TUBB4A tubulin beta 4A class IVa [Homo sapiens (human)] - Gene

Summary

Official Symbol: TUBB4Aprovided by HGNC
Official Full Name: tubulin beta 4A class IVaprovided by HGNC
Primary source: HGNC:HGNC:20774
See related: Ensembl:ENSG00000104833 MIM:602662; AllianceGenome:HGNC:20774
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DYT4; TUBB4; beta-5
Summary: This gene encodes a member of the beta tubulin family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene cause hypomyelinating leukodystrophy-6 and autosomal dominant torsion dystonia-4. Alternate splicing results in multiple transcript variants encoding different isoforms. A pseudogene of this gene is found on chromosome X. [provided by RefSeq, Jan 2014]
Expression: Biased expression in brain (RPKM 224.5), adrenal (RPKM 54.5) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (6494319..6502848, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (6483817..6492345, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (6494330..6502859, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India.
Title: Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India.
[Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum].
Title: [Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum].
Mutation in the beta-tubulin gene TUBB4A results in epileptic encephalopathy associated with hypomyelinated leucodystrophy: Unexpected findings reveal genetic mosaicism.
Title: Mutation in the β-tubulin gene TUBB4A results in epileptic encephalopathy associated with hypomyelinated leucodystrophy: Unexpected findings reveal genetic mosaicism.
Novel TUBB4A mutation in a family with hereditary spastic paraplegia.
Title: Novel TUBB4A mutation in a family with hereditary spastic paraplegia.
TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3beta/beta-catenin signalling.
Title: TUBB4A interacts with MYH9 to protect the nucleus during cell migration and promotes prostate cancer via GSK3β/β-catenin signalling.
H-ABC- and dystonia-causing TUBB4A mutations show distinct pathogenic effects.
Title: H-ABC- and dystonia-causing TUBB4A mutations show distinct pathogenic effects.
In-silico phenotype prediction by normal mode variant analysis in TUBB4A-related disease.
Title: In-silico phenotype prediction by normal mode variant analysis in TUBB4A-related disease.
Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy.
Title: Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy.
Corpus callosum thinning in autosomal dominant hereditary spastic paraplegia associated with a novel TUBbeta4A mutation.
Title: Corpus callosum thinning in autosomal dominant hereditary spastic paraplegia associated with a novel TUBβ4A mutation.
Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing.
Title: Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hypomyelinating leukodystrophy 6 MedGen: C2676244 OMIM: 612438 GeneReviews: TUBB4A-Related Leukodystrophy	not available
Torsion dystonia 4 MedGen: C1851943 OMIM: 128101 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2014-11-19) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2014-11-19) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	Treatment of cells with actin-depolymerizing agents or tubulin polymerization inhibitors largely reduces the percentage of cells with capped HIV-1 Gag and Env, indicating an intact actin and tubulin cytoskeleton is required for efficient assembly of HIV-1	PubMed
Pr55(Gag)	gag	Treatment of cells with actin-depolymerizing agents or tubulin polymerization inhibitors largely reduces the percentage of cells with capped HIV-1 Gag and Env, indicating an intact actin and tubulin cytoskeleton is required for efficient assembly of HIV-1	PubMed
Rev	rev	HIV-1 Rev interacting protein, tubulin beta 4 (TUBB4A), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed
	rev	Rev acts to depolymerize microtubules that are formed by tubulin, an effect that is observed during HIV-1 infection	PubMed
Tat	tat	HIV-1 Tat K29A, K50R, and K51R lysine mutations downregulate the proportion of soluble tubulin in cells, while the majority of other lysine mutations upregulate the percentage of soluble tubulin compared with the wild-type	PubMed
	tat	In Jurkat cells expressing HIV-1 Tat, decreased expression levels are found for basic cytoskeletal proteins such as actin, beta-tubulin, annexin, cofilin, gelsolin, and Rac/Rho-GDI complex	PubMed
	tat	HIV-1 Tat (specifically, amino acids 38-72), enhances tubulin polymerization and triggers the mitochondrial pathway to induce T cell apoptosis as shown in vitro by the release of cytochrome c from isolated mitochondria	PubMed
	tat	HIV-1 Tat (amino acids 36-39) binds tubulin alpha/beta dimers and polymerized microtubules leading to the alteration of microtubule dynamics and activation of a mitochondria-dependent apoptotic pathway that is facilitated by the Bcl-2 relative Bim	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC156124P3 (e-PCR)
- UniSTS:271361

A002C41 (e-PCR)
- UniSTS:37395

RH66664 (e-PCR)
- UniSTS:44829

G19977 (e-PCR)
- UniSTS:16171

PMC314434P2 (e-PCR)
- UniSTS:272948

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in microtubule cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of microtubule polymerization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in axoneme	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in intercellular bridge	IDA Inferred from Direct Assay more info
located_in internode region of axon	IEA Inferred from Electronic Annotation more info
is_active_in microtubule	IBA Inferred from Biological aspect of Ancestor more info
located_in microtubule	IDA Inferred from Direct Assay more info	PubMed
located_in microtubule cytoskeleton	IDA Inferred from Direct Assay more info
located_in mitotic spindle	IDA Inferred from Direct Assay more info
located_in myelin sheath	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in nucleus	HDA more info	PubMed

General protein information

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Preferred Names: tubulin beta-4A chain

Names: dystonia 4, torsion (autosomal dominant); tubulin beta-4 chain; tubulin, beta 4; tubulin, beta, 5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033896.1 RefSeqGene

Range

5540..13530

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001289123.2 → NP_001276052.1 tubulin beta-4A chain isoform 1

See identical proteins and their annotated locations for NP_001276052.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC010503, BC013683, DC303150

UniProtKB/TrEMBL

M0QZL7, Q8IZ29, Q8N6N5

Related

ENSP00000470627.2, ENST00000598635.2

Conserved Domains (2) summary

PLN00220
Location:52 → 478

PLN00220; tubulin beta chain; Provisional

cd02187
Location:53 → 477

beta_tubulin; The beta-tubulin family
NM_001289127.2 → NP_001276056.1 tubulin beta-4A chain isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate splice site in the 5' coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.

Source sequence(s)

AC010503, AK075307, BC013683, DC354036

UniProtKB/TrEMBL

M0R278, Q8IZ29, Q8N6N5

Related

ENSP00000472375.2, ENST00000597686.6

Conserved Domains (1) summary

PLN00220
Location:46 → 472

PLN00220; tubulin beta chain; Provisional
NM_001289129.2 → NP_001276058.1 tubulin beta-4A chain isoform 3

See identical proteins and their annotated locations for NP_001276058.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an alternate splice site in the 5' region, which results in translation initiation at a downstream AUG codon, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1. Both variants 3 and 4 encode the same isoform 3.

Source sequence(s)

AC010503, BC013683, DC353527

Consensus CDS

CCDS12168.1

UniProtKB/Swiss-Prot

B3KQP4, P04350, Q969E5

UniProtKB/TrEMBL

Q8IZ29, Q8N6N5

Conserved Domains (1) summary

PLN00220
Location:1 → 427

PLN00220; tubulin beta chain; Provisional
NM_001289130.2 → NP_001276059.1 tubulin beta-4A chain isoform 4

See identical proteins and their annotated locations for NP_001276059.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and translation initiation at a downstream start codon, compared to variant 1. The resulting isoform (4) has a shorter N-terminus, compared to isoform 1. Both variants 5 and 6 encode the same isoform 4.

Source sequence(s)

BC013683, DA265791

UniProtKB/TrEMBL

B4DQN9, B7ZAK1, M0R1I1

Conserved Domains (1) summary

PLN00220
Location:1 → 355

PLN00220; tubulin beta chain; Provisional
NM_001289131.2 → NP_001276060.1 tubulin beta-4A chain isoform 4

See identical proteins and their annotated locations for NP_001276060.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and translation initiation at a downstream start codon, compared to variant 1. The resulting isoform (4) has a shorter N-terminus, compared to isoform 1. Both variants 5 and 6 encode the same isoform 4.

Source sequence(s)

BC013683, DA302559, DC314277

UniProtKB/TrEMBL

B4DQN9, B7ZAK1, M0R1I1

Related

ENSP00000471880.2, ENST00000596291.2

Conserved Domains (1) summary

PLN00220
Location:1 → 355

PLN00220; tubulin beta chain; Provisional
NM_006087.4 → NP_006078.2 tubulin beta-4A chain isoform 3

See identical proteins and their annotated locations for NP_006078.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and lacks a portion of the 5' coding region, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1. Both variants 3 and 4 encode the same isoform 3.

Source sequence(s)

BC013683

Consensus CDS

CCDS12168.1

UniProtKB/Swiss-Prot

B3KQP4, P04350, Q969E5

UniProtKB/TrEMBL

Q8IZ29, Q8N6N5

Related

ENSP00000264071.1, ENST00000264071.7

Conserved Domains (1) summary

PLN00220
Location:1 → 427

PLN00220; tubulin beta chain; Provisional