UniProtKB/Swiss-Prot O15118: Variant p.Ile1061Thr

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 1061 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 Isoleucine (I) to Threonine (T) at position 1061 (I1061T, p.Ile1061Thr). 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 (I) to medium size and polar (T) 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; late infantile form. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs80358259 [ dbSNP | Ensembl ]

Sequence information

Variant position: 1061 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: YHTVLQTSADFIDALKKARL I ASNVTETMGINGSAYRVFPY 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	854 – 1097	Lumenal
Glycosylation	1064 – 1064	N-linked (GlcNAc...) asparagine
Glycosylation	1072 – 1072	N-linked (GlcNAc...) asparagine
Helix	1048 – 1069

Literature citations

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; Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain.
Greer W.L.; Dobson M.J.; Girouard G.S.; Byers D.M.; Riddell D.C.; Neumann P.E.;
Am. J. Hum. Genet. 65:1252-1260(1999)
Cited for: VARIANTS NPC1 GLN-934; LEU-940; ASN-948; LEU-954; TRP-992; ALA-1007; THR-1061 AND VAL-1213; Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype.
Millat G.; Marcais C.; Rafi M.A.; Yamamoto T.; Morris J.A.; Pentchev P.G.; Ohno K.; Wenger D.A.; Vanier M.T.;
Am. J. Hum. Genet. 65:1321-1329(1999)
Cited for: VARIANT NPC1 THR-1061; 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; 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; 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; Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families.
Millat G.; Baielo N.; Molinero S.; Rodriguez C.; Chikh K.; Vanier M.T.;
Mol. Genet. Metab. 86:220-232(2005)
Cited for: VARIANTS NPC1 SER-166; TYR-177; PRO-404; LEU-537; LEU-543; LEU-615; ARG-631; LEU-763; CYS-825; LEU-862; LEU-865; CYS-871; TYR-917; GLN-934; LEU-940; MET-950; SER-968; ALA-992; ARG-992; TRP-992; ALA-1007; MET-1036; THR-1061; VAL-1062; ASN-1097; VAL-1174; HIS-1186; VAL-1216 AND ARG-1240; VARIANT MET-511;