UniProtKB/Swiss-Prot O15118: Variant p.Thr137Met

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 137 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Threonine (T) to Methionine (M) at position 137 (T137M, p.Thr137Met). 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 (T) to medium size and hydrophobic (M) 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: In NPC1. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs372947142 [ dbSNP | Ensembl ]

Sequence information

Variant position: 137 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 1278 The length of the canonical sequence.
Location on the sequence: QSQFLNVTATEDYVDPVTNQ T KTNVKELQYYVGQSFANAMY 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.
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	23 – 1278	NPC intracellular cholesterol transporter 1
Topological domain	23 – 261	Lumenal
Glycosylation	122 – 122	N-linked (GlcNAc...) asparagine
Glycosylation	135 – 135	N-linked (GlcNAc...) asparagine
Disulfide bond	97 – 238
Disulfide bond	100 – 160
Alternative sequence	1 – 267	Missing. In isoform 2.
Mutagenesis	25 – 257	Missing. Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1.
Mutagenesis	122 – 122	N -> Q. Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding.
Beta strand	137 – 148

Literature citations

Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1.
Sun X.; Marks D.L.; Park W.D.; Wheatley C.L.; Puri V.; O'Brien J.F.; Kraft D.L.; Lundquist P.A.; Patterson M.C.; Pagano R.E.; Snow K.;
Am. J. Hum. Genet. 68:1361-1372(2001)
Cited for: VARIANTS NPC1 ARG-92; MET-137; ASN-242; VAL-248; THR-401; GLN-404; ASP-612; TRP-652; CYS-789; CYS-825; VAL-874; SER-888; PRO-929; LEU-940; ASN-944; ASN-948; GLN-958; ARG-976; CYS-978; LEU-1004; ALA-1007; GLY-1023; THR-1061; LYS-1089; THR-1142; LYS-1150; SER-1156; MET-1165; HIS-1186 AND GLY-1189; VARIANT SER-237; Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations.
Fernandez-Valero E.M.; Ballart A.; Iturriaga C.; Lluch M.; Macias J.; Vanier M.T.; Pineda M.; Coll M.J.;
Clin. Genet. 68:245-254(2005)
Cited for: VARIANTS NPC1 MET-137; TYR-177; TRP-372; LEU-434; LEU-474; TYR-479; ARG-576; MET-664; PHE-727; LYS-754; PRO-775; LEU-865; THR-926; CYS-942; ASN-944; HIS-948; GLU-959; 961-ASN--PHE-966 DELINS SER; ALA-1007; VAL-1035; LYS-1036; THR-1061; ASN-1066; ILE-1156; SER-1156 AND LEU-1224; VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266; Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia.
Akizu N.; Shembesh N.M.; Ben-Omran T.; Bastaki L.; Al-Tawari A.; Zaki M.S.; Koul R.; Spencer E.; Rosti R.O.; Scott E.; Nickerson E.; Gabriel S.; da Gente G.; Li J.; Deardorff M.A.; Conlin L.K.; Horton M.A.; Zackai E.H.; Sherr E.H.; Gleeson J.G.;
Am. J. Hum. Genet. 92:392-400(2013)
Cited for: VARIANT NCP1 MET-137;