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UniProtKB/Swiss-Prot Q5JVL4: Variant p.Asp253Tyr

EF-hand domain-containing protein 1
Gene: EFHC1
Variant information

Variant position:  253
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 Aspartate (D) to Tyrosine (Y) at position 253 (D253Y, p.Asp253Tyr).
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 acidic (D) to large size and aromatic (Y)
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:  Juvenile myoclonic epilepsy 1 (EJM1) [MIM:254770]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. {ECO:0000269|PubMed:15258581, ECO:0000269|PubMed:17634063, ECO:0000269|PubMed:22690745, ECO:0000269|PubMed:22727576, ECO:0000269|PubMed:22926142, ECO:0000269|PubMed:28370826}. Note=Disease susceptibility is associated with variations 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 EJM1; reduces substantially the cell death effect; reduces partly the calcium influx; normally binds to CACNA1E; does not affect subcellular location; results in impaired cell migration.
Any additional useful information about the variant.

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



Sequence information

Variant position:  253
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  640
The length of the canonical sequence.

Location on the sequence:   KQFLTFDKQVLRFYAIWDDT  D SMYGECRTYIIHYYLMDDTV
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                         KQFLTFDKQVLRFYAIWDDTDSMYGECRTYIIHYYLMDDTV

Mouse                         KQFLTFDKQVLRFYAIWDDTDSLFGECRHYIIHYYLMDDTV

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 – 640 EF-hand domain-containing protein 1
Domain 239 – 359 DM10 2
Alternative sequence 243 – 278 LRFYAIWDDTDSMYGECRTYIIHYYLMDDTVEIREV -> SDIGTTIGLLISKCDLHLLAKGLGSCIGNYFETLQL. In isoform 2.


Literature citations

Mutations in EFHC1 cause juvenile myoclonic epilepsy.
Suzuki T.; Delgado-Escueta A.V.; Aguan K.; Alonso M.E.; Shi J.; Hara Y.; Nishida M.; Numata T.; Medina M.T.; Takeuchi T.; Morita R.; Bai D.; Ganesh S.; Sugimoto Y.; Inazawa J.; Bailey J.N.; Ochoa A.; Jara-Prado A.; Rasmussen A.; Ramos-Peek J.; Cordova S.; Rubio-Donnadieu F.; Inoue Y.; Osawa M.; Kaneko S.; Oguni H.; Mori Y.; Yamakawa K.;
Nat. Genet. 36:842-849(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2); NUCLEOTIDE SEQUENCE [MRNA] OF 557-640 (ISOFORM 1); FUNCTION; INTERACTION WITH CACNA1E; TISSUE SPECIFICITY; VARIANTS EJM1 THR-77; ASN-210; HIS-221; LEU-229 AND TYR-253; CHARACTERIZATION OF VARIANTS EJM1 THR-77; ASN-210; HIS-221; LEU-229 AND TYR-253; VARIANTS TRP-159; HIS-182 AND LEU-619; CHARACTERIZATION OF VARIANTS TRP-159; HIS-182 AND LEU-619;

Mutations of EFHC1, linked to juvenile myoclonic epilepsy, disrupt radial and tangential migrations during brain development.
de Nijs L.; Wolkoff N.; Coumans B.; Delgado-Escueta A.V.; Grisar T.; Lakaye B.;
Hum. Mol. Genet. 21:5106-5117(2012)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS EJM1 ASN-210; HIS-221; LEU-229 AND TYR-253; CHARACTERIZATION OF VARIANTS TRP-159 AND LEU-619;

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.