UniProtKB/Swiss-Prot O15118: Variant p.Met642Ile

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 642 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 Methionine (M) to Isoleucine (I) at position 642 (M642I, p.Met642Ile). 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: Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Other resources: Links to websites of interest for the variant.

• Variant rs1788799 [ dbSNP | Ensembl ]

Sequence information

Variant position: 642 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: FTVVISYAIMFLYISLALGH M KSCRRLLVDSKVSLGIAGIL 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	642 – 653	Cytoplasmic
Domain	620 – 785	SSD
Mutagenesis	660 – 660	G -> R. Loss of function.

Literature citations

Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
Carstea E.D.; Morris J.A.; Coleman K.G.; Loftus S.K.; Zhang D.; Cummings C.; Gu J.; Rosenfeld M.A.; Pavan W.J.; Krizman D.B.; Nagle J.; Polymeropoulos M.H.; Sturley S.L.; Ioannou Y.A.; Higgins M.E.; Comly M.; Cooney A.; Brown A.; Kaneski C.R.; Blanchette-Mackie E.J.; Dwyer N.K.; Neufeld E.B.; Chang T.-Y.; Liscum L.; Strauss J.F. III; Ohno K.; Zeigler M.; Carmi R.; Sokol J.; Markie D.; O'Neill R.R.; van Diggelen O.P.; Elleder M.; Patterson M.C.; Brady R.O.; Vanier M.T.; Pentchev P.G.; Tagle D.A.;
Science 277:228-231(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; VARIANT ILE-642; VARIANTS NPC1; NPC1: complete genomic sequence, mutation analysis, and characterization of haplotypes.
Bauer P.; Knoblich R.; Bauer C.; Finckh U.; Hufen A.; Kropp J.; Braun S.; Kustermann-Kuhn B.; Schmidt D.; Harzer K.; Rolfs A.;
Hum. Mutat. 19:30-38(2002)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS NPC1 ARG-512; TRP-670; CYS-825; ILE-849; VAL-874; TYR-948; LEU-954; LEU-958; ALA-1007 AND THR-1061; VARIANTS ARG-215; ILE-642; VAL-858; GLY-971 AND VAL-1049; The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANTS GLY-151 AND ILE-642; Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations.
Ribeiro I.; Marcao A.; Amaral O.; Sa Miranda M.C.; Vanier M.T.; Millat G.;
Hum. Genet. 109:24-32(2001)
Cited for: VARIANTS NPC1 ARG-92; TYR-177; TRP-518; CYS-942; CYS-978; ALA-1007; VAL-1035 AND THR-1061; VARIANTS ARG-215; ILE-642 AND VAL-858; 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; Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts.
Tarugi P.; Ballarini G.; Bembi B.; Battisti C.; Palmeri S.; Panzani F.; Di Leo E.; Martini C.; Federico A.; Calandra S.;
J. Lipid Res. 43:1908-1919(2002)
Cited for: VARIANTS NPC1 LYS-451; LEU-474; CYS-890; ASP-899; SER-910; TRP-992; ALA-1007; THR-1061 AND SER-1156; VARIANTS ARG-215; ILE-642 AND VAL-858; 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; Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C.
Yang C.-C.; Su Y.-N.; Chiou P.-C.; Fietz M.J.; Yu C.-L.; Hwu W.-L.; Lee M.-J.;
J. Neurol. Neurosurg. Psych. 76:592-595(2005)
Cited for: VARIANTS NPC1 SER-968; VAL-1015; ARG-1034 AND LEU-1212; VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266;