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UniProtKB/Swiss-Prot Q5SZK8: Variant p.Glu1972Lys

FRAS1-related extracellular matrix protein 2
Gene: FREM2
Variant information

Variant position:  1972
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 Glutamate (E) to Lysine (K) at position 1972 (E1972K, p.Glu1972Lys).
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 (E) to large size and basic (K)
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:  Fraser syndrome 2 (FRASRS2) [MIM:617666]: A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities. {ECO:0000269|PubMed:15838507, ECO:0000269|PubMed:29688405, ECO:0000269|PubMed:30802441}. 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 FRASRS2; may impair calcium-binding in the 2nd Calx-beta domain; decreases cell adhesion; decreases interaction with FREM1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1972
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  3169
The length of the canonical sequence.

Location on the sequence:   FDKDEREKLCRIVIIDDSLY  E EEETFHVLLSMPMGGRIGSE
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                         FDKDEREKLCRIVIIDDSLYEEEETFHVLLSMPMGGRIGSE

Mouse                         FDKDEREKMCRILVIDDSLYEEEETFQVLLSMPMGGRIGDK

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 47 – 3169 FRAS1-related extracellular matrix protein 2
Topological domain 47 – 3113 Extracellular
Domain 1871 – 1982 Calx-beta 2


Literature citations

Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs.
Jadeja S.; Smyth I.; Pitera J.E.; Taylor M.S.; van Haelst M.; Bentley E.; McGregor L.; Hopkins J.; Chalepakis G.; Philip N.; Perez Aytes A.; Watt F.M.; Darling S.M.; Jackson I.; Woolf A.S.; Scambler P.J.;
Nat. Genet. 37:520-525(2005)
Cited for: IDENTIFICATION (ISOFORM 1); FUNCTION; INVOLVEMENT IN FRASRS2; VARIANT FRASRS2 LYS-1972;

A homozygous mutation p.Arg2167Trp in FREM2 causes isolated cryptophthalmos.
Yu Q.; Lin B.; Xie S.; Gao S.; Li W.; Liu Y.; Wang H.; Huang D.; Xie Z.;
Hum. Mol. Genet. 27:2357-2366(2018)
Cited for: FUNCTION; INTERACTION WITH FREM1; INVOLVEMENT IN CRYPTOP; VARIANT CRYPTOP TRP-2167; CHARACTERIZATION OF VARIANT CRYPTOP TRP-2167; VARIANT FRASRS2 TRP-2167; CHARACTERIZATION OF VARIANTS FRASRS2 LYS-1972 AND TRP-2167;

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.