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UniProtKB/Swiss-Prot P21333: Variant p.Pro207Leu

Filamin-A
Gene: FLNA
Variant information

Variant position:  207
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 207 (P207L, p.Pro207Leu).
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:  Otopalatodigital syndrome 1 (OPD1) [MIM:311300]: X-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto-palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. FLNA is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. Males with OPD1 have cleft palate, malformations of the ossicles causing deafness and milder bone and limb defects than those associated with OPD2. Obligate female carriers of mutations causing both OPD1 and OPD2 have variable (often milder) expression of a similar phenotypic spectrum. {ECO:0000269|PubMed:12612583, ECO:0000269|PubMed:15940695, ECO:0000269|PubMed:27193221}. 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 OPD1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  207
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2647
The length of the canonical sequence.

Location on the sequence:   NFSRDWQSGRALGALVDSCA  P GLCPDWDSWDASKPVTNARE
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                         NFSRDWQSGRALGALVDSCAPGLCPDWDSWDASKPVTNARE

Mouse                         NFSRDWQSGRALGALVDSCAPGLCPDWDSWDASKPVNNARE

Drosophila                    NFTNDWTTGKAVGALVDACAPGLCPDWELWDPKDAVQNASE

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 – 2647 Filamin-A
Domain 166 – 269 Calponin-homology (CH) 2
Region 2 – 274 Actin-binding


Literature citations

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans.
Robertson S.P.; Twigg S.R.F.; Sutherland-Smith A.J.; Biancalana V.; Gorlin R.J.; Horn D.; Kenwrick S.J.; Kim C.A.; Morava E.; Newbury-Ecob R.; Oerstavik K.H.; Quarrell O.W.J.; Schwartz C.E.; Shears D.J.; Suri M.; Kendrick-Jones J.; Wilkie A.O.M.;
Nat. Genet. 33:487-491(2003)
Cited for: VARIANTS OPD1 PHE-172; TRP-196 AND LEU-207; VARIANTS OPD2 PRO-170; GLY-196; SER-200; LYS-254; PRO-273; LYS-555 AND PHE-1645; VARIANTS FMD1 ALA-1159; LEU-1186 AND ILE-1620 DEL; VARIANTS MNS GLU-1184; THR-1188 AND LEU-1199; VARIANTS MET-429 AND THR-1764;

Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.
Moutton S.; Fergelot P.; Naudion S.; Cordier M.P.; Sole G.; Guerineau E.; Hubert C.; Rooryck C.; Vuillaume M.L.; Houcinat N.; Deforges J.; Bouron J.; Deves S.; Le Merrer M.; David A.; Genevieve D.; Giuliano F.; Journel H.; Megarbane A.; Faivre L.; Chassaing N.; Francannet C.; Sarrazin E.; Stattin E.L.; Vigneron J.; Leclair D.; Abadie C.; Sarda P.; Baumann C.; Delrue M.A.; Arveiler B.; Lacombe D.; Goizet C.; Coupry I.;
J. Hum. Genet. 61:693-699(2016)
Cited for: VARIANTS OPD2 SER-187 AND GLY-196; VARIANTS OPD1 LEU-207; THR-267; ASP-804 AND HIS-2391; VARIANTS FMD1 VAL-1142; LEU-1186 AND ARG-1840; VARIANTS MNS LEU-1163 AND THR-1188;

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.