TTLL12

Chr 22

tubulin tyrosine ligase like 12

Also known as: dJ526I14.2

NCBI Gene: 23170 ENSG00000100304 UniProt: Q14166 OMIM: 619410

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 1.07

Clinical Summary— TTLL12

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

142 VUS of 181 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.81Z-score

OE missense 1.12 (1.03–1.21)

440 obs / 394.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.57–1.07)

0≤0.351.4

Missense OE?1.12 (1.03–1.21)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 27 / 34.7Missense obs/exp: 440 / 394.5Syn Z: -1.15

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

VUS142

Likely Benign17

Benign5

142

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	142	0	0	142
Likely Benign	10	0	7	17
Benign	0	1	4	5
Total	152	1	11	164

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 50) ClinVar copy-number / structural variants overlap TTLL12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →