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UniProtKB/Swiss-Prot Q9NZC2: Variant p.Ala28Val

Triggering receptor expressed on myeloid cells 2
Gene: TREM2
Variant information

Variant position:  28
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 Alanine (A) to Valine (V) at position 28 (A28V, p.Ala28Val).
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 (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 late onset Alzheimer disease; unknown pathological significance; increases cell membrane localization.
Any additional useful information about the variant.

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



Sequence information

Variant position:  28
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  230
The length of the canonical sequence.

Location on the sequence:   ILLFVTELSGAHNTTVFQGV  A GQSLQVSCPYDSMKHWGRRK
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                         ILLFVTELSGAHNTTVFQGVAGQSLQVSCPYDSMKHWGRRK

Mouse                         LLLLITALSQALNTTVLQGMAGQSLRVSCTYDALKHWGRRK

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 19 – 230 Triggering receptor expressed on myeloid cells 2
Topological domain 19 – 174 Extracellular
Glycosylation 20 – 20 N-linked (GlcNAc...) asparagine
Mutagenesis 20 – 20 N -> D. Loss of glycosylation.
Mutagenesis 36 – 36 C -> A. Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization.
Mutagenesis 48 – 48 K -> M. Loss of LDL, CLU and APOE binding.


Literature citations

Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression.
Sirkis D.W.; Bonham L.W.; Aparicio R.E.; Geier E.G.; Ramos E.M.; Wang Q.; Karydas A.; Miller Z.A.; Miller B.L.; Coppola G.; Yokoyama J.S.;
Acta Neuropathol. Commun. 4:98-98(2016)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS MET-27; VAL-28; PHE-31; CYS-38; CYS-47; HIS-47; ASN-87; SER-130; GLN-136; TRP-136; LYS-151; ARG-162 AND ILE-223;

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.