TUBB2B

tubulin beta 2B class IIb, the group of Tubulins

Basic information

Region (hg38): 6:3223324-3231730

Links

ENSG00000137285 ∙ NCBI:347733 ∙ OMIM:612850 ∙ HGNC:30829 ∙ Uniprot:Q9BVA1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the TUBB2B gene.

• 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	37	1	43
missense	18	53	76	5		152
nonsense		1	1			2
start loss			1			1
frameshift			4			4
splice donor/acceptor (+/-2bp)						0
Total	18	54	87	42	1

Highest pathogenic variant AF is 0.0000143846

GnomAD

Source: gnomAD

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: dbNSFP

• 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
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• 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