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UniProtKB/Swiss-Prot Q9BTW9: Variant p.Ala586Val

Tubulin-specific chaperone D
Gene: TBCD
Variant information

Variant position:  586
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Valine (V) at position 586 (A586V, p.Ala586Val).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from small size and hydrophobic (A) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum (PEBAT) [MIM:617193]: An autosomal recessive disease with neurodevelopmental and neurodegenerative features. PEBAT is characterized by early-onset cortical atrophy, hypomyelination, microcephaly, thin corpus callosum, delayed psychomotor development, developmental regression, intellectual disability, seizures, optic atrophy, muscle weakness and atrophy, spastic quadriplegia, and respiratory insufficiency due to hypotonia. {ECO:0000269|PubMed:27666370, ECO:0000269|PubMed:27666374, ECO:0000269|PubMed:27807845, ECO:0000269|PubMed:28158450}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PEBAT; decreased function in tubulin complex assembly.
Any additional useful information about the variant.



Sequence information

Variant position:  586
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1192
The length of the canonical sequence.

Location on the sequence:   HLVTMKISHWDGVIRELAAR  A LHNLAQQAPEFSATQVFPRL
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         HLVTMKISHWDGVIRELAARALHNLAQQAPEFSATQVFPRL

Mouse                         HLVSMKINHWDGAIRELSAKALHNLTPQVPEYIAMHVFPAL

Bovine                        HLVTMKVGHWDGTIRELSAKALRNLAQRAPEHTAREVFPRL

Chicken                       HLVNMKINHWDSVIRELSTKALHNLTPRAPEYMANVVLPRL

Caenorhabditis elegans        HLITKKVVHWDEKIREQAAISLEKISEIRLENVSDDYYMEI

Slime mold                    HLATIKIYNWDLEIRQLASKSIHLLTNINPNDIVSNYLPLI

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 1192 Tubulin-specific chaperone D
Repeat 557 – 594 HEAT 2
Alternative sequence 1 – 1008 Missing. In isoform 2.


Literature citations

Infantile neurodegenerative disorder associated with mutations in TBCD, an essential gene in the tubulin heterodimer assembly pathway.
Edvardson S.; Tian G.; Cullen H.; Vanyai H.; Ngo L.; Bhat S.; Aran A.; Daana M.; Da'amseh N.; Abu-Libdeh B.; Cowan N.J.; Heng J.; Elpeleg O.;
Hum. Mol. Genet. 25:4635-4648(2016)
Cited for: FUNCTION; VARIANTS PEBAT THR-475 AND VAL-586; CHARACTERIZATION OF VARIANTS PEBAT THR-475 AND VAL-586;

Microcephaly, intractable seizures and developmental delay caused by biallelic variants in TBCD: further delineation of a new chaperone-mediated tubulinopathy.
Pode-Shakked B.; Barash H.; Ziv L.; Gripp K.W.; Flex E.; Barel O.; Carvalho K.S.; Scavina M.; Chillemi G.; Niceta M.; Eyal E.; Kol N.; Ben-Zeev B.; Bar-Yosef O.; Marek-Yagel D.; Bertini E.; Duker A.L.; Anikster Y.; Tartaglia M.; Raas-Rothschild A.;
Clin. Genet. 91:725-738(2017)
Cited for: VARIANTS PEBAT THR-475; VAL-586 AND ARG-937;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.