TTLL3
protein-codingtubulin tyrosine ligase like 3, the group of Tubulin tyrosine ligase family
Gene summary
Enables protein-glycine ligase activity. Predicted to be involved in axoneme assembly; flagellated sperm motility; and spermatogenesis. Predicted to be located in cilium. Predicted to be active in axoneme; microtubule cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.1 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 TTLL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001387446.1. 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 | 3 | 1 | 4 | |||
| missense | 92 | 2 | 94 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 95 | 2 | 1 | 98 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001374375.1 | 13 | MANE Select | |
| Ensembl | ENSP00000510679.1 | 13 | MANE Select | |
| RefSeq | NP_001021100.3 | 13 | Standard | |
| RefSeq | NP_001352980.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ttll3 | 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
- protein polyglycylation
- axoneme assembly
- cilium assembly
Molecular Function
- ATP binding
- protein-glycine ligase activity
- protein-glycine ligase activity, initiating
Cellular Component
- cytosol
- microtubule
- cilium
- axoneme
- microtubule cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000426895
- Coding exons
- 13
- Length
- 47053
- Individuals with no LoFs
- 116676
- Homozygous LoFs
- 266
- Heterozygous LoFs
- 8806
- Defined
- 125748
- p
- 0.0367
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0565 | 510 | 506 | 1.01 | 0.0000302 | 5904 |
| Missense (PolyPhen) | 142 | 131.75 | 1.0778 | 1515 | ||
| Synonymous | 0.593 | 196 | 207 | 0.948 | 0.0000123 | 1881 |
| Loss of Function | 0.495 | 31 | 34.1 | 0.909 | 0.00000175 | 383 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0087 | 0.0083 | notable |
| Latino/Admixed American | 0.015 | 0.015 | notable |
| Ashkenazi Jewish | 0.067 | 0.066 | notable |
| East Asian | 0.00097 | 0.00092 | rare |
| Finnish | 0.033 | 0.032 | notable |
| European (Non-Finnish) | 0.042 | 0.041 | notable |
| South Asian | 0.078 | 0.078 | notable |
| Other | 0.036 | 0.035 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Monoglycylase which modifies alpha- and beta-tubulin, generating side chains of glycine on the gamma-carboxyl groups of specific glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Involved in the side-chain initiation step of the glycylation reaction by adding a single glycine chain to generate monoglycine side chains. Not involved in elongation step of the polyglycylation reaction. {ECO:0000269|PubMed:19524510}.;
Recessive Scores
- pRec
- 0.0989
Intolerance Scores
- LoFtool
- 0.952
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 37.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0425
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |