TUBA8

tubulin alpha 8, the group of Tubulins

Basic information

Region (hg38): 22:18110100-18146683

Previous symbols: [ "TUBAL2" ]

Links

ENSG00000183785 ∙ NCBI:51807 ∙ OMIM:605742 ∙ HGNC:12410 ∙ Uniprot:Q9NY65 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polymicrogyria with optic nerve hypoplasia (Limited), mode of inheritance: AR
• polymicrogyria with optic nerve hypoplasia (Supportive), mode of inheritance: AR
• polymicrogyria with optic nerve hypoplasia (Limited), mode of inheritance: Unknown
• polymicrogyria with optic nerve hypoplasia (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrothrombocytopenia, isolated, 2, autosomal dominant; Polymicrogyria with optic nerve hypoplasia	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	Hematologic; Neurologic; Ophthalmologic	19896110; 34704371

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBA8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBA8 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			3	74	3	80
missense			136	4	1	141
nonsense			3			3
start loss			1			1
frameshift			8			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region				2	2	4
non coding			5	33	11	49
Total	0	0	159	111	15

Variants in TUBA8

This is a list of pathogenic ClinVar variants found in the TUBA8 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-18110361-C-T			Likely benign (Aug 12, 2018)
22-18110385-C-T			Likely benign (Apr 29, 2019)
22-18110474-C-T			Likely benign (Dec 24, 2018)
22-18110514-G-A			Benign (Jul 21, 2018)
22-18110859-G-C		not specified • TUBA8-related disorder	Likely benign (Mar 11, 2016)
22-18110861-CAGCGATGGTG-C			Uncertain significance (Sep 30, 2023)
22-18110870-T-G			Uncertain significance (May 03, 2021)
22-18110883-G-T			Likely benign (Oct 23, 2022)
22-18110885-C-G			Likely benign (Jun 09, 2023)
22-18110916-G-A			Likely benign (Feb 06, 2019)
22-18111053-A-G			Likely benign (Feb 06, 2019)
22-18111124-G-A			Likely benign (Dec 01, 2018)
22-18111181-A-C			Likely benign (Aug 17, 2018)
22-18121367-C-T			Likely benign (Jul 15, 2018)
22-18121454-CCTCGTTGCTTCCCT-C		Polymicrogyria with optic nerve hypoplasia	Uncertain significance (Nov 01, 2009)
22-18121460-T-G			Likely benign (Aug 17, 2023)
22-18121464-T-C			Likely benign (Jan 29, 2024)
22-18121469-C-A			Uncertain significance (Nov 10, 2021)
22-18121469-C-T			Likely benign (Jan 30, 2023)
22-18121470-TC-T			Benign (Jul 12, 2022)
22-18121479-C-T			Uncertain significance (Sep 01, 2022)
22-18121480-G-A		Polymicrogyria with optic nerve hypoplasia	Uncertain significance (Nov 03, 2022)
22-18121500-G-C			Uncertain significance (Dec 14, 2023)
22-18121515-G-T			Uncertain significance (Jan 12, 2015)
22-18121530-G-T			Uncertain significance (Nov 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBA8	protein_coding	protein_coding	ENST00000330423	5	36225

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000357	0.832	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.631	250	280	0.894	0.0000179	2956
Missense in Polyphen		145	161.8	0.89618		1760
Synonymous	0.160	111	113	0.981	0.00000766	899
Loss of Function	1.31	9	14.3	0.627	6.15e-7	179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000532	0.000532
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000489	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000489	0.000489
South Asian	0.0000986	0.0000980
Other	0.000490	0.000489

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.
• Disease: DISEASE: Cortical dysplasia, complex, with other brain malformations 8 (CDCBM8) [MIM:613180]: A disease characterized by extensive polymicrogyria, optic nerve hypoplasia, severe developmental delay, hypotonia, seizures, a dysplastic or absent corpus callosum and colpocephaly. Polymicrogyria is 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:19896110}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);Phagosome - Homo sapiens (human);Gap junction - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Apoptosis - Homo sapiens (human);Pathogenic Escherichia coli infection;Parkin-Ubiquitin Proteasomal System pathway;stathmin and breast cancer resistance to antimicrotubule agents;downregulated of mta-3 in er-negative breast tumors;Metabolism of proteins;Chaperonin-mediated protein folding;Formation of tubulin folding intermediates by CCT/TriC;Protein folding;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;Post-chaperonin tubulin folding pathway (Consensus)

Recessive Scores

• pRec: 0.350

Intolerance Scores

• loftool: 0.181
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.42

Haploinsufficiency Scores

• pHI: 0.514
• hipred: Y
• hipred_score: 0.528
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.954

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tuba8
• Phenotype: normal phenotype

Gene ontology

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