TTLL4: Tubulin Tyrosine Ligase Like 4
A key regulator of tubulin post-translational modification and microtubule dynamics
Gene Information Card
| Symbol | TTLL4 |
|---|---|
| Full Name | Tubulin Tyrosine Ligase Like 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 9654 ncbi.nlm.nih.gov/gene/9654 |
| Ensembl ID | ENSG00000115970 |
| UniProt ID | Q14679 |
| OMIM ID | 612009 |
| HGNC ID | 28955 |
| Aliases | KIAA0173, TTL4 |
Description
TTLL4 encodes a member of the tubulin tyrosine ligase-like (TTLL) family. This enzyme catalyzes the addition of glutamate side chains (polyglutamylation) to tubulin, a post-translational modification that regulates microtubule stability, dynamics, and interactions with microtubule-associated proteins. TTLL4 is involved in neuronal development, ciliary function, and cell division.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | TTLL4 overexpression or mutation alters microtubule glutamylation, affecting cell proliferation and migration | COSMIC; PMID: 25686125 |
| Neurodevelopmental disorders | Disrupted polyglutamylation impacts neuronal microtubule function | ClinVar; PMID: 29053956 |
| Ciliopathies | Defective ciliary microtubule modification leads to impaired cilia function | UniProt; PMID: 23001566 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Testis | 12.8 | Medium |
| Lung | 8.5 | Low |
| Liver | 4.1 | Low |
| Kidney | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.5 | High expression |
| HeLa | 14.2 | Moderate expression |
| A549 | 9.8 | Low expression |
| MCF7 | 11.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1246G>A (p.Gly416Arg) | Missense | <0.01% | Altered enzyme activity; ClinVar |
| c.1873C>T (p.Arg625Trp) | Missense | <0.01% | Potential loss of function; ClinVar |
| c.2101_2102insA | Frameshift | <0.01% | Truncated protein; COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to reduce polyglutamylation activity.
Gain of Function (GOF)
Not well documented; some missense variants may increase activity.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Microtubule-dependent transport (Reactome: R-HSA-190840)
• Post-translational modification of tubulin (Reactome: R-HSA-8955332)
Protein Summary
TTLL4 is a 642-amino acid protein localized to the cytoplasm and cilia. It belongs to the ATP-dependent tubulin tyrosine ligase-like family and specifically adds glutamate branches to the C-terminal tails of alpha- and beta-tubulin. This modification is critical for microtubule stability, neuronal differentiation, and ciliary motility. Dysregulation of TTLL4 is implicated in cancer progression and neurodevelopmental conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TTLL4 Knockout HEK293 Cell Line | EDJ-KQ6679 | Human | 9654 | Details Get a Quote |
| TTLL4 Knockout A-549 Cell Line | EDJ-KQ31008 | Human | 9654 | Details Get a Quote |
| TTLL4 Knockout HeLa Cell Line | EDJ-KQ31010 | Human | 9654 | Details Get a Quote |
| TTLL4 Knockout HCT 116 Cell Line | EDJ-KQ29651 | Human | 9654 | Details Get a Quote |
