UniProtKB/Swiss-Prot O15118: Variant p.His215Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 215 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 Histidine (H) to Arginine (R) at position 215 (H215R, p.His215Arg). 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 (H) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 0 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 rs1805081 [ dbSNP | Ensembl ]

Sequence information

Variant position: 215 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: NKDNGQAPFTITPVFSDFPV H GMEPMNNATKGCDESVDEVT 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
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

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; NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C.
Yamamoto T.; Nanba E.; Ninomiya H.; Higaki K.; Taniguchi M.; Zhang H.; Akaboshi S.; Watanabe Y.; Takeshima T.; Inui K.; Okada S.; Tanaka A.; Sakuragawa N.; Millat G.; Vanier M.T.; Morris J.A.; Pentchev P.G.; Ohno K.;
Hum. Genet. 105:10-16(1999)
Cited for: VARIANTS NPC1; VARIANTS ARG-215; VAL-858 AND GLN-1266; 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 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; 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;