TTBK1

Chr 6

tau tubulin kinase 1

Also known as: BDTK

NCBI Gene: 84630ENSG00000146216UniProt: Q5TCY1

Summary:This gene belongs to the casein kinase 1 superfamily. The encoded protein is a neuron-specific, serine/threonine and tyrosine kinase, which regulates phosphorylation of tau, a protein that associates with microtubule assemblies and stabilizes them. Genetic variants in this gene are associated with Alzheimer's disease. [provided by RefSeq, Jul 2016]

250
ClinVar variants
11
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TTBK1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 212 VUS of 250 total submissions
Some data sources returned errors (2)

omim: Error: OMIM fetch failed: 429

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.23LOEUF
pLI 1.000
Z-score 5.53
OE 0.11 (0.06–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.63Z-score
OE missense 0.73 (0.68–0.78)
555 obs / 759.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.06–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.68–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 5 / 45.0Missense obs/exp: 555 / 759.2Syn Z: 0.17

ClinVar Variant Classifications

250 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS212
Likely Benign20
Benign7
9
Pathogenic
2
Likely Pathogenic
212
VUS
20
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
1
1
0
0
2
VUS
0
208
4
0
212
Likely Benign
1
14
0
5
20
Benign
0
3
0
4
7
Total2226139250

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

View in ClinVar →

Protein Context — Lollipop Plot

TTBK1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Biallelic TTBK1 variant causes a severe syndromic neurodevelopmental disorder: clinical and genetic insights from two siblings.
Manav Yigit Z et al.·J Med Genet
2026
A Multiscale Computational Study for the Identification of Novel Inhibitors Targeting Tau-Tubulin Kinase 1 (TTBK1) in Alzheimer's Disease.
Kurkute P et al.·Curr Comput Aided Drug Des
2025
Environmental enrichment attenuates sevoflurane anesthesia-induced learning deficits in aged mice through regulating TTBK1 and phosphorylated Tau expression.
Chang X et al.·Exp Brain Res
2025
Enriched environment mitigates cognitive impairment in pre-adolescent mice following repeated neonatal sevoflurane exposure by reducing TTBK1 expression and Tau phosphorylation.
Yu Y et al.·Neuropharmacology
2025
Computational identification of potential tau tubulin kinase 1 (TTBK1) inhibitors: a structural analog approach.
Purushothaman K et al.·In Silico Pharmacol
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools