# CLSTN1 Gene: Structure, Function, and Clinical Significance ## Key Takeaways - *CLSTN1* encodes a type I transmembrane protein functioning as a synaptic adhesion molecule, regulating dendritic spine morphology, and modulating amyloid precursor protein (APP) processing, with its genomic locus at 1p36.21 being a region frequently deleted in neuroblastoma. - The protein's domain architecture includes extracellular cadherin repeats for homophilic adhesion, a juxtamembrane region susceptible to ADAM10 cleavage, a transmembrane helix, and a cytoplasmic tail interacting with adaptor proteins like Mint1/X11 and PDZ-domain proteins, crucial for APP trafficking and synaptic localization. - Alternative splicing generates CLSTN1-α and CLSTN1-β isoforms, with the longer α-isoform containing a critical cytoplasmic insert regulated by MBNL1 and RBFOX2, essential for proper APP trafficking and non-amyloidogenic processing, thereby influencing amyloid-beta production relevant to Alzheimer's disease. - Dysregulation of *CLSTN1* is implicated in various pathologies, including neurodevelopmental disorders (e.g., Fragile X syndrome), neurodegenerative diseases (e.g., Alzheimer's, Parkinson's), and cancers (e.g., neuroblastoma, gastric cancer), often due to genomic deletions, promoter hypermethylation, or altered splicing patterns. - While no direct CLSTN1-targeting drugs are approved, therapeutic strategies could involve modulating APP processing, targeting aberrant splicing events with antisense oligonucleotides, or utilizing CLSTN1 as a biomarker for conditions like dilated cardiomyopathy and type 2 diabetes mellitus. --- ## Executive Summary & Key Metadata The *CLSTN1* gene (calsyntenin-1, also known as alcadein-α) encodes a type I transmembrane protein belonging to the cadherin superfamily. It is predominantly expressed in the nervous system, where it functions as a synaptic adhesion molecule, a regulator of dendritic spine morphology, and a modulator of amyloid precursor protein (APP) processing. Beyond its canonical roles in neurobiology, *CLSTN1* has been implicated in a broad spectrum of pathological conditions, including neurodevelopmental disorders, neurodegenerative diseases, various malignancies, and metabolic disorders. Its genomic locus at chromosome 1p36.21 is a region frequently deleted in neuroblastoma and other cancers, positioning *CLSTN1* as a potential tumor suppressor. The protein's unique domain architecture—comprising extracellular cadherin repeats, a juxtamembrane region, a single transmembrane helix, and a cytoplasmic tail with conserved phosphorylation sites—enables its dual functions in cell adhesion and intracellular signaling. | **Metadata Field** | **Value** | | :--- | :--- | | **HGNC Symbol** | CLSTN1 | | **UniProt Accession** | O94985 | | **Representative PDB ID** | True (see Section 2 for details) | | **Chromosomal Locus** | 1p36.21 | | **Primary Molecular Function** | Calcium-dependent homophilic cell adhesion; regulation of APP metabolism; modulation of dendritic spine maturation | | **Disease & Pathology Associations** | Neuroblastoma, Alzheimer's disease, Fragile X syndrome, gastric cancer, dilated cardiomyopathy, type 2 diabetes mellitus, Parkinson's disease, bipolar disorder, pancreatic cancer | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Chromosomal Localization and Gene Structure The *CLSTN1* gene is located on the short arm of chromosome 1 at cytogenetic band p36.21 (GRCh38/hg38: chr1:9,718,100-9,815,000). This genomic interval is approximately 97 kilobases (kb) in length and is oriented on the minus strand of the chromosome. The 1p36 region is a gene-dense area that has been extensively studied for its role in tumorigenesis, particularly in neuroblastoma, where loss of heterozygosity (LOH) at 1p36 is a well-established marker of poor prognosis [1, 2]. The *CLSTN1* gene is positioned within a cluster of genes that are frequently co-deleted in aggressive neuroblastoma, suggesting that its loss may contribute to the malignant phenotype. The gene comprises 14 exons, with the translation initiation codon located in exon 1 and the stop codon in exon 14. The intron-exon boundaries are conserved across mammalian species, indicating strong selective pressure on the genomic architecture. The promoter region of *CLSTN1* lacks a canonical TATA box but contains a high-density CpG island spanning approximately 1.5 kb upstream of the transcription start site (TSS). This CpG island is a target for DNA methylation, and hypermethylation of this region has been observed in several cancer types, leading to transcriptional silencing [3, 4]. The promoter also contains multiple binding sites for the transcription factor Specificity Protein 1 (Sp1), which is known to regulate the expression of genes involved in neuronal development and synaptic plasticity. ### 1.2 Promoter Architecture and Transcriptional Regulation The *CLSTN1* promoter is characterized by a complex regulatory landscape. In addition to the CpG island and Sp1 sites, the promoter region contains consensus sequences for the transcription factors cAMP-response element binding protein (CREB), Nuclear Factor-kappa B (NF-κB), and the neuronal-restrictive silencer factor (NRSF/REST). The presence of a NRSF binding site is particularly notable, as REST is a master repressor of neuronal genes in non-neuronal tissues. This suggests that *CLSTN1* expression is tightly controlled in a cell-type-specific manner, with active repression in non-neuronal cells and de-repression upon neuronal differentiation. Transcriptional regulation of *CLSTN1* is also influenced by epigenetic modifications. The BTB and CNC homology 1 (BACH1) transcription factor, which is involved in the oxidative stress response, has been shown to bind to the *CLSTN1* promoter and repress its transcription [5]. BACH1 functions as a heme-binding repressor, and its activity is modulated by cellular redox status. This links *CLSTN1* expression to oxidative stress pathways, which are relevant in the context of neurodegenerative diseases and cancer. ### 1.3 Alternative Splicing and Isoform Diversity Alternative splicing of the *CLSTN1* pre-mRNA generates multiple transcript variants that encode distinct protein isoforms. The two major isoforms, designated CLSTN1-α (long form) and CLSTN1-β (short form), differ in their cytoplasmic domains. The long isoform contains a 50-amino acid insert in the cytoplasmic tail that is absent in the short isoform. This insert harbors a casein kinase II (CK2) phosphorylation site and a binding motif for the adaptor protein Mint1/X11, which is critical for the protein's role in APP metabolism [6]. The splicing of *CLSTN1* is regulated by the RNA-binding proteins MBNL1 and RBFOX2 [7, 8]. These proteins are master regulators of alternative splicing in the brain and muscle, and their dysregulation has been implicated in myotonic dystrophy and cancer. In the context of *CLSTN1*, MBNL1 and RBFOX2 cooperate to promote the inclusion of the alternatively spliced exon 13, which encodes the cytoplasmic insert. In pluripotent stem cells, the expression of these splicing factors is low, leading to the predominant expression of the short isoform. Upon differentiation into neurons, the expression of MBNL1 and RBFOX2 increases, shifting the splicing pattern towards the long isoform [7]. This developmental switch is functionally significant, as the long isoform is required for the proper trafficking of APP and the regulation of amyloid-β (Aβ) production. In addition to the α and β isoforms, several minor splice variants have been reported. These include transcripts with alternative 5' untranslated regions (UTRs) and transcripts that skip exons encoding portions of the extracellular domain. The functional significance of these minor variants is not fully understood, but they may contribute to the tissue-specific and developmental regulation of CLSTN1 function. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Primary Structure and Domain Organization The CLSTN1 protein is a type I transmembrane glycoprotein of approximately 980 amino acids (UniProt O94985). Its domain architecture is organized into three major regions: a large N-terminal extracellular domain, a single-pass transmembrane helix, and a C-terminal cytoplasmic domain. The extracellular domain is responsible for mediating cell-cell adhesion, while the cytoplasmic domain transduces signals to the intracellular machinery. The domain organization from N-terminus to C-terminus is as follows: 1. **Signal Peptide (aa 1-23):** Directs the nascent polypeptide to the endoplasmic reticulum for co-translational translocation. 2. **Cadherin Repeats (CR1-CR2, aa 24-250):** Two tandem calcium-binding cadherin repeats. These domains mediate homophilic trans-interactions between CLSTN1 molecules on adjacent cells [9]. Each repeat adopts a Greek-key β-sandwich fold, characteristic of the cadherin superfamily, with calcium ions bound at the interdomain interface. 3. **Laminin G-like Domain (aa 251-450):** A domain with structural similarity to the G domain of the laminin α-chain. This domain is involved in protein-protein interactions and may contribute to the adhesive properties of CLSTN1. 4. **Juxtamembrane Region (aa 451-750):** A poorly structured region that is heavily O-glycosylated. This region is thought to act as a rigid stalk, extending the cadherin repeats away from the cell surface. It contains a cleavage site for the metalloprotease ADAM10, which mediates the ectodomain shedding of CLSTN1. 5. **Transmembrane Helix (aa 751-773):** A hydrophobic α-helix that anchors the protein to the plasma membrane. 6. **Cytoplasmic Domain (aa 774-980):** The intracellular portion of the protein. This domain contains several conserved motifs, including: - A binding site for the neuronal adaptor protein Mint1/X11 (aa 850-870). - Multiple phosphorylation sites for CK2 and protein kinase C (PKC). - A PDZ-binding motif at the extreme C-terminus (ETSF), which mediates interactions with PDZ domain-containing scaffolding proteins. ### 2.2 Structural Biology and 3D Conformation High-resolution structural studies of the full-length CLSTN1 protein are challenging due to the presence of the flexible juxtamembrane region and the intrinsically disordered cytoplasmic domain. However, the structures of the individual cadherin repeats have been solved using X-ray crystallography and NMR spectroscopy. The cadherin repeats of CLSTN1 adopt the canonical cadherin fold, consisting of seven β-strands arranged in two β-sheets. The calcium-binding sites at the interface between the two repeats are critical for the structural integrity of the domain pair and for mediating homophilic adhesion. Mutations that disrupt calcium binding abolish the adhesive function of CLSTN1 [9]. The cytoplasmic domain of CLSTN1 is largely unstructured in isolation but adopts a more defined conformation upon binding to its interaction partners. The Mint1/X11 binding site forms an amphipathic helix that inserts into a hydrophobic groove on the surface of Mint1. This interaction is essential for the role of CLSTN1 in APP trafficking and processing [6]. The C-terminal PDZ-binding motif (ETSF) is a class I PDZ ligand, which binds to the PDZ domains of proteins such as PSD-95 and SAP97, linking CLSTN1 to the postsynaptic density. ### 2.3 Post-Translational Modifications CLSTN1 is subject to extensive post-translational modifications that regulate its function and localization. The extracellular domain is N-glycosylated at multiple sites, which is required for proper folding and trafficking to the cell surface. The juxtamembrane region is O-glycosylated, which may protect the protein from proteolytic cleavage and modulate its adhesive properties. Proteolytic processing of CLSTN1 is a key regulatory mechanism. The protein is cleaved by ADAM10 in the juxtamembrane region, resulting in the shedding of the ectodomain. This is followed by intramembrane cleavage by the γ-secretase complex, which releases the cytoplasmic domain into the cytosol. The released cytoplasmic domain can then translocate to the nucleus, where it may function as a transcriptional regulator. This regulated intramembrane proteolysis (RIP) is analogous to the processing of APP and Notch, and it represents a major pathway for CLSTN1 signaling. > **Interactive 3D Protein Visualizer: Load CLSTN1 (PDB: true)** > [Interactive 3D Protein Visualizer: Load CLSTN1 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O94985) > *Use the visualizer to explore the domain architecture, calcium-binding sites, and phosphorylation motifs of CLSTN1 in three dimensions.* --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 Synaptic Adhesion and Dendritic Spine Morphogenesis CLSTN1 is a core component of the synaptic adhesion machinery. Through its extracellular cadherin repeats, CLSTN1 mediates homophilic trans-synaptic interactions, bridging the pre- and postsynaptic membranes. These interactions are calcium-dependent and are essential for the formation and stabilization of synapses. In the postsynaptic compartment, CLSTN1 is localized to the postsynaptic density, where it interacts with scaffolding proteins such as PSD-95 and SAP97 via its C-terminal PDZ-binding motif. The function of CLSTN1 in dendritic spine maturation is particularly well-characterized. Dendritic spines are small protrusions on the surface of dendrites that receive excitatory synaptic input. The morphology of these spines is highly dynamic and is correlated with synaptic strength. CLSTN1 negatively regulates the accumulation of ICAM5 (intercellular adhesion molecule 5) at the postsynaptic membrane [10]. ICAM5 is a transmembrane protein that promotes the formation of filopodia-like immature spines. By limiting ICAM5 accumulation, CLSTN1 promotes the maturation of dendritic spines into their characteristic mushroom shape. This process is critical for normal cognitive function, and its dysregulation is observed in Fragile X syndrome, a neurodevelopmental disorder characterized by intellectual disability and autism spectrum disorder [10]. ### 3.2 Regulation of APP Metabolism and Alzheimer's Disease One of the most extensively studied functions of CLSTN1 is its role in the regulation of amyloid precursor protein (APP) metabolism. APP is the precursor to the amyloid-β (Aβ) peptide, which is the major component of senile plaques in Alzheimer's disease (AD). CLSTN1 forms a complex with APP and the adaptor protein Mint1/X11. This complex is involved in the intracellular trafficking of APP, directing it away from the amyloidogenic processing pathway. The cytoplasmic domain of CLSTN1 binds to Mint1/X11, which in turn binds to the YENPTY motif in the cytoplasmic tail of APP. This tripartite complex promotes the sorting of APP into vesicles that are targeted for non-amyloidogenic processing. In the absence of CLSTN1, APP is more readily cleaved by β-secretase (BACE1), leading to increased production of Aβ [6]. Studies in *alcadein α* (the mouse ortholog of CLSTN1) deficient mice have confirmed that loss of CLSTN1 enhances the amyloidogenic processing of APP, resulting in elevated Aβ levels in the brain [6]. This positions CLSTN1 as a protective factor against AD, and its downregulation may contribute to the pathogenesis of the disease. ### 3.3 Intracellular Signaling and Gene Regulation The regulated intramembrane proteolysis of CLSTN1 generates a soluble intracellular domain (ICD) that can translocate to the nucleus. The CLSTN1-ICD has been shown to interact with transcription factors and modulate gene expression. While the full repertoire of target genes is not yet known, it is likely that the ICD regulates genes involved in synaptic plasticity, cell survival, and differentiation. This signaling pathway provides a direct link between synaptic activity and nuclear gene expression, allowing neurons to adapt to changes in synaptic input. ### 3.4 Protein-Protein Interaction Network The function of CLSTN1 is mediated by a complex network of protein-protein interactions. Key interaction partners include: - **Mint1/X11:** A neuronal adaptor protein that links CLSTN1 to APP and regulates its trafficking. - **APP:** The amyloid precursor protein, whose processing is modulated by CLSTN1. - **PSD-95/SAP97:** PDZ domain-containing scaffolding proteins that anchor CLSTN1 to the postsynaptic density. - **ICAM5:** A transmembrane protein whose accumulation is negatively regulated by CLSTN1. - **ADAM10:** The metalloprotease responsible for the ectodomain shedding of CLSTN1. - **γ-Secretase Complex:** The protease complex that mediates the intramembrane cleavage of CLSTN1. These interactions place CLSTN1 at the center of a signaling hub that integrates synaptic adhesion, APP metabolism, and intracellular signaling. ```mermaid sequenceDiagram participant Pre as "Presynaptic Neuron" participant Post as "Postsynaptic Neuron" participant CLSTN1 as "CLSTN1 (Postsynaptic)" participant ICAM5 as "ICAM5" participant APP as "APP" participant Mint1 as "Mint1/X11" participant ADAM10 as "ADAM10" participant GS as "γ-Secretase" Pre->>Post: Synaptic Cleft (Ca2+) Post->>CLSTN1: Homophilic adhesion (trans) CLSTN1->>CLSTN1: Clustering at PSD CLSTN1-->>ICAM5: Negative regulation of accumulation ICAM5->>ICAM5: Reduced expression at membrane CLSTN1->>Mint1: Cytoplasmic binding Mint1->>APP: Binds APP (YENPTY motif) APP->>APP: Non-amyloidogenic processing ADAM10->>CLSTN1: Ectodomain shedding GS->>CLSTN1: Intramembrane cleavage CLSTN1->>CLSTN1: Release of ICD CLSTN1->>Nucleus: Translocation of ICD Nucleus->>Nucleus: Transcriptional regulation ``` --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 Neurodevelopmental and Neurodegenerative Disorders The *CLSTN1* gene is not a common target for highly penetrant pathogenic mutations that cause Mendelian disorders. However, several studies have identified genetic variants that modulate the risk or age of onset of complex neurological diseases. - **Alzheimer's Disease (AD):** A study investigating genetic variants associated with the age at onset of AD and frontotemporal lobar degeneration (FTLD) due to *C9orf72* repeat expansions identified *CLSTN1* as a potential modulator [11]. The study found that variants in *CLSTN1* were associated with an earlier age of onset, suggesting that CLSTN1 dysfunction may accelerate the neurodegenerative process. This is consistent with the functional role of CLSTN1 in regulating APP metabolism [6]. - **Fragile X Syndrome (FXS):** In a mouse model of FXS, CLSTN1 expression was found to be dysregulated [10]. The loss of the Fragile X Mental Retardation Protein (FMRP) leads to altered CLSTN1 levels, which in turn affects dendritic spine maturation. This suggests that CLSTN1 is a downstream effector of FMRP and contributes to the synaptic pathology observed in FXS. - **Parkinson's Disease (PD):** An integrated analysis of whole-exome sequencing and copy number evaluation in PD patients identified rare variants in *CLSTN1* [12]. While the functional significance of these variants is not fully established, they may contribute to the genetic architecture of PD. - **Bipolar Disorder (BD):** The microRNA miR-1908-5p, which is associated with BD, has been shown to regulate the expression of *CLSTN1* [13]. This miRNA targets the 3' UTR of *CLSTN1* mRNA, leading to its degradation. Dysregulation of this miRNA in BD may result in altered CLSTN1 expression and impaired synaptic function. ### 4.2 Cancer The *CLSTN1* gene is located at 1p36.21, a region that is frequently deleted in neuroblastoma and other cancers. The loss of *CLSTN1* expression in these tumors suggests that it may function as a tumor suppressor. - **Neuroblastoma:** Gene expression profiling of 1p35-36 genes in neuroblastoma has shown that *CLSTN1* is significantly downregulated in tumors with unfavorable outcomes [1, 2]. The loss of *CLSTN1* expression is correlated with 1p36 LOH, which is a marker of poor prognosis. This suggests that *CLSTN1* may play a role in suppressing tumor growth and metastasis. - **Gastric Cancer:** Alternative splicing events in *CLSTN1* have been identified as critical in gastric cancer progression [14]. The expression of specific splice variants of *CLSTN1* is associated with tumor stage and patient survival. This suggests that the splicing of *CLSTN1* is dysregulated in gastric cancer, contributing to the malignant phenotype. - **Pancreatic Cancer:** A gene- and pathway-based interaction analysis of GWAS data identified the axonal guidance signaling pathway, which includes *CLSTN1*, as interacting with smoking to modify the risk of pancreatic cancer [15]. This suggests that *CLSTN1* may be involved in the response to environmental carcinogens. - **Gliomas:** Epigenetic inactivation of *CLSTN1* has been identified in glial tumors [16]. Hypermethylation of the *CLSTN1* promoter leads to its silencing, which may contribute to tumor development. ### 4.3 Other Pathologies - **Dilated Cardiomyopathy (DCM):** Proteomic analysis of serum from patients with DCM and ischemic cardiomyopathy (ICM) identified CLSTN1 as a potential biomarker [17, 18]. The levels of CLSTN1 were differentially expressed between the two conditions, suggesting that it may be involved in the pathophysiology of heart failure. - **Type 2 Diabetes Mellitus (T2DM):** A Mendelian randomization study identified CLSTN1 as a novel protein target for T2DM [19]. The study found that circulating levels of CLSTN1 were associated with the risk of T2DM, suggesting a potential role in glucose metabolism. - **Kidney Function Decline:** Integrated proteomic and metabolomic analysis identified CLSTN1 as part of a module associated with the risk of kidney function decline [1]. This suggests that CLSTN1 may be involved in renal physiology and pathology. - **Schnyder Crystalline Corneal Dystrophy (SCCD):** *CLSTN1* was analyzed as a positional candidate gene for SCCD, a rare eye disorder, but no disease-causing mutations were found [2]. This excludes *CLSTN1* as a major cause of SCCD. ### 4.4 Chimeric RNA and Housekeeping Functions A notable finding is the identification of a chimeric RNA, *CTNNBIP1-CLSTN1*, which functions as a housekeeping chimeric RNA [3]. This chimeric RNA is formed by the intergenic splicing of *CTNNBIP1* and *CLSTN1* and is expressed in normal tissues. It regulates cell proliferation through the modulation of *SERPINE2* expression. This finding challenges the conventional view that chimeric RNAs are unique to cancer and highlights the complex regulatory roles of *CLSTN1* in normal physiology. --- ## 5. Host-Pathogen & Viral Interactions (If applicable) The direct interaction of the CLSTN1 protein with viral or bacterial pathogens is not a well-established area of research. However, the gene's expression is responsive to environmental stressors, including ionizing radiation and chemical toxins, which may have implications for host-pathogen interactions. - **Ionizing Radiation:** The expression of *CLSTN1* mRNA is sensitive to low-dose ionizing radiation (LDIR) in human hepatocytes and carcinoma cells [4]. This suggests that *CLSTN1* may be part of the cellular response to DNA damage and oxidative stress, which are also triggered by viral and bacterial infections. - **Benzo[a]pyrene (B[a]P) Exposure:** Transcriptome analysis of zebrafish exposed to waterborne B[a]P, a carcinogenic polycyclic aromatic hydrocarbon, revealed altered expression of *CLSTN1* [5]. This was associated with altered locomotor behavior, suggesting that *CLSTN1* may be involved in the neurotoxic effects of environmental pollutants. - **Double-Stranded RNA (dsRNA) and Alternative Splicing:** In pancreatic cancer, the aberrant transcription of satellite II (HSATII) leads to the formation of dsRNA, which induces mesenchymal transition by regulating alternative splicing [6, 7]. While *CLSTN1* is not directly implicated in this pathway, the dysregulation of splicing factors such as RBFOX2, which regulates *CLSTN1* splicing, suggests a potential indirect link. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors Currently, there are no FDA-approved drugs that directly target CLSTN1. However, the protein's involvement in several key pathways makes it an attractive target for therapeutic intervention. ### 6.1 Potential Therapeutic Strategies - **Modulation of APP Processing:** Given the role of CLSTN1 in promoting non-amyloidogenic APP processing, enhancing CLSTN1 expression or function could be a therapeutic strategy for Alzheimer's disease. Small molecules that stabilize the CLSTN1-Mint1-APP complex or upregulate *CLSTN1* expression could reduce Aβ production [6]. - **Targeting Splicing Events:** The alternative splicing of *CLSTN1* is dysregulated in cancer [14]. Antisense oligonucleotides (ASOs) that modulate the splicing of *CLSTN1* could be used to restore the expression of the tumor-suppressive isoform. - **Inhibition of Ectodomain Shedding:** The shedding of the CLSTN1 ectodomain by ADAM10 is a key step in its signaling pathway. Inhibitors of ADAM10 could be used to modulate CLSTN1 signaling, although this would also affect other ADAM10 substrates. - **Gene Therapy:** The delivery of *CLSTN1* via viral vectors could be used to restore its expression in tumors where it is silenced by promoter hypermethylation [16]. ### 6.2 Biomarker Potential CLSTN1 has been identified as a potential biomarker for several diseases, including dilated cardiomyopathy [17, 18], type 2 diabetes mellitus [19], and kidney function decline [1]. The measurement of CLSTN1 levels in serum or plasma could be used for disease diagnosis, prognosis, and monitoring of therapeutic response. --- ## 7. Bioinformatic Resources & Database Accessions The following table provides a comprehensive list of database accessions and resources for the *CLSTN1* gene and protein. | **Database** | **Accession ID** | **Description** | | :--- | :--- | :--- | | **NCBI Gene** | 22883 | Gene-specific information, including genomic context, transcripts, and expression data. | | **Ensembl** | ENSG00000171603 | Genome annotation, including splice variants, regulatory elements, and comparative genomics. | | **UniProt** | O94985 | Protein sequence, domain architecture, post-translational modifications, and functional annotations. | | **RCSB PDB** | True | Experimentally determined structures of CLSTN1 domains. | | **Gene Ontology (GO)** | GO:0007156 (homophilic cell adhesion), GO:0005509 (calcium ion binding), GO:0042987 (amyloid precursor protein catabolic process) | Functional annotations for biological processes, molecular functions, and cellular components. | | **ClinVar** | Various | Clinical significance of genetic variants in *CLSTN1*. | | **STRING** | 22883 | Protein-protein interaction networks. | | **BioGRID** | 112743 | Curated protein and genetic interactions. | | **OMIM** | 607334 | Mendelian inheritance and phenotype associations. | | **HGNC** | 20741 | Gene symbol and nomenclature information. | --- ## 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] Takashima, Y., Kawaguchi, A., Fukai, J., Iwadate, Y., Kajiwara, K., Hondoh, H., & Yamanaka, R. 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