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UniProtKB/Swiss-Prot Q15437: Variant p.Val594Gly

Protein transport protein Sec23B
Gene: SEC23B
Chromosomal location: 20pter-p12.3
Variant information

Variant position:  594
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 Valine (V) to Glycine (G) at position 594 (V594G, p.Val594Gly).
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 hydrophobic (V) to glycine (G)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Cowden syndrome 7 (CWS7) [MIM:616858]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. CWS7 inheritance is autosomal dominant. {ECO:0000269|PubMed:26522472}. 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 CWS7; aberrant aggregation; causes mislocalization of the protein in the cytoplasm; reduces interaction with SAR1A; confers endoplasmic reticulum (ER) stress-mediated cell growth advantage.
Any additional useful information about the variant.

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



Sequence information

Variant position:  594
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  767
The length of the canonical sequence.

Location on the sequence:   DSFSLYPQFMFHLRRSPFLQ  V FNNSPDESSYYRHHFARQDL
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                         DSFSLYPQFMFHLRRSPFLQVFNNSPDESSYYRHHFARQDL

Mouse                         DSFSLYPQFMFHLRRSPFLQVFNNSPDESSYYRHHFARQDL

Bovine                        DSFSLYPQFMFHLRRSPFLQVFNNSPDESSYYRHHFARQDL

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 2 – 767 Protein transport protein Sec23B


Literature citations

Germline heterozygous variants in SEC23B are associated with Cowden syndrome and enriched in apparently sporadic thyroid cancer.
Yehia L.; Niazi F.; Ni Y.; Ngeow J.; Sankunny M.; Liu Z.; Wei W.; Mester J.L.; Keri R.A.; Zhang B.; Eng C.;
Am. J. Hum. Genet. 97:661-676(2015)
Cited for: VARIANTS CWS7 LEU-164 AND GLY-594; CHARACTERIZATION OF VARIANT CWS7 GLY-594; INTERACTION WITH SAR1A; SUBCELLULAR LOCATION;

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.