Home  |  Contact

UniProtKB/Swiss-Prot O75030: Variant p.Ala294Thr

Microphthalmia-associated transcription factor
Gene: MITF
Variant information

Variant position:  294
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Threonine (T) at position 294 (A294T, p.Ala294Thr).
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 polar (T)
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:  Waardenburg syndrome 2A (WS2A) [MIM:193510]: WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1. {ECO:0000269|PubMed:28236341, ECO:0000269|PubMed:8589691}. 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 WS2A; unknown pathological significance.
Any additional useful information about the variant.



Sequence information

Variant position:  294
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  526
The length of the canonical sequence.

Location on the sequence:   GLTISNSCPANLPNIKRELT  A CIFPTESEARALAKERQKKD
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                         GLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKD

Mouse                         GLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKD

Rat                           GLTISNSCPANLPNIKRELTACIFPTESEARALAKERQKKD

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 – 526 Microphthalmia-associated transcription factor
Region 224 – 295 Transactivation
Cross 289 – 289 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Alternative sequence 293 – 298 Missing. In isoform Mdel and isoform 12.
Alternative sequence 294 – 299 Missing. In isoform A2, isoform B2, isoform C2, isoform H2 and isoform M2.
Mutagenesis 289 – 289 K -> R. Loss of sumoylation; when associated with R-423.


Literature citations

EDNRB mutations cause Waardenburg syndrome type II in the heterozygous state.
Issa S.; Bondurand N.; Faubert E.; Poisson S.; Lecerf L.; Nitschke P.; Deggouj N.; Loundon N.; Jonard L.; David A.; Sznajer Y.; Blanchet P.; Marlin S.; Pingault V.;
Hum. Mutat. 38:581-593(2017)
Cited for: VARIANT WS2A THR-294;

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.