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UniProtKB/Swiss-Prot O43914: Variant p.Val55Leu

TYRO protein tyrosine kinase-binding protein
Gene: TYROBP
Variant information

Variant position:  55
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Leucine (L) at position 55 (V55L, p.Val55Leu).
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

Variant description:  Found in patients with early-onset Alzheimer disease; unknown pathological significance; associated in cis with E-2 in some patients.
Any additional useful information about the variant.

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



Sequence information

Variant position:  55
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  113
The length of the canonical sequence.

Location on the sequence:   CSTVSPGVLAGIVMGDLVLT  V LIALAVYFLGRLVPRGRGAA
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                         CSTVSPGVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAA

Rhesus macaque                CSTVSPGVLAGIVLGDLVLTVLIALAVYFLGRLVPRGRGAA

Chimpanzee                    CSTVSPGVLAGIVMGDLVLTVLIALAVYFLGRLVHRGRGAA

Mouse                         CSSVSPGVLAGIVLGDLVLTLLIALAVYSLGRLVSRGQGTA

Rat                           CSSVSPGVLAGIVLGDLVLTLLIALAVYSLGRLVSRGRGTA

Pig                           CSAVSPGILAGIVLGDLVLTLLIALAVYSLGRLVPRTRGAV

Bovine                        CSSVSPGVLAGIVLGDLMLTLLIALAVYYLGRLVPRGRGAT

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 22 – 113 TYRO protein tyrosine kinase-binding protein
Transmembrane 41 – 61 Helical
Metal binding 50 – 50 Metal cation; shared with neighboring subunit in homooligomer
Site 54 – 54 Important for interaction with transmembrane receptors
Disulfide bond 35 – 35 Interchain
Mutagenesis 41 – 41 G -> L. Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-45 and L-49.
Mutagenesis 45 – 45 G -> L. Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-41 and L-49.
Mutagenesis 49 – 49 G -> L. Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-41 and L-45.
Mutagenesis 50 – 50 D -> A. Reduced cell surface expression of KIR2DS1. Severely impairs formation of homotrimers and homotetramers. Abolishes interaction with TREM2 and stabilization of TREM2-CTF.
Mutagenesis 50 – 50 D -> EQ. Severely impairs formation of homotrimers and homotetramers.
Mutagenesis 50 – 50 D -> N. Reduces formation of homotrimers and homotetramers.
Mutagenesis 54 – 54 T -> A. Reduced interaction with KLRC2 and KIR2DS3. Reduces homotrimer formation and increases homotetramer formation.
Helix 40 – 65


Literature citations

TYROBP genetic variants in early-onset Alzheimer's disease.
Pottier C.; Ravenscroft T.A.; Brown P.H.; Finch N.A.; Baker M.; Parsons M.; Asmann Y.W.; Ren Y.; Christopher E.; Levitch D.; van Blitterswijk M.; Cruchaga C.; Campion D.; Nicolas G.; Richard A.C.; Guerreiro R.; Bras J.T.; Zuchner S.; Gonzalez M.A.; Bu G.; Younkin S.; Knopman D.S.; Josephs K.A.; Parisi J.E.; Petersen R.C.; Ertekin-Taner N.; Graff-Radford N.R.; Boeve B.F.; Dickson D.W.; Rademakers R.;
Neurobiol. Aging 48:222.E9-222.E15(2016)
Cited for: VARIANTS GLU-2; CYS-23; ALA-47; PRO-ALA-ASP-GLY-ARG-LEU-VAL-LEU-GLY-ASP-ARG-ASP-GLY-ARG-50 INS; LEU-55; TRP-80; VAL-84 AND LEU-89;

Mutations in TYROBP are not a common cause of dementia in a Turkish cohort.
Darwent L.; Carmona S.; Lohmann E.; Guven G.; Kun-Rodrigues C.; Bilgic B.; Hanagasi H.; Gurvit H.; Erginel-Unaltuna N.; Pak M.; Hardy J.; Singleton A.; Bras J.; Guerreiro R.;
Neurobiol. Aging 58:240.E1-240.E3(2017)
Cited for: VARIANT LEU-55;

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.