TUBAL3

Chr 10

tubulin alpha like 3

NCBI Gene: 79861ENSG00000178462UniProt: A6NHL2

This protein is a beta-tubulin that forms heterodimers with alpha-tubulin to create microtubules, which are essential cytoskeletal structures that grow through GTP-dependent polymerization. Mutations cause cortical dysplasia-focal epilepsy syndrome, which presents with developmental cortical malformations and seizures, following an autosomal recessive inheritance pattern. The gene shows extreme constraint against loss-of-function variants (pLI near 1), indicating that complete loss of protein function is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
1.39
LOEUF
DN
Mechanism· predicted
Clinical Summary— TUBAL3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 86 VUS of 129 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
1.39LOEUF
pLI 0.000
Z-score 0.48
OE 0.86 (0.55–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.32Z-score
OE missense 1.05 (0.96–1.16)
283 obs / 268.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.55–1.39)
0≤0.351.4
Missense OE1.05 (0.96–1.16)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 12 / 13.9Missense obs/exp: 283 / 268.3Syn Z: -0.07
DN
0.7327th %ile
GOF
0.3788th %ile
LOF
0.3453th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic2
VUS86
Likely Benign10
Benign4
23
Pathogenic
2
Likely Pathogenic
86
VUS
10
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
2
0
2
VUS
0
76
10
0
86
Likely Benign
0
6
1
3
10
Benign
0
1
1
2
4
Total083375125

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBAL3 · 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
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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 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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