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UniProtKB/Swiss-Prot O60500: Variant p.Arg367Cys

Nephrin
Gene: NPHS1
Variant information

Variant position:  367
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Cysteine (C) at position 367 (R367C, p.Arg367Cys).
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 large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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

Involvement in disease:  Nephrotic syndrome 1 (NPHS1) [MIM:256300]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. {ECO:0000269|PubMed:10652016, ECO:0000269|PubMed:11317351, ECO:0000269|PubMed:11726550, ECO:0000269|PubMed:17290294, ECO:0000269|PubMed:18503012, ECO:0000269|PubMed:18614772, ECO:0000269|PubMed:20172850, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:22009864, ECO:0000269|PubMed:22565185, ECO:0000269|PubMed:22732337, ECO:0000269|PubMed:25804400, ECO:0000269|PubMed:26560236, ECO:0000269|PubMed:9660941, ECO:0000269|PubMed:9915943}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In NPHS1; lack of protein expression on the cell surface.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  367
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1241
The length of the canonical sequence.

Location on the sequence:   GSASQTENKNVTLSCVSKSS  R PRVLLRWWLGWRQLLPMEET
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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GSASQTENKNVTLSCVSKSSRPRVLLRWWLGWRQLLPMEET

Mouse                         GSTSQSENKNVTLCCLTKSSRPRVLLRWWLGGRQLLPTDET

Rat                           GSVSQSENKNVTLCCLTKSSRPRVLLRWWLGGRQLLPTDET

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.

TypePositionsDescription
Chain 23 – 1241 Nephrin
Topological domain 23 – 1055 Extracellular
Domain 340 – 434 Ig-like C2-type 4
Glycosylation 356 – 356 N-linked (GlcNAc...) asparagine
Disulfide bond 361 – 417


Literature citations

Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations.
Lenkkeri U.; Maennikkoe M.; McCready P.; Lamerdin J.; Gribouval O.; Niaudet P.M.; Antignac C.K.; Kashtan C.E.; Homberg C.; Olsen A.; Kestilae M.; Tryggvason K.;
Am. J. Hum. Genet. 64:51-61(1999)
Cited for: VARIANTS LYS-117; GLN-408 AND SER-1077; VARIANTS NPHS1 SER-64; ASN-171; THR-172 DEL; ASN-173; 205-THR--ARG-207 DELINS ILE; CYS-270; PRO-350; ARG-366; CYS-367; SER-368; VAL-376; TYR-465; PHE-528; GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831 AND CYS-1140;

Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome.
Liu L.; Done S.C.; Khoshnoodi J.; Bertorello A.; Wartiovaara J.; Berggren P.O.; Tryggvason K.;
Hum. Mol. Genet. 10:2637-2644(2001)
Cited for: CHARACTERIZATION OF VARIANTS NPHS1 SER-64; ASN-171; ASN-173; CYS-270; PRO-350; ARG-366; CYS-367; SER-368; VAL-376; TYR-465; PHE-528; GLN-610; PHE-623; CYS-724; CYS-743; TRP-802; PRO-802; ASP-806; CYS-831 AND CYS-1140; CHARACTERIZATION OF VARIANT GLN-408;

Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome.
Beltcheva O.; Martin P.; Lenkkeri U.; Tryggvason K.;
Hum. Mutat. 17:368-373(2001)
Cited for: VARIANTS NPHS1 SER-64; ASN-171; THR-172 DEL; ASN-173; CYS-270; PRO-350; ARG-366; CYS-367; LEU-368; SER-368; VAL-376; TRP-379; PHE-417; GLN-460; TYR-465; PHE-528; CYS-558; GLN-610; PHE-623; CYS-724; VAL-739; CYS-743; TRP-802; PRO-802; ASP-806; VAL-819 AND PHE-834; VARIANTS LYS-117; ARG-264; GLN-408; LYS-447; ARG-617; ASP-725; VAL-851 AND SER-1077;

Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome.
Heeringa S.F.; Vlangos C.N.; Chernin G.; Hinkes B.; Gbadegesin R.; Liu J.; Hoskins B.E.; Ozaltin F.; Hildebrandt F.;
Nephrol. Dial. Transplant. 23:3527-3533(2008)
Cited for: VARIANTS NPHS1 TRP-256; CYS-367; CYS-412; SER-519; ARG-569 AND GLY-709;

Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS).
Schoeb D.S.; Chernin G.; Heeringa S.F.; Matejas V.; Held S.; Vega-Warner V.; Bockenhauer D.; Vlangos C.N.; Moorani K.N.; Neuhaus T.J.; Kari J.A.; MacDonald J.; Saisawat P.; Ashraf S.; Ovunc B.; Zenker M.; Hildebrandt F.;
Nephrol. Dial. Transplant. 25:2970-2976(2010)
Cited for: VARIANTS NPHS1 VAL-107; LEU-167; THR-172 DEL; 205-THR--ARG-207 DELINS ILE; CYS-299; HIS-340; GLU-347; PRO-350; ARG-366; CYS-367; TRP-407; GLN-460; CYS-558; ASN-572; GLY-586; ARG-587; PHE-623; LYS-673; CYS-681; CYS-743; PRO-910; SER-976 AND CYS-1140; VARIANT GLN-408;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.