TTLL12

Chr 22

tubulin tyrosine ligase like 12

Also known as: dJ526I14.2

NCBI Gene: 23170ENSG00000100304UniProt: Q14166

Enables histone H4K20me3 reader activity and tubulin binding activity. Involved in negative regulation of type I interferon-mediated signaling pathway and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

231
ClinVar variants
44
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TTLL12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 147 VUS of 231 total submissions

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.
1.07LOEUF
pLI 0.000
Z-score 1.20
OE 0.78 (0.57–1.07)
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.
-0.81Z-score
OE missense 1.12 (1.03–1.21)
440 obs / 394.5 exp
Tolerant

Tolerant to missense variation

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.0.78 (0.57–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.03–1.21)
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.1.11
0≤1.21.6
LoF obs/exp: 27 / 34.7Missense obs/exp: 440 / 394.5Syn Z: -1.15

ClinVar Variant Classifications

231 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
VUS147
Likely Benign18
Benign5
44
Pathogenic
147
VUS
18
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
44
0
44
Likely Pathogenic
0
0
0
0
0
VUS
0
142
5
0
147
Likely Benign
0
10
1
7
18
Benign
0
0
1
4
5
Total01525111214

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

View in ClinVar →

Protein Context — Lollipop Plot

TTLL12 · 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
Tumor-intrinsic TTLL12 drives resistance to cancer immunotherapy via modulating myeloid-derived suppressor cells.
Chen DW et al.·J Immunother Cancer
2025🔓 Open Access
TTLL12 has a potential oncogenic activity, suppression of ligation of nitrotyrosine to the C-terminus of detyrosinated α-tubulin, that can be overcome by molecules identified by screening a compound library.
Deshpande A et al.·PLoS One
2024🔓 Open Access
TTLL12 is required for primary ciliary axoneme formation in polarized epithelial cells.
Ceglowski J et al.·EMBO Rep
2024🔓 Open Access
Effect of TTLL12 on tubulin tyrosine nitration as a novel target for screening anticancer drugs in vitro.
Xue L et al.·Oncol Lett
2020🔓 Open Access
TTLL12 expression in ovarian cancer correlates with a poor outcome.
Yang S et al.·Int J Clin Exp Pathol
2020
Top 5 resultsSearch Europe PMC ↗

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