Home  |  Contact

UniProtKB/Swiss-Prot O43567: Variant p.Leu312Pro

E3 ubiquitin-protein ligase RNF13
Gene: RNF13
Variant information

Variant position:  312
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 312 (L312P, p.Leu312Pro).
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:  Epileptic encephalopathy, early infantile, 73 (EIEE73) [MIM:618379]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE73 is an autosomal dominant form with onset at birth. {ECO:0000269|PubMed:30595371}. 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 EIEE73.
Any additional useful information about the variant.



Sequence information

Variant position:  312
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  381
The length of the canonical sequence.

Location on the sequence:   SDSDTDSSQEENEVTEHTPL  L RPLASVSAQSFGALSESRSH
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                         SDSDTDSSQEENEVTEHTPLLRPLASVSAQSFGALSESRSH

Mouse                         SDSDTDSSQEENQVSEHTPLLPPSASARTQSFGSLSESHSH

Rat                           SDSDTDSSQEENQVSEHTPLLPPSASARTQSFGSLSESHSH

Bovine                        SDSDTDSSQEENEVSEHTPLLRPLASASTQSFGALSESRSH

Chicken                       SDSETDSSQEENEVSENTPLLRPLASVSTQSFGALSESHSH

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 35 – 381 E3 ubiquitin-protein ligase RNF13
Topological domain 204 – 381 Cytoplasmic
Mutagenesis 165 – 381 Missing. Abolishes ER stress-induced JNK activation and apoptosis.


Literature citations

Heterozygous RNF13 gain-of-function variants are associated with congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive.
Edvardson S.; Nicolae C.M.; Noh G.J.; Burton J.E.; Punzi G.; Shaag A.; Bischetsrieder J.; De Grassi A.; Pierri C.L.; Elpeleg O.; Moldovan G.L.;
Am. J. Hum. Genet. 104:179-185(2019)
Cited for: FUNCTION; INVOLVEMENT IN EIEE73; VARIANTS EIEE73 SER-311 AND PRO-312; CHARACTERIZATION OF VARIANT EIEE73 SER-311;

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.