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UniProtKB/Swiss-Prot Q9Y4W6: Variant p.Tyr689His

AFG3-like protein 2
Gene: AFG3L2
Variant information

Variant position:  689
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 Tyrosine (Y) to Histidine (H) at position 689 (Y689H, p.Tyr689His).
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 large size and aromatic (Y) to medium size and polar (H)
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:  Spinocerebellar ataxia 28 (SCA28) [MIM:610246]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment. {ECO:0000269|PubMed:20208537, ECO:0000269|PubMed:20354562, ECO:0000269|PubMed:20725928, ECO:0000269|PubMed:24293060, ECO:0000269|PubMed:26677414, ECO:0000269|PubMed:29053796}. 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 SCA28.
Any additional useful information about the variant.



Sequence information

Variant position:  689
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  797
The length of the canonical sequence.

Location on the sequence:   KVGQISFDLPRQGDMVLEKP  Y SEATARLIDDEVRILINDAY
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                         KVGQISFDLPRQGDMVLEKPYSEATARLIDDEVRILINDAY

Mouse                         KVGQISFDLPRQGDMVLEKPYSEATARMIDDEVRILISDAY

Bovine                        KVGQISFDLPRQGDMVLEKPYSEATARLIDDEVRILINDAY

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 67 – 797 AFG3-like protein 2


Literature citations

A novel missense mutation in AFG3L2 associated with late onset and slow progression of spinocerebellar ataxia type 28.
Loebbe A.M.; Kang J.S.; Hilker R.; Hackstein H.; Mueller U.; Nolte D.;
J. Mol. Neurosci. 52:493-496(2014)
Cited for: VARIANT SCA28 HIS-689;

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.