TUBB4B

Chr 9AD

tubulin beta 4B class IVb

Also known as: Beta2, LCAEOD, TUBB2, TUBB2C

NCBI Gene: 10383ENSG00000188229UniProt: P68371OMIM: 602660

TUBB4B encodes a beta-tubulin protein that forms heterodimers with alpha-tubulin to create microtubules, the structural components essential for cellular organization and mitotic spindle formation. Mutations cause Leber congenital amaurosis with early-onset deafness, a condition affecting vision from infancy and hearing in early childhood. This follows an autosomal dominant inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 0.441 OMIM phenotype
Clinical Summary— TUBB4B
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Gene-Disease Validity (ClinGen)
TUBB4B-related ciliopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
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ClinVar Variants
103 unique Pathogenic / Likely Pathogenic· 36 VUS of 278 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — TUBB4B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.44LOEUF
pLI 0.809
Z-score 3.00
OE 0.14 (0.06–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
4.50Z-score
OE missense 0.24 (0.20–0.29)
66 obs / 276.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.14 (0.06–0.44)
0≤0.351.4
Missense OE0.24 (0.20–0.29)
0≤0.61.4
Synonymous OE2.06
0≤1.21.6
LoF obs/exp: 2 / 14.2Missense obs/exp: 66 / 276.4Syn Z: -9.11

ClinVar Variant Classifications

278 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic11
VUS36
Likely Benign113
Benign17
Conflicting5
92
Pathogenic
11
Likely Pathogenic
36
VUS
113
Likely Benign
17
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
90
0
92
Likely Pathogenic
0
4
7
0
11
VUS
2
21
12
1
36
Likely Benign
0
0
18
95
113
Benign
0
0
9
8
17
Conflicting
—5
Total227136104274

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

View in ClinVar →

Protein Context — Lollipop Plot

TUBB4B · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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 5 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