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UniProtKB/Swiss-Prot P35240: Variant p.Gln538Pro

Merlin
Gene: NF2
Chromosomal location: 22q12.2
Variant information

Variant position:  538
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 Glutamine (Q) to Proline (P) at position 538 (Q538P, p.Gln538Pro).
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 (Q) to medium size and hydrophobic (P)
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:  Neurofibromatosis 2 (NF2) [MIM:101000]: Genetic disorder characterized by bilateral vestibular schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas, and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management difficult, and patients suffer great morbidity and mortality. {ECO:0000269|PubMed:10090912, ECO:0000269|PubMed:10669747, ECO:0000269|PubMed:10790209, ECO:0000269|PubMed:12709270, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:20445339, ECO:0000269|PubMed:7666400, ECO:0000269|PubMed:7759081, ECO:0000269|PubMed:7913580, ECO:0000269|PubMed:8081368, ECO:0000269|PubMed:8230593, ECO:0000269|PubMed:8566958, ECO:0000269|PubMed:8698340, ECO:0000269|PubMed:9643284}. 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 NF2; mild.
Any additional useful information about the variant.

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



Sequence information

Variant position:  538
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  595
The length of the canonical sequence.

Location on the sequence:   SMEIEKEKVEYMEKSKHLQE  Q LNELKTEIEALKLKERETAL
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                         SMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETAL

Mouse                         SMEIEKEKVEYMEKSKHLQEQLNELKTEIEALKLKERETAL

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 – 595 Merlin
Modified residue 518 – 518 Phosphoserine; by PAK
Alternative sequence 150 – 579 Missing. In isoform 9.
Alternative sequence 260 – 595 Missing. In isoform 7.
Alternative sequence 380 – 595 Missing. In isoform 10.
Mutagenesis 518 – 518 S -> A. Loss of phosphorylation. Significant accumulation in the nucleus and no effect on binding to DCAF1.
Mutagenesis 518 – 518 S -> D. No effect on phosphorylation. Defective nuclear accumulation. Significant decrease in binding to DCAF1 and in ability to inhibit cell proliferation.
Helix 513 – 547


Literature citations

A missense mutation in the NF2 gene results in moderate and mild clinical phenotypes of neurofibromatosis type 2.
Kluwe L.; Mautner V.-F.;
Hum. Genet. 97:224-227(1996)
Cited for: VARIANT NF2 PRO-538;

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.