GeneBe

TUBB

protein-coding

tubulin beta class I, the group of Tubulins

Gene summary

This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13. [provided by RefSeq, Jun 2014]

MANE transcript

NM_178014.4

Inheritance

AD

ClinVar variants

P:48U:71B:7

Top phenotype

Congenital symmetric circumferential skin creases 1; Cortical dysplasia, complex, with other brain malformations 6

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr6:30,717,435-30,725,538

External References & Databases

Ensembl (ENSG00000196230)NCBI Gene (203068)OMIM (191130)HGNC:20778GenCCUniProt (P07437)AlphaFoldClinVar (TUBB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~8.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex cortical dysplasia with other brain malformations 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014341

Submitter: PanelApp Australia

complex cortical dysplasia with other brain malformations 6STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014341

Submitter: Labcorp Genetics (formerly Invitae)

skin creases, congenital symmetric circumferential, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020738

Submitter: G2P

skin creases, congenital symmetric circumferential, 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0020738

Submitter: Ambry Genetics

TUBB3-related tubulinopathyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100154

Submitter: Illumina

multiple benign circumferential skin creases on limbsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007990

Submitter: Orphanet

complex cortical dysplasia with other brain malformations 6MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014341

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Congenital symmetric circumferential skin creases 1; Cortical dysplasia, complex, with other brain malformations 6AD

Manifestation: Craniofacial; Dermatologic; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 12239728; 23246003; 23324645; 26637975Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TUBB variants in ClinVar

16 Conditions Cataloged
not providedTotal: 82
Complex cortical dysplasia with other brain malformations 6Total: 41
Inborn genetic diseasesTotal: 18
Skin creases, congenital symmetric circumferential, 1Total: 14
TUBB-related disorderTotal: 9
not specifiedTotal: 7
VentriculomegalyTotal: 1
TUBB-related tubulinopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178014.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
1
clinvar
 6
missense
10
clinvar
37
clinvar
61
clinvar
1
clinvar
 109
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
6
clinvar
 7
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total11377161126
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_178014.4RefSeqNP_821133.14MANE Select
ENST00000327892.13EnsemblENSP00000339001.74MANE Select
NM_001293212.2RefSeqNP_001280141.14Standard
NM_001293213.2RefSeqNP_001280142.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • G2/M transition of mitotic cell cycle
  • microtubule cytoskeleton organization
  • mitotic cell cycle
  • microtubule-based process
  • cellular process

Molecular Function

  • GTPase activity
  • structural molecule activity
  • structural constituent of cytoskeleton
  • protein binding
  • GTP binding

Cellular Component

  • extracellular region
  • nucleus
  • nuclear envelope lumen
  • cytoplasm
  • cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000327892
Coding exons
4
Length
5226
Individuals with no LoFs
125668
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125670
p
0.00000796
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense5.63182850.06310.00001712954
Missense (PolyPhen)3135.20.022191401
Synonymous0.3011061100.9640.00000689875
Loss of Function3.50116.20.06179.30e-7164

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool
0.115
RVIS EVS
-0.14
RVIS percentile EVS
42.88

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.974
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