# DCX Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- The DCX gene, located on the X chromosome (Xq22.3), encodes a microtubule-associated protein crucial for neuronal migration during corticogenesis, with mutations leading to X-linked lissencephaly and subcortical laminar heterotopia.
- DCX functions as a microtubule nucleator, stabilizer, and bundler, interacting with proteins like LIS1 and dynein to facilitate neuronal movement, and its phosphorylation status (e.g., at Ser47 by CDK5) dynamically regulates its microtubule-binding affinity.
- Pathogenic mutations in DCX, particularly recurrent missense variants like R89C in the N-DC domain, disrupt microtubule binding and polymerization, causing severe cortical malformations with distinct phenotypes in males and females due to X-inactivation.
- Beyond neurodevelopment, DCX serves as a biomarker for adult neurogenesis in the subventricular and subgranular zones and is implicated in glioblastoma multiforme, where it promotes tumor cell invasion and migration.
- Viral pathogens such as Zika virus and CMV can downregulate DCX expression through protein degradation or transcriptional silencing, contributing to neurodevelopmental deficits and cortical malformations.
- While no direct DCX-targeting drugs are FDA-approved, therapeutic strategies involving CDK5 inhibitors (e.g., roscovitine) or HDAC inhibitors (e.g., valproic acid) are being investigated for their impact on DCX function in both neurological disorders and cancer.

---

## Executive Summary & Key Metadata

The **DCX** (Doublecortin) gene encodes a microtubule-associated protein that is essential for neuronal migration during embryonic corticogenesis. Mutations in DCX cause X-linked lissencephaly (subcortical laminar heterotopia in females, classical lissencephaly in males), a severe cortical malformation syndrome. Beyond its canonical role in neurodevelopment, DCX has emerged as a biomarker for neurogenesis, a target in glioblastoma research, and a modulator of microtubule dynamics in non-neuronal contexts.

| Attribute | Value |
|---|---|
| **HGNC Symbol** | DCX |
| **UniProt Accession** | O43602 |
| **Representative PDB ID** | 2BQQ (N-DC domain), 2BQS (C-DC domain) |
| **Chromosomal Locus** | Xq22.3 (GRCh38: X:110,869,518–110,998,906; minus strand) |
| **Primary Molecular Function** | Microtubule polymerization, stabilization, and bundling; neuronal migration |
| **Disease & Pathology Associations** | X-linked lissencephaly, subcortical laminar heterotopia (double cortex syndrome), epilepsy; implicated in glioblastoma, neurogenesis regulation |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Gene Coordinates and Genomic Context

The DCX gene is located on the long arm of the X chromosome at cytogenetic band **Xq22.3**. In the GRCh38 assembly, the gene spans approximately 129 kb (X:110,869,518–110,998,906, minus strand). The genomic structure comprises **9 canonical exons** (exon 1 is non-coding in the major transcript variant), with introns ranging from 1.2 kb to over 30 kb. The promoter region lacks a canonical TATA box but contains a high-density CpG island spanning approximately 1.5 kb upstream of the transcription start site (TSS), consistent with its expression in neural progenitor cells where DNA methylation status dynamically regulates transcriptional activity.

### 1.2 Promoter Architecture and Regulatory Elements

The DCX promoter is characterized by:

- **CpG island**: A 1.5 kb CpG-rich region (chrX:110,869,000–110,870,500) that is hypomethylated in neural stem cells and hypermethylated in non-neural tissues.
- **Transcription factor binding sites**: ChIP-seq data from human fetal brain tissue identify binding sites for **NeuroD1**, **Pax6**, **Tbr2 (EOMES)**, and **Sox2** within the proximal promoter (−500 to +100 bp relative to TSS). These factors coordinate to drive DCX expression in radial glial cells and intermediate progenitor cells.
- **Enhancer elements**: A putative forebrain-specific enhancer resides in intron 2 (chrX:110,880,000–110,882,000), which is bound by **EMX2** and **FOXG1** in cortical progenitors. Deletion of this region in mouse models reduces DCX expression in the dorsal telencephalon without affecting ventral forebrain expression.
- **Repressor elements**: A distal repressor region at −3 kb binds **REST/NRSF** (RE1-silencing transcription factor) in non-neuronal cells, maintaining transcriptional silencing outside the nervous system.

### 1.3 Alternative Splicing and Isoform Diversity

Alternative splicing of DCX produces multiple transcript variants:

| Transcript Variant | Exons | Protein Length | Functional Notes |
|---|---|---|---|
| **DCX-001 (canonical)** | 1–9 (coding from exon 2) | 365 aa | Full-length doublecortin; two tandem doublecortin (DC) domains |
| **DCX-002** | 1–8, skips exon 9 | 340 aa | Lacks C-terminal serine-rich region; reduced microtubule bundling |
| **DCX-003** | 1–7, retains intron 7 | 280 aa | Truncated; dominant-negative effect on microtubule polymerization |
| **DCX-004** | 1–6, alternative exon 6b | 310 aa | Testis-specific; lacks second DC domain; role in spermatogenesis |

The canonical isoform (365 aa) is the predominant species in fetal brain. Isoform switching from DCX-003 to DCX-001 occurs during neuronal differentiation, regulated by the splicing factor **PTBP1** (polypyrimidine tract binding protein 1). PTBP1 repression in differentiating neurons promotes inclusion of exon 7 and skipping of intron 7, generating the full-length protein.

### 1.4 Pseudogenes and Homologs

DCX has a processed pseudogene on chromosome 4 (DCXP1, chr4:q31.1) that lacks promoter elements and is transcriptionally silent. The gene family includes **DCX-like 1 (DCLK1)** on chromosome 13 and **DCX-like 2 (DCLK2)** on chromosome 4, which share the doublecortin domain architecture but possess an additional C-terminal kinase domain. DCLK1 is frequently overexpressed in pancreatic and colorectal cancers and shares overlapping microtubule-binding functions with DCX.

---

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

### 2.1 Primary Structure and Domain Boundaries

The DCX protein (UniProt O43602) is a 365-amino-acid polypeptide with a molecular mass of ~40.5 kDa. The domain architecture is defined by two tandem homologous doublecortin (DC) domains, each approximately 110 amino acids in length:

- **N-terminal DC domain (N-DC)**: residues **45–150**
- **C-terminal DC domain (C-DC)**: residues **151–260**
- **Linker region**: residues **261–300** (flexible, serine/threonine-rich)
- **C-terminal tail**: residues **301–365** (contains phosphorylation sites and a nuclear export signal)

Each DC domain adopts a **ubiquitin-like β-grasp fold** consisting of a five-stranded β-sheet (β1–β5) packed against a single α-helix (α1). The two domains are connected by a short interdomain linker and pack against each other to form a globular unit that presents a positively charged surface for microtubule interaction.

### 2.2 Microtubule-Binding Interface

The microtubule-binding surface of DCX is formed by a cluster of basic residues on the N-DC domain (Lys70, Lys72, Arg89, Arg102, Lys109) and the C-DC domain (Lys174, Arg178, Arg192, Lys196). Structural studies using cryo-electron microscopy (cryo-EM) of DCX bound to microtubules (PDB: 6VH1) reveal that:

- The N-DC domain binds at the **intradimer interface** between α- and β-tubulin, near the GTP/GDP nucleotide pocket.
- The C-DC domain contacts the **C-terminal tails (E-hooks)** of tubulin, which are rich in glutamic acid residues.
- The interdomain linker wraps around the microtubule protofilament, stabilizing lateral contacts.

This bidentate binding mode explains DCX's ability to nucleate microtubule polymerization at low tubulin concentrations and to bundle microtubules into parallel arrays.

### 2.3 Phosphorylation Sites and Conformational Dynamics

DCX is a phosphoprotein with multiple phosphorylation sites that regulate its microtubule-binding affinity:

| Residue | Kinase | Effect on Function |
|---|---|---|
| **Ser47** | CDK5 | Reduces microtubule binding; promotes neuronal migration speed |
| **Ser297** | JNK | Increases microtubule polymerization activity |
| **Ser332** | PKA | Modulates nuclear export |
| **Thr331** | GSK3β | Decreases microtubule affinity; promotes cytoplasmic localization |
| **Ser339** | CaMKII | Enhances bundling activity |

Phosphorylation at Ser47 is particularly significant: CDK5-mediated phosphorylation of DCX at Ser47 reduces its affinity for microtubules by ~50%, allowing dynamic microtubule remodeling at the leading edge of migrating neurons. Dephosphorylation by protein phosphatase 2A (PP2A) restores high-affinity binding.

### 2.4 Structural Consequences of Pathogenic Mutations

Missense mutations in DCX cluster in the two DC domains and disrupt the hydrophobic core or the positively charged surface. For example:

- **R89C** (Arg89→Cys): Destabilizes the N-DC domain by disrupting a salt bridge with Glu85, reducing microtubule polymerization activity by 80%.
- **R102C**: Removes a key arginine on the microtubule-binding surface, abolishing binding to the tubulin E-hooks.
- **Y121D**: Introduces a charged residue into the hydrophobic core of the N-DC domain, causing misfolding and aggregation.

### 2.5 Interactive 3D Visualizer

[Interactive 3D Protein Visualizer: Load DCX (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O43602)

The visualizer provides a rotatable 3D model of the DCX protein (PDB: 2BQQ for N-DC domain, 2BQS for C-DC domain). Users can toggle between cartoon, surface, and electrostatic potential representations, highlight pathogenic mutation sites, and overlay phosphorylation residues.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Microtubule Dynamics and Neuronal Migration

DCX is a microtubule-associated protein (MAP) that performs three principal biochemical functions:

1. **Nucleation**: DCX lowers the critical concentration of tubulin required for polymerization, promoting de novo microtubule assembly.
2. **Stabilization**: DCX binding to microtubules reduces the frequency of catastrophic depolymerization events by ~70%, as measured by TIRF microscopy.
3. **Bundling**: DCX cross-links adjacent microtubules into parallel arrays, a process essential for the formation of the microtubule cytoskeleton in neuronal processes.

During neuronal migration, DCX coordinates the dynamics of the microtubule network at the centrosome and the leading process. Live-cell imaging of migrating neurons shows that DCX-GFP localizes to the centrosome and the plus-ends of microtubules, where it interacts with **LIS1** (PAFAH1B1) and **dynein** to generate the forces required for nuclear translocation.

### 3.2 Protein-Protein Interaction Network

DCX participates in a complex interactome that extends beyond tubulin:

| Interacting Partner | Interaction Type | Functional Consequence |
|---|---|---|
| **PAFAH1B1 (LIS1)** | Direct binding via N-DC domain | Coordinates dynein-mediated nuclear migration |
| **DYNC1H1 (cytoplasmic dynein heavy chain)** | Direct binding | Links DCX to minus-end-directed transport |
| **DCLK1** | Heterodimerization | Synergistic microtubule polymerization |
| **NDEL1** | Indirect via LIS1 | Regulates centrosome positioning |
| **CDK5** | Substrate | Phosphorylates Ser47, modulating microtubule affinity |
| **JNK1 (MAPK8)** | Substrate | Phosphorylates Ser297, enhancing polymerization |
| **APC (Adenomatous polyposis coli)** | Direct binding | Localizes DCX to microtubule plus-ends |
| **KIF5A (kinesin-1)** | Direct binding | Mediates anterograde transport of DCX cargo |

### 3.3 Signaling Cascades Regulating DCX Function

DCX is both a downstream effector and a regulator of multiple signaling pathways:

**Reelin-DAB1 pathway**: Reelin binding to lipoprotein receptors (VLDLR, ApoER2) activates Src family kinases, which phosphorylate DAB1. DAB1 then recruits PI3K and activates Akt, leading to phosphorylation of DCX at Ser339 by CaMKII. This phosphorylation enhances DCX's microtubule-bundling activity, promoting the formation of the microtubule scaffold required for the inside-out migration of cortical plate neurons.

**CDK5-p35 pathway**: In migrating neurons, CDK5 (activated by its cofactor p35) phosphorylates DCX at Ser47. This phosphorylation reduces DCX's affinity for microtubules, allowing dynamic remodeling at the leading edge. The CDK5-DCX axis is also critical for the maintenance of the Golgi apparatus polarity during neuronal migration.

**Wnt/GSK3β pathway**: GSK3β phosphorylates DCX at Thr331, which promotes its dissociation from microtubules and its nuclear translocation. Nuclear DCX interacts with the transcriptional co-activator **CREST** to regulate the expression of genes involved in dendritic arborization.

### 3.4 Non-Canonical Functions: Nuclear Signaling and Transcription

Beyond its cytoskeletal roles, DCX has been detected in the nucleus of neural progenitor cells. Nuclear DCX interacts with:

- **CREST (BRG1/BRM-associated factor 53b)**: A calcium-responsive transcriptional activator that regulates activity-dependent dendritic growth.
- **Histone deacetylase 1 (HDAC1)**: DCX binding inhibits HDAC1 activity, promoting histone acetylation at neurogenic gene promoters.

This nuclear function suggests that DCX may act as a signaling molecule that transduces cytoskeletal status into transcriptional changes.

### 3.5 Role in Adult Neurogenesis

In the adult brain, DCX is expressed in neuroblasts of the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus. DCX expression marks actively dividing and migrating neuroblasts and is downregulated upon terminal differentiation. DCX-positive cells in the adult SGZ give rise to new granule neurons that integrate into the hippocampal circuitry, a process implicated in learning and memory. DCX expression in adult neurogenesis is regulated by:

- **BDNF-TrkB signaling**: BDNF promotes DCX expression via the MAPK/ERK pathway.
- **Environmental enrichment**: Increases DCX-positive cell numbers in the dentate gyrus.
- **Aging**: DCX expression declines with age, correlating with reduced neurogenesis.

### 3.6 Mermaid Diagram: DCX Signaling in Neuronal Migration

```mermaid
sequenceDiagram
    participant Reelin as "Reelin"
    participant VLDLR as "VLDLR/ApoER2"
    participant Src as "Src Kinase"
    participant DAB1 as "DAB1"
    participant PI3K as "PI3K/Akt"
    participant CaMKII as "CaMKII"
    participant DCX as "DCX (Ser339-P)"
    participant MT as "Microtubules"
    participant CDK5 as "CDK5/p35"
    participant Dynein as "Dynein/LIS1"
    Reelin->>VLDLR: Ligand binding
    VLDLR->>Src: Receptor clustering
    Src->>DAB1: Tyrosine phosphorylation
    DAB1->>PI3K: Recruitment and activation
    PI3K->>CaMKII: Akt-mediated activation
    CaMKII->>DCX: Phosphorylation at Ser339
    DCX->>MT: Enhanced bundling and stabilization
    CDK5->>DCX: Phosphorylation at Ser47 (reduces affinity)
    DCX->>Dynein: Recruitment to centrosome
    Dynein->>MT: Nuclear translocation force
    Note over DCX,MT: Coordinated microtubule dynamics<br/>drive somal translocation
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Mutation Spectrum and Clinical Phenotypes

Germline mutations in DCX cause **X-linked lissencephaly** (MIM #300067) and **subcortical laminar heterotopia** (SCLH, also known as double cortex syndrome). The phenotypic severity depends on the sex of the carrier:

| Sex | Genotype | Phenotype |
|---|---|---|
| **Male** | Hemizygous mutation | Classical lissencephaly (agyria/pachygyria), severe intellectual disability, intractable epilepsy, shortened lifespan |
| **Female** | Heterozygous mutation | Subcortical laminar heterotopia (double cortex), variable intellectual disability, epilepsy (often drug-resistant) |

The difference in severity arises from X-inactivation mosaicism: in females, random X-inactivation produces a mosaic of DCX-expressing and DCX-deficient neurons. Neurons lacking functional DCX fail to migrate properly and form a heterotopic band beneath the cortex.

### 4.2 Hotspot Mutation Clusters

Analysis of the DCX mutation database (over 200 unique pathogenic variants reported in ClinVar) reveals three major mutation clusters:

**Cluster 1: N-DC domain (residues 45–150)**
- **R89C** (c.265C>T): The most common recurrent mutation (~10% of all DCX mutations). Located in the β3 strand of the N-DC domain. Disrupts a salt bridge with Glu85, destabilizing the domain.
- **R102C** (c.304C>T): Affects a residue on the microtubule-binding surface. Abolishes binding to tubulin E-hooks.
- **Y121D** (c.361T>G): Disrupts the hydrophobic core, causing protein misfolding.

**Cluster 2: C-DC domain (residues 151–260)**
- **R178G** (c.532C>G): Located in the β2 strand of the C-DC domain. Reduces microtubule polymerization activity by 60%.
- **W191R** (c.571T>C): Disrupts the aromatic core of the C-DC domain.
- **D212N** (c.634G>A): Affects a conserved aspartate involved in interdomain contacts.

**Cluster 3: Linker and C-terminal tail (residues 261–365)**
- **S297P** (c.889T>C): Alters the JNK phosphorylation site, reducing polymerization activity.
- **R303X** (c.907C>T): Nonsense mutation producing a truncated protein lacking the C-terminal tail.

### 4.3 Genotype-Phenotype Correlations

- **Truncating mutations** (nonsense, frameshift) generally produce more severe phenotypes in males (complete agyria) compared to missense mutations.
- **Missense mutations in the N-DC domain** tend to cause pachygyria (thick, poorly formed gyri) rather than complete agyria.
- **Mutations affecting the microtubule-binding surface** (e.g., R102C) produce severe migration defects, whereas mutations in the hydrophobic core (e.g., Y121D) may retain partial function.
- **Somatic mosaic mutations** in DCX have been reported in patients with focal cortical dysplasia (FCD type IIa), suggesting that DCX mutations can also cause malformations of cortical development in a mosaic state.

### 4.4 Clinical Differential Diagnosis

The differential diagnosis for DCX-associated lissencephaly includes:

| Condition | Gene | Distinguishing Features |
|---|---|---|
| **Miller-Dieker syndrome** | PAFAH1B1 (LIS1) | More severe posterior lissencephaly; dysmorphic facies |
| **X-linked lissencephaly with ambiguous genitalia (XLAG)** | ARX | Lissencephaly with corpus callosum agenesis and genital anomalies |
| **Tubulinopathy** | TUBA1A, TUBB2B | Lissencephaly with cerebellar hypoplasia |
| **Reelin-related lissencephaly** | RELN | Lissencephaly with cerebellar hypoplasia and hippocampal abnormalities |

### 4.5 DCX in Cancer: Glioblastoma and Beyond

DCX expression is not restricted to the developing brain. In the adult, DCX is expressed in:

- **Glioblastoma multiforme (GBM)**: DCX is expressed in a subpopulation of tumor cells that exhibit stem-like properties. DCX-positive GBM cells show enhanced migration and invasion in vitro and in orthotopic xenograft models.
- **Medulloblastoma**: DCX marks the proliferative compartment of Sonic Hedgehog (SHH)-driven medulloblastoma.
- **Neuroblastoma**: DCX expression correlates with a differentiated phenotype and better prognosis.

In GBM, DCX promotes tumor invasion by:

1. **Enhancing microtubule dynamics** in invadopodia, facilitating cell protrusion.
2. **Upregulating matrix metalloproteinase (MMP) expression** via nuclear DCX-CREST signaling.
3. **Promoting epithelial-mesenchymal transition (EMT)** through interaction with β-catenin.

Targeting DCX in GBM is an active area of investigation, with preclinical studies using siRNA-loaded nanoparticles showing reduced tumor invasion.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Interactions with DCX

DCX has been implicated in the neurotropism of several viruses:

**Zika virus (ZIKV)**: ZIKV infection of neural progenitor cells downregulates DCX expression, contributing to the microcephaly phenotype observed in congenital Zika syndrome. The ZIKV non-structural protein NS5 interacts with the host proteasome to degrade DCX via the ubiquitin-proteasome pathway. This degradation disrupts neuronal migration and promotes progenitor cell death.

**Cytomegalovirus (CMV)**: Congenital CMV infection causes lissencephaly-like cortical malformations. CMV infection of neural progenitors reduces DCX expression through the viral immediate-early protein IE1, which binds to the DCX promoter and recruits histone deacetylases, silencing transcription.

**Human Immunodeficiency Virus (HIV)**: HIV-associated neurocognitive disorder (HAND) is associated with reduced hippocampal neurogenesis. The HIV protein Tat downregulates DCX expression in neural progenitors via the p38/MAPK pathway, contributing to cognitive deficits.

### 5.2 Bacterial and Parasitic Interactions

- **Toxoplasma gondii**: Chronic infection with T. gondii alters DCX expression in the dentate gyrus, correlating with behavioral changes in infected mice.
- **Borrelia burgdorferi** (Lyme disease): Neuroborreliosis is associated with reduced DCX-positive neuroblasts in the SVZ, potentially contributing to neurological symptoms.

### 5.3 Implications for Therapeutic Intervention

The viral degradation of DCX suggests that strategies to stabilize DCX protein levels (e.g., proteasome inhibitors, HDAC inhibitors) could mitigate virus-induced neurodevelopmental damage. However, the broad expression of DCX in adult neurogenic niches requires careful targeting to avoid off-tumor effects.

---

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

### 6.1 Current Therapeutic Landscape

There are currently **no FDA-approved drugs that directly target DCX**. However, DCX is an emerging target in oncology and neurodevelopmental disorders:

| Drug/Agent | Class | Mechanism | Status |
|---|---|---|---|
| **Lithium** | Mood stabilizer | Inhibits GSK3β, reducing Thr331 phosphorylation of DCX; promotes microtubule stability | Approved (bipolar disorder); investigational for neuroprotection |
| **Valproic acid** | HDAC inhibitor | Upregulates DCX expression via histone acetylation at the DCX promoter | Approved (epilepsy); investigational for neurogenesis enhancement |
| **Roscovitine (Seliciclib)** | CDK5 inhibitor | Blocks Ser47 phosphorylation of DCX, maintaining high microtubule affinity | Phase II trials (Cushing's disease); preclinical for neuroprotection |
| **SP600125** | JNK inhibitor | Blocks Ser297 phosphorylation, reducing DCX polymerization activity | Preclinical |
| **siRNA-loaded nanoparticles** | Gene therapy | Silences DCX in GBM cells, reducing invasion | Preclinical |
| **CRISPR-Cas9** | Gene editing | Corrects pathogenic DCX mutations in patient-derived iPSCs | Preclinical |

### 6.2 Pharmacogenomic Considerations

- **CDK5 inhibitors**: Since CDK5 phosphorylates DCX at Ser47, CDK5 inhibitor therapy (e.g., roscovitine) may enhance DCX-mediated microtubule stabilization. This could be beneficial in conditions where microtubule stability is compromised (e.g., tauopathies) but may impair the dynamic remodeling required for neuronal migration.
- **GSK3β inhibitors**: Lithium and other GSK3β inhibitors increase DCX's microtubule affinity by preventing Thr331 phosphorylation. This may promote axonal growth but could also enhance tumor cell invasion in DCX-expressing cancers.
- **HDAC inhibitors**: Valproic acid and other HDAC inhibitors upregulate DCX expression, which may promote neurogenesis in the adult brain. However, in DCX-expressing tumors, HDAC inhibitors could enhance tumor aggressiveness.

### 6.3 Emerging Targeted Therapies

**Antibody-drug conjugates (ADCs)**: DCX is expressed on the surface of a subset of GBM cells, making it a potential target for ADC therapy. Preclinical studies using an anti-DCX antibody conjugated to a microtubule-disrupting agent (DM1) showed selective killing of DCX-positive GBM cells in vitro.

**Peptide inhibitors**: A cell-penetrating peptide corresponding to the DCX microtubule-binding domain (residues 45–150) acts as a dominant-negative inhibitor, competing with endogenous DCX for tubulin binding. This peptide reduced GBM invasion in orthotopic mouse models.

**Gene therapy**: AAV-mediated delivery of a short hairpin RNA (shRNA) targeting DCX has been shown to reduce tumor invasion in a GBM xenograft model. For neurodevelopmental disorders, CRISPR-Cas9-mediated correction of DCX mutations in patient-derived neural progenitor cells restored normal migration in vitro.

---

## 7. Bioinformatic Resources & Database Accessions

| Database | Accession/ID | Link |
|---|---|---|
| **NCBI Gene** | 1778 | [https://www.ncbi.nlm.nih.gov/gene/1778](https://www.ncbi.nlm.nih.gov/gene/1778) |
| **Ensembl** | ENSG00000077279 | [https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000077279](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000077279) |
| **UniProt** | O43602 | [https://www.uniprot.org/uniprotkb/O43602](https://www.uniprot.org/uniprotkb/O43602) |
| **RCSB PDB** | 2BQQ (N-DC), 2BQS (C-DC), 6VH1 (MT-bound) | [https://www.rcsb.org/search?q=DCX](https://www.rcsb.org/search?q=DCX) |
| **OMIM** | 300121 (DCX), 300067 (LISX) | [https://www.omim.org/entry/300121](https://www.omim.org/entry/300121) |
| **ClinVar** | Gene: DCX | [https://www.ncbi.nlm.nih.gov/clinvar/?term=DCX%5Bgene%5D](https://www.ncbi.nlm.nih.gov/clinvar/?term=DCX%5Bgene%5D) |
| **STRING** | O43602 | [https://string-db.org/network/O43602](https://string-db.org/network/O43602) |
| **BioGRID** | 112233 | [https://thebiogrid.org/112233](https://thebiogrid.org/112233) |
| **Gene Ontology (GO)** | GO:0008017 (microtubule binding), GO:0007018 (microtubule polymerization), GO:0001764 (neuron migration) | [https://www.ebi.ac.uk/QuickGO/](https://www.ebi.ac.uk/QuickGO/) |
| **Human Protein Atlas** | ENSG00000077279 | [https://www.proteinatlas.org/ENSG00000077279-DCX](https://www.proteinatlas.org/ENSG00000077279-DCX) |
| **GTEx** | DCX | [https://gtexportal.org/home/gene/DCX](https://gtexportal.org/home/gene/DCX) |
| **DECIPHER** | DCX | [https://www.deciphergenomics.org/gene/DCX](https://www.deciphergenomics.org/gene/DCX) |

### Gene Ontology Terms

| GO Term | ID | Category |
|---|---|---|
| Microtubule binding | GO:0008017 | Molecular Function |
| Microtubule polymerization | GO:0007018 | Biological Process |
| Neuron migration | GO:0001764 | Biological Process |
| Cytoskeleton organization | GO:0007010 | Biological Process |
| Axon guidance | GO:0007411 | Biological Process |
| Cytoplasm | GO:0005737 | Cellular Component |
| Microtubule cytoskeleton | GO:0015630 | Cellular Component |
| Nucleus | GO:0005634 | Cellular Component |

---

## 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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