TTLL3

Chr 3

tubulin tyrosine ligase like 3

Also known as: HOTTL

The protein modifies tubulin by adding glycine residues, which is essential for microtubule stability and maintenance in primary and motile cilia as well as sperm flagella. Mutations cause male infertility due to sperm motility defects and can lead to ciliopathies affecting multiple organ systems. Inheritance follows an autosomal recessive pattern.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.23
Clinical SummaryTTLL3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.000
Z-score 0.49
OE 0.91 (0.681.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.941.08)
510 obs / 506.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.91 (0.681.23)
00.351.4
Missense OE1.01 (0.941.08)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 31 / 34.1Missense obs/exp: 510 / 506.4Syn Z: 0.59
DN
0.6163th %ile
GOF
0.75top 25%
LOF
0.3745th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TTLL3 · 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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