UniProtKB/Swiss-Prot O43914: Variant p.Val55Leu

TYRO protein tyrosine kinase-binding protein
Gene: TYROBP
Feedback?

Variant information Variant position:

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

US 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:

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; uncertain 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.

Variant rs77782321 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
Chain	22 – 113	TYRO protein tyrosine kinase-binding protein
Transmembrane	41 – 61	Helical
Binding site	50 – 50
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. Impairs the expression of KLRD1-KLRC2 on the cell surface.
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.