TUBA4A Gene

HGNC Family	Tubulins (TUB)
Name	tubulin, alpha 4a
Description	Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified TUBA4A as an α‐tubulin isoform critically involved in the integrity and dynamics of the microtubule network, with mutations in its gene being linked to several neurodegenerative disorders. Analyses in familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients revealed an overrepresentation of rare variants in TUBA4A. Functional assays demonstrated that pathogenic mutations in TUBA4A impair microtubule repolymerization and destabilize the cytoskeletal network, underscoring its central role in maintaining neuronal architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, in-depth investigations using molecular-dynamic modeling and transcriptomic-proteomic approaches have shown that defective TUBA4A compromises crucial biochemical interactions. Specifically, abnormal variants are predicted to disrupt GTP binding and the proper folding required for α/β-tubulin heterodimer formation while also enhancing the aggregation propensity of the protein. These findings suggest that such structural perturbations in TUBA4A can trigger motor axon defects and contribute to the cascade of neurodegenerative processes observed in ALS."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neuronal implications, TUBA4A plays a pivotal role in non-neuronal tissues. In platelets, TUBA4A is the predominant α-tubulin isotype, and its regulated expression is essential for the formation of the marginal band—a unique microtubule structure crucial for platelet biogenesis. Missense mutations in TUBA4A have been linked to macrothrombocytopenia, indicating that alterations in its function can impair microtubule organization in megakaryocytes. Moreover, recent reports documenting novel TUBA4A variants in patients with spastic ataxia and congenital myopathy further expand the spectrum of neuromuscular disorders associated with its dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bradley N Smith, Nicola Ticozzi, Claudia Fallini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2014.09.027"}], "href": "https://doi.org/10.1016/j.neuron.2014.09.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25374358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25374358"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Federica Perrone, Hung Phuoc Nguyen, Sara Van Mossevelde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2016.12.008"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2016.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28069311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28069311"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anika M Helferich, Sarah J Brockmann, Jörg Reinders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of a novel miR-1825/TBCB/TUBA4A pathway in sporadic and familial ALS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-018-2873-1"}], "href": "https://doi.org/10.1007/s00018-018-2873-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30030593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30030593"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Akshatha Ganne, Meenakshisundaram Balasubramaniam, Haarika Ayyadevara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In silico analysis of TUBA4A mutations in Amyotrophic Lateral Sclerosis to define mechanisms of microtubule disintegration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-023-28381-x"}], "href": "https://doi.org/10.1038/s41598-023-28381-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36747013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36747013"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Catherine Strassel, Maria M Magiera, Arnaud Dupuis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An essential role for α4A-tubulin in platelet biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci Alliance (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26508/lsa.201900309"}], "href": "https://doi.org/10.26508/lsa.201900309"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30760556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30760556"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Annalaura Torella, Ivana Ricca, Giulio Piluso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new genetic cause of spastic ataxia: the p.Glu415Lys variant in TUBA4A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00415-023-11816-w"}], "href": "https://doi.org/10.1007/s00415-023-11816-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37418012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37418012"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yalan Wan, Chao Zhou, Xingzhi Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "TUBA4A"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " variant causes congenital myopathy with focal myofibrillar disorganisation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg-2023-109786"}], "href": "https://doi.org/10.1136/jmg-2023-109786"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38413182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38413182"}]}]}]}
Synonyms	ALS22, TUBA1
Proteins	TBA4A_HUMAN
NCBI Gene ID	7277
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TUBA4A has 11,397 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 116 datasets.

Click the + buttons to view associations for TUBA4A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TUBA4A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TUBA4A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TUBA4A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of TUBA4A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TUBA4A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving TUBA4A protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of TUBA4A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TUBA4A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TUBA4A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TUBA4A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of TUBA4A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TUBA4A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TUBA4A gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TUBA4A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TUBA4A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of TUBA4A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TUBA4A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TUBA4A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TUBA4A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TUBA4A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with TUBA4A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing TUBA4A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TUBA4A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TUBA4A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TUBA4A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of TUBA4A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TUBA4A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TUBA4A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TUBA4A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with TUBA4A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with TUBA4A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TUBA4A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for TUBA4A protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TUBA4A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TUBA4A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TUBA4A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing TUBA4A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TUBA4A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TUBA4A gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TUBA4A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TUBA4A gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.