UniProtKB/SwissProt variant VAR

Variant information

Variant position:

477

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

Type of variant:

Unclassified

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 Alanine (A) to Valine (V) at position 477 (A477V, p.Ala477Val).

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 hydrophobic (A) to medium size and hydrophobic (V)

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

Involvement in disease:

Nephrotic syndrome 17 (NPHS17) [MIM:618176]: 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. NPHS17 is an autosomal recessive, steroid-resistant progressive form with onset in the first decade of life. {ECO:0000269|PubMed:30179222}. 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 NPHS17; unknown pathological significance.

Any additional useful information about the variant.

Sequence information

Variant position:

477

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

Protein sequence length:

656

The length of the canonical sequence.

Location on the sequence:

CEQRQMTEQVRSICKILAMK A VRNNRLGSALSWSIRAKDAA

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                         CEQRQMTEQVR-SICKILAMKAVRNNRLGSALSWSIRAKDAA

Mouse                         CEQRQMTEQVK-SICKILAMKAVRNNRLGSALSWSIRAKDA

Rat                           CEQRQMTEQVG-SICKILAMKAVRNNRLGSALSWSIRAKDA

Bovine                        CEQRQMTEQVR-SICKVLAMKAVRNNRLGSALSWSIRAKDA

Xenopus laevis                CEQRQMTEQVR-SICKTMAMQSLCNRRLGSALSWSIRAKDA

Xenopus tropicalis            CEKRQMTEQVR-SICKTMAMQSLCNGRLGSALSWSIRAKDA

Zebrafish                     CEDRQMSEQVR-SICKIMAKRALRNNRLGSALSWSIRAKDA

Slime mold                    -DKWATSVETKNSIYKMLSLQDFKRKRYAASLNWLMLANDN

Baker's yeast                 CVEWRLPEIAK-EIYTTLGNQMLSAHNIIESIANFSRAGKY

Fission yeast                 CKQLKLRDEAQ-LVLTHWADELIARNHYGEALIALDNAANY

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	1 – 656	Nuclear pore complex protein Nup85

Literature citations

Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome.
Braun D.A.; Lovric S.; Schapiro D.; Schneider R.; Marquez J.; Asif M.; Hussain M.S.; Daga A.; Widmeier E.; Rao J.; Ashraf S.; Tan W.; Lusk C.P.; Kolb A.; Jobst-Schwan T.; Schmidt J.M.; Hoogstraten C.A.; Eddy K.; Kitzler T.M.; Shril S.; Moawia A.; Schrage K.; Khayyat A.I.A.; Lawson J.A.; Gee H.Y.; Warejko J.K.; Hermle T.; Majmundar A.J.; Hugo H.; Budde B.; Motameny S.; Altmueller J.; Noegel A.A.; Fathy H.M.; Gale D.P.; Waseem S.S.; Khan A.; Kerecuk L.; Hashmi S.; Mohebbi N.; Ettenger R.; Serdaroglu E.; Alhasan K.A.; Hashem M.; Goncalves S.; Ariceta G.; Ubetagoyena M.; Antonin W.; Baig S.M.; Alkuraya F.S.; Shen Q.; Xu H.; Antignac C.; Lifton R.P.; Mane S.; Nuernberg P.; Khokha M.K.; Hildebrandt F.;
J. Clin. Invest. 128:4313-4328(2018)
Cited for: FUNCTION; INTERACTION WITH NUP160; INVOLVEMENT IN NPHS17; VARIANTS NPHS17 VAL-477; PRO-581 AND TRP-645; CHARACTERIZATION OF VARIANTS NPHS17 VAL-477; PRO-581 AND TRP-645;

UniProtKB/Swiss-Prot Q9BW27: Variant p.Ala477Val