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UniProtKB/Swiss-Prot O60500: Variant p.Cys623Phe

Gene: NPHS1
Variant information

Variant position:  623
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 Cysteine (C) to Phenylalanine (F) at position 623 (C623F, p.Cys623Phe).
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 (C) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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 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:  623
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.




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.

Chain 23 – 1241 Nephrin
Topological domain 23 – 1055 Extracellular
Domain 544 – 635 Ig-like C2-type 6
Disulfide bond 567 – 623

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;

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;

Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome.
Buescher A.K.; Kranz B.; Buescher R.; Hildebrandt F.; Dworniczak B.; Pennekamp P.; Kuwertz-Broeking E.; Wingen A.M.; John U.; Kemper M.; Monnens L.; Hoyer P.F.; Weber S.; Konrad M.;
Clin. J. Am. Soc. Nephrol. 5:2075-2084(2010)
Cited for: VARIANTS NPHS1 GLU-107; THR-172 DEL; ILE-188; 205-THR--ARG-207 DELINS ILE; SER-567; PHE-623; VAL-851 AND CYS-1096;

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.