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 (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
polymicrogyria with optic nerve hypoplasia (Limited), 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.

not_provided (300 variants)
not_specified (70 variants)
TUBA8-related_disorder (11 variants)
Polymicrogyria_with_optic_nerve_hypoplasia (8 variants)
Macrothrombocytopenia,_isolated,_2,_autosomal_dominant (6 variants)
Duane_retraction_syndrome (1 variants)
Microcephaly (1 variants)

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. These statistics are base on transcript: NM_000018943.3. 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			1 clinvar	92 clinvar	2 clinvar	95
missense	1 clinvar		173 clinvar	5 clinvar	2 clinvar	181
nonsense			4 clinvar			4
start loss			1			1
frameshift			11 clinvar			11
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	193	97	4

Loading clinvar variants...

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