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UniProtKB/Swiss-Prot P51159: Variant p.Ala152Pro

Ras-related protein Rab-27A
Gene: RAB27A
Variant information

Variant position:  152
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 Proline (P) at position 152 (A152P, p.Ala152Pro).
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 (P)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Griscelli syndrome 2 (GS2) [MIM:607624]: Rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. GS2 patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome, known as hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation. Neurological impairment is present in some patients, likely as a result of hemophagocytic syndrome. {ECO:0000269|PubMed:10835631, ECO:0000269|PubMed:12446441, ECO:0000269|PubMed:12531900, ECO:0000269|PubMed:15548590}. 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 GS2; interferes with melanosome transport.
Any additional useful information about the variant.

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

Sequence information

Variant position:  152
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  221
The length of the canonical sequence.

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.






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.

Chain 2 – 221 Ras-related protein Rab-27A
Disulfide bond 123 – 188
Alternative sequence 146 – 153 Missing. In isoform Short.
Helix 145 – 155

Literature citations

Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome.
Menasche G.; Pastural E.; Feldmann J.; Certain S.; Ersoy F.; Dupuis S.; Wulffraat N.; Bianchi D.; Fischer A.; Le Deist F.; de Saint Basile G.;
Nat. Genet. 25:173-176(2000)
Cited for: VARIANTS GS2 GLY-73; PRO-130 AND PRO-152;

Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients.
Menasche G.; Feldmann J.; Houdusse A.; Desaymard C.; Fischer A.; Goud B.; de Saint Basile G.;
Blood 101:2736-2742(2003)

Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome.
Bahadoran P.; Busca R.; Chiaverini C.; Westbroek W.; Lambert J.; Bille K.; Valony G.; Fukuda M.; Naeyaert J.-M.; Ortonne J.-P.; Ballotti R.;
J. Biol. Chem. 278:11386-11392(2003)

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.