TUBB6

tubulin beta 6 class V, the group of Tubulins

Basic information

Region (hg38): 18:12307668-12344320

Links

ENSG00000176014 ∙ NCBI:84617 ∙ OMIM:615103 ∙ HGNC:20776 ∙ Uniprot:Q9BUF5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• facial palsy, congenital, with ptosis and velopharyngeal dysfunction (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Facial palsy, congenital, with ptosis and velopharyngeal dysfunction (FPVEPD)	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	29016863

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBB6 gene.

• not provided (24 variants)
• Inborn genetic diseases (14 variants)
• Spinocerebellar ataxia type 28 (13 variants)
• not specified (5 variants)
• Facial palsy, congenital, with ptosis and velopharyngeal dysfunction (5 variants)
• Spastic ataxia 5 (3 variants)
• Optic atrophy 12 (1 variants)
• TUBB6-related condition (1 variants)
• - (1 variants)
• Optic atrophy 12;Spinocerebellar ataxia type 28;Spastic ataxia 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB6 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				1	1	2
missense			14			14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			21	5	7	33
Total	0	0	35	6	8

Variants in TUBB6

This is a list of pathogenic ClinVar variants found in the TUBB6 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-12308244-T-A		Facial palsy, congenital, with ptosis and velopharyngeal dysfunction	Benign (Dec 05, 2021)
18-12308246-C-T		Facial palsy, congenital, with ptosis and velopharyngeal dysfunction	Benign (Dec 05, 2021)
18-12308274-G-T		Facial palsy, congenital, with ptosis and velopharyngeal dysfunction	Benign (Dec 05, 2021)
18-12308317-G-T		not specified	Uncertain significance (Jun 29, 2022)
18-12308378-C-A		Facial palsy, congenital, with ptosis and velopharyngeal dysfunction	Benign (Dec 05, 2021)
18-12308719-C-G		not specified	Uncertain significance (Oct 18, 2019)
18-12308721-A-T		not specified	Uncertain significance (Apr 07, 2023)
18-12308794-G-C		Facial palsy, congenital, with ptosis and velopharyngeal dysfunction • TUBB6-related disorder	Benign (Dec 05, 2021)
18-12311033-G-A		not specified	Uncertain significance (Mar 29, 2022)
18-12325104-C-A		not specified	Uncertain significance (Nov 03, 2023)
18-12325115-G-A		not specified	Uncertain significance (May 26, 2023)
18-12325143-C-T			Benign (Aug 01, 2023)
18-12325150-C-G		not specified	Uncertain significance (Nov 03, 2023)
18-12325164-G-C		Facial palsy, congenital, with ptosis and velopharyngeal dysfunction	Uncertain significance (Mar 12, 2024)
18-12325203-G-A		TUBB6-related disorder	Likely benign (Mar 14, 2019)
18-12325294-G-A		not specified	Uncertain significance (Jul 06, 2021)
18-12325327-G-A		not specified	Uncertain significance (Oct 25, 2022)
18-12325353-G-A		TUBB6-related disorder	Benign (Apr 08, 2019)
18-12325371-G-A			Likely benign (Apr 01, 2023)
18-12325381-G-A		not specified	Uncertain significance (Jul 29, 2023)
18-12325382-A-T		not specified	Uncertain significance (Nov 09, 2021)
18-12325456-G-A		not specified	Uncertain significance (Jan 17, 2024)
18-12325496-T-A		TUBB6-related disorder	Uncertain significance (May 26, 2023)
18-12325616-G-A		not specified	Uncertain significance (Jan 05, 2022)
18-12325723-A-G		TUBB6-related disorder	Benign (Sep 25, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBB6	protein_coding	protein_coding	ENST00000317702	4	36652

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000166	0.892	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.64	171	299	0.571	0.0000225	2958
Missense in Polyphen		107	190.79	0.56084		1835
Synonymous	0.526	127	135	0.942	0.0000116	871
Loss of Function	1.46	8	13.9	0.577	6.05e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000388	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000806	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
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. {ECO:0000250|UniProtKB:P02557}.
• Disease: DISEASE: Facial palsy, congenital, with ptosis and velopharyngeal dysfunction (FPVEPD) [MIM:617732]: An autosomal dominant congenital disorder characterized by non-progressive bilateral facial palsy, velopharyngeal dysfunction presenting with varying degrees of hypomimia, rhinophonia and impaired gag reflex, and bilateral ptosis. {ECO:0000269|PubMed:29016863}. 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;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 (Consensus)

Recessive Scores

• pRec: 0.249

Intolerance Scores

• loftool: 0.287
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.627
• hipred: N
• hipred_score: 0.420
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.786

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tubb6

Gene ontology

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