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UniProtKB/Swiss-Prot P50993: Variant p.Leu764Pro

Sodium/potassium-transporting ATPase subunit alpha-2
Gene: ATP1A2
Chromosomal location: 1q21-q23
Variant information

Variant position:  764
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 Leucine (L) to Proline (P) at position 764 (L764P, p.Leu764Pro).
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:  Migraine, familial hemiplegic, 2 (FHM2) [MIM:602481]: A subtype of migraine with aura associated with hemiparesis in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. {ECO:0000269|PubMed:12539047, ECO:0000269|PubMed:12953268, ECO:0000269|PubMed:21352219, ECO:0000269|PubMed:23838748, ECO:0000269|PubMed:23918834}. 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 FHM2; loss of function.
Any additional useful information about the variant.

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



Sequence information

Variant position:  764
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1020
The length of the canonical sequence.

Location on the sequence:   DMILLDDNFASIVTGVEEGR  L IFDNLKKSIAYTLTSNIPEI
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                         DMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEI

Mouse                         DMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEI

Rat                           DMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEI

Pig                           DMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEI

Bovine                        DMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEI

Chicken                       DMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEI

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 6 – 1020 Sodium/potassium-transporting ATPase subunit alpha-2
Topological domain 337 – 769 Cytoplasmic


Literature citations

Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.
De Fusco M.; Marconi R.; Silvestri L.; Atorino L.; Rampoldi L.; Morgante L.; Ballabio A.; Aridon P.; Casari G.;
Nat. Genet. 33:192-196(2003)
Cited for: VARIANTS FHM2 PRO-764 AND ARG-887; CHARACTERIZATION OF VARIANTS FMH2 PRO-764 AND ARG-887;

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.