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UniProtKB/Swiss-Prot P41091: Variant p.Ile222Thr

Eukaryotic translation initiation factor 2 subunit 3
Gene: EIF2S3
Variant information

Variant position:  222
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 Isoleucine (I) to Threonine (T) at position 222 (I222T, p.Ile222Thr).
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 (T)
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:  MEHMO syndrome (MEHMO) [MIM:300148]: An X-linked recessive mental retardation syndrome characterized by intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity. {ECO:0000269|PubMed:23063529, ECO:0000269|PubMed:27333055, ECO:0000269|PubMed:28055140}. 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 MEHMO; decreased interaction with the other eIF2 complex subunits EIF2S1 and EIF2S2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  222
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  472
The length of the canonical sequence.

Location on the sequence:   EQYEQILAFVQGTVAEGAPI  I PISAQLKYNIEVVCEYIVKK
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                         EQYEQILAFVQGTVAEGAPIIPISAQLKYNIEVVCEYIVKK

Mouse                         EQYEQILAFVQGTVAEGAPIIPISAQLKYNIEVVCEYIVKK

Rat                           EQYEQILAFVQGTVAEGAPIIPISAQLKYNIEVVCEYIVKK

Bovine                        EQYEQILAFVQGTVAEGAPIIPISAQLKYNIEVVCEYIVKK

Chicken                       EQYEQILAFVQGTVAEGAPIIPISAQLKYSIEVVCEYIVKK

Zebrafish                     EQYEQILAFVQGTVAEGAPIIPISAQLKYNIEVVCEYIVNK

Drosophila                    EQYEEITKFVQGTVAEGAPIIPISAQLKYNIDVLCEYIVNK

Slime mold                    EQYGQILKFIQGTIAENAPIIPISAQMKYNIDVICEYIVKK

Baker's yeast                 EHQKSILKFIRGTIADGAPIVPISAQLKYNIDAVNEFIVKT

Fission yeast                 EHYQSILKFIKGTVAENSPIVPISAQLKYNIDAILEYIVKK

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 2 – 472 Eukaryotic translation initiation factor 2 subunit 3
Domain 39 – 248 tr-type G


Literature citations

eIF2gamma mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.
Borck G.; Shin B.S.; Stiller B.; Mimouni-Bloch A.; Thiele H.; Kim J.R.; Thakur M.; Skinner C.; Aschenbach L.; Smirin-Yosef P.; Har-Zahav A.; Nuernberg G.; Altmueller J.; Frommolt P.; Hofmann K.; Konen O.; Nuernberg P.; Munnich A.; Schwartz C.E.; Gothelf D.; Colleaux L.; Dever T.E.; Kubisch C.; Basel-Vanagaite L.;
Mol. Cell 48:641-646(2012)
Cited for: INVOLVEMENT IN MEHMO; VARIANT MEHMO THR-222; CHARACTERIZATION OF VARIANT MEHMO THR-222; SUBUNIT;

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.