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UniProtKB/Swiss-Prot P35548: Variant p.Pro148Leu

Homeobox protein MSX-2
Gene: MSX2
Chromosomal location: 5q34-q35
Variant information

Variant position:  148
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 Proline (P) to Leucine (L) at position 148 (P148L, p.Pro148Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Craniosynostosis 2 (CRS2) [MIM:604757]: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. CRS2 is characterized by either fronto-orbital recession, or frontal bossing, or turribrachycephaly, or cloverleaf skull. Associated features include severe headache, high incidence of visual problems (myopia or hyperopia), and short first metatarsals. Intelligence is normal. {ECO:0000269|PubMed:23918290, ECO:0000269|PubMed:23949913, ECO:0000269|PubMed:8106171}. 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 CRS2.
Any additional useful information about the variant.

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

Sequence information

Variant position:  148
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  267
The length of the canonical sequence.

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.








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.

Chain 1 – 267 Homeobox protein MSX-2
DNA binding 142 – 201 Homeobox
Mutagenesis 147 – 147 T -> A. Does not bind DNA but still suppresses OCFRE activation.

Literature citations

Second family with the Boston-type craniosynostosis syndrome: novel mutation and expansion of the clinical spectrum.
Janssen A.; Hosen M.J.; Jeannin P.; Coucke P.J.; De Paepe A.; Vanakker O.M.;
Am. J. Med. Genet. A 161A:2352-2357(2013)
Cited for: VARIANT CRS2 LEU-148;

Boston type craniosynostosis: report of a second mutation in MSX2.
Florisson J.M.; Verkerk A.J.; Huigh D.; Hoogeboom A.J.; Swagemakers S.; Kremer A.; Heijsman D.; Lequin M.H.; Mathijssen I.M.; van der Spek P.J.;
Am. J. Med. Genet. A 161:2626-2633(2013)
Cited for: VARIANT CRS2 LEU-148;

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.