TUBB3
tubulin beta 3 class III, the group of Tubulins
Basic information
Region (hg38): 16:89921392-89938761
Previous symbols: [ "FEOM3" ]
Links
Phenotypes
GenCC
Source:
- fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement (Strong), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations 1 (Strong), mode of inheritance: AD
- fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement (Strong), mode of inheritance: AD
- congenital fibrosis of extraocular muscles (Supportive), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations 1 (Supportive), mode of inheritance: AD
- tubulinopathy-associated dysgyria (Supportive), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations 1 (Strong), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations 1 (Strong), mode of inheritance: AD
- fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cortical dysplasia, complex, with other brain malformations 1; Fibrosis of extraocular muscles, congenital, 3A | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic | 7724178; 10393037; 12073023; 20829227; 20074521 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (12 variants)
- Fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement (6 variants)
- Complex cortical dysplasia with other brain malformations 1 (5 variants)
- TUBB3-related disorder (2 variants)
- TUBB3-related tubulinopathy (2 variants)
- TUBB3-Releated Disorders (1 variants)
- Inborn genetic diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB3 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 66 | 76 | ||||
| missense | 12 | 27 | 105 | 149 | ||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 12 | 27 | 114 | 70 | 7 |
Highest pathogenic variant AF is 0.00000657134
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TUBB3 | protein_coding | protein_coding | ENST00000315491 | 4 | 17370 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.968 | 0.0324 | 125709 | 0 | 3 | 125712 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.58 | 77 | 300 | 0.256 | 0.0000234 | 2991 |
| Missense in Polyphen | 14 | 123.86 | 0.11303 | 1323 | ||
| Synonymous | -2.22 | 172 | 139 | 1.24 | 0.0000130 | 879 |
| Loss of Function | 3.36 | 1 | 15.0 | 0.0665 | 7.29e-7 | 163 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000616 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a critical role in proper axon guidance and mantainance. {ECO:0000269|PubMed:20074521}.;
- Disease
- DISEASE: Fibrosis of extraocular muscles, congenital, 3A (CFEOM3A) [MIM:600638]: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases, the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy. {ECO:0000269|PubMed:20074521}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cortical dysplasia, complex, with other brain malformations 1 (CDCBM1) [MIM:614039]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved. {ECO:0000269|PubMed:20829227}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Phagosome - Homo sapiens (human);Gap junction - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Pathogenic Escherichia coli infection;Parkin-Ubiquitin Proteasomal System pathway;Exercise-induced Circadian Regulation;Post-translational protein modification;Metabolism of proteins;Chaperonin-mediated protein folding;Formation of tubulin folding intermediates by CCT/TriC;Carboxyterminal post-translational modifications of tubulin;Protein folding;Prefoldin mediated transfer of substrate to CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;Post-chaperonin tubulin folding pathway
(Consensus)
Recessive Scores
- pRec
- 0.701
Intolerance Scores
- loftool
- 0.244
- rvis_EVS
- -0.76
- rvis_percentile_EVS
- 13.33
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.626
- ghis
- 0.589
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.927
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tubb3
- Phenotype
- cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- microtubule cytoskeleton organization;mitotic cell cycle;microtubule-based process;axon guidance;neuron differentiation
- Cellular component
- nucleus;cytoplasm;microtubule;axon;dendrite;extracellular exosome
- Molecular function
- GTPase activity;structural constituent of cytoskeleton;protein binding;GTP binding