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UniProtKB/Swiss-Prot Q9ULP9: Variant p.Ser178Leu

TBC1 domain family member 24
Gene: TBC1D24
Variant information

Variant position:  178
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 Serine (S) to Leucine (L) at position 178 (S178L, p.Ser178Leu).
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 polar (S) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Deafness, autosomal dominant, 65 (DFNA65) [MIM:616044]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA65 is characterized by post-lingual onset of slowly progressive hearing loss in the third decade. Initially affecting the high frequencies, the hearing loss eventually affects all frequencies and results in severe to profound deafness in the seventh decade. Vestibular function is normal. {ECO:0000269|PubMed:24729539, ECO:0000269|PubMed:24729547}. 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 DFNA65.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  178
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  559
The length of the canonical sequence.

Location on the sequence:   ILACNDPGRRLIDQSFLAFE  S SCMTFGDLVNKYCQAAHKLM
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                         ILACNDPGRRLIDQSFLAFESSCMTFGDLVNKYCQAAHKLM

Mouse                         ILSCNDPTKKLIDQSFLAFESSCMTFGDLVNKYCQAAHKLM

Bovine                        ILACNDSSRKLVDQSFLAFESSCMTFGDLVNKYCQAAHKLM

Xenopus laevis                ILACNDPNRRLVDQTFLAFESSCMTFGDLAGKYCQGPHKLM

Xenopus tropicalis            ILACNDPNRRLVDQTFLAFESSCMTFGDLAGKYCQGPHKLM

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 – 559 TBC1 domain family member 24
Domain 47 – 262 Rab-GAP TBC


Literature citations

A dominant mutation in the stereocilia-expressing gene TBC1D24 is a probable cause for nonsyndromic hearing impairment.
Zhang L.; Hu L.; Chai Y.; Pang X.; Yang T.; Wu H.;
Hum. Mutat. 35:814-818(2014)
Cited for: INVOLVEMENT IN DFNA65; VARIANT DFNA65 LEU-178;

TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss.
Azaiez H.; Booth K.T.; Bu F.; Huygen P.; Shibata S.B.; Shearer A.E.; Kolbe D.; Meyer N.; Black-Ziegelbein E.A.; Smith R.J.;
Hum. Mutat. 35:819-823(2014)
Cited for: VARIANT DFNA65 LEU-178;

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.