TUBA3C

Chr 13

tubulin alpha 3c

Also known as: TUBA2, bA408E5.3

This alpha tubulin protein is a major constituent of microtubules, forming heterodimers with beta-tubulin that polymerize into the cytoskeletal structures essential for cell division, intracellular transport, and neuronal function. Mutations in TUBA3C cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early infancy. The gene shows tolerance to loss-of-function variants (pLI 0.005), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.86
Clinical SummaryTUBA3C
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 63 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.005
Z-score 1.93
OE 0.44 (0.240.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.78Z-score
OE missense 0.71 (0.630.79)
204 obs / 288.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.240.86)
00.351.4
Missense OE0.71 (0.630.79)
00.61.4
Synonymous OE1.32
01.21.6
LoF obs/exp: 6 / 13.7Missense obs/exp: 204 / 288.9Syn Z: -2.78
DN
0.83top 10%
GOF
0.5857th %ile
LOF
0.2968th %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

98 submitted variants in ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic1
VUS63
Likely Benign3
28
Pathogenic
1
Likely Pathogenic
63
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
1
0
1
VUS
0
57
6
0
63
Likely Benign
0
0
1
2
3
Benign
0
0
0
0
0
Total05736295

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBA3C · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found