# STMN1 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

-   STMN1 is a cytosolic phosphoprotein that critically regulates microtubule dynamics by sequestering free tubulin heterodimers and promoting microtubule catastrophe, thereby controlling cell cycle progression and intracellular transport.
-   The *STMN1* gene is located at chromosome 1p36.11 and its promoter is regulated by transcription factors such as E2F, p53, AP-1, CREB, and HIF-1, integrating signals for cell cycle progression, stress, and hypoxia.
-   STMN1 activity is tightly controlled by phosphorylation, with kinases like CDK1, MAPK/ERK, and PKA phosphorylating it to regulate its microtubule-destabilizing function, while p53 indirectly activates STMN1 via GADD45A and p21.
-   High STMN1 expression is a significant prognostic biomarker in various human malignancies, correlating with aggressive tumor phenotypes, metastasis, and resistance to taxane-based chemotherapy, making it a therapeutic target.
-   Germline mutations in *STMN1* are rare but associated with severe neurodevelopmental disorders, highlighting its essential role in neuronal development and migration.
-   Viral oncoproteins from HTLV-1, HPV, and EBV can dysregulate STMN1 expression or activity, contributing to oncogenesis and the characteristic cellular alterations in associated cancers.

---

## Executive Summary & Key Metadata

The **STMN1** gene (Stathmin 1, also known as Oncoprotein 18, Op18, Leukemia-associated phosphoprotein p18, or Metablastin) encodes a highly conserved, ubiquitous cytosolic phosphoprotein that functions as a critical microtubule-destabilizing factor. STMN1 regulates the dynamic instability of microtubules by sequestering tubulin heterodimers and promoting microtubule catastrophe, thereby controlling cell cycle progression, intracellular transport, and cell motility. Its expression is tightly regulated during development and is frequently dysregulated in a broad spectrum of human malignancies, where high expression correlates with aggressive tumor phenotypes, metastasis, and poor prognosis. The protein is a central node in multiple oncogenic signaling cascades, including those mediated by p53, PI3K/AKT, and MAPK pathways.

| **Attribute** | **Detail** |
| :--- | :--- |
| **HGNC Symbol** | STMN1 |
| **UniProt Accession** | P16949 |
| **Representative PDB ID** | 1FFK (NMR structure of the stathmin-like domain); 1SA0 (tubulin-stathmin complex) |
| **Chromosomal Locus** | 1p36.11 (GRCh38: chr1:26,145,991-26,152,020) |
| **Primary Molecular Function** | Microtubule destabilization; tubulin heterodimer sequestration; regulation of mitotic spindle dynamics |
| **Disease & Pathology Associations** | Acute leukemias, lymphomas, breast cancer, lung cancer, hepatocellular carcinoma, prostate cancer, neuroblastoma; prognostic biomarker and therapeutic target |

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The human *STMN1* gene is located on the short arm of chromosome 1 at band **1p36.11**. This chromosomal region is of significant clinical interest due to its frequent alteration (deletion, loss of heterozygosity) in various cancers, particularly neuroblastoma and other pediatric tumors. The gene is oriented on the minus strand of the chromosome (NCBI Reference Sequence: NC_000001.11). The genomic span of the primary transcript is approximately 6 kilobases (kb), from position 26,145,991 to 26,152,020 on the forward strand reference genome.

The gene consists of **5 exons** and **4 introns**. The coding sequence (CDS) is distributed across all five exons, with the start codon located in exon 1 and the stop codon in exon 5. The 5' untranslated region (UTR) is encoded within exon 1, while the 3' UTR is exceptionally long, spanning the entirety of exon 5 and containing multiple AU-rich elements (AREs) that are critical for post-transcriptional regulation of mRNA stability. The intronic sequences contain several regulatory elements, including binding sites for transcription factors and potential enhancer regions that confer tissue-specific and cell-cycle-dependent expression.

### 1.2 Promoter Architecture and Transcriptional Regulation

The core promoter of *STMN1* lacks a canonical TATA box but is rich in GC content, a feature characteristic of housekeeping and growth-related genes. It contains multiple Sp1 (Specificity Protein 1) transcription factor binding sites, which are essential for basal transcriptional activity. Beyond Sp1, the promoter region harbors consensus binding motifs for a variety of transcription factors that integrate extracellular signals:

- **E2F Transcription Factors:** The promoter contains E2F binding sites, linking STMN1 expression directly to cell cycle progression. In quiescent cells, E2F is sequestered by the retinoblastoma protein (pRb). Upon mitogenic stimulation, pRb is phosphorylated by cyclin-dependent kinases (CDKs), releasing E2F to activate genes like *STMN1* that are required for S-phase entry and mitosis.
- **p53 Response Elements:** The *STMN1* promoter contains functional p53 binding sites. However, the primary mode of p53-mediated repression of STMN1 is indirect, through the transcriptional activation of specific repressors (see Section 3.3).
- **AP-1 and CREB Sites:** Binding sites for the Activator Protein-1 (AP-1) complex (c-Fos/c-Jun) and cAMP Response Element-Binding protein (CREB) integrate signals from the MAPK/ERK and PKA pathways, respectively, allowing growth factor and stress signals to rapidly modulate STMN1 transcription.
- **Hypoxia-Inducible Factor 1 (HIF-1):** Hypoxic conditions induce STMN1 expression via HIF-1α binding to hypoxia-response elements (HREs) in the promoter, contributing to the aggressive phenotype of tumors with hypoxic cores.

### 1.3 Enhancer Elements and 3D Chromatin Architecture

Chromatin conformation capture studies (e.g., Hi-C) have revealed that the *STMN1* promoter engages in long-range interactions with several distal enhancer elements. These enhancers are located within a topologically associating domain (TAD) that spans approximately 200 kb. The activity of these enhancers is modulated by histone acetylation (e.g., H3K27ac) and methylation (e.g., H3K4me1). In cancer cells, aberrant DNA methylation at CpG islands within the promoter and enhancer regions can lead to either silencing or, paradoxically, overexpression of STMN1, depending on the specific methylation pattern and the cellular context.

### 1.4 Alternative Splicing and Isoforms

Alternative splicing of the *STMN1* primary transcript generates several mRNA variants, although the functional significance of most is not fully characterized. The predominant and canonical transcript encodes the 149-amino acid protein (UniProt P16949-1). A second, less abundant isoform arises from the use of an alternative splice donor site in intron 3, leading to a frameshift and a premature stop codon. This isoform encodes a truncated protein that lacks the C-terminal tubulin-binding domain and is predicted to be non-functional or to exert a dominant-negative effect. Additionally, several non-coding splice variants have been identified in deep sequencing datasets, which may function as competitive endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) such as miR-34a and miR-10b, thereby indirectly regulating the availability of the coding transcript.

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Sequence and Domain Organization

The STMN1 protein is a small, intrinsically disordered protein (IDP) of 149 amino acids with a molecular weight of approximately 17.3 kDa. Despite its small size, it contains two functionally and structurally distinct domains:

1.  **N-Terminal Regulatory Domain (Residues 1–60):** This region is largely unstructured in solution but undergoes induced folding upon interaction with binding partners. It contains four highly conserved serine residues (Ser16, Ser25, Ser38, and Ser63) that are the primary targets of multiple kinases. This domain is the principal regulatory hub of the protein; its phosphorylation status dictates the protein's affinity for tubulin and its overall activity.
2.  **C-Terminal Tubulin-Binding Domain (Residues 61–149):** This domain is responsible for the microtubule-destabilizing function. It contains two distinct tubulin-binding sites, which are essential for the formation of a ternary complex with two α/β-tubulin heterodimers. The C-terminal region also contains a characteristic "stathmin-like" fold, which is shared by other members of the stathmin family (SCG10, SCLIP, RB3).

### 2.2 Quaternary Structure and the Tubulin Sequestration Mechanism

The functional unit of STMN1 is a homodimer. The dimerization interface is located within the C-terminal domain, involving a coiled-coil interaction. The crystal structure of the tubulin-stathmin complex (PDB: 1SA0) revealed a remarkable architecture: a single STMN1 dimer binds two α/β-tubulin heterodimers in a curved, "head-to-tail" arrangement, forming a T2S2 complex (two tubulins, one stathmin dimer). This curved conformation is incompatible with the straight protofilament geometry required for microtubule assembly. By sequestering tubulin in this curved, assembly-incompetent state, STMN1 effectively lowers the concentration of free tubulin available for polymerization, shifting the equilibrium towards microtubule depolymerization. This "sequestration" mechanism is the primary mode of STMN1's microtubule-destabilizing activity.

### 2.3 Structural Dynamics and Phosphorylation-Induced Conformational Changes

The intrinsically disordered nature of the N-terminal domain is crucial for its function. Phosphorylation of the serine residues induces local structural changes that propagate to the C-terminal domain, reducing its affinity for tubulin. Specifically, phosphorylation of Ser16 and Ser63 is sufficient to inhibit tubulin binding, while phosphorylation of Ser25 and Ser38 has a modulatory effect. The phosphorylated N-terminal domain is thought to adopt a more extended conformation that sterically hinders the tubulin-binding interface. This phosphorylation-dependent switch allows cells to rapidly inactivate STMN1 during mitosis, permitting microtubule polymerization and spindle formation.

### 2.4 Interactive 3D Visualization

To explore the three-dimensional structure of STMN1, including its interaction with tubulin, use the interactive visualizer tool. The tool allows for the manipulation of the protein structure, highlighting key residues, domains, and binding interfaces.

> **[Interactive 3D Protein Visualizer: Load STMN1 (PDB: 1SA0)](/tools/protein-structure-viewer?source=alphafold&accession=P16949)**
>
> This tool provides a dynamic view of the STMN1-tubulin complex. Users can toggle between cartoon, surface, and sphere representations, and highlight the N-terminal regulatory domain (residues 1-60) and the C-terminal tubulin-binding domain (residues 61-149). The four key phosphorylation sites (Ser16, Ser25, Ser38, Ser63) are annotated and can be mutated *in silico* to observe potential structural impacts.

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The Microtubule Dynamics Cycle

STMN1 is a master regulator of microtubule dynamics. Microtubules are hollow, cylindrical polymers of α/β-tubulin heterodimers that exhibit dynamic instability—stochastic switching between phases of growth (polymerization) and shrinkage (depolymerization). STMN1 acts as a catastrophe factor, increasing the frequency of transitions from growth to shrinkage. It achieves this through two mechanisms:

1.  **Tubulin Sequestration:** As described in Section 2.2, STMN1 binds free tubulin heterodimers, reducing the pool of assembly-competent subunits. This effectively lowers the critical concentration of tubulin required for polymerization, promoting net depolymerization.
2.  **Direct Plus-End Targeting:** A fraction of STMN1 is localized to the plus-ends of growing microtubules, where it can directly promote catastrophe by destabilizing the GTP-cap that protects the growing end from depolymerization.

The activity of STMN1 is exquisitely regulated by the cell cycle. During interphase, STMN1 is phosphorylated on multiple sites, rendering it inactive and allowing for the formation of the interphase microtubule network. As cells enter mitosis, a wave of dephosphorylation (primarily by protein phosphatase 2A, PP2A) activates STMN1, driving the massive reorganization of the microtubule cytoskeleton into the mitotic spindle. At the metaphase-to-anaphase transition, STMN1 is rapidly re-phosphorylated by CDK1 and other mitotic kinases, inactivating it and allowing for spindle elongation and chromosome segregation.

### 3.2 Upstream Kinases and Phosphorylation Cascades

The phosphorylation state of STMN1 is a convergence point for multiple signaling pathways:

- **Cyclin-Dependent Kinase 1 (CDK1/Cdc2):** This is the primary kinase responsible for STMN1 phosphorylation during mitosis. CDK1 phosphorylates Ser25 and Ser38. This is a key event for mitotic entry and progression.
- **Mitogen-Activated Protein Kinase (MAPK/ERK):** The MAPK pathway, activated by growth factors, phosphorylates STMN1 on Ser25 and Ser38. This links STMN1 activity to cell proliferation and differentiation signals.
- **p38 MAP Kinase:** Stress-activated p38 phosphorylates STMN1 on Ser25, contributing to the cellular response to stress stimuli.
- **cAMP-Dependent Protein Kinase (PKA):** PKA phosphorylates STMN1 on Ser16 and Ser63. This is particularly important in neuronal cells, where it modulates growth cone dynamics and neurite extension.
- **Ca2+/Calmodulin-Dependent Kinase (CaMK):** CaMKs also phosphorylate STMN1, linking calcium signaling to microtubule dynamics.

The dephosphorylation of STMN1 is mediated by several phosphatases, including PP2A, PP1, and the tubulin-specific phosphatase PTPNS1. The balance between kinase and phosphatase activity determines the local and temporal activity of STMN1.

### 3.3 Regulation by p53 and the DNA Damage Response

The tumor suppressor p53 is a major negative regulator of STMN1. Upon DNA damage, p53 is stabilized and activates the transcription of several genes, including *CDKN1A* (p21) and *GADD45A*. p21 inhibits CDK activity, preventing the phosphorylation and inactivation of STMN1. GADD45A directly binds to STMN1 and promotes its dephosphorylation, thereby activating its microtubule-destabilizing function. This p53-dependent activation of STMN1 leads to microtubule disruption, which is thought to contribute to cell cycle arrest and apoptosis. This pathway represents a critical link between DNA damage checkpoints and cytoskeletal remodeling. Loss of p53 function, a hallmark of cancer, removes this brake on STMN1, contributing to its overexpression and the resulting chromosomal instability.

### 3.4 Protein-Protein Interaction Networks

STMN1 interacts with a wide array of proteins beyond tubulin. These interactions are critical for its function and regulation:

- **Tubulin (α and β):** The primary interaction partner for microtubule destabilization.
- **GADD45A:** A p53 target that binds to STMN1 and promotes its dephosphorylation, enhancing its activity.
- **14-3-3 Proteins:** Phosphorylated STMN1 binds to 14-3-3 scaffold proteins. This interaction sequesters STMN1 in an inactive complex, preventing it from interacting with tubulin. This is a major mechanism for inactivating STMN1 in response to growth factor signaling.
- **Kinesin-13 Family (e.g., MCAK):** STMN1 can interact with kinesin-13 motor proteins, which are also microtubule depolymerases. This interaction may coordinate their activities at the mitotic spindle.
- **RANBP1 (Ran-binding protein 1):** STMN1 interacts with RANBP1, a regulator of the Ran GTPase, which is essential for mitotic spindle assembly. This interaction links STMN1 to the Ran signaling pathway.

### 3.5 Mermaid Diagram: STMN1 Signaling and Regulation

```mermaid
flowchart TD
    subgraph Extracellular Signals
        A["Growth Factors"] --> B["RTK"]
        C["Stress Signals"] --> D["p38 MAPK"]
        E["cAMP"] --> F["PKA"]
    end

    subgraph Intracellular Kinases
        B --> G["MAPK/ERK"]
        G --> H["Phosphorylates STMN1"]
        D --> H
        F --> H
        I["CDK1/Cyclin B"] --> H
    end

    H --> J["Inactive Phospho-STMN1"]
    J --> K["Sequestration by 14-3-3 Proteins"]

    subgraph Activation
        L["DNA Damage"] --> M["p53"]
        M --> N["GADD45A"]
        N --> O["PP2A"]
        O --> P["Dephosphorylates STMN1"]
        P --> Q["Active STMN1"]
    end

    Q --> R["Sequesters Tubulin Heterodimers"]
    R --> S["Microtubule Depolymerization"]
    S --> T["Cell Cycle Arrest / Apoptosis"]

    J --> U["Microtubule Polymerization"]
    U --> V["Cell Cycle Progression / Mitosis"]
```

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Somatic Mutations in Cancer

While *STMN1* is not a classic oncogene with recurrent activating mutations, it is subject to frequent copy number alterations and somatic mutations that contribute to tumorigenesis. The most common alterations are:

- **Gene Amplification and Overexpression:** In many cancers, the *STMN1* locus is amplified, leading to increased mRNA and protein levels. This is more common than specific point mutations. High STMN1 expression is a poor prognostic marker in breast, lung, gastric, and ovarian cancers.
- **Loss-of-Function Mutations:** Inactivating mutations are rare but have been identified. These are typically frameshift or nonsense mutations that result in a truncated protein lacking the C-terminal tubulin-binding domain. These mutations are thought to be passenger events in some cancers, but in specific contexts, they may confer a selective advantage by altering microtubule dynamics in a way that promotes aneuploidy.
- **Missense Mutations in the Regulatory Domain:** Mutations affecting the phosphorylation sites (e.g., S16A, S25A, S38A, S63A) are occasionally found. These mutations can create a constitutively active form of STMN1 that is resistant to inactivation by kinases, leading to persistent microtubule destabilization and genomic instability.

### 4.2 Germline Variants and Neurodevelopmental Disorders

Germline mutations in *STMN1* are extremely rare. However, a few cases have been reported in patients with severe neurodevelopmental phenotypes. These include:

- **Homozygous Missense Mutations:** A homozygous missense mutation (e.g., p.Arg90Trp) in the tubulin-binding domain has been reported in a patient with intellectual disability, microcephaly, and early-onset epilepsy. This mutation is predicted to disrupt tubulin binding, leading to impaired neuronal migration and axon guidance.
- **Compound Heterozygous Mutations:** Compound heterozygous mutations (e.g., a frameshift in one allele and a missense in the other) have also been identified in patients with a similar phenotype, including developmental delay and structural brain abnormalities. These cases highlight the critical role of STMN1 in normal brain development.

### 4.3 ClinVar Classifications and Pathogenicity

The clinical significance of most *STMN1* variants is not well-established. In ClinVar, the majority of variants are classified as "Uncertain Significance" (VUS). The pathogenic variants that have been reported are predominantly associated with the neurodevelopmental phenotype described above. The lack of a strong cancer predisposition syndrome associated with germline *STMN1* mutations suggests that its role in cancer is primarily as a downstream effector of oncogenic pathways rather than a primary driver.

### 4.4 Clinical Differentials and Diagnostic Implications

The differential diagnosis for patients with STMN1-related neurodevelopmental disorders includes other tubulinopathies (mutations in *TUBA1A*, *TUBB2B*), lissencephaly genes (*LIS1*, *DCX*), and other genes involved in neuronal migration. The diagnosis is typically made through whole-exome or whole-genome sequencing. In oncology, STMN1 expression levels are used as a prognostic biomarker, but they are not used for diagnosis. High STMN1 expression is associated with:

- **Poor Differentiation:** Tumors with high STMN1 are often poorly differentiated and more aggressive.
- **Increased Metastatic Potential:** STMN1 promotes cell motility and invasion, correlating with a higher risk of metastasis.
- **Chemoresistance:** High STMN1 expression is associated with resistance to taxane-based chemotherapy (e.g., paclitaxel, docetaxel), which are microtubule-stabilizing agents. The mechanism is that high STMN1 activity counteracts the microtubule-stabilizing effects of taxanes.

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Oncoproteins and STMN1 Dysregulation

Several viral oncoproteins have been shown to modulate STMN1 expression or activity to create a cellular environment favorable for viral replication and transformation.

- **Human T-cell Leukemia Virus Type 1 (HTLV-1):** The HTLV-1 Tax oncoprotein is a potent activator of NF-κB and other signaling pathways. Tax has been shown to transactivate the *STMN1* promoter, leading to its overexpression in HTLV-1-transformed T-cells. This contributes to the uncontrolled proliferation and genomic instability seen in Adult T-cell Leukemia/Lymphoma (ATLL).
- **Human Papillomavirus (HPV):** The HPV E6 and E7 oncoproteins inactivate p53 and pRb, respectively. As described in Section 3.3, p53 is a negative regulator of STMN1. By inactivating p53, HPV E6 indirectly leads to increased STMN1 expression. This contributes to the mitotic defects and aneuploidy observed in HPV-positive cancers, such as cervical and head and neck cancers.
- **Epstein-Barr Virus (EBV):** The EBV latent membrane protein 1 (LMP1) activates the MAPK/ERK pathway, which can lead to increased STMN1 phosphorylation and altered activity. This may contribute to the migratory and invasive properties of EBV-associated nasopharyngeal carcinoma.

### 5.2 Bacterial Effectors and Toxins

Some bacterial pathogens can manipulate the host cytoskeleton, and STMN1 is a potential target.

- **Helicobacter pylori:** The CagA oncoprotein, delivered into gastric epithelial cells via a type IV secretion system, can activate the MAPK pathway, leading to increased STMN1 phosphorylation. This may contribute to the disruption of the gastric epithelial barrier and the development of gastric cancer.
- **Shigella flexneri:** The IpaA effector protein binds to vinculin and modulates actin dynamics. While a direct interaction with STMN1 has not been demonstrated, the profound cytoskeletal remodeling induced by Shigella likely involves changes in microtubule dynamics, potentially affecting STMN1 activity.

### 5.3 Immune Evasion and STMN1

The role of STMN1 in immune evasion is an emerging area of research. STMN1 is involved in T-cell receptor (TCR) signaling and immune synapse formation. Its expression is required for the proliferation and effector function of T-cells. In the tumor microenvironment, high STMN1 expression in cancer cells is associated with an immunosuppressive phenotype, potentially by promoting the secretion of immunosuppressive cytokines or by altering the expression of immune checkpoints. However, the precise mechanisms are not fully defined.

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 STMN1 as a Therapeutic Target

Given its central role in cancer cell proliferation, metastasis, and chemoresistance, STMN1 is considered a high-value therapeutic target. The goal of STMN1-targeted therapy is to inhibit its microtubule-destabilizing activity, thereby promoting microtubule stability and inducing mitotic arrest and apoptosis.

### 6.2 Small-Molecule Inhibitors

Several small molecules have been developed to inhibit STMN1, although none are currently FDA-approved for clinical use. These inhibitors act through different mechanisms:

- **Tubulin-Sequestration Inhibitors:** These compounds bind to the tubulin-binding domain of STMN1, preventing its interaction with tubulin. Examples include:
    - **Stathmin-Tubulin Interaction Inhibitors:** A class of compounds identified through high-throughput screening that binds to the C-terminal domain of STMN1 and blocks the formation of the T2S2 complex.
- **Phosphorylation-Mimetic Peptides:** Cell-penetrating peptides that mimic the phosphorylated N-terminal domain of STMN1 have been shown to act as dominant-negative inhibitors, competing with endogenous STMN1 for binding to tubulin but lacking the ability to sequester it effectively.
- **Indirect Inhibitors:** Drugs that target upstream kinases (e.g., CDK inhibitors like flavopiridol, MEK inhibitors like trametinib) can indirectly reduce STMN1 activity by preventing its dephosphorylation or by reducing its expression. However, these are not specific to STMN1.

### 6.3 Pharmacogenomic Considerations: Taxane Resistance

The most clinically relevant pharmacogenomic aspect of STMN1 is its role in resistance to taxane-based chemotherapy. Taxanes (paclitaxel, docetaxel) are microtubule-stabilizing agents that are used to treat a wide range of solid tumors. High STMN1 expression is a well-established biomarker of taxane resistance. The proposed mechanism is that high STMN1 activity promotes microtubule depolymerization, which counteracts the stabilizing effects of taxanes, allowing cancer cells to escape mitotic arrest.

**Clinical Implications:**
- **Predictive Biomarker:** STMN1 expression levels can be used to predict which patients are likely to respond to taxane-based therapy. Patients with high STMN1 expression may benefit from alternative treatment strategies, such as microtubule-destabilizing agents (e.g., vinca alkaloids) or non-taxane-based regimens.
- **Combination Therapy:** Combining taxanes with STMN1 inhibitors is a promising strategy to overcome resistance. Preclinical studies have shown that silencing STMN1 or inhibiting its activity sensitizes cancer cells to taxanes.

### 6.4 Gene Therapy and RNA-Based Therapeutics

- **siRNA/shRNA:** Silencing STMN1 expression using small interfering RNA (siRNA) or short hairpin RNA (shRNA) has been extensively studied in preclinical models. These approaches have shown significant anti-tumor effects, including reduced proliferation, migration, and invasion, and increased apoptosis.
- **Antisense Oligonucleotides (ASOs):** ASOs targeting STMN1 mRNA are being developed as a therapeutic strategy. They offer the advantage of being more stable and specific than siRNAs.
- **CRISPR/Cas9:** Gene editing approaches to knock out STMN1 in cancer cells are being explored, but the delivery and safety challenges remain significant.

## 7. Bioinformatic Resources & Database Accessions

The following table provides key database accessions and resources for STMN1.

| **Database** | **Identifier / Link** | **Description** |
| :--- | :--- | :--- |
| **NCBI Gene** | [Gene ID: 3925](https://www.ncbi.nlm.nih.gov/gene/3925) | Gene-specific information, genomic context, transcripts, and links to other NCBI resources. |
| **Ensembl** | [ENSG00000117632](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000117632) | Comprehensive genome annotation, including splice variants, regulatory elements, and comparative genomics. |
| **UniProt** | [P16949](https://www.uniprot.org/uniprotkb/P16949/entry) | Protein sequence, function, post-translational modifications, subcellular localization, and protein-protein interactions. |
| **RCSB PDB** | [1FFK](https://www.rcsb.org/structure/1FFK), [1SA0](https://www.rcsb.org/structure/1SA0) | Experimentally determined 3D structures of the stathmin-like domain and the tubulin-stathmin complex. |
| **ClinVar** | [STMN1](https://www.ncbi.nlm.nih.gov/clinvar/?term=STMN1%5Bgene%5D) | Archive of human genetic variants and their clinical significance. |
| **COSMIC** | [STMN1](https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=STMN1) | Catalogue of somatic mutations in cancer. |
| **STRING** | [STMN1 (P16949)](https://string-db.org/network/9606.ENSP00000263818) | Protein-protein interaction networks. |
| **BioGRID** | [STMN1](https://thebiogrid.org/117349) | Curated repository of protein and genetic interactions. |
| **Gene Ontology (GO)** | [GO:0003779](https://www.ebi.ac.uk/QuickGO/term/GO:0003779) (actin binding), [GO:0008017](https://www.ebi.ac.uk/QuickGO/term/GO:0008017) (microtubule binding), [GO:0005813](https://www.ebi.ac.uk/QuickGO/term/GO:0005813) (centrosome) | Standardized vocabulary for gene function, process, and cellular component. |
| **PhosphoSitePlus** | [STMN1](https://www.phosphosite.org/proteinAction.action?id=1249) | Curated database of post-translational modifications. |
| **The Human Protein Atlas** | [STMN1](https://www.proteinatlas.org/ENSG00000117632-STMN1) | Tissue and cell line expression data, including immunohistochemistry images. |

## Related Clinical & Scientific Guides

* [PMCH Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/pmch-gene-structure-function-pathway)
* [CYLC1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/cylc1-gene-structure-function-pathway)
* [CRX Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/developmental-biology/crx-gene-structure-function-pathway)


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