TUBB1

tubulin beta 1 class VI, the group of Tubulins

Basic information

Region (hg38): 20:59019429-59026654

Links

ENSG00000101162 ∙ NCBI:81027 ∙ OMIM:612901 ∙ HGNC:16257 ∙ Uniprot:Q9H4B7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• macrothrombocytopenia, isolated, 1, autosomal dominant (Moderate), mode of inheritance: AD
• macrothrombocytopenia, isolated, 1, autosomal dominant (Strong), mode of inheritance: AD
• macrothrombocytopenia, isolated, 1, autosomal dominant (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrothrombocytopenia, isolated, autosomal dominant 1	AD	General	The clinical significance is unclear	Hematologic	15956286; 18849486

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBB1 gene.

• Macrothrombocytopenia, isolated, 1, autosomal dominant (1 variants)
• Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB1 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				30	7	37
missense	1	1	102	8	8	120
nonsense	1	1	3			5
start loss			1			1
frameshift		1	2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	2			4
splice region			2	2		4
non coding			1	8	3	12
Total	2	5	112	46	18

Variants in TUBB1

This is a list of pathogenic ClinVar variants found in the TUBB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-59019435-G-C		Macrothrombocytopenia, isolated, 1, autosomal dominant	Uncertain significance (-)
20-59019525-G-A			Uncertain significance (Oct 27, 2022)
20-59019526-C-T		not specified • Thrombocytopenia;Abnormal bleeding	Uncertain significance (Sep 17, 2024)
20-59019527-G-C		Macrothrombocytopenia, isolated, 1, autosomal dominant	Uncertain significance (-)
20-59019535-G-A		Abnormal bleeding;Thrombocytopenia • Macrothrombocytopenia, isolated, 1, autosomal dominant	Conflicting classifications of pathogenicity (Jan 08, 2024)
20-59019539-A-G			Conflicting classifications of pathogenicity (Nov 01, 2024)
20-59019541-A-G			Uncertain significance (Jun 16, 2023)
20-59019550-G-C		Thrombocytopenia	Uncertain significance (Feb 01, 2019)
20-59019554-A-C		Macrothrombocytopenia, isolated, 1, autosomal dominant	Uncertain significance (Apr 16, 2021)
20-59019556-T-A			Uncertain significance (Apr 17, 2023)
20-59019556-TG-T		Congenital hypothyroidism • Macrothrombocytopenia, isolated, 1, autosomal dominant • TUBB1-related disorder	Conflicting classifications of pathogenicity (Nov 14, 2024)
20-59019559-G-A		Macrothrombocytopenia, isolated, 1, autosomal dominant	Uncertain significance (-)
20-59019564-C-G			Uncertain significance (Sep 01, 2023)
20-59019571-G-A		TUBB1-related disorder	Uncertain significance (Aug 26, 2022)
20-59019580-G-A		Macrothrombocytopenia, isolated, 1, autosomal dominant	Likely pathogenic (Jan 10, 2020)
20-59019588-T-C			Likely benign (Mar 18, 2022)
20-59019589-G-A			Likely benign (Jan 25, 2024)
20-59019596-T-A			Likely benign (Sep 25, 2022)
20-59019598-C-G			Likely benign (Sep 25, 2022)
20-59022590-A-G			Benign (Jun 19, 2021)
20-59022843-A-G			Uncertain significance (Oct 13, 2023)
20-59022855-T-C		Abnormal bleeding;Thrombocytopenia	Uncertain significance (Feb 23, 2022)
20-59022866-GA-TT			Uncertain significance (May 01, 2024)
20-59022871-C-T		not specified	Benign (Jan 25, 2024)
20-59022873-G-A			Uncertain significance (Nov 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBB1	protein_coding	protein_coding	ENST00000217133	4	7401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.02e-7	0.332	125599	0	149	125748	0.000593

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00274	272	272	1.00	0.0000179	3008
Missense in Polyphen		157	159.84	0.98222		1700
Synonymous	-0.253	119	116	1.03	0.00000892	878
Loss of Function	0.580	12	14.4	0.835	8.65e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000358	0.000358
Ashkenazi Jewish	0.00616	0.00617
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000510	0.000510
Middle Eastern	0.000544	0.000544
South Asian	0.000229	0.000196
Other	0.000652	0.000652

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). {ECO:0000250}.
• Disease: DISEASE: Macrothrombocytopenia, autosomal dominant, TUBB1-related (MAD-TUBB1) [MIM:613112]: A congenital blood disorder characterized by increased platelet size and decreased number of circulating platelets. {ECO:0000269|PubMed:18849486}. 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);Docetaxel Action Pathway;Paclitaxel Action Pathway;Vincristine Action Pathway;Vinblastine Action Pathway;Vinorelbine Action Pathway;Vindesine Action Pathway;Pathogenic Escherichia coli infection;Parkin-Ubiquitin Proteasomal System pathway;stathmin and breast cancer resistance to antimicrotubule agents;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: 0.252

Intolerance Scores

• loftool: 0.420
• rvis_EVS: 0.87
• rvis_percentile_EVS: 88.85

Haploinsufficiency Scores

• pHI: 0.236
• hipred: Y
• hipred_score: 0.725
• ghis: 0.439

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.938

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tubb1
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype

Gene ontology

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