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UniProtKB/Swiss-Prot P13637: Variant p.Ile274Asn

Sodium/potassium-transporting ATPase subunit alpha-3
Gene: ATP1A3
Variant information

Variant position:  274
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Isoleucine (I) to Asparagine (N) at position 274 (I274N, p.Ile274Asn).
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 (I) to medium size and polar (N)
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

Variant description:  In AHC2; strong decrease in ATPase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  274
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1013
The length of the canonical sequence.

Location on the sequence:   RTVMGRIATLASGLEVGKTP  I AIEIEHFIQLITGVAVFLGV
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                         RTVMGRIATLASGLEVGKTPIAIEIEHFIQLITGVAVFLGV

Mouse                         RTVMGRIATLASGLEVGKTPIAIEIEHFIQLITGVAVFLGV

Rat                           RTVMGRIATLASGLEVGKTPIAIEIEHFIQLITGVAVFLGV

Chicken                       RTVMGRIATLASGLEVGKTPIAVEIEHFIQLITGVAVFLGI

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 1 – 1013 Sodium/potassium-transporting ATPase subunit alpha-3
Topological domain 143 – 278 Cytoplasmic
Modified residue 265 – 265 Phosphoserine


Literature citations

Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study.
Rosewich H.; Thiele H.; Ohlenbusch A.; Maschke U.; Altmuller J.; Frommolt P.; Zirn B.; Ebinger F.; Siemes H.; Nurnberg P.; Brockmann K.; Gartner J.;
Lancet Neurol. 11:764-773(2012)
Cited for: VARIANTS AHC2 ASN-274; ASP-322; PRO-371; CYS-755; ARG-772; ILE-773; ASN-801; LYS-815 AND TYR-923;

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood.
Heinzen E.L.; Swoboda K.J.; Hitomi Y.; Gurrieri F.; Nicole S.; de Vries B.; Tiziano F.D.; Fontaine B.; Walley N.M.; Heavin S.; Panagiotakaki E.; Neri G.; Koelewijn S.; Kamphorst J.; Geilenkirchen M.; Pelzer N.; Laan L.; Haan J.; Ferrari M.; van den Maagdenberg A.M.; Zucca C.; Bassi M.T.; Franchini F.; Vavassori R.; Giannotta M.; Gobbi G.; Granata T.; Nardocci N.; De Grandis E.; Veneselli E.; Stagnaro M.; Vigevano F.; Oechsler C.; Arzimanoglou A.; Ninan M.; Neville B.; Ebinger F.; Fons C.; Campistol J.; Kemlink D.; Nevsimalova S.; Peeters-Scholte C.; Casaer P.; Casari G.; Sange G.; Spiel G.; Martinelli Boneschi F.; Schyns T.; Crawley F.; Poncelin D.; Fiori S.; Abiusi E.; Di Pietro L.; Sweney M.T.; Newcomb T.M.; Viollet L.; Huff C.; Jorde L.B.; Reyna S.P.; Murphy K.J.; Shianna K.V.; Gumbs C.E.; Little L.; Silver K.; Ptacek L.J.; Ferrari M.D.; Bye A.M.; Herkes G.K.; Whitelaw C.M.; Webb D.; Lynch B.J.; Uldall P.; King M.D.; Scheffer I.E.; Sisodiya S.M.; Mikati M.A.; Goldstein D.B.;
Nat. Genet. 44:1030-1034(2012)
Cited for: VARIANTS AHC2 TYR-137; PHE-137; LEU-140; ASN-220; ASN-274; PHE-333; SER-755; SER-773; ASN-801; ARG-806; SER-810; PRO-811; LYS-815; VAL-919 DEL; ARG-947; ASP-955 AND TYR-992; CHARACTERIZATION OF VARIANTS AHC2 PHE-137; PHE-333; ASN-801; PRO-811 AND LYS-815;

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.