TTLL6
protein-codingtubulin tyrosine ligase like 6, the group of Tubulin tyrosine ligase family
Gene summary
Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule bundle formation; protein polyglutamylation; and regulation of cilium beat frequency involved in ciliary motility. Predicted to act upstream of or within microtubule severing and positive regulation of cilium movement. Located in ciliary basal body. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TTLL6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001130918.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 115 | 20 | 135 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 117 | 20 | 0 | 137 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001124390.1 | 15 | MANE Select | |
| Ensembl | ENSP00000377043.3 | 15 | MANE Select | |
| RefSeq | NP_001353243.1 | 11 | Standard | |
| RefSeq | NP_775894.2 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ttll6 | Danio rerio | Structure: post-vent region Quality: curved abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Carboxyterminal post-translational modifications of tubulin
Biological Process
- microtubule bundle formation
- positive regulation of cilium movement
- protein polyglutamylation
- microtubule severing
Molecular Function
- protein binding
- ATP binding
- tubulin binding
- protein-glutamic acid ligase activity
- tubulin-glutamic acid ligase activity
Cellular Component
- cytosol
- microtubule
- ciliary basal body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393382
- Coding exons
- 15
- Length
- 54980
- Individuals with no LoFs
- 125210
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 533
- Defined
- 125747
- p
- 0.00214
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.01 | 426 | 489 | 0.871 | 0.0000266 | 5902 |
| Missense (PolyPhen) | 107 | 147.84 | 0.72373 | 1831 | ||
| Synonymous | 0.0941 | 195 | 197 | 0.991 | 0.0000113 | 1653 |
| Loss of Function | 1.15 | 34 | 42.0 | 0.809 | 0.00000206 | 514 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.0019 | 0.0018 | notable |
| Ashkenazi Jewish | 0.00099 | 0.00099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0016 | 0.0016 | notable |
| South Asian | 0.0089 | 0.0088 | notable |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Polyglutamylase which preferentially modifies alpha- tubulin. Mediates tubulin polyglutamylation in cilia. Involved in the side-chain elongation step of the polyglutamylation reaction rather than in the initiation step. Generates long side-chains. Generates polyglutamylation of CGAS, leading to impair the DNA- binding activity of CGAS. {ECO:0000250|UniProtKB:A4Q9E8}.;
Intolerance Scores
- LoFtool
- 0.931
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 44.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0234
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |