UniProtKB/Swiss-Prot Q7L5A8: Variant p.Asp35Tyr

Fatty acid 2-hydroxylase
Gene: FA2H
Chromosomal location: 16q23.1
Variant information

Variant position:  35
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Aspartate (D) to Tyrosine (Y) at position 35 (D35Y, p.Asp35Tyr).
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 medium size and acidic (D) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Spastic paraplegia 35, autosomal recessive (SPG35) [MIM:612319]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur. 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 SPG35; patients present spastic paraparesis associated with leukodystrophy and dystonia.
Any additional useful information about the variant.



Sequence information

Variant position:  35
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  372
The length of the canonical sequence.

Location on the sequence:   EVQRRLAAGACWVRRGARLY  D LSSFVRHHPGGEQLLRARAG
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                         EVQRRLAAGACWVRRGARLYDLSSFVRHHPGGEQLLRARAG

Mouse                         EVQRRLAAGACWVRRGASLYDLTSFVRHHPGGEQLLLARAG

Rat                           EVQRRLAAGACWVRRGASLYDLTGFVRHHPGGEQLLLARAG

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 – 372 Fatty acid 2-hydroxylase
Domain 8 – 86 Cytochrome b5 heme-binding
Metal binding 43 – 43 Iron (heme axial ligand)


Literature citations

Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.
Edvardson S.; Hama H.; Shaag A.; Gomori J.M.; Berger I.; Soffer D.; Korman S.H.; Taustein I.; Saada A.; Elpeleg O.;
Am. J. Hum. Genet. 83:643-648(2008)
Cited for: VARIANT SPG35 TYR-35;

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.