TUBB

tubulin beta class I, the group of Tubulins

Basic information

Region (hg38): 6:30717435-30725538

Links

ENSG00000196230 ∙ NCBI:203068 ∙ OMIM:191130 ∙ HGNC:20778 ∙ Uniprot:P07437 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex cortical dysplasia with other brain malformations 6 (Definitive), mode of inheritance: AD
• multiple benign circumferential skin creases on limbs 1 (Definitive), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 6 (Moderate), mode of inheritance: AD
• multiple benign circumferential skin creases on limbs 1 (Moderate), mode of inheritance: AD
• multiple benign circumferential skin creases on limbs (Supportive), mode of inheritance: AD
• TUBB3-related tubulinopathy (Definitive), mode of inheritance: AD
• complex cortical dysplasia with other brain malformations 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital symmetric circumferential skin creases 1; Cortical dysplasia, complex, with other brain malformations 6	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	Craniofacial; Dermatologic; Neurologic; Ophthalmologic	12239728; 23246003; 23324645; 26637975

ClinVar

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

• Complex cortical dysplasia with other brain malformations 6 (4 variants)
• not provided (2 variants)
• Inborn genetic diseases (2 variants)
• Multiple benign circumferential skin creases on limbs 1 (1 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUBB 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				2	2	4
missense	5	18	28	1		52
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				7	12	19
Total	5	18	32	10	14

Variants in TUBB

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

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

Position	Type	Phenotype	Significance	ClinVar
6-30719937-T-A			Benign (Jun 28, 2018)
6-30720290-C-G			Benign (Jun 30, 2018)
6-30720549-C-A		Multiple benign circumferential skin creases on limbs 1	Pathogenic (Apr 01, 2013)
6-30720551-G-C		Multiple benign circumferential skin creases on limbs 1	Likely pathogenic (May 04, 2022)
6-30720556-G-T			Uncertain significance (Dec 15, 2023)
6-30720581-CTT-C			Likely benign (Jun 14, 2018)
6-30720650-G-T			Benign (Jun 26, 2018)
6-30720798-G-C			Benign (Jun 26, 2018)
6-30721941-TCCTGGGCAACAAAGCGAGA-T		-	no classification for the single variant (-)
6-30721963-C-A		-	no classification for the single variant (-)
6-30721970-A-G		TUBB-related disorder	Likely benign (Jul 29, 2023)
6-30722236-G-A			Likely benign (Mar 29, 2019)
6-30722324-T-A			Likely benign (Jun 26, 2018)
6-30722392-G-A			Likely benign (Jun 26, 2018)
6-30722488-A-T			Benign (Jun 28, 2018)
6-30722528-C-T			Likely benign (Mar 24, 2020)
6-30722570-G-A		Complex cortical dysplasia with other brain malformations 6	Likely pathogenic (Jun 01, 2022)
6-30722618-A-G		Complex cortical dysplasia with other brain malformations 6	Likely pathogenic (Apr 19, 2020)
6-30722631-A-G			Uncertain significance (Jan 17, 2022)
6-30722634-A-G		Complex cortical dysplasia with other brain malformations 6	Likely pathogenic (Apr 05, 2024)
6-30722640-C-T		Multiple benign circumferential skin creases on limbs 1 • Complex cortical dysplasia with other brain malformations 6	Uncertain significance (Jun 24, 2022)
6-30722858-G-A			Benign (Aug 15, 2018)
6-30722924-A-G			Uncertain significance (Apr 14, 2022)
6-30722927-A-G			Uncertain significance (May 24, 2022)
6-30722953-C-A			Likely pathogenic (Mar 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUBB	protein_coding	protein_coding	ENST00000327892	4	5226

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.979	0.0211	125668	0	2	125670	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.63	18	285	0.0631	0.0000171	2954
Missense in Polyphen		3	135.2	0.02219		1401
Synonymous	0.301	106	110	0.964	0.00000689	875
Loss of Function	3.50	1	16.2	0.0617	9.30e-7	164

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)	0.0000177	0.0000176
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: Cortical dysplasia, complex, with other brain malformations 6 (CDCBM6) [MIM:615771]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have microcephaly, ataxia, and severe delayed psychomotor development. Brain imaging shows variable malformations of cortical development, including white matter streaks, dysmorphic basal ganglia, corpus callosum abnormalities, brainstem and cerebellar hypoplasia, cortical dysplasia, polymicrogyria. {ECO:0000269|PubMed:23246003}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Skin creases, congenital symmetric circumferential, 1 (CSCSC1) [MIM:156610]: An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features. {ECO:0000269|PubMed:26637975}. 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);Pathogenic Escherichia coli infection;Parkin-Ubiquitin Proteasomal System pathway;Neutrophil degranulation;TCR;Innate Immune System;Immune System;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;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Intolerance Scores

• loftool: 0.115
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.738
• hipred: Y
• hipred_score: 0.675
• ghis: 0.596

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Mouse Genome Informatics

• Gene name: Tubb5
• Phenotype: 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule cytoskeleton organization;mitotic cell cycle;microtubule-based process;cellular process;regulation of G2/M transition of mitotic cell cycle;cytoskeleton-dependent intracellular transport;natural killer cell mediated cytotoxicity;neutrophil degranulation;regulation of synapse organization;spindle assembly;cell division;ciliary basal body-plasma membrane docking
• Cellular component: extracellular region;nucleus;nuclear envelope lumen;cytoplasm;cytoskeleton;microtubule;azurophil granule lumen;cytoplasmic ribonucleoprotein granule;cell body;membrane raft;extracellular exosome
• Molecular function: GTPase activity;structural molecule activity;structural constituent of cytoskeleton;protein binding;GTP binding;protein domain specific binding;ubiquitin protein ligase binding;GTPase activating protein binding;MHC class I protein binding;protein-containing complex binding