TUBA1A

tubulin alpha 1a, the group of Tubulins

Basic information

Region (hg38): 12:49184685-49189080

Links

ENSG00000167552 ∙ NCBI:7846 ∙ OMIM:602529 ∙ HGNC:20766 ∙ Uniprot:Q71U36 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• lissencephaly due to TUBA1A mutation (Definitive), mode of inheritance: AD
• lissencephaly due to TUBA1A mutation (Strong), mode of inheritance: AD
• lissencephaly due to TUBA1A mutation (Supportive), mode of inheritance: AD
• tubulinopathy-associated dysgyria (Supportive), mode of inheritance: AD
• lissencephaly due to TUBA1A mutation (Strong), mode of inheritance: AD
• lissencephaly due to TUBA1A mutation (Strong), mode of inheritance: AD
• tubulinopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lissencephaly 3	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	17218254; 17584854; 18728072; 18954413; 21403111; 22264709; 22633752; 22948023; 23317684; 23528852; 23361065

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUBA1A gene.

• not provided (180 variants)
• Tubulinopathy (113 variants)
• Lissencephaly due to TUBA1A mutation (93 variants)
• not specified (34 variants)
• Inborn genetic diseases (21 variants)
• Tubulinopathy-associated dysgyria (7 variants)
• TUBA1A-related condition (6 variants)
• Lissencephaly (5 variants)
• TUBA1A-associated tubulinopathy (4 variants)
• Lissencephaly type 3 (3 variants)
• Cerebral palsy (2 variants)
• Congenital fibrosis of extraocular muscles;Congenital bilateral perisylvian syndrome (2 variants)
• Abnormal brainstem morphology;Abnormal cortical gyration (1 variants)
• Abnormal cerebral morphology (1 variants)
• Abnormality of neuronal migration (1 variants)
• Neurodevelopmental disorder (1 variants)
• Lissencephaly;Polymicrogyria (1 variants)
• Abnormality of the nervous system (1 variants)
• Movement disorder (1 variants)
• Rare genetic intellectual disability (1 variants)
• Lissencephaly due to LIS1 mutation (1 variants)
• Dandy-Walker syndrome (1 variants)
• Congenital bilateral perisylvian syndrome (1 variants)
• Continuous spike and waves during slow sleep;Tubulinopathy-associated dysgyria;Early myoclonic encephalopathy (1 variants)
• Lissencephaly due to TUBA1A mutation;Corpus callosum, agenesis of;Genetic syndrome with a Dandy-Walker malformation as major feature (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2D (1 variants)
• Seizure;Global developmental delay;Decreased head circumference (1 variants)
• Congenital fibrosis of extraocular muscles (1 variants)
• Tubulinopathy-associated dysgyria;West syndrome (1 variants)
• Lissencephaly;Cryptorchidism;Corpus callosum, agenesis of (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBA1A 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				37	9	46
missense	54	97	45	1		197
nonsense						0
start loss						0
frameshift	1	1	2			4
inframe indel	1	2	2			5
splice donor/acceptor (+/-2bp)			1			1
splice region		1		3		4
non coding		6	1	15	4	26
Total	56	106	51	53	13

Variants in TUBA1A

This is a list of pathogenic ClinVar variants found in the TUBA1A region.

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

Position	Type	Phenotype	Significance	ClinVar
12-49184799-T-C			Likely benign (Jun 14, 2018)
12-49185008-CT-C		not specified	Likely benign (Nov 19, 2019)
12-49185019-C-T			Likely benign (Jan 19, 2024)
12-49185024-CT-C		Tubulinopathy	Likely pathogenic (Jul 01, 2018)
12-49185037-C-T			Benign (Oct 20, 2018)
12-49185059-C-T		Tubulinopathy • TUBA1A-associated tubulinopathy	Pathogenic/Likely pathogenic (Jul 29, 2021)
12-49185060-C-G		Tubulinopathy	Pathogenic (Jul 01, 2018)
12-49185062-A-G		Lissencephaly due to TUBA1A mutation • Tubulinopathy	Likely pathogenic (Jul 01, 2018)
12-49185062-ACCT-A		not specified • Polymicrogyria;Lissencephaly • Inborn genetic diseases	Uncertain significance (Apr 09, 2021)
12-49185063-CCTCCTCATAATCCTT-C		Lissencephaly due to TUBA1A mutation	Pathogenic (Sep 26, 2019)
12-49185075-C-T			Uncertain significance (Jul 01, 2018)
12-49185081-C-G		Tubulinopathy	Pathogenic (Jul 01, 2018)
12-49185083-A-T			Uncertain significance (Feb 06, 2022)
12-49185090-C-T			Uncertain significance (May 12, 2022)
12-49185092-A-T		Lissencephaly due to TUBA1A mutation • Tubulinopathy	Pathogenic/Likely pathogenic (Jul 01, 2018)
12-49185098-T-C		Lissencephaly due to TUBA1A mutation	Likely pathogenic (Mar 23, 2023)
12-49185100-A-C			Benign (Dec 02, 2023)
12-49185101-C-T		Lissencephaly due to TUBA1A mutation • Tubulinopathy • Lissencephaly	Pathogenic (Jun 03, 2022)
12-49185102-G-A		Lissencephaly due to TUBA1A mutation • Inborn genetic diseases • Tubulinopathy	Pathogenic (Jul 13, 2021)
12-49185102-G-T		Tubulinopathy-associated dysgyria	Pathogenic (Nov 01, 2021)
12-49185103-G-A			Likely benign (Dec 02, 2021)
12-49185105-C-T		Lissencephaly due to TUBA1A mutation	Likely pathogenic (May 28, 2019)
12-49185109-T-C		not specified	Likely benign (Mar 10, 2016)
12-49185110-G-A		Lissencephaly due to TUBA1A mutation • Tubulinopathy	Pathogenic/Likely pathogenic (Jul 22, 2022)
12-49185118-A-G		not specified	Conflicting classifications of pathogenicity (Oct 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBA1A	protein_coding	protein_coding	ENST00000301071	4	4529

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.967	0.0334	125720	0	1	125721	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.58	7	261	0.0268	0.0000155	2964
Missense in Polyphen		1	119.15	0.0083928		1437
Synonymous	-0.775	104	94.4	1.10	0.00000507	898
Loss of Function	3.34	1	15.0	0.0669	8.32e-7	178

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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.
• Disease: DISEASE: Lissencephaly 3 (LIS3) [MIM:611603]: A classic type lissencephaly associated with psychomotor retardation and seizures. Features include agyria or pachygyria or laminar heterotopia, severe mental retardation, motor delay, variable presence of seizures, and abnormalities of corpus callosum, hippocampus, cerebellar vermis and brainstem. {ECO:0000269|PubMed:17584854, ECO:0000269|PubMed:25818041}. 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);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;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;Post-translational protein modification;Metabolism of proteins;Chaperonin-mediated protein folding;TCR;Formation of tubulin folding intermediates by CCT/TriC;p73 transcription factor network;Carboxyterminal post-translational modifications of tubulin;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;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)

Intolerance Scores

• loftool: 0.278
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.926
• hipred: Y
• hipred_score: 0.771
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.681

Mouse Genome Informatics

• Gene name: Tuba1a
• Phenotype: growth/size/body region phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: tuba1a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: dead

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;mitotic cell cycle;microtubule-based process;regulation of G2/M transition of mitotic cell cycle;cytoskeleton-dependent intracellular transport;regulation of synapse organization;cell division;ciliary basal body-plasma membrane docking
• Cellular component: nucleus;cytoplasm;cytosol;microtubule;cytoplasmic microtubule;microtubule cytoskeleton;neuromuscular junction;cytoplasmic ribonucleoprotein granule;myelin sheath;membrane raft;recycling endosome;extracellular exosome
• Molecular function: GTPase activity;structural molecule activity;structural constituent of cytoskeleton;protein binding;GTP binding;protein domain specific binding