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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P11233: Variant p.Val25Met

Ras-related protein Ral-A
Gene: RALA
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Variant information Variant position: help 25 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Valine (V) to Methionine (M) at position 25 (V25M, p.Val25Met). 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: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In HINCONS; decreased GTPase activity; decreased RALA effector binding. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 25 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 206 The length of the canonical sequence.
Location on the sequence: help KPKGQNSLALHKVIMVGSGG V GKSALTLQFMYDEFVEDYEP 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KPKGQNSLALHKVIMVGSGGVGKSALTLQFMYDEFVEDYEP

Mouse                         KPKGQNSLALHKVIMVGSGGVGKSALTLQFMYDEFVEDYEP

Rat                           KPKGQNSLALHKVIMVGSGGVGKSALTLQFMYDEFVEDYEP

Drosophila                    PTAGP---ALHKVIMVGSGGVGKSALTLQFMYDEFVEDYEP
Sequence annotation in neighborhood: help 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 – 203 Ras-related protein Ral-A
Binding site 24 – 29
Mutagenesis 23 – 23 G -> V. Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on interaction with EXOC2 and EXOC8. No effect on cytokinesis; when associated with R-38 or W-48. Decreased interaction with EXOC2 and EXOC8; when associated with R-38 or W-48.
Mutagenesis 38 – 38 E -> R. Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on cytokinesis; when associated with V-23. Decreased interaction with EXOC2 and EXOC8; when associated with V-23.



Literature citations
De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay.
Hiatt S.M.; Neu M.B.; Ramaker R.C.; Hardigan A.A.; Prokop J.W.; Hancarova M.; Prchalova D.; Havlovicova M.; Prchal J.; Stranecky V.; Yim D.K.C.; Powis Z.; Keren B.; Nava C.; Mignot C.; Rio M.; Revah-Politi A.; Hemati P.; Stong N.; Iglesias A.D.; Suchy S.F.; Willaert R.; Wentzensen I.M.; Wheeler P.G.; Brick L.; Kozenko M.; Hurst A.C.E.; Wheless J.W.; Lacassie Y.; Myers R.M.; Barsh G.S.; Sedlacek Z.; Cooper G.M.;
PLoS Genet. 14:e1007671-e1007671(2018)
Cited for: INVOLVEMENT IN HINCONS; VARIANTS HINCONS LEU-25; MET-25; ARG-128; GLY-130; ALA-157; ALA-158 DEL AND 176-ARG--LEU-206 DEL; CHARACTERIZATION OF VARIANTS HINCONS LEU-25; MET-25; GLY-130; ALA-157 AND 176-ARG--LEU-206 DEL; FUNCTION; CATALYTIC ACTIVITY; RALA mutation in a patient with autism spectrum disorder and Noonan syndrome-like phenotype.
Okamoto N.; Takata A.; Miyake N.; Matsumoto N.;
Congenit. Anom. (Kyoto) 59:195-196(2019)
Cited for: VARIANT HINCONS MET-25;
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.