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UniProtKB/Swiss-Prot Q15907: Variant p.Val22Met

Ras-related protein Rab-11B
Gene: RAB11B
Variant information

Variant position:  22
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 Valine (V) to Methionine (M) at position 22 (V22M, p.Val22Met).
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:  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:  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:  Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (NDAGSCW) [MIM:617807]: An autosomal dominant neurodevelopmental disorder apparent in infancy and characterized by severe intellectual disability with absent speech, epilepsy, and hypotonia. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly can be present. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem. {ECO:0000269|PubMed:29106825}. 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 NDAGSCW.
Any additional useful information about the variant.

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



Sequence information

Variant position:  22
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  218
The length of the canonical sequence.

Location on the sequence:   GTRDDEYDYLFKVVLIGDSG  V GKSNLLSRFTRNEFNLESKS
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                         GTRDDEYDYLFKVVLIGDSGVGKSNLLSRFTRNEFNLESKS

Mouse                         GTRDDEYDYLFKVVLIGDSGVGKSNLLSRFTRNEFNLESKS

Rat                           GTRDDEYDYLFKVVLIGDSGVGKSNLLSRFTRNEFNLESKS

Bovine                        GTRDDEYDYLFKVVLIGDSGVGKSNLLSRFTRNEFNLESKS

Slime mold                    VLKTIEYDYLCKIVVIGDSGVGKSNLLSRYNKNEFSVGKLS

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 2 – 215 Ras-related protein Rab-11B
Nucleotide binding 18 – 26 GTP
Modified residue 2 – 2 N-acetylglycine
Modified residue 4 – 4 Citrulline
Mutagenesis 25 – 25 S -> N. Dominant negative mutant locked in the inactive GDP-bound form; alters apical recycling. Does not interact with ZFYV2E and KIF5A.


Literature citations

Recurrent de novo mutations disturbing the GTP/GDP binding pocket of RAB11B cause intellectual disability and a distinctive brain phenotype.
Lamers I.J.C.; Reijnders M.R.F.; Venselaar H.; Kraus A.; Jansen S.; de Vries B.B.A.; Houge G.; Gradek G.A.; Seo J.; Choi M.; Chae J.H.; van der Burgt I.; Pfundt R.; Letteboer S.J.F.; van Beersum S.E.C.; Dusseljee S.; Brunner H.G.; Doherty D.; Kleefstra T.; Roepman R.;
Am. J. Hum. Genet. 101:824-832(2017)
Cited for: INVOLVEMENT IN NDAGSCW; VARIANTS NDAGSCW MET-22 AND THR-68;

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.