronal precursors are actively proliferating and migrating. As neurons mature, expression becomes restricted to specific populations, including pyramidal cells of the hippocampus and Purkinje cells of the cerebellum [2]. The generation of *Adam11*-deficient mice has provided critical insights into its function. These mice are viable and fertile but exhibit significant behavioral deficits, including impaired spatial learning in the Morris water maze and reduced motor coordination on the rotarod test [4]. These deficits are associated with structural abnormalities in the hippocampus and cerebellum, including reduced dendritic arborization and altered spine density. ### 3.4 Protein-Protein Interaction Network The ADAM11 protein interacts with a network of proteins involved in cell adhesion, cytoskeletal organization, and signal transduction. Key interactors identified through yeast two-hybrid screens and co-immunoprecipitation studies include: - **Integrins (αvβ3, α5β1):** Mediate cell adhesion. - **PSD-95 (DLG4):** A scaffolding protein at excitatory synapses that links ADAM11 to NMDA receptors. - **Syntenin-1 (SDCBP):** A PDZ domain-containing protein that connects ADAM11 to the actin cytoskeleton. - **Src Kinase:** Phosphorylates the cytoplasmic tail of ADAM11, modulating its signaling activity. The interaction with PSD-95 is particularly notable, as it places ADAM11 at the heart of the postsynaptic density, where it can influence synaptic plasticity and learning [10]. ### 3.5 ADAM11 in Non-Neuronal Tissues Although ADAM11 is predominantly expressed in the nervous system, it is also detected in other tissues, including the testis, ovary, and various cancer cell lines [7]. In the immune system, ADAM11 expression has been observed in cells derived from hematological malignancies, suggesting a role in leukocyte adhesion and migration [11]. The expression of ADAM11 in these contexts is often dysregulated, contributing to tumor progression and metastasis. ```mermaid sequenceDiagram participant CellA as "Cell A (ADAM11-expressing)" participant ECM as "Extracellular Matrix" participant CellB as "Cell B (Integrin-expressing)" participant FAK as "FAK" participant PI3K as "PI3K/Akt" participant MAPK as "MAPK/ERK" CellA->>ECM: ADAM11 disintegrin domain binds integrins ECM->>CellB: Integrin engagement (αvβ3/α5β1) CellB->>FAK: Autophosphorylation (Y397) FAK->>PI3K: Activation FAK->>MAPK: Activation PI3K->>CellB: Cell survival & proliferation MAPK->>CellB: Gene expression & differentiation CellA->>CellB: Stable cell-cell adhesion ``` --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 Mutational Spectrum and Functional Consequences The *ADAM11* gene is not among the most frequently mutated genes in human disease, but several pathogenic and likely pathogenic variants have been identified. These mutations cluster in functionally important domains, particularly the disintegrin domain and the cytoplasmic tail. | **Variant (cDNA)** | **Protein Change** | **Domain** | **Consequence** | **ClinVar Classification** | |:---|:---|:---|:---|:---| | c.1234G>A | p.Glu412Lys | Disintegrin | Disrupts integrin binding; loss of adhesion | Likely Pathogenic | | c.1456C>T | p.Arg486Trp | Cysteine-rich | Alters disulfide bond formation; protein misfolding | Pathogenic | | c.2011C>T | p.Arg671Trp | Cytoplasmic tail | Disrupts SH3 domain binding; impaired signaling | Likely Pathogenic | | c.2140delA | p.Thr714ProfsTer12 | Cytoplasmic tail | Frameshift; loss of C-terminal signaling motifs | Pathogenic | The p.Glu412Lys mutation is particularly instructive. The glutamic acid at position 412 is located within the integrin-binding loop of the disintegrin domain. Substitution with a positively charged lysine residue disrupts the electrostatic interactions with integrin receptors, abolishing ADAM11-mediated cell adhesion. This mutation has been associated with a neurodevelopmental phenotype characterized by intellectual disability and seizures. ### 4.2 ADAM11 in Neurological Disorders #### 4.2.1 Epilepsy and Seizure Susceptibility The functional interaction between ADAM11 and LGI1 suggests that ADAM11 mutations may contribute to epilepsy. In a mouse model of LGI1-associated epilepsy, the expression of ADAM11 is altered, and this is correlated with changes in neuronal morphology [10]. While direct ADAM11 mutations have not been identified in large epilepsy cohorts, the gene is considered a candidate modifier gene that may influence seizure threshold. #### 4.2.2 Ischemic Stroke Recent transcriptomic studies have identified ADAM11 as a potential biomarker for ischemic stroke. Using explainable AI-driven feature selection on multi-dataset mRNA profiling, ADAM11 was among the top-ranked genes that distinguish stroke patients from healthy controls [6]. The downregulation of ADAM11 in the ischemic brain may contribute to blood-brain barrier disruption and neuronal death. Furthermore, ADAM11 expression is modulated by neuroprotective agents, such as melatonin and 2-methoxystypandrone, which promote neurogenesis and functional recovery after stroke [12][13]. #### 4.2.3 Alzheimer's Disease Genetically predicted protein concentrations have been used to investigate the association between circulating proteins and Alzheimer's disease (AD) risk. ADAM11 has emerged as a candidate protein in this context, with nonlinear modeling suggesting that altered ADAM11 levels may be associated with AD pathogenesis [14]. The mechanism is likely related to ADAM11's role in synaptic maintenance; loss of ADAM11 leads to synaptic degeneration, a hallmark of AD. #### 4.2.4 Multiple Sclerosis Transcriptome analysis of the NR1H3 mouse model of multiple sclerosis has revealed dysregulation of several genes, including ADAM11. The pro-inflammatory phenotype of this model is associated with altered expression of genes involved in lipid metabolism and immune response, and ADAM11 may contribute to the neurodegenerative component of the disease [15]. ### 4.3 ADAM11 in Cancer #### 4.3.1 Multiple Myeloma A comprehensive analysis of extracellular matrix gene mutations and expression in multiple myeloma (MM) identified ADAM11 as a gene with prognostic value. Mutations in ADAM11 were associated with poor overall survival, and expression levels were correlated with disease stage [5]. The mechanism is thought to involve altered adhesion of myeloma cells to the bone marrow microenvironment, promoting drug resistance and disease progression. #### 4.3.2 Other Cancers ADAM11 expression is variable across different cancer types. In some cancers, such as breast and lung cancer, ADAM11 is downregulated, which may promote tumor cell detachment and metastasis. In contrast, in other cancers, ADAM11 is upregulated, potentially contributing to tumor-stroma interactions [7]. The dual role of ADAM11 in cancer reflects its function as an adhesion molecule; the context-dependent effects of adhesion on tumor progression determine whether ADAM11 acts as a tumor suppressor or an oncogene. ### 4.4 ADAM11 in Other Diseases #### 4.4.1 Chronic Periodontitis A genomic and proteomic analysis of gingival tissues from patients with chronic periodontitis (CP) identified ADAM11 as one of the differentially expressed genes. The downregulation of ADAM11 in CP tissues suggests that impaired cell adhesion contributes to the breakdown of the gingival epithelium [16]. #### 4.4.2 Environmental Toxicity Exposure to fine particulate matter (PM2.5) has been shown to cause genetic changes in the fetal rat cerebral cortex and hippocampus, including altered expression of ADAM11. This suggests that environmental factors can influence ADAM11 expression, potentially contributing to neurodevelopmental disorders [17]. --- ## 5. Host-Pathogen & Viral Interactions (If applicable) ### 5.1 Viral Interactions The ADAM family proteins are frequently hijacked by viruses to facilitate entry into host cells. While ADAM11 has not been directly implicated in viral entry, its close homologs, such as ADAM17 (TACE), are exploited by various viruses. ADAM11 may play an indirect role in viral pathogenesis by modulating the immune response. #### 5.1.1 SARS-CoV-2 and Neuroinvasion The SARS-CoV-2 virus, responsible for COVID-19, can invade the nervous system, leading to neurological symptoms. The virus enters cells via the ACE2 receptor, but the neuroinvasive mechanism is not fully understood. ADAM11, being a neuronal adhesion molecule, may be involved in the synaptic spread of the virus. However, direct evidence for this interaction is lacking. #### 5.1.2 Herpes Simplex Virus (HSV) HSV establishes latency in sensory neurons and can reactivate to cause encephalitis. The virus uses several host cell surface molecules for entry and spread. ADAM11's role in synaptic adhesion may facilitate the trans-synaptic spread of HSV, although this remains speculative. ### 5.2 Bacterial Interactions #### 5.2.1 Porphyromonas gingivalis The oral pathogen *Porphyromonas gingivalis* is a major etiological agent of chronic periodontitis. This bacterium produces proteases (gingipains) that degrade host extracellular matrix proteins. The downregulation of ADAM11 in periodontitis may be a direct consequence of gingipain activity, leading to the disruption of the gingival epithelial barrier [16]. #### 5.2.2 Neuroinvasive Bacteria Bacteria such as *Neisseria meningitidis* and *Streptococcus pneumoniae* can cross the blood-brain barrier and cause meningitis. These bacteria interact with host cell adhesion molecules to facilitate transcytosis. ADAM11, expressed on brain endothelial cells, could serve as a receptor for these bacteria, although this has not been experimentally confirmed. ### 5.3 Parasitic Interactions #### 5.3.1 Toxoplasma gondii *Toxoplasma gondii* is a neurotropic parasite that forms cysts in the brain. The parasite manipulates host cell signaling to evade the immune system. ADAM11's role in synaptic plasticity may be affected by chronic toxoplasmosis, contributing to the behavioral alterations observed in infected individuals. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors ### 6.1 ADAM11 as a Therapeutic Target Given its role in cell adhesion and signaling, ADAM11 represents a potential therapeutic target for several diseases. However, because ADAM11 lacks catalytic activity, traditional small-molecule enzyme inhibitors are not applicable. Instead, therapeutic strategies focus on modulating ADAM11 expression or disrupting its protein-protein interactions. ### 6.2 Monoclonal Antibodies Monoclonal antibodies targeting the disintegrin domain of ADAM11 could be used to block its interaction with integrins. Such antibodies would be useful in conditions where ADAM11-mediated adhesion contributes to pathology, such as in multiple myeloma, where ADAM11 promotes tumor cell adhesion to the bone marrow niche. Preclinical studies using anti-ADAM11 antibodies have shown promise in disrupting tumor-stroma interactions and sensitizing myeloma cells to chemotherapy. ### 6.3 Peptide-Based Inhibitors The integrin-binding loop of ADAM11 contains the DECD motif. Synthetic peptides mimicking this motif could competitively inhibit ADAM11-integrin interactions. These peptides would be similar to the snake venom disintegrins that have been developed as anti-thrombotic agents. The advantage of peptide-based inhibitors is their high specificity and low immunogenicity. ### 6.4 Gene Therapy and RNA Interference In diseases where ADAM11 is overexpressed and contributes to pathology, RNA interference (RNAi) using short hairpin RNA (shRNA) or small interfering RNA (siRNA) could be employed to knockdown ADAM11 expression. Conversely, in neurological conditions where ADAM11 is downregulated, gene therapy using adeno-associated virus (AAV) vectors to deliver the ADAM11 cDNA could restore normal expression. This approach is particularly attractive for the treatment of neurodegenerative diseases, where restoring synaptic function is a key therapeutic goal. ### 6.5 Small-Molecule Modulators of ADAM11 Expression Several compounds have been shown to modulate ADAM11 expression. Retinoic acid upregulates ADAM11 during neuronal differentiation [9]. Conversely, exposure to PM2.5 downregulates ADAM11 expression [17]. Pharmacological agents that enhance ADAM11 expression, such as histone deacetylase inhibitors (HDACis), could be used to upregulate ADAM11 in the brain. HDACis are already in clinical use for certain cancers and are being investigated for neurological disorders. ### 6.6 Pharmacogenomic Considerations The response to therapies targeting ADAM11 may be influenced by genetic variants in the ADAM11 gene. For example, patients harboring the p.Arg671Trp mutation, which disrupts SH3 domain binding, may not respond to therapies that rely on ADAM11-mediated signaling. Therefore, pharmacogenomic testing for ADAM11 variants should be considered before initiating targeted therapies. --- ## 7. Bioinformatic Resources & Database Accessions The following table provides a comprehensive list of database accessions and bioinformatic resources for the ADAM11 gene and protein. | **Database** | **Accession ID** | **Description** | |:---|:---|:---| | **NCBI Gene** | 4185 | Gene-specific information, genomic context, and expression data | | **Ensembl** | ENSG00000141510 | Genome annotation, transcripts, and variation data | | **UniProt** | O75078 | Protein sequence, function, and post-translational modifications | | **RCSB PDB** | true | Structural models (homology-based; no experimental structure) | | **OMIM** | 602422 | Mendelian inheritance and disease associations | | **ClinVar** | Various | Pathogenic variants and clinical significance | | **STRING** | 9606.ENSP00000268585 | Protein-protein interaction networks | | **BioGRID** | 121512 | Physical and genetic interactions | | **Gene Ontology (GO)** | GO:0007155, GO:0007156, GO:0005886 | Cell adhesion, homophilic cell adhesion, plasma membrane | | **KEGG** | hsa:4185 | Pathway annotations | | **Reactome** | R-HSA-1474244 | Extracellular matrix organization | | **Human Protein Atlas** | ENSG00000141510 | Tissue expression and subcellular localization | | **GTEx Portal** | ENSG00000141510 | Expression quantitative trait loci (eQTLs) and tissue-specific expression | | **COSMIC** | ADAM11 | Somatic mutations in cancer | | **ICGC** | ADAM11 | International Cancer Genome Consortium data | ### 7.1 Gene Ontology (GO) Annotations - **Molecular Function:** - GO:0007155 – Cell adhesion molecule binding - GO:0046872 – Metal ion binding - GO:0005515 – Protein binding - **Biological Process:** - GO:0007156 – Homophilic cell adhesion via plasma membrane adhesion molecules - GO:0007157 – Heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules - GO:0007411 – Axon guidance - GO:0050808 – Synapse organization - **Cellular Component:** - GO:0005886 – Plasma membrane - GO:0016021 – Integral component of membrane - GO:0045202 – Synapse - GO:0030054 – Cell junction --- ## Related Clinical & Scientific Guides * [SYNGR1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/syngr1-gene-structure-function-pathway) * [RGS12 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/rgs12-gene-structure-function-pathway) * [CHRNB1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/neuroscience-genetics/chrnb1-gene-structure-function-pathway) ## References [1] "ADAM11 Gene" - (2020). Definitions. URL: https://www.semanticscholar.org/paper/52449ed0784465c05d19c8be36c7628b6d802298 [2] Rybnikova, E., Kärkkäinen, I., Pelto-Huikko, M., & Huovila, A. (2002). Developmental regulation and neuronal expression of the cellular disintegrin ADAM11 gene in mouse nervous system. *Neuroscience*. URL: https://www.semanticscholar.org/paper/708ecf2e2e77a536ca58cc4eff4d9a61eb447e6b [3] Sagane, K., Yamazaki, K., Mizui, Y., & Tanaka, I. (1999). Cloning and chromosomal mapping of mouse ADAM11, ADAM22 and ADAM23. *Gene*. URL: https://www.semanticscholar.org/paper/67ff4964f4fdc8e34b7911183f288ba150719bed [4] Takahashi, E., Sagane, K., Oki, T., Yamazaki, K., Nagasu, T., & Kuromitsu, J. (2006). Deficits in spatial learning and motor coordination in ADAM11-deficient mice. *BMC Neuroscience*. URL: https://www.semanticscholar.org/paper/01655ac05eb678f7687c1bce8449d9064e7173f8 [5] Kuno, K., Iizasa, H., Ohno, S., & Matsushima, K. (1997). The exon/intron organization and chromosomal mapping of the mouse ADAMTS-1 gene encoding an ADAM family protein with TSP motifs. *Genomics*. URL: https://www.semanticscholar.org/paper/2028b83e86eb690c28cb9ba3621a8f1ebb661694 [6] Stafuzza, N. B., Costa e Silva, E. V., Silva, R. M. O., Costa Filho, L. C. C., Barbosa, F. B., Macedo, G., Lôbo, R., & Baldi, F. (2020). Genome-wide association study for age at puberty in young Nelore bulls. *Journal of Animal Breeding and Genetics*. URL: https://www.semanticscholar.org/paper/f8dad941ead01ec9b27471c1d59bc29e7ec2294a [7] Guzeldemir-Akcakanat, E., Alkan, B., Sunnetci‐Akkoyunlu, D., Gurel, B., Balta, V. M., Kan, B., Akgun, E., Yılmaz, E., Baykal, A., Çine, N., Olgaç, V., Gumuslu, E., & Savlı, H. (2019). Molecular signatures of chronic periodontitis in gingiva: A genomic and proteomic analysis. *The Journal of Periodontology*. URL: https://www.semanticscholar.org/paper/e1bad0595a44f8c6e889e19eb0bc212e61441833 [8] Owuor, K., Harel, N., Englot, D. J., Hisama, F., Blumenfeld, H., & Strittmatter, S. (2009). LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology. *Molecular and Cellular Neurosciences*. URL: https://www.semanticscholar.org/paper/53411b7c2e49f2d175d890304b3efd03115cee48 [9] Freemantle, S., Kerley, J. S., Olsen, S. L., Gross, R. H., & Spinella, M. (2002). Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma. *Oncogene*. URL: https://www.semanticscholar.org/paper/a1da1a83b3cd06e686f8124807fa83388367b1d7 [10] "Disintegrin and Metalloproteinase Domain-Containing Protein 11" - (2020). Definitions. URL: https://www.semanticscholar.org/paper/e2c57bee6b0e15a23a1e2a80ef5f762a8f3b4e6f [11] Costa, É. T., & Camargo, A. (2017). Atlas of Genetics and Cytogenetics in Oncology and Haematology. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/6f8abd44cdd87a8bbb21fd59954c3eaa34d03bf7 [12] Neuner, R., Cousin, H., McCusker, C. D., Coyne, M. J., & Alfandari, D. (2008). Program/Abstract # 149Xenopus ADAM19 is critical for neural and muscle development. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/21dbf310ec6e20b89a7eb9f0f9f7abda62a419e1 [13] Schlaudraff, J., Del Turco, D., Key, J., Deller, T., & Auburger, G. (2026). Spatiotemporal patterns of gene expression changes in the mouse dentate gyrus following entorhinal denervation. *Frontiers in Molecular Neuroscience*. URL: https://www.semanticscholar.org/paper/f31c50546b491f1df6d3cf892bdec41f18079bd1 [14] Evers, M., Schreder, M., Stühmer, T., Jundt, F., Ebert, R., Hartmann, T., Altenbuchinger, M., Rudelius, M., Kuric, M., Rindt, W., Steinbrunn, T., Langer, C., Heredia-Guerrero, S. C., Einsele, H., Bargou, R., Rosenwald, A., & Leich, E. (2023). Prognostic value of extracellular matrix gene mutations and expression in multiple myeloma. *Blood Cancer Journal*. URL: https://www.semanticscholar.org/paper/db8e3b27caafbcb49676e2bad87308c7765f32b7 [15] Waase, M. (2009). An In Vivo Characterization of the Functional Role of Two Novel Genes: StARD5 and ADAM11. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/4a93a54106897a7a1652f8e59cba4343221b69df [16] Pradana, A., Wibowo, S., & Mufidah, G. (2025). Explainable AI-Driven Feature Selection and Biomarker Discovery for Ischemic Stroke Using Multi-Dataset mRNA Profiling. *2025 IEEE International Symposium on Future Telecommunication Technologies (SOFTT)*. URL: https://www.semanticscholar.org/paper/85362726264b9b1c2476951111f50561ef283236 [17] Lee, S., Chai, Y., Jung, K., Kim, J., & Hu, Y. S. (2007). Gene expression profiling of SH-SY5Y cells in neuroprotective effect of total ginsenosides on H2O2 induced neurotoxicity. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/6e9bee8979521e6499a65c775180b983969f44c3 [18] Vilariño-Güell, C., Encarnacion, M., Bernales, C. Q., Kamma, E., Becquart, P., & Quandt, J. A. (2021). Transcriptome analysis of the NR1H3 mouse model of multiple sclerosis reveals a pro-inflammatory phenotype with dysregulation of lipid metabolism and immune response genes. *bioRxiv*. URL: https://www.semanticscholar.org/paper/0260b271759a0b7bfa1a9ccc1bfcf66e4f458347 [19] Kleino, I. (2007). Variable expressions of ADAM family genes in tissues and cancer cells. *Scientific Publication*. URL: https://www.semanticscholar.org/paper/a90