TUBB4B

Chr 9AD

tubulin beta 4B class IVb

Also known as: Beta2, LCAEOD, TUBB2, TUBB2C

NCBI Gene: 10383 ENSG00000188229 UniProt: P68371 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in axonemal microtubule; intercellular bridge; and mitotic spindle. Implicated in Leber congenital amaurosis with early-onset deafness. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

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

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 28 VUS of 169 total submissions

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GeneReview available — TUBB4B

Authoritative clinical overview · Recommended first read

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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 OE?0.14 (0.06–0.44)

0≤0.351.4

Missense OE?0.24 (0.20–0.29)

0≤0.61.4

Synonymous OE?2.06

0≤1.21.6

LoF obs/exp: 2 / 14.2Missense obs/exp: 66 / 276.4Syn Z: -9.11

ClinVar Variant Classifications

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic4

VUS28

Likely Benign113

Benign16

Conflicting2

Pathogenic

Likely Pathogenic

VUS

113

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	0	4	0	0	4
VUS	2	21	4	1	28
Likely Benign	0	0	18	95	113
Benign	0	0	8	8	16
Conflicting	—				2
Total	2	27	30	104	165

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

View in ClinVar →

97 pathogenic / likely-pathogenic (of 110) ClinVar copy-number / structural variants overlap TUBB4B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →