TTLL12

Chr 22

tubulin tyrosine ligase like 12

Also known as: dJ526I14.2

This protein regulates tubulin post-translational modifications including detyrosination and polyglutamylation, promotes histone H4 trimethylation at lysine 20, and negatively regulates the RIG-I antiviral pathway. Mutations in TTLL12 have not yet been definitively associated with human disease. The gene shows minimal constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.07
Clinical SummaryTTLL12
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 147 VUS of 231 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.20
OE 0.78 (0.571.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.81Z-score
OE missense 1.12 (1.031.21)
440 obs / 394.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.571.07)
00.351.4
Missense OE1.12 (1.031.21)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 27 / 34.7Missense obs/exp: 440 / 394.5Syn Z: -1.15

ClinVar Variant Classifications

231 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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