TTLL8
Chr 22tubulin tyrosine ligase like 8
This protein is a monoglycylase that adds glycine modifications to tubulin and other proteins, which is essential for microtubule stability and maintenance in cilia and sperm flagella. Mutations cause autosomal recessive primary ciliary dyskinesia, a disorder affecting respiratory function, fertility, and sometimes organ positioning due to defective ciliary motility. The gene shows minimal constraint against loss-of-function variants in the general population.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
154 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 136 |
Likely Pathogenic | — | — | — | — | 2 |
VUS | — | — | — | — | 12 |
Likely Benign | — | — | — | — | 3 |
Benign | — | — | — | — | 1 |
| Total | — | 154 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TTLL8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools