TUBB8

protein-coding

tubulin beta 8 class VIII, the group of Tubulins

Gene summary

The protein encoded by this gene represents the primary beta-tubulin subunit of oocytes and the early embryo. Defects in this gene, which is primate-specific, are a cause of oocyte maturation defect 2 and infertility. [provided by RefSeq, Mar 2016]

MANE transcript

NM_177987.3

Inheritance

AD, SD, AR

ClinVar variants

P:46U:46B:24

Top phenotype

Oocyte maturation defect 2

Max pathogenic AF

—

Genomic locus

chr10:46,888-74,163

External References & Databases

Ensembl (ENSG00000261456)

Transcript & Mutation Effects

hg38 • Region Span ~27.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oocyte maturation defect 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0021573

Submitter: PanelApp Australia

oocyte maturation defect 2DEFINITIVE

Inheritance Pattern: SD

Disease ID:MONDO:0021573

Submitter: Ambry Genetics

oocyte maturation defect 2LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0021573

Submitter: Ambry Genetics

oocyte maturation defect 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0021573

Submitter: Ambry Genetics

oocyte maturation defect 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0021573

Submitter: PanelApp Australia

oocyte maturation defect 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0021573

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Oocyte maturation defect 2AD/AR

Manifestation: Obstetric

Intervention: General

Rationale: 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

Comments: Attempts at IVF were not described as effective

Refs: 26789871; 27273344

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TUBB8 variants in ClinVar

7 Conditions Cataloged

Oocyte maturation defect 2Total: 66

not providedTotal: 21

not specifiedTotal: 17

Inborn genetic diseasesTotal: 17

CIC-rearranged sarcomaTotal: 1

Inherited oocyte maturation defectTotal: 1

Female infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177987.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	19 clinvar	1 clinvar	22
missense	9 clinvar	33 clinvar	41 clinvar	4 clinvar		87
nonsense			2 clinvar			2
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	11	35	46	23	1	116

Highest pathogenic variant AF is 0.003774054

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_177987.3	RefSeq	NP_817124.1	4	MANE Select
ENST00000568584.6	Ensembl	ENSP00000456206.2	4	MANE Select
NM_001389618.1	RefSeq	NP_001376547.1	2	Standard
NM_001389619.1	RefSeq	NP_001376548.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

microtubule cytoskeleton organization
mitotic cell cycle
oocyte maturation
microtubule-based process
spindle assembly involved in female meiosis

Molecular Function

molecular_function
GTPase activity
structural constituent of cytoskeleton
GTP binding

Cellular Component

cytoplasm
microtubule
extracellular exosome
meiotic spindle

dbNSFP Gene Annotations

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.;

Intolerance Scores

RVIS EVS: 0.15
RVIS percentile EVS: 64.51

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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