TTLL6

Chr 17

tubulin tyrosine ligase like 6

Also known as: TTL.6

NCBI Gene: 284076UniProt: Q8N841

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]

0
Active trials
152
ClinVar variants
11
Pathogenic / LP
1.0
Missense Z
1.08
LOEUF
6
Pubs (2 yr)
Clinical Summary— TTLL6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 119 VUS of 152 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/TTLL6?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.000
Z-score 1.15
OE 0.81 (0.61–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.01Z-score
OE missense 0.87 (0.80–0.94)
426 obs / 489.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.81 (0.61–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.80–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 34 / 42.0Missense obs/exp: 426 / 489.1Syn Z: 0.09

ClinVar Variant Classifications

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS119
Likely Benign20
Benign2
10
Pathogenic
1
Likely Pathogenic
119
VUS
20
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
114
5
0
119
Likely Benign
0
20
0
0
20
Benign
1
1
0
0
2
Total1135160152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TTLL6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Structural basis for alpha-tubulin-specific and modification state-dependent glutamylation
Mahalingan KK et al.·Nat Chem Biol
2024
Identification of hypoxia-related gene signatures based on multi-omics analysis in lung adenocarcinoma
Luo Q et al.·J Cell Mol Med
2023
Tubulin glutamylation regulates axon guidance via the selective tuning of microtubule-severing enzymes
Ten Martin D et al.·EMBO J
2024
Analysis of independent cohorts of outbred CFW mice reveals novel loci for behavioral and physiological traits and identifies factors determining reproducibility
Zou J et al.·G3 (Bethesda)
2022Cohort
Proteomic analysis of the serum in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease: the preliminary study
Sakarin S et al.·Front Vet Sci
2024
Characterization of tubulin post-translational modifications and their enzymes during human oocyte meiosis.
Karamtzioti P et al.·Reprod Biomed Online
2024
Top 6 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients