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UniProtKB/Swiss-Prot P19544: Variant p.Asp396Asn

Wilms tumor protein
Gene: WT1
Variant information

Variant position:  396
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 Aspartate (D) to Asparagine (N) at position 396 (D396N, p.Asp396Asn).
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 acidic (D) to medium size and polar (N)
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

Involvement in disease:  Nephrotic syndrome 4 (NPHS4) [MIM:256370]: 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. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. {ECO:0000269|PubMed:11182928, ECO:0000269|PubMed:15253707, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:9529364, ECO:0000269|PubMed:9607189}. 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.

Involvement in disease:  Denys-Drash syndrome (DDS) [MIM:194080]: Typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic. {ECO:0000269|PubMed:10738002, ECO:0000269|PubMed:10799199, ECO:0000269|PubMed:11182928, ECO:0000269|PubMed:11519891, ECO:0000269|PubMed:1302008, ECO:0000269|PubMed:1338906, ECO:0000269|PubMed:15349765, ECO:0000269|PubMed:1655284, ECO:0000269|PubMed:8111391, ECO:0000269|PubMed:8112732, ECO:0000269|PubMed:8295405, ECO:0000269|PubMed:8388765, ECO:0000269|PubMed:8411073, ECO:0000269|PubMed:8741319, ECO:0000269|PubMed:8956030, ECO:0000269|PubMed:9475094, ECO:0000269|PubMed:9529364}. 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 DDS and NPHS4.
Any additional useful information about the variant.



Sequence information

Variant position:  396
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  449
The length of the canonical sequence.

Location on the sequence:   RHTGVKPFQCKTCQRKFSRS  D HLKTHTRTHTGKTSEKPFSC
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                         RHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSC

Mouse                         RHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSC

Rat                           RHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSC

Pig                           RHTGVKPFQCKTCQRKFSRSDHLKTHTRTHTGKTSEKPFSC

Xenopus tropicalis            RHTGIKPFQCKTCQRKFSRSDHLKTHTRTHTG---EKPFSC

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 – 449 Wilms tumor protein
Zinc finger 383 – 405 C2H2-type 3
Region 393 – 401 Important for interaction with target DNA
Mutagenesis 394 – 394 R -> AS. Strongly reduced binding of DNA and RNA.
Helix 395 – 401


Literature citations

Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database.
Jeanpierre C.; Denamur E.; Henry I.; Cabanis M.-O.; Luce S.; Cecille A.; Elion J.; Peuchmaur M.; Loirat C.; Niaudet P.; Gubler M.-C.; Junien C.;
Am. J. Hum. Genet. 62:824-833(1998)
Cited for: VARIANTS NPHS4 TYR-377; LEU-383 AND ASN-396; VARIANTS DDS CYS-366; GLN-394; TRP-394 AND PRO-398; VARIANT WT1 ASN-223;

Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations.
Schumacher V.; Schaerer K.; Wuehl E.; Altrogge H.; Bonzel K.-E.; Guschmann M.; Neuhaus T.J.; Pollastro R.M.; Kuwertz-Broeking E.; Bulla M.; Tondera A.-M.; Mundel P.; Helmchen U.; Waldherr R.; Weirich A.; Royer-Pokora B.;
Kidney Int. 53:1594-1600(1998)
Cited for: VARIANTS NPHS4 LEU-364; HIS-366; CYS-379; ARG-385; GLN-394; TRP-394 AND ASN-396;

Constitutional WT1 correlate with clinical features in children with progressive nephropathy.
Takata A.; Kikuchi H.; Fukuzawa R.; Ito S.; Honda M.; Hata J.;
J. Med. Genet. 37:698-701(2000)
Cited for: VARIANTS DDS ARG-342; TYR-355; HIS-366; ARG-385; PHE-388; TRP-394 AND ASN-396; VARIANT NPHS4 GLN-312;

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.