TUBB8

tubulin beta 8 class VIII, the group of Tubulins

Basic information

Region (hg38): 10:46887-74163

Links

ENSG00000261456 ∙ NCBI:347688 ∙ OMIM:616768 ∙ HGNC:20773 ∙ Uniprot:Q3ZCM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oocyte maturation defect 2 (Definitive), mode of inheritance: Semidominant
• oocyte maturation defect 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte maturation defect 2	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	Obstetric	26789871; 27273344
Attempts at IVF were not described as effective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBB8 gene.

• Oocyte maturation defect 2 (22 variants)
• not provided (13 variants)
• Inborn genetic diseases (7 variants)
• not specified (2 variants)
• - (2 variants)
• Streaky metaphyseal sclerosis;Aplasia/Hypoplasia of the phalanges of the 4th toe (1 variants)
• CIC-DUX Sarcoma (1 variants)
• Female infertility (1 variants)
• Inherited oocyte maturation defect (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB8 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				10	3	13
missense	7	2	12			21
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					9	9
Total	7	2	12	11	12

Highest pathogenic variant AF is 0.000224

Variants in TUBB8

This is a list of pathogenic ClinVar variants found in the TUBB8 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-47064-ACCTCCTCCTCGGCATACTCCTCATCCT-A			Likely benign (Apr 01, 2021)
10-47121-T-C		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47143-C-T		Oocyte maturation defect 2	Pathogenic (Jan 21, 2016)
10-47150-G-C		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47188-C-CAG		Oocyte maturation defect 2	Pathogenic (Aug 31, 2020)
10-47203-A-C		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47214-G-T		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47220-C-T		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47229-A-G		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47253-C-T		Oocyte maturation defect 2	Uncertain significance (Nov 04, 2022)
10-47262-A-G		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47304-A-G		Oocyte maturation defect 2	Pathogenic (Jan 21, 2016)
10-47319-G-A		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47347-C-T		Oocyte maturation defect 2 • not specified	Uncertain significance (May 04, 2022)
10-47353-T-C		-	no classification for the single variant (-)
10-47356-G-T		Oocyte maturation defect 2	Uncertain significance (Apr 04, 2024)
10-47359-G-A		-	no classification for the single variant (-)
10-47452-C-A		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47454-G-A		Oocyte maturation defect 2 • not specified	Uncertain significance (May 04, 2022)
10-47470-C-T		Oocyte maturation defect 2	Pathogenic (Feb 09, 2021)
10-47492-C-T		Oocyte maturation defect 2	Pathogenic (Jan 21, 2016)
10-47499-T-C		Oocyte maturation defect 2	Likely pathogenic (Aug 31, 2020)
10-47525-A-G			Likely benign (Jul 01, 2023)
10-47547-C-G		Oocyte maturation defect 2	Uncertain significance (Aug 19, 2019)
10-47549-G-C		CIC-DUX Sarcoma	not provided (-)

GnomAD

Source: gnomAD

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). TUBB8 has a key role in meiotic spindle assembly and oocyte maturation (PubMed:26789871). {ECO:0000250, ECO:0000269|PubMed:26789871}.
• Disease: DISEASE: Oocyte maturation defect 2 (OOMD2) [MIM:616780]: An autosomal dominant infertility disorder caused by defective oocyte maturation. Oocytes are arrested at metaphase I, and have an abnormal or no detectable spindle on polarization microscopy. {ECO:0000269|PubMed:26789871, ECO:0000269|PubMed:27273344}. 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;Carboxyterminal post-translational modifications of tubulin (Consensus)

Intolerance Scores

• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.51

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.255
• ghis: 0.398

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Gene ontology

• Biological process: microtubule cytoskeleton organization;mitotic cell cycle;oocyte maturation;microtubule-based process;spindle assembly involved in female meiosis
• Cellular component: cytoplasm;microtubule;extracellular exosome;meiotic spindle
• Molecular function: molecular_function;GTPase activity;structural constituent of cytoskeleton;GTP binding