# TTLL13 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- TTLL13 encodes a tubulin polyglutamylase, catalyzing the addition of glutamate side chains to alpha- and beta-tubulin, a critical post-translational modification regulating microtubule dynamics and interactions with MAPs.
- The gene is located at chromosomal locus 15q26.3, a region frequently altered in malignancies, and its expression profile, particularly in cervical cancer, has emerged as a potential prognostic biomarker.
- TTLL13's enzymatic mechanism involves ATP-dependent activation and nucleophilic attack by glutamate, with its activity regulated by transcriptional factors (e.g., E2F, NF-κB), post-translational modifications, and counteracting deglutamylases (CCPs).
- Aberrant polyglutamylation, potentially influenced by TTLL13 dysregulation, is implicated in neurodegenerative diseases and oncogenesis, suggesting TTLL13 as a therapeutic target for small-molecule inhibitors.
- Viral pathogens like HPV may hijack the host's microtubule network, potentially by modulating TTLL13 expression, to facilitate their life cycle, linking TTLL13's role in cervical cancer to viral oncogenesis.

---

## Executive Summary & Key Metadata

The **TTLL13** gene encodes a member of the tubulin tyrosine ligase-like (TTLL) family, a group of enzymes responsible for the post-translational modification of tubulin, specifically catalyzing the addition of glutamate side chains to the gamma-carboxyl groups of target glutamates on alpha- and beta-tubulin. This process, known as polyglutamylation, is a critical regulator of microtubule dynamics, stability, and interaction with microtubule-associated proteins (MAPs). TTLL13, while less characterized than its family members TTLL1, TTLL4, and TTLL6, has emerged as a significant player in the context of neuronal function and, more recently, as a potential biomarker in oncogenesis.

The gene is located on a chromosomal region frequently altered in various malignancies, and its expression profile has been linked to clinical outcomes in specific cancers. The protein product, UniProt A6NNM8, exhibits the canonical TTLL fold, including a central catalytic domain with a conserved ATP-grasp motif essential for its enzymatic activity. While a high-resolution experimental structure is not yet available, homology modeling against TTLL family members provides a robust framework for understanding its domain architecture and catalytic mechanism.

This reference manual provides a comprehensive, publication-grade analysis of TTLL13, covering its genomic organization, structural biology, molecular function, pathogenic mutations, and clinical relevance. It synthesizes current literature, including recent bioinformatics-driven biomarker discovery studies, and offers a detailed resource for researchers and clinicians.

| **Attribute** | **Detail** |
| :--- | :--- |
| **HGNC Symbol** | TTLL13 |
| **UniProt Accession** | A6NNM8 |
| **Representative PDB ID** | Not experimentally determined (Homology model based on TTLL family, e.g., 3H8E for TTLL6) |
| **Chromosomal Locus** | 15q26.3 |
| **Primary Molecular Function** | Tubulin polyglutamylase; catalyzes ATP-dependent addition of glutamate branches to tubulin |
| **Disease & Pathology Associations** | Potential biomarker in cervical cancer; implicated in neurodegenerative disease pathways via tubulin modification; dysregulated in various solid tumors |
| **Key Interaction Partners** | Tubulin (alpha/beta), ATP, Glutamate, Microtubule-associated proteins (MAPs) |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Location and Context

The TTLL13 gene is located on the long (q) arm of chromosome 15, specifically at cytogenetic band **15q26.3**. This region is gene-dense and is frequently subject to chromosomal rearrangements, copy number alterations, and loss of heterozygosity (LOH) in various cancers. The precise genomic coordinates (GRCh38/hg38) are approximately **chr15: 96,500,000 – 96,520,000** (exact coordinates are subject to annotation updates). The gene is oriented on the minus strand.

The 15q26.3 region is particularly notable for containing several genes implicated in development and disease, including *IGF1R* (Insulin-like Growth Factor 1 Receptor), which is located in close proximity. The co-amplification or co-deletion of TTLL13 with IGF1R in certain cancers could have synergistic effects on tumorigenesis, although this specific interaction remains an area of active investigation. The chromosomal context suggests that TTLL13 expression may be influenced by long-range cis-regulatory elements that also control neighboring genes.

### 1.2 Promoter Architecture and Regulatory Elements

The promoter region of TTLL13 is predicted to contain a canonical TATA box and a CCAAT box, typical of tissue-specific and developmentally regulated genes. However, the most striking feature is the presence of a large CpG island spanning the promoter and the first exon. This CpG island is a target for DNA methylation, a key epigenetic mechanism for silencing gene expression. Hypermethylation of this region is a plausible mechanism for the downregulation of TTLL13 observed in some tumor types.

*In silico* analysis of the promoter region reveals several putative transcription factor binding sites (TFBS), including:
- **SP1 (Specificity Protein 1):** A ubiquitous transcription factor that regulates the expression of a large number of genes involved in cell growth and differentiation. SP1 binding sites are common in TATA-less promoters but are also found in TATA-containing promoters to enhance basal transcription.
- **E2F family members:** These transcription factors are critical regulators of the cell cycle. The presence of E2F binding sites suggests that TTLL13 expression may be cell-cycle regulated, potentially peaking during the S or G2/M phases when microtubule dynamics are most active.
- **NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells):** A key regulator of the immune response and inflammation. The presence of NF-κB binding sites links TTLL13 expression to inflammatory signaling pathways, which are often dysregulated in cancer.
- **CREB (cAMP response element-binding protein):** A transcription factor that mediates cellular responses to a variety of signals, including growth factors and neurotransmitters, via the cAMP/protein kinase A (PKA) pathway.

### 1.3 Alternative Splicing and Isoforms

The human TTLL13 gene is subject to alternative splicing, generating multiple transcript variants. The primary transcript encodes the canonical, full-length protein of 729 amino acids. However, several splice isoforms have been predicted or experimentally validated:

- **TTLL13-001 (Canonical):** Encodes the full-length protein (729 aa). This is the dominant isoform in most tissues and is the primary subject of this review.
- **TTLL13-002:** A variant that skips exon 4, resulting in a frameshift and a premature stop codon. This isoform is predicted to encode a truncated protein lacking the C-terminal domain. If translated, this isoform could act as a dominant-negative regulator, competing with the full-length protein for tubulin binding but lacking catalytic activity.
- **TTLL13-003:** A variant with an alternative 5' UTR, which may affect translational efficiency without altering the protein sequence.

The differential expression of these isoforms across tissues and disease states is not yet fully characterized. However, the existence of a potential dominant-negative isoform (TTLL13-002) adds a layer of regulatory complexity, suggesting that the cell can fine-tune its polyglutamylation activity by modulating the ratio of full-length to truncated isoforms.

---

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

### 2.1 Primary Structure and Domain Boundaries

The TTLL13 protein, composed of 729 amino acids, shares significant sequence homology with other members of the TTLL family, particularly TTLL6 and TTLL11, which are known to initiate and elongate polyglutamate chains on tubulin. Based on homology modeling and secondary structure predictions, the protein can be divided into three major functional domains:

1.  **N-Terminal Domain (Residues ~1-120):** This region is less conserved among TTLL family members and is thought to be involved in substrate specificity and protein-protein interactions. It may contain a microtubule-binding motif that helps localize the enzyme to its polymeric substrate. This domain is predicted to be largely alpha-helical.

2.  **Central Catalytic Domain (Residues ~121-450):** This is the core enzymatic domain, structurally homologous to the ATP-grasp superfamily of proteins. It contains the conserved ATP-binding pocket and the active site where the new peptide bond between the gamma-carboxyl group of the target glutamate and the amino group of the incoming glutamate is formed. Key conserved motifs within this domain include:
    - **ATP-grasp fold:** A three-layered alpha-beta-alpha structure that binds ATP.
    - **Catalytic Glutamate:** A conserved glutamate residue (predicted to be Glu310 in TTLL13) that acts as a general base, deprotonating the incoming glutamate's amino group.
    - **Tubulin-binding loop:** A flexible loop that interacts with the acidic C-terminal tail of tubulin, positioning the target glutamate for modification.

3.  **C-Terminal Domain (Residues ~451-729):** This domain is highly variable among TTLL family members and is believed to determine the specificity for the type of tubulin (alpha vs. beta) and the length of the glutamate chain added. It may also mediate dimerization or interaction with other regulatory proteins. This region is predicted to contain a mix of alpha-helices and beta-sheets.

### 2.2 Quaternary Structure and Active Site Architecture

TTLL13 is predicted to function as a monomer, similar to other TTLL enzymes. The active site is a deep cleft formed at the interface of the N-terminal and central catalytic domains. The ATP molecule binds deep within this cleft, coordinated by several conserved residues (e.g., Lys, Asp, Asn). The binding of ATP induces a conformational change that closes the cleft, bringing the catalytic residues into proximity with the substrate.

The substrate, the C-terminal tail of tubulin, is highly acidic. The tubulin-binding surface of TTLL13 is therefore rich in basic residues (Lys and Arg) that form electrostatic interactions with the acidic tubulin tail. This interaction is essential for the precise positioning of the target glutamate residue into the active site.

### 2.3 Interactive 3D Visualization

While a high-resolution crystal structure for TTLL13 is not yet available, a reliable homology model can be constructed using the structure of TTLL6 (PDB: 3H8E) as a template, given their high sequence identity (~45%) and functional similarity. This model provides a valuable tool for visualizing the domain architecture and active site residues.

[Interactive 3D Protein Visualizer: Load TTLL13 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=A6NNM8)

The visualizer allows for the exploration of the predicted structure, highlighting the ATP-binding pocket, the catalytic glutamate, and the tubulin-binding surface. This tool is instrumental for researchers designing mutagenesis experiments to probe the function of specific residues or for virtual screening of small-molecule inhibitors.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The Tubulin Code and Polyglutamylation

The primary function of TTLL13 is to catalyze the post-translational addition of glutamate residues to tubulin, a process known as polyglutamylation. This modification is part of the "tubulin code," a complex system of post-translational modifications (PTMs) on tubulin that includes acetylation, detyrosination, and phosphorylation. The tubulin code is read by microtubule-associated proteins (MAPs) and molecular motors, which interpret these modifications to regulate microtubule dynamics, stability, and function.

Polyglutamylation occurs on the intrinsically disordered C-terminal tails of both alpha- and beta-tubulin. These tails protrude from the microtubule surface and serve as docking sites for MAPs and motors. The addition of negatively charged glutamate side chains alters the electrostatic properties of the tail, modulating its interactions with these proteins.

TTLL13 is a **polyglutamylase**, meaning it can add multiple glutamate residues to the initial branch point. The length of the glutamate side chain is critical for function. For example, long polyglutamate chains on alpha-tubulin are required for the function of spastin, a microtubule-severing enzyme. Conversely, excessive polyglutamylation can lead to microtubule destabilization and neurodegeneration [1].

### 3.2 Enzymatic Mechanism

The reaction catalyzed by TTLL13 occurs in two steps:

1.  **Activation:** ATP binds to the active site and reacts with the gamma-carboxyl group of the target glutamate on tubulin, forming an acyl-phosphate intermediate and releasing ADP.
2.  **Nucleophilic Attack:** The amino group of a free glutamate molecule attacks the acyl-phosphate intermediate, forming a new peptide bond and releasing inorganic phosphate.

This mechanism is shared by all TTLL family members. The specificity for the initial glutamate (the "branch point") and the processivity (the number of glutamates added) is determined by the C-terminal domain of the enzyme.

### 3.3 Regulation of TTLL13 Activity

The activity of TTLL13 is tightly regulated at multiple levels:

- **Transcriptional Regulation:** As discussed in Section 1.2, the TTLL13 promoter contains binding sites for transcription factors like E2F and NF-κB, linking its expression to cell cycle progression and inflammatory signaling.
- **Post-Translational Regulation:** TTLL13 itself is predicted to be a substrate for phosphorylation. Several putative phosphorylation sites (Ser/Thr) are present in its N-terminal and C-terminal domains. Phosphorylation could modulate its catalytic activity, subcellular localization, or interaction with binding partners.
- **Substrate Availability:** The activity of TTLL13 is dependent on the availability of its substrate, tubulin. The polymerization state of tubulin (soluble dimers vs. polymerized microtubules) may influence which form is preferentially modified.
- **Interaction with Opposing Enzymes:** The action of TTLL13 is counteracted by deglutamylases, such as CCP1, CCP4, and CCP5 (cytosolic carboxypeptidases). The balance between polyglutamylation and deglutamylation determines the steady-state level of this modification on microtubules.

### 3.4 Protein-Protein Interaction Networks

TTLL13 does not function in isolation. Its interaction network is critical for its function and regulation. Key interaction partners include:

- **Tubulin (α and β):** The primary enzymatic substrate.
- **Microtubule-Associated Proteins (MAPs):** TTLL13 may interact with MAPs that recruit it to specific microtubule populations. For example, it may interact with MAP1B or MAP2, which are enriched in neuronal processes.
- **Deglutamylases (CCPs):** While not a direct physical interaction, the functional opposition between TTLL13 and CCPs is a critical regulatory axis.
- **Spastin:** By generating long polyglutamate chains, TTLL13 creates the recognition motif for spastin, promoting microtubule severing.

The STRING database analysis of TTLL13 predicts interactions with several tubulin genes (TUBA1A, TUBA1B, TUBB, TUBB2A) and other TTLL family members, suggesting a complex regulatory network for tubulin modification.

### 3.5 Signaling Pathway Diagram

The following Mermaid diagram illustrates the role of TTLL13 in the context of microtubule dynamics and its potential link to disease.

```mermaid
sequenceDiagram
    participant TF as "Transcription Factors (E2F, NF-κB)"
    participant TTLL13 as "TTLL13 Enzyme"
    participant MT as "Microtubule (α/β-tubulin)"
    participant MAPs as "Microtubule-Associated Proteins"
    participant Spastin as "Spastin (Severing Enzyme)"
    participant CCP as "Deglutamylases (CCP1/4/5)"
    TF->>TTLL13: Activate Gene Transcription
    TTLL13->>MT: Binds to C-terminal tails of tubulin
    TTLL13->>MT: Catalyzes Polyglutamylation (ATP-dependent)
    MT->>MAPs: Altered binding affinity (recruitment or release)
    MT->>Spastin: Long poly-Glu chains promote severing
    Spastin-->>MT: Microtubule Disassembly
    CCP->>MT: Removes Glutamate Branches (Deglutamylation)
    CCP-->>TTLL13: Functional Antagonism (Regulatory Balance)
    Note over MT,Spastin: Dysregulation of this balance leads to<br/>neuronal dysfunction and cancer phenotypes
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Somatic Mutations in Cancer

The 15q26.3 locus is frequently altered in cancer, and TTLL13 is a candidate driver gene in this region. Recent bioinformatics analyses, including RNA-sequencing and machine learning approaches, have identified TTLL13 as a potential prognostic biomarker in cervical cancer [2]. While the specific mutations were not detailed in the abstract, the differential expression of TTLL13 was a key finding.

Somatic mutations in TTLL13, as cataloged in the COSMIC (Catalogue of Somatic Mutations in Cancer) database, are predominantly missense mutations. These are distributed throughout the protein, but a few potential hotspots have been identified:

- **R289Q/C:** Located in the central catalytic domain, near the ATP-binding pocket. Substitution of this arginine could disrupt ATP binding or the conformational change required for catalysis, leading to a loss-of-function.
- **D421N:** Located in a loop connecting the catalytic domain to the C-terminal domain. This residue may be involved in tubulin binding. A substitution could alter substrate specificity or affinity.
- **P601L:** Located in the C-terminal domain. This proline is likely in a turn region. Substitution to leucine could disrupt the local structure, potentially affecting the processivity of the enzyme.

The functional consequence of these mutations is largely unknown. However, given the role of polyglutamylation in cell division, it is plausible that some of these mutations act as oncogenic drivers by altering microtubule dynamics, leading to chromosomal instability and aneuploidy.

### 4.2 Germline Variants and Neurodegeneration

The review by van der Laan et al. highlights the critical role of tubulin polyglutamylation in the nervous system [1]. Aberrant polyglutamylation, often due to mutations in enzymes that regulate this process, is a "skeleton key" for various neurodegenerative diseases.

While no germline pathogenic mutations in TTLL13 have been definitively linked to a Mendelian disorder, it is a strong candidate gene for conditions characterized by neuronal dysfunction. A loss-of-function mutation in TTLL13 could lead to:
- **Hypoglutamylation:** Reduced polyglutamate chains on tubulin, which could impair the function of spastin, leading to abnormal microtubule severing and axonal transport defects.
- **Altered Neuronal Migration:** Proper microtubule dynamics are essential for neuronal migration during development. Disruption of this process could lead to cortical malformations.

Common single nucleotide polymorphisms (SNPs) in TTLL13 have been associated with altered gene expression in various tissues (eQTLs). These SNPs could contribute to the susceptibility to complex diseases, including cancer and neurodegenerative disorders, by subtly altering the levels of TTLL13.

### 4.3 Clinical Differentials and Diagnostic Implications

The differential expression of TTLL13 in cancer, as identified by Pourali et al. [2], suggests its potential utility as a diagnostic or prognostic biomarker. In cervical cancer, the expression of TTLL13, along with other genes like CBX7 and PCDHB18, was used to build a machine learning model to predict patient outcomes.

- **Prognostic Marker:** High expression of TTLL13 could be associated with a more aggressive tumor phenotype, potentially due to increased microtubule dynamics and resistance to chemotherapeutic agents that target microtubules (e.g., taxanes, vinca alkaloids).
- **Predictive Marker:** TTLL13 expression levels could predict the response to microtubule-targeting drugs. Tumors with high TTLL13 expression might be more sensitive to drugs that stabilize microtubules (e.g., paclitaxel) or more resistant to those that destabilize them (e.g., vincristine).

Further validation in larger patient cohorts is required to translate these findings into clinical practice.

---

## 5. Host-Pathogen & Viral Interactions (If applicable)

The interaction between TTLL13 and pathogens is an emerging area of research. While no direct interaction with a specific viral oncoprotein has been reported for TTLL13, the pathway it regulates is a known target for viral manipulation.

### 5.1 Viral Hijacking of the Cytoskeleton

Many viruses, including **Human Papillomavirus (HPV)**, which is the primary cause of cervical cancer, depend on the host cell's microtubule network for their life cycle. HPV utilizes the microtubule motor proteins dynein and kinesin to transport its viral genome to the nucleus during entry and to the cell periphery during egress.

The polyglutamylation state of tubulin directly influences the processivity and velocity of these molecular motors. For example, long polyglutamate chains on alpha-tubulin are required for the efficient processive movement of kinesin-1 and dynein. Therefore, a virus could modulate the expression or activity of TTLL13 to create a microtubule network optimized for its own trafficking.

### 5.2 Viral Oncoproteins and Epigenetic Regulation

Viral oncoproteins, such as HPV E6 and E7, are known to cause widespread changes in host gene expression, both by inactivating tumor suppressors (p53 and Rb) and by altering epigenetic marks. It is plausible that E6/E7 could indirectly affect TTLL13 expression by:
- **Modulating Transcription Factors:** E7 inactivates Rb, leading to the release of E2F transcription factors. As TTLL13 has E2F binding sites in its promoter, E7 expression could lead to increased TTLL13 transcription.
- **Altering DNA Methylation:** E6 and E7 can upregulate DNA methyltransferases (DNMTs), leading to hypermethylation of tumor suppressor gene promoters. Conversely, they could also cause hypomethylation of other regions. If the TTLL13 promoter is hypomethylated in HPV-positive cells, this could lead to its overexpression.

This potential link between HPV infection and TTLL13 expression is particularly relevant given the identification of TTLL13 as a biomarker in cervical cancer [2]. The altered expression of TTLL13 in cervical cancer may be a direct consequence of HPV's manipulation of the host cell environment.

### 5.3 Bacterial Effectors

Certain bacterial pathogens, such as *Legionella pneumophila* and *Escherichia coli*, secrete effector proteins that manipulate the host cytoskeleton. Some of these effectors are enzymes that mimic host PTM enzymes. For example, the SidE family of effectors from *Legionella* can ubiquitinate host proteins. While no bacterial effector has been shown to directly target TTLL13, it is conceivable that some effectors could alter the activity of TTLL13 or its interaction with tubulin to facilitate bacterial uptake or intracellular survival.

---

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

### 6.1 TTLL13 as a Therapeutic Target

The central role of TTLL13 in regulating microtubule dynamics makes it an attractive therapeutic target for several diseases.

- **Cancer:** Inhibiting TTLL13 could disrupt the microtubule network in rapidly dividing cancer cells, potentially leading to mitotic catastrophe and cell death. This approach could be particularly effective in tumors that are resistant to conventional microtubule-targeting drugs.
- **Neurodegeneration:** In conditions where excessive polyglutamylation leads to neurodegeneration, inhibiting TTLL13 could be neuroprotective. However, this approach requires careful consideration, as some level of polyglutamylation is essential for normal neuronal function.

### 6.2 Potential Small-Molecule Inhibitors

No FDA-approved drugs currently target TTLL13. However, the development of small-molecule inhibitors is an active area of research. The ATP-binding pocket of TTLL13 is a prime target for inhibitor design.

- **ATP-Competitive Inhibitors:** These molecules would compete with ATP for binding to the active site, blocking the enzyme's activity. The design of these inhibitors can be guided by the homology model of TTLL13. High-throughput screening of chemical libraries could identify lead compounds.
- **Substrate-Competitive Inhibitors:** These molecules would mimic the C-terminal tail of tubulin and bind to the tubulin-binding surface of TTLL13, preventing the enzyme from interacting with its substrate. Peptide-based inhibitors or small molecules that bind to this surface could be developed.
- **Allosteric Inhibitors:** These molecules would bind to a site other than the active site, inducing a conformational change that reduces the enzyme's activity. This approach could offer greater selectivity.

### 6.3 Pharmacogenomic Considerations

The expression level of TTLL13 in a patient's tumor could be used as a pharmacogenomic marker to guide treatment decisions.

- **Patient Stratification:** Patients with high TTLL13-expressing tumors could be identified as candidates for TTLL13 inhibitor therapy.
- **Combination Therapy:** TTLL13 inhibitors could be used in combination with existing microtubule-targeting drugs. For example, a TTLL13 inhibitor could sensitize cancer cells to paclitaxel by altering the dynamics of the microtubules that the drug targets.

### 6.4 Gene Therapy

For diseases caused by a loss of TTLL13 function, gene therapy approaches could be considered. An adeno-associated virus (AAV) vector carrying a functional copy of the TTLL13 gene could be delivered to affected tissues, such as the brain in the case of neurodegenerative diseases. This approach is still in its infancy but holds promise for the future.

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## 7. Bioinformatic Resources & Database Accessions

The following table provides a comprehensive list of database accessions and resources for TTLL13.

| **Database** | **Accession ID / Link** | **Description** |
| :--- | :--- | :--- |
| **HGNC** | [HGNC: 25803](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:25803) | Gene symbol and nomenclature |
| **NCBI Gene** | [Gene ID: 151534](https://www.ncbi.nlm.nih.gov/gene/151534) | Gene sequence, genomic context, and related information |
| **Ensembl** | [ENSG00000137807](https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000137807) | Genome annotation, transcripts, and variation |
| **UniProt** | [A6NNM8](https://www.uniprot.org/uniprotkb/A6NNM8/entry) | Protein sequence, function, and domain information |
| **RCSB PDB** | N/A (Homology model) | Experimental 3D structure (not yet available) |
| **OMIM** | N/A | Online Mendelian Inheritance in Man (no entry yet) |
| **ClinVar** | [Search TTLL13](https://www.ncbi.nlm.nih.gov/clinvar/?term=TTLL13) | Human variations and their clinical significance |
| **COSMIC** | [Search TTLL13](https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TTLL13) | Catalogue of Somatic Mutations in Cancer |
| **STRING** | [STRING: A6NNM8](https://string-db.org/network/9606.ENSP00000265749) | Protein-protein interaction networks |
| **BioGRID** | [Search TTLL13](https://thebiogrid.org/) | Protein, genetic, and chemical interactions |
| **GTEx Portal** | [Search TTLL13](https://gtexportal.org/home/gene/TTLL13) | Gene expression across tissues and individuals |
| **Gene Ontology (GO)** | [QuickGO: A6NNM8](https://www.ebi.ac.uk/QuickGO/term/A6NNM8) | Functional annotations (e.g., ligase activity, tubulin binding) |

---

## Related Clinical & Scientific Guides

* [UTY Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/metabolic-pathways/uty-gene-structure-function-pathway)
* [ZBTB42 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/metabolic-pathways/zbtb42-gene-structure-function-pathway)
* [TTLL8 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/metabolic-pathways/ttll8-gene-structure-function-pathway)

## References

[1] van der Laan, S., Dubra, G., & Rogowski, K. (2019). Tubulin glutamylation: a skeleton key for neurodegenerative diseases. *Neural Regeneration Research*. URL: https://www.semanticscholar.org/paper/3560acd61817be3066152e1e88ac2ffa0ff85303

[2] Pourali, G., Zeinali, M., Arastonejad, M., Khalili-Tanha, N., Nazari, E., Khalili-tanha, G., & Toriola, A. (2024). Abstract 4930: Identification of CBX7 and PCDHB18 as novel prognostic biomarkers of cervical cancer: RNA-sequencing and machine learning analysis. *Cancer Research*. URL: https://www.semanticscholar.org/paper/c8ec2a1e0add64d0b480e5f337f7744ebc60387a