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UniProtKB/Swiss-Prot P24468: Variant p.Ala412Ser

COUP transcription factor 2
Gene: NR2F2
Variant information

Variant position:  412
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 Alanine (A) to Serine (S) at position 412 (A412S, p.Ala412Ser).
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 small size and hydrophobic (A) to small size and polar (S)
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:  Congenital heart defects, multiple types, 4 (CHTD4) [MIM:615779]: A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. {ECO:0000269|PubMed:24702954}. 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 CHTD4.
Any additional useful information about the variant.

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

Sequence information

Variant position:  412
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  414
The length of the canonical sequence.

Location on the sequence:   IETLIRDMLLSGSSFNWPYM  A IQ
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                         IETLIRDMLLSGSSFNWPYMAIQ

Mouse                         IETLIRDMLLSGSSFNWPYMAIQ

Rat                           IETLIRDMLLSGSSFNWPYMAIQ

Bovine                        IETLIRDMLLSGSSFNWPYMAIQ

Chicken                       IETLIRDMLLSGSSFNWPYMSIQ

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 – 414 COUP transcription factor 2
Region 117 – 414 Interaction with ZFPM2
Region 337 – 414 Important for dimerization
Mutagenesis 398 – 398 D -> R. Reduces transcription activation by 40%; when associated with E-228.

Literature citations

Rare variants in NR2F2 cause congenital heart defects in humans.
Al Turki S.; Manickaraj A.K.; Mercer C.L.; Gerety S.S.; Hitz M.P.; Lindsay S.; D'Alessandro L.C.; Swaminathan G.J.; Bentham J.; Arndt A.K.; Low J.; Breckpot J.; Gewillig M.; Thienpont B.; Abdul-Khaliq H.; Harnack C.; Hoff K.; Kramer H.H.; Schubert S.; Siebert R.; Toka O.; Cosgrove C.; Watkins H.; Lucassen A.M.; O'Kelly I.M.; Salmon A.P.; Bu'lock F.A.; Granados-Riveron J.; Setchfield K.; Thornborough C.; Brook J.D.; Mulder B.; Klaassen S.; Bhattacharya S.; Devriendt K.; Fitzpatrick D.F.; Wilson D.I.; Mital S.; Hurles M.E.;
Am. J. Hum. Genet. 94:574-585(2014)

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.