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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TTLL12
tubulin tyrosine ligase like 12
Chromosome 22 · 22q13.2
NCBI Gene: 23170Ensembl: ENSG00000100304.13HGNC: HGNC:28974UniProt: Q14166
75PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
tubulin-tyrosine ligase activityhistone H4K20 trimethyltransferase activityprotein bindinghistone H4K20me2 reader activityMyoclonusneoplasmcancercolorectal carcinoma
✦AI Summary

TTLL12 (tubulin tyrosine ligase like 12) is a multifunctional protein that primarily serves as a negative regulator of tubulin post-translational modifications and antiviral signaling pathways. The protein negatively regulates tubulin detyrosination and polyglutamylation modifications 1. In antiviral immunity, TTLL12 acts as a negative regulator of the RIG-I pathway by directly interacting with VISA/MAVS, TBK1, and IKKε, thereby inhibiting virus-induced type I interferon expression and promoting viral replication 1. During SARS-CoV-2 infection, vitamin D reduces TTLL12 expression through vitamin D receptor-mediated DNA methylation, which enhances interferon responses and reduces viral replication 2. In cancer, TTLL12 is upregulated across multiple cancer types and promotes tumor progression by modulating myeloid-derived suppressor cells through CCL9 chemokine secretion, leading to immunosuppression and resistance to anti-PD-1 therapy 3. The protein is also associated with poor prognosis in gastric cancer patients when overexpressed 4. TTLL12 expression varies during human oocyte meiosis, with differential expression patterns between in-vivo and in-vitro matured oocytes, suggesting a role in developmental competence 5. These findings establish TTLL12 as a key regulator linking tubulin modifications, immune responses, and cancer progression.

Sources cited
1
TTLL12 negatively regulates RIG-I pathway and tubulin modifications by interacting with VISA/MAVS
PMID: 28011935
2
Vitamin D reduces TTLL12 expression during SARS-CoV-2 infection through DNA methylation
PMID: 37574128
3
TTLL12 promotes tumor progression and immunotherapy resistance via MDSC modulation
PMID: 40461158
4
TTLL12 overexpression is associated with poor prognosis in gastric cancer
PMID: 33351778
5
TTLL12 expression varies during human oocyte meiosis with differential patterns
PMID: 39920028
Disease Associationsⓘ20
MyoclonusOpen Targets
0.32Weak
neoplasmOpen Targets
0.08Suggestive
cancerOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
gastric cancerOpen Targets
0.03Suggestive
kidney transplantOpen Targets
0.03Suggestive
stomatitisOpen Targets
0.02Suggestive
corneal degenerationOpen Targets
0.02Suggestive
mucositisOpen Targets
0.02Suggestive
prostate carcinomaOpen Targets
0.02Suggestive
lung cancerOpen Targets
0.02Suggestive
ovarian cancerOpen Targets
0.01Suggestive
prostate cancerOpen Targets
0.01Suggestive
melanomaOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
anemiaOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
colon adenocarcinomaOpen Targets
0.00Suggestive
squamous cell carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PBDC1Protein interaction83%EEF1A1Protein interaction81%DNAJB1Protein interaction80%EEF1AKMT1Protein interaction79%EEF1A2Protein interaction72%TTLL4Protein interaction72%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
88%
Ovary
86%
Brain
43%
Lung
38%
Heart
27%
Gene Interaction Network
Click a node to explore
TTLL12PBDC1EEF1A1DNAJB1EEF1AKMT1EEF1A2TTLL4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q14166
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.28LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.06 [0.88–1.28]
RankingsWhere TTLL12 stands among ~20K protein-coding genes
  • #6,371of 20,598
    Most Researched75
  • #13,537of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedTTLL12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Tumor-intrinsic TTLL12 drives resistance to cancer immunotherapy via modulating myeloid-derived suppressor cells.
PMID: 40461158
J Immunother Cancer · 2025
1.00
2
Identification of a novel transcript isoform of the TTLL12 gene in human cancers.
PMID: 27748896
Oncol Rep · 2016
0.90
3
Downregulated genes by silencing
PMID: 33351778
Aging (Albany NY) · 2020
0.80
4
TTLL12 Inhibits the Activation of Cellular Antiviral Signaling through Interaction with VISA/MAVS.
PMID: 28011935
J Immunol · 2017
0.70
5
CRISPR library screening to develop HEK293-derived cell lines with improved lentiviral vector titers.
PMID: 37520398
Front Genome Ed · 2023
0.60