TTLL5: Tubulin Tyrosine Ligase Like 5
A key regulator of tubulin glutamylation involved in ciliary function and retinal degeneration
Gene Information Card
| Symbol | TTLL5 |
|---|---|
| Full Name | Tubulin Tyrosine Ligase Like 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 23093 ncbi.nlm.nih.gov/gene/23093 |
| Ensembl ID | ENSG00000100836 |
| UniProt ID | Q6EMB2 |
| OMIM ID | 612268 |
| HGNC ID | 25183 |
| Aliases | C14orf10, STAMP, dJ468O1.1 |
Description
TTLL5 encodes a member of the tubulin tyrosine ligase-like (TTLL) family, which catalyzes the addition of glutamate side chains to tubulin (polyglutamylation). This post-translational modification is critical for microtubule stability and function, particularly in cilia and flagella. TTLL5 is essential for normal ciliary motility and sensory function, and mutations in this gene are associated with retinal degeneration and male infertility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cone-rod dystrophy (CORD) | Loss of TTLL5 function disrupts tubulin glutamylation in photoreceptor cilia, impairing ciliary transport and leading to progressive retinal degeneration. | ClinVar, OMIM |
| Retinitis pigmentosa | Similar mechanism as CORD; TTLL5 mutations cause photoreceptor cell death due to defective ciliary maintenance. | ClinVar, OMIM |
| Male infertility (sperm motility defects) | TTLL5 deficiency in sperm flagella reduces microtubule glutamylation, impairing flagellar beating and sperm motility. | NCBI Gene, UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Retina | 15.2 | Medium |
| Brain | 10.1 | Medium |
| Lung | 6.3 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 12.0 | Retinal cell model |
| HeLa | 8.5 | Cervical cancer cell line |
| HEK293 | 7.2 | Embryonic kidney cells |
| SH-SY5Y | 9.1 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1246C>T (p.Arg416*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1723G>A (p.Gly575Arg) | Missense | Rare | Impaired catalytic activity |
| c.2389_2390del (p.Leu797Valfs*3) | Frameshift | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most TTLL5 mutations are loss-of-function, leading to reduced tubulin glutamylation and ciliary dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tubulin polyglutamylation pathway
• Ciliary assembly and maintenance
Protein Summary
TTLL5 is a 797-amino acid protein (UniProt Q6EMB2) localized to the cytoplasm and cilium. It functions as a tubulin polyglutamylase, adding glutamate side chains to the C-terminal tails of alpha- and beta-tubulin. This modification is essential for microtubule stability, ciliary motility, and sensory transduction. TTLL5 is highly expressed in testis and retina, consistent with its role in sperm flagella and photoreceptor cilia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TTLL5 Knockout HEK293 Cell Line | EDJ-KQ7825 | Human | 23093 | Details Get a Quote |
| TTLL5 Knockout A-549 Cell Line | EDJ-KQ33358 | Human | 23093 | Details Get a Quote |
| TTLL5 Knockout HCT 116 Cell Line | EDJ-KQ33359 | Human | 23093 | Details Get a Quote |
| TTLL5 Knockout HeLa Cell Line | EDJ-KQ33360 | Human | 23093 | Details Get a Quote |
