UniProtKB/Swiss-Prot Q9NZC2: Variant p.His157Tyr

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

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

LB/B 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 Histidine (H) to Tyrosine (Y) at position 157 (H157Y, p.His157Tyr). 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 medium size and polar (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

2 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:

Probable risk factor for late-onset Alzheimer disease; accelerates ectodomain shedding but does not alter the cleavage site; decreases cell membrane localization; decreases phagocytosis. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2234255 [ dbSNP | Ensembl ]

Sequence information Variant position:

157 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:

DAGDLWFPGESESFEDAHVE H SISRSLLEGEIPFPPTSILL 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                         DAGDLWFPGESESFEDAHVEHSISRSLLEGEIPFPPTSILL

Mouse                         DAGDLWVPEESSSFEGAQVEHSTSRN---QETSFPPTSILL

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	19 – 230	Triggering receptor expressed on myeloid cells 2
Topological domain	19 – 174	Extracellular
Site	157 – 158	Cleavage of ectodomain

Literature citations
A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese.
Jiang T.; Tan L.; Chen Q.; Tan M.S.; Zhou J.S.; Zhu X.C.; Lu H.; Wang H.F.; Zhang Y.D.; Yu J.T.;
Neurobiol. Aging 42:E1-E3(2016)
Cited for: VARIANTS TYR-157 AND THR-192; VARIANTS CYS-183 AND CYS-200 (ISOFORM 2); An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.
Schlepckow K.; Kleinberger G.; Fukumori A.; Feederle R.; Lichtenthaler S.F.; Steiner H.; Haass C.;
EMBO Mol. Med. 9:1356-1365(2017)
Cited for: SUBCELLULAR LOCATION; PROTEOLYTIC PROCESSING; CHARACTERIZATION OF VARIANT TYR-157; TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant.
Thornton P.; Sevalle J.; Deery M.J.; Fraser G.; Zhou Y.; Staahl S.; Franssen E.H.; Dodd R.B.; Qamar S.; Gomez Perez-Nievas B.; Nicol L.S.; Eketjaell S.; Revell J.; Jones C.; Billinton A.; St George-Hyslop P.H.; Chessell I.; Crowther D.C.;
EMBO Mol. Med. 9:1366-1378(2017)
Cited for: SUBCELLULAR LOCATION; TISSUE SPECIFICITY; PROTEOLYTIC PROCESSING; CHARACTERIZATION OF VARIANT TYR-157;

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.