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UniProtKB/Swiss-Prot Q63ZY3: Variant p.Ser676Phe

KN motif and ankyrin repeat domain-containing protein 2
Gene: KANK2
Chromosomal location: 19p13.2
Variant information

Variant position:  676
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 Serine (S) to Phenylalanine (F) at position 676 (S676F, p.Ser676Phe).
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 small size and polar (S) 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

Involvement in disease:  Nephrotic syndrome 16 (NPHS16) [MIM:617783]: 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 that progresses to end-stage renal failure. NPHS16 inheritance is autosomal recessive. {ECO:0000269|PubMed:25961457}. 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 NPHS16; loss of function in regulation of the Rho signaling pathway; no effect on cytoplasmic localization; decreased function in podocytes migration.
Any additional useful information about the variant.

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



Sequence information

Variant position:  676
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  851
The length of the canonical sequence.

Location on the sequence:   LDYVVNIADSNGNTALHYSV  S HANFPVVQQLLDSGVCKVDK
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                         LDYVVNIADSNGNTALHYSVSHANFPVVQQLLDSGVCKVDK

Mouse                         LDYVVNIADSNGNTALHYSVSHANFPVVRQLLDSGVCHVDK

Rat                           LDYVVNIADSNGNTALHYSVSHANFPVVRQLLDSGVCQVDK

Bovine                        LDYVVNIADSNGNTALHYSVSHANFPVVQQLLDSGVCQVDK

Zebrafish                     LEFVINMADGNGNTALHYTVSHSNFPVVKLLLDTGLCNADK

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 1 – 851 KN motif and ankyrin repeat domain-containing protein 2
Repeat 666 – 696 ANK 1
Region 669 – 835 Interaction with NCOA1
Helix 670 – 676


Literature citations

KANK deficiency leads to podocyte dysfunction and nephrotic syndrome.
Gee H.Y.; Zhang F.; Ashraf S.; Kohl S.; Sadowski C.E.; Vega-Warner V.; Zhou W.; Lovric S.; Fang H.; Nettleton M.; Zhu J.Y.; Hoefele J.; Weber L.T.; Podracka L.; Boor A.; Fehrenbach H.; Innis J.W.; Washburn J.; Levy S.; Lifton R.P.; Otto E.A.; Han Z.; Hildebrandt F.;
J. Clin. Invest. 125:2375-2384(2015)
Cited for: FUNCTION; INTERACTION WITH ARHGDIA; SUBCELLULAR LOCATION; INVOLVEMENT IN NPHS16; VARIANTS NPHS16 GLY-181 AND PHE-676; CHARACTERIZATION OF VARIANTS NPHS16 GLY-181 AND PHE-684;

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.