TUBB4A |
- 0
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- TUBB4A (HGNC:20774) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- tubulin beta 4A class IVa
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- TUBB4, DYT4
- Alias symbols
- beta-5
- %HI
- 42.56(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.11(Read more about gnomAD pLI score)
- LOEUF
- 0.67(Read more about gnomAD LOEUF score)
- Cytoband
- 19p13.3
- Genomic Coordinates
-
GRCh37/hg19: chr19:6494330-6502859 NCBI Ensembl UCSC GRCh38/hg38: chr19:6494319-6502848 NCBI Ensembl UCSC - MANE Select Transcript
- NM_006087.4 ENST00000264071.7 (Read more about MANE Select)
- Function
- Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-24487
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency
(0)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
11/19/2014
Haploinsufficiency (HI) Score Details
HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence Comments:
Variants in TUBB4A have been associated with autosomal dominant torsion dystonia 4 (OMIM:128101) and hypomyelinating leukodystrophy 6 (OMIM: 612438). Hamilton et al. 2014 (PMID:24785942) remark that, thus far, only heterozygous missense variants have been reported in TUBB4A, and hypothesize that TUBB4A-associated conditions are caused by "dominant negative, toxic effects." They also postulate that TUBB4A-associated disorders represent "a continuum with the two known phenotypes (autosomal dominant torsion dystonia 4 and hypomyelinating leukodystrophy 6) as extremes," with the only shared features being "the occurrence of extrapyramidal signs." Since the mechanism by which TUBB4A variants result in human disease is not yet understood, the haploinsufficiency and triplosensitivity scores for this gene will remain a 0 at this time.
In regards to autosomal dominant torsion dystonia 4 (DYT4): Lohmann et al. (2013)(PMID:23595291) describe a missense variant (Arg2Gly) in the N-terminal autoregulatory domain segregating with disease in a multi-generational Australian family with "whispering dystonia" found by genome sequencing after linkage implicated a 23cM region on 19p13.3-p13.2. Another variant, a missense variant in DOT1L, was also detected in the 9 affected individuals tested. This variant was dismissed as potentially causative by the authors because it was also detected in several unaffected family members that had passed the latest observed age of onset of DYT4, and variants in DOT1L are observed at much higher frequencies in control populations than variants in TUBB4A. mRNA analysis revealed decreased mutant RNA levels using 2 different methods in 3 different cell types. No additional functional studies were performed. Subsequent TUBB4A sequencing in 394 unrelated dystonia patients identified another missense TUBB4A variant in a 71-year-old affected female, whose reportedly affected mother was deceased and unavailable for segregation analysis.
Additional reports of missense variants in patients with the above phenotypes include: PMIDs 25168210, 25085639, 24974158, 24850488, 24742798, 24706558, 24526230, 23582646, 23424103.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000019.9)
(NC_000019.10)