UniProtKB/Swiss-Prot O15118: Variant p.Pro237Ser

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 237 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 Proline (P) to Serine (S) at position 237 (P237S, p.Pro237Ser). 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 hydrophobic (P) to small size and polar (S) 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: No effect on function; colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs80358251 [ dbSNP | Ensembl ]

Sequence information

Variant position: 237 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: MEPMNNATKGCDESVDEVTA P CSCQDCSIVCGPKPQPPPPP 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	222 – 222	N-linked (GlcNAc...) asparagine
Disulfide bond	97 – 238
Disulfide bond	227 – 243
Alternative sequence	1 – 267	Missing. In isoform 2.
Mutagenesis	25 – 257	Missing. Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1.

Literature citations

Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts.
Yamamoto T.; Ninomiya H.; Matsumoto M.; Ohta Y.; Nanba E.; Tsutsumi Y.; Yamakawa K.; Millat G.; Vanier M.T.; Pentchev P.G.; Ohno K.;
J. Med. Genet. 37:707-712(2000)
Cited for: VARIANTS NPC1 GLY-177; PRO-473; PRO-510; GLN-518; SER-703; MET-889; LEU-954; TYR-956; ARG-996; THR-1061; CYS-1088; ARG-1205; PHE-1213 AND GLU-1236; VARIANTS SER-237 AND ALA-873; 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; Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop.
Millat G.; Marcais C.; Tomasetto C.; Chikh K.; Fensom A.H.; Harzer K.; Wenger D.A.; Ohno K.; Vanier M.T.;
Am. J. Hum. Genet. 68:1373-1385(2001)
Cited for: VARIANTS NPC1 HIS-242; ARG-272; ALA-378; GLN-404; GLN-518; VAL-605; ARG-631; PRO-724; PRO-775; CYS-825; VAL-874; GLN-934; MET-943; ASN-944; MET-950; SER-986; ARG-992; ALA-1007; THR-1054; THR-1061; THR-1142; TYR-1168 AND HIS-1186; VARIANT SER-237; Identification of novel mutations in the NPC1 gene in German patients with Niemann-Pick C disease.
Kaminski W.E.; Kluenemann H.H.; Ibach B.; Aslanidis C.; Klein H.E.; Schmitz G.;
J. Inherit. Metab. Dis. 25:385-389(2002)
Cited for: VARIANTS NPC1 GLY-231; VAL-874; ASN-948 AND THR-1094; VARIANTS SER-237; CYS-381 AND ILE-642; Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease.
Blom T.S.; Linder M.D.; Snow K.; Pihko H.; Hess M.W.; Jokitalo E.; Veckman V.; Syvaenen A.-C.; Ikonen E.;
Hum. Mol. Genet. 12:257-272(2003)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANT NPC1 ARG-113; VARIANT SER-237; CHARACTERIZATION OF VARIANT NPC1 ARG-113; CHARACTERIZATION OF VARIANT SER-237; Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1.
Park W.D.; O'Brien J.F.; Lundquist P.A.; Kraft D.L.; Vockley C.W.; Karnes P.S.; Patterson M.C.; Snow K.;
Hum. Mutat. 22:313-325(2003)
Cited for: VARIANTS NPC1 TYR-74; SER-166; SER-222; TYR-247; PHE-380; PRO-388; CYS-389; TRP-404; LEU-433; SER-509; SER-521; LEU-543; CYS-615; ARG-640; SER-660; MET-664; VAL-673; PHE-684; LEU-691; VAL-695; ASN-700; ILE-734; LYS-742; GLU-745; VAL-767; GLY-789; ASN-945; ARG-1016; GLN-1059; LEU-1087; ILE-1137; VAL-1140; LYS-1205 AND GLY-1249; VARIANTS ARG-215; SER-237; SER-434 AND GLN-1266;