TUBB6

Chr 18AD

tubulin beta 6 class V

Also known as: FPVEPD, HsT1601, TUBB-5

NCBI Gene: 84617ENSG00000176014UniProt: Q9BUF5

Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in intercellular bridge; microtubule; and mitotic spindle. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

?Facial palsy, congenital, with ptosis and velopharyngeal dysfunctionMIM #617732
AD
221
ClinVar variants
91
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TUBB6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
91 Pathogenic / Likely Pathogenic· 91 VUS of 221 total submissions
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.04LOEUF
pLI 0.000
Z-score 1.46
OE 0.58 (0.34–1.04)
Tolerant

Highly tolerant — LoF variants common in population

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.
2.64Z-score
OE missense 0.57 (0.50–0.65)
171 obs / 299.4 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.0.58 (0.34–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.50–0.65)
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.0.94
0≤1.21.6
LoF obs/exp: 8 / 13.9Missense obs/exp: 171 / 299.4Syn Z: 0.53

ClinVar Variant Classifications

221 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic3
VUS91
Likely Benign12
Benign12
Conflicting3
88
Pathogenic
3
Likely Pathogenic
91
VUS
12
Likely Benign
12
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
86
0
88
Likely Pathogenic
0
1
2
0
3
VUS
4
66
20
1
91
Likely Benign
0
1
3
8
12
Benign
0
1
7
4
12
Conflicting
—3
Total57011813209

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBB6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUBULIN, BETA-6; TUBB6
MIM #615103 · *

?Facial palsy, congenital, with ptosis and velopharyngeal dysfunction

MIM #617732

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of Genes Associated with Familial Focal Segmental Glomerulosclerosis Through Transcriptomics and In Silico Analysis, Including RPL27, TUBB6, and PFDN5.
Mahmoud AH et al.·Int J Mol Sci
2024
Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.
Jurgens JA et al.·Genet Med
2025
Quantitative proteomics identifies TUBB6 as a biomarker of muscle-invasion and poor prognosis in bladder cancer.
Kim B et al.·Int J Cancer
2023
A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction.
Fazeli W et al.·Hum Mol Genet
2017
Gender influences the class III and V β-tubulin ability to predict poor outcome in colorectal cancer.
Mariani M et al.·Clin Cancer Res
2012
Maternal whole blood mRNA signatures identify women at risk of early preeclampsia: a longitudinal study.
Tarca AL et al.·J Matern Fetal Neonatal Med
2021Natural history
Development and Validation of a Prognostic Nomogram for Gastric Cancer Based on DNA Methylation-Driven Differentially Expressed Genes.
Bai Y et al.·Int J Biol Sci
2020
Four-Generation Pedigree of Monozygotic Female Twins Reveals Genetic Factors in Twinning Process by Whole-Genome Sequencing.
Liu S et al.·Twin Res Hum Genet
2018
A Novel Pyroptosis-Related Prognostic Signature for Risk Stratification and Clinical Prognosis in Clear Cell Renal Cell Carcinoma.
Pan XQ et al.·Dis Markers
2022
Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma.
Zhang J et al.·Sci Rep
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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