TTLL9

Chr 20

tubulin tyrosine ligase like 9

Also known as: C20orf125

NCBI Gene: 164395ENSG00000131044UniProt: Q3SXZ7

The TTLL9 protein is a tubulin polyglutamylase that modifies tubulin by adding glutamate side chains, which is essential for establishing proper microtubule structure in sperm flagella and normal sperm motility. Mutations cause male infertility due to defective sperm flagella function, following an autosomal recessive inheritance pattern. This gene shows minimal constraint against loss-of-function variants, consistent with its specialized role in male reproductive function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
1.28
LOEUF
—
Mechanism
Clinical Summary— TTLL9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 81 VUS of 111 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
1.28LOEUF
pLI 0.000
Z-score 0.32
OE 0.94 (0.69–1.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.44Z-score
OE missense 0.93 (0.83–1.03)
250 obs / 270.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.94 (0.69–1.28)
0≤0.351.4
Missense OE0.93 (0.83–1.03)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 28 / 29.9Missense obs/exp: 250 / 270.2Syn Z: 1.21

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS81
Likely Benign4
10
Pathogenic
6
Likely Pathogenic
81
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
6
0
6
VUS
0
74
7
0
81
Likely Benign
0
0
3
1
4
Benign
0
0
0
0
0
Total074261101

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

View in ClinVar →

Protein Context — Lollipop Plot

TTLL9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients