TUBA1A
tubulin alpha 1a, the group of Tubulins
Basic information
Region (hg38): 12:49184686-49189324
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- not_provided (237 variants)
- Lissencephaly_due_to_TUBA1A_mutation (127 variants)
- Tubulinopathy (113 variants)
- not_specified (31 variants)
- TUBA1A-related_disorder (30 variants)
- Inborn_genetic_diseases (23 variants)
- Tubulinopathy-associated_dysgyria (9 variants)
- Lissencephaly (8 variants)
- Lissencephaly_type_3 (6 variants)
- TUBA1A-associated_tubulinopathy (4 variants)
- Corpus_callosum,_agenesis_of (3 variants)
- Congenital_bilateral_perisylvian_syndrome (3 variants)
- Congenital_fibrosis_of_extraocular_muscles (3 variants)
- Intellectual_disability (2 variants)
- Seizure (2 variants)
- Cerebral_palsy (2 variants)
- Abnormal_cerebral_morphology (1 variants)
- West_syndrome (1 variants)
- Movement_disorder (1 variants)
- Lissencephaly_due_to_LIS1_mutation (1 variants)
- Abnormal_cortical_gyration (1 variants)
- Rare_genetic_intellectual_disability (1 variants)
- Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2D (1 variants)
- Abnormality_of_neuronal_migration (1 variants)
- Recurrent_hand_flapping (1 variants)
- Early_myoclonic_encephalopathy (1 variants)
- Dandy-Walker_syndrome (1 variants)
- Continuous_spike_and_waves_during_slow_sleep (1 variants)
- Abnormal_brainstem_morphology (1 variants)
- Neurodevelopmental_disorder (1 variants)
- Polymicrogyria (1 variants)
- Cryptorchidism (1 variants)
- Global_developmental_delay (1 variants)
- Cerebellar_vermis_hypoplasia (1 variants)
- Abnormal_brain_morphology (1 variants)
- Abnormality_of_the_nervous_system (1 variants)
- Genetic_syndrome_with_a_Dandy-Walker_malformation_as_major_feature (1 variants)
- Congenital_cerebellar_hypoplasia (1 variants)
- Decreased_head_circumference (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. These statistics are base on transcript: NM_000006009.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 63 | 72 | ||||
| missense | 61 | 145 | 70 | 277 | ||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 62 | 147 | 74 | 64 | 9 |
Highest pathogenic variant AF is 0.0000013682
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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