TUBB2A

tubulin beta 2A class IIa, the group of Tubulins

Basic information

Region (hg38): 6:3153496-3157544

Previous symbols: [ "TUBB", "TUBB2" ]

Links

ENSG00000137267 ∙ NCBI:7280 ∙ OMIM:615101 ∙ HGNC:12412 ∙ Uniprot:Q13885 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex cortical dysplasia with other brain malformations 5 (Definitive), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 5 (Definitive), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 5 (Strong), mode of inheritance: AD
• tubulinopathy (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 5	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	24702957

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBB2A gene.

• not provided (224 variants)
• Complex cortical dysplasia with other brain malformations 5 (26 variants)
• not specified (16 variants)
• Inborn genetic diseases (5 variants)
• TUBB2A-related condition (2 variants)
• Congenital cerebellar hypoplasia (1 variants)
• Abnormal cerebral morphology (1 variants)
• Developmental disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• Seizure (1 variants)
• TUBB2A-related tubulinopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB2A gene is commonly pathogenic or not.

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				90	7	97
missense	9	21	62	6	2	100
nonsense			4			4
start loss						0
frameshift			4			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			3	2		5
non coding			1	10	8	19
Total	9	21	73	106	17

Variants in TUBB2A

This is a list of pathogenic ClinVar variants found in the TUBB2A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-3153540-A-C			Benign (Jul 15, 2018)
6-3153867-G-A			Uncertain significance (Feb 18, 2021)
6-3153868-C-G			Uncertain significance (Dec 04, 2023)
6-3153867-G-GACTCGT			Uncertain significance (Jan 13, 2022)
6-3153869-C-T			Likely benign (Mar 16, 2023)
6-3153870-T-A			Benign (Aug 30, 2023)
6-3153871-C-T			Likely benign (Sep 07, 2022)
6-3153873-T-C			Uncertain significance (Jan 13, 2022)
6-3153877-C-A			Uncertain significance (Feb 26, 2023)
6-3153878-G-A		not specified	Benign (Feb 01, 2024)
6-3153879-CCCT-C			Uncertain significance (Aug 14, 2023)
6-3153884-C-T			Likely benign (Apr 09, 2023)
6-3153887-C-T			Likely benign (Aug 26, 2022)
6-3153892-C-T		Vascular dementia	Uncertain significance (Oct 01, 2021)
6-3153893-G-A			Likely benign (Apr 24, 2021)
6-3153907-C-G			Uncertain significance (Aug 17, 2023)
6-3153907-C-T			Likely benign (Aug 16, 2023)
6-3153910-C-T			Uncertain significance (Mar 09, 2023)
6-3153911-G-A			Likely benign (Dec 09, 2023)
6-3153911-G-T			Likely benign (Jun 14, 2023)
6-3153912-G-A			Uncertain significance (Oct 27, 2022)
6-3153914-C-T			Likely benign (Jul 12, 2022)
6-3153925-G-A			Uncertain significance (Jan 24, 2023)
6-3153952-C-T			Pathogenic (Apr 15, 2023)
6-3153954-T-C			Likely pathogenic (Sep 01, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBB2A	protein_coding	protein_coding	ENST00000333628	4	3858

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.935	0.0652	125713	0	2	125715	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.26	31	278	0.112	0.0000182	2958
Missense in Polyphen		10	121.2	0.082509		1309
Synonymous	-0.0636	125	124	1.01	0.00000974	856
Loss of Function	3.10	1	13.1	0.0764	5.58e-7	160

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000294	0.0000294
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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 (By similarity). {ECO:0000250}.
• Disease: DISEASE: Cortical dysplasia, complex, with other brain malformations 5 (CDCBM5) [MIM:615763]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include seizures, global developmental delay, and various brain malformations such as a diffuse simplified gyral pattern with reduced volume of white matter, globular basal ganglia, thin and dysmorphic corpus callosum, mild brainstem hypoplasia with a flat pons, mild cerebellar vermis hypoplasia, and mildly enlarged posterior fossa. {ECO:0000269|PubMed:24702957}. 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;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;Signaling events mediated by HDAC Class II;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;Signaling events mediated by HDAC Class III (Consensus)

Recessive Scores

• pRec: 0.336

Intolerance Scores

• loftool: 0.426
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.54

Haploinsufficiency Scores

• pHI: 0.878
• hipred: Y
• hipred_score: 0.675
• ghis: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.845

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Tubb2a

Gene ontology

• Biological process: microtubule cytoskeleton organization;mitotic cell cycle;microtubule-based process
• Cellular component: nucleus;cytoplasm;microtubule;extracellular exosome;extracellular vesicle
• Molecular function: GTPase activity;structural constituent of cytoskeleton;protein binding;GTP binding