UniProtKB/Swiss-Prot Q9NZC2: Variant p.Tyr38Cys

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

38 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 Tyrosine (Y) to Cysteine (C) at position 38 (Y38C, p.Tyr38Cys). 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 large size and aromatic (Y) to medium size and polar (C) 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:

Results in defective protein maturation and trafficking; loss of proteolytic cleavage by ADAM10 and ectodomain shedding; increases protein aggregation; decreases cell membrane localization; decreased phagocytosis; loss of LDL, CLU and APOE binding; greatly decreases LDL and CLU uptake into cells. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs797044603 [ dbSNP | Ensembl ]

Sequence information Variant position:

38 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:

AHNTTVFQGVAGQSLQVSCP Y DSMKHWGRRKAWCRQLGEKG 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                         AHNTTVFQGVAGQSLQVSCPYDSMKHWGRRKAWCRQLGEKG

Mouse                         ALNTTVLQGMAGQSLRVSCTYDALKHWGRRKAWCRQLGEEG

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
Domain	29 – 112	Ig-like V-type
Glycosylation	20 – 20	N-linked (GlcNAc...) asparagine
Disulfide bond	36 – 110
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
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis.
Kleinberger G.; Yamanishi Y.; Suarez-Calvet M.; Czirr E.; Lohmann E.; Cuyvers E.; Struyfs H.; Pettkus N.; Wenninger-Weinzierl A.; Mazaheri F.; Tahirovic S.; Lleo A.; Alcolea D.; Fortea J.; Willem M.; Lammich S.; Molinuevo J.L.; Sanchez-Valle R.; Antonell A.; Ramirez A.; Heneka M.T.; Sleegers K.; van der Zee J.; Martin J.J.; Engelborghs S.; Demirtas-Tatlidede A.; Zetterberg H.; Van Broeckhoven C.; Gurvit H.; Wyss-Coray T.; Hardy J.; Colonna M.; Haass C.;
Sci. Transl. Med. 6:243RA86-243RA86(2014)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PROTEOLYTIC PROCESSING; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47 AND MET-66; MUTAGENESIS OF CYS-36 AND CYS-60; 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; TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia.
Yeh F.L.; Wang Y.; Tom I.; Gonzalez L.C.; Sheng M.;
Neuron 91:328-340(2016)
Cited for: FUNCTION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66 AND ASN-87; MUTAGENESIS OF LYS-48; Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment.
Sirkis D.W.; Aparicio R.E.; Schekman R.;
Mol. Biol. Cell 28:2723-2733(2017)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS CYS-38 AND MET-66; CHARACTERIZATION OF VARIANTS PLOSL2 GLY-126; GLY-134 AND ASN-186; Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms.
Kober D.L.; Alexander-Brett J.M.; Karch C.M.; Cruchaga C.; Colonna M.; Holtzman M.J.; Brett T.J.;
Elife 5:E20391-E20391(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 19-133; DISULFIDE BONDS; SUBUNIT; SUBCELLULAR LOCATION; MUTAGENESIS OF ASN-68; ARG-76 AND ARG-77; GLYCOSYLATION AT ASN-79; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47; HIS-62; MET-66; ASN-87 AND LYS-96; CHARACTERIZATION OF VARIANT PLOSL2 GLY-126; Disease-associated mutations of TREM2 alter the processing of N-linked oligosaccharides in the Golgi apparatus.
Park J.S.; Ji I.J.; An H.J.; Kang M.J.; Kang S.W.; Kim D.H.; Yoon S.Y.;
Traffic 16:510-518(2015)
Cited for: CHARACTERIZATION OF VARIANT PLOSL2 33-GLN--THR-230 DEL; CHARACTERIZATION OF VARIANTS CYS-38; HIS-47 AND MET-66; SUBCELLULAR LOCATION;

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.