TUBB2B
Basic information
Region (hg38): 6:3223324-3231730
Links
Phenotypes
GenCC
Source:
- complex cortical dysplasia with other brain malformations 7 (Definitive), mode of inheritance: AD
- congenital fibrosis of extraocular muscles (Limited), mode of inheritance: AD
- cerebellar ataxia, intellectual disability, and dysequilibrium (Supportive), mode of inheritance: AR
- congenital fibrosis of extraocular muscles (Supportive), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations 7 (Supportive), mode of inheritance: AD
- tubulinopathy-associated dysgyria (Supportive), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations 7 (Strong), mode of inheritance: AD
- complex cortical dysplasia with other brain malformations (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Cortical dysplasia, complex, with other brain malformations 7 | AD | 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 | Neurologic | 19465910; 22333901; 23361065; 23495813 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (144 variants)
- Complex_cortical_dysplasia_with_other_brain_malformations_7 (66 variants)
- not_specified (15 variants)
- Inborn_genetic_diseases (9 variants)
- TUBB2B-related_disorder (8 variants)
- Lissencephaly (5 variants)
- Complex_cortical_dysplasia_with_other_brain_malformations_1 (2 variants)
- Tubulinopathy (2 variants)
- TUBB2B-related_tubulinopathy (1 variants)
- Congenital_bilateral_perisylvian_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB2B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000178012.5. 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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 37 | 43 | ||||
missense | 18 | 53 | 76 | 152 | ||
nonsense | 2 | |||||
start loss | 1 | 1 | ||||
frameshift | 4 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
Total | 18 | 54 | 87 | 42 | 1 |
Highest pathogenic variant AF is 0.0000143846
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
TUBB2B | protein_coding | protein_coding | ENST00000259818 | 4 | 7470 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.988 | 0.0116 | 114523 | 0 | 1 | 114524 | 0.00000437 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 5.12 | 30 | 264 | 0.114 | 0.0000173 | 2948 |
Missense in Polyphen | 9 | 105.61 | 0.085216 | 1218 | ||
Synonymous | 1.53 | 100 | 121 | 0.823 | 0.00000962 | 857 |
Loss of Function | 3.40 | 0 | 13.4 | 0.00 | 5.78e-7 | 164 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00 | 0.00 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00 | 0.00 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.0000337 | 0.0000337 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Tubulin is the major constituent of microtubules (PubMed:23001566, PubMed:28013290, PubMed:26732629). 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 (By similarity). Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910). {ECO:0000250, ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:23001566, ECO:0000269|PubMed:26732629, ECO:0000269|PubMed:28013290}.;
- Disease
- DISEASE: Cortical dysplasia, complex, with other brain malformations 7 (CDCBM7) [MIM:610031]: A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. {ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:22333901, ECO:0000269|PubMed:23001566}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fetal akinesia deformation sequence (FADS) [MIM:208150]: A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. {ECO:0000269|PubMed:26732629}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in TUBB2B may be involved in cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ). {ECO:0000269|PubMed:28013290}.;
- 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;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
- 0.270
Haploinsufficiency Scores
- pHI
- 0.724
- hipred
- hipred_score
- ghis
- 0.522
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.903
Mouse Genome Informatics
- Gene name
- Tubb2b
- 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); growth/size/body region phenotype; cellular phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- microtubule cytoskeleton organization;mitotic cell cycle;neuron migration;microtubule-based process;modulation of chemical synaptic transmission;positive regulation of axon guidance
- Cellular component
- nucleus;cytoplasm;microtubule;microtubule cytoskeleton;Schaffer collateral - CA1 synapse
- Molecular function
- GTPase activity;structural constituent of cytoskeleton;protein binding;GTP binding;protein heterodimerization activity