TUBA4A

tubulin alpha 4a, the group of Tubulins

Basic information

Region (hg38): 2:219249709-219277902

Previous symbols: [ "TUBA1" ]

Links

ENSG00000127824 ∙ NCBI:7277 ∙ OMIM:191110 ∙ HGNC:12407 ∙ Uniprot:P68366 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis type 22 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis type 22 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis type 22 (Limited), mode of inheritance: Unknown
• amyotrophic lateral sclerosis type 22 (Moderate), mode of inheritance: AD
• autosomal dominant macrothrombocytopenia (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 22	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	25374358

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBA4A gene.

• not provided (33 variants)
• Amyotrophic lateral sclerosis type 22 (4 variants)
• not specified (2 variants)
• Amyotrophic lateral sclerosis (1 variants)
• - (1 variants)
• Amyotrophic lateral sclerosis type 10 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBA4A 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	4	4	9
missense		2	8	1		11
nonsense			1			1
start loss						0
frameshift		3				3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				6	8	14
Total	0	5	10	11	12

Highest pathogenic variant AF is 0.00000657

Variants in TUBA4A

This is a list of pathogenic ClinVar variants found in the TUBA4A region.

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

Position	Type	Phenotype	Significance	ClinVar
2-219250304-C-T			Benign (Sep 18, 2018)
2-219250388-G-A			Likely benign (Jun 16, 2020)
2-219250433-A-C		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250442-G-A		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250456-C-T		Amyotrophic lateral sclerosis type 22 • not specified	Uncertain significance (Jun 01, 2023)
2-219250469-A-G		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250475-A-G		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250479-C-T		Amyotrophic lateral sclerosis type 22	Pathogenic (Oct 22, 2014)
2-219250485-A-C		Amyotrophic lateral sclerosis	Uncertain significance (Jan 01, 2022)
2-219250530-C-T		Amyotrophic lateral sclerosis type 22	Uncertain significance (Mar 12, 2024)
2-219250544-G-A		TUBA4A-related disorder	Benign/Likely benign (Dec 15, 2022)
2-219250552-C-T		Amyotrophic lateral sclerosis type 22	Pathogenic (Oct 22, 2014)
2-219250553-G-A		TUBA4A-related disorder	Likely benign (Jan 10, 2023)
2-219250556-C-T			Likely benign (Jun 01, 2021)
2-219250616-A-G		TUBA4A-related disorder	Likely benign (Jul 12, 2023)
2-219250622-A-G		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250643-C-CTTGAA			Likely pathogenic (Feb 01, 2021)
2-219250652-T-C		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250674-T-C		Amyotrophic lateral sclerosis type 22	Uncertain significance (Jul 18, 2022)
2-219250676-A-G		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250679-G-A		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250700-G-A		TUBA4A-related disorder	Benign (May 08, 2023)
2-219250703-A-G		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250709-A-G		TUBA4A-related disorder	Likely benign (Oct 03, 2023)
2-219250712-G-A		TUBA4A-related disorder	Likely benign (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBA4A	protein_coding	protein_coding	ENST00000248437	4	28460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.160	0.837	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.30	120	274	0.438	0.0000170	2942
Missense in Polyphen		29	102.58	0.28271		1204
Synonymous	0.0670	108	109	0.992	0.00000690	910
Loss of Function	2.60	4	14.8	0.271	8.11e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000163	0.000163

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: Amyotrophic lateral sclerosis 22, with or without frontotemporal dementia (ALS22) [MIM:616208]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS22 may develop frontotemporal dementia. {ECO:0000269|PubMed:25374358}. 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;TCR;Formation of tubulin folding intermediates by CCT/TriC;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;Hemostasis;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Protein folding;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Prefoldin mediated transfer of substrate to CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;Post-chaperonin tubulin folding pathway;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.649

Intolerance Scores

• loftool: 0.294
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.993
• hipred: Y
• hipred_score: 0.800
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tuba4a

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;mitotic cell cycle;platelet degranulation;microtubule-based process;regulation of G2/M transition of mitotic cell cycle;ciliary basal body-plasma membrane docking
• Cellular component: extracellular region;cytoplasm;cytosol;cytoskeleton;microtubule;microtubule cytoskeleton;extracellular exosome
• Molecular function: GTPase activity;structural constituent of cytoskeleton;protein binding;GTP binding;protein kinase binding