UniProtKB/Swiss-Prot P19525: Variant p.Met11Leu

Interferon-induced, double-stranded RNA-activated protein kinase
Gene: EIF2AK2
Feedback?

Variant information Variant position:

11 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Methionine (M) to Leucine (L) at position 11 (M11L, p.Met11Leu). 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:

2 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 LEUDEN; uncertain significance; reduced phosphorylation of eukaryotic translation initiation factor 2-alpha in patient cells. Any additional useful information about the variant.

Sequence information Variant position:

11 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

551 The length of the canonical sequence.
Location on the sequence:

MAGDLSAGFF M EELNTYRQKQGVVLKYQELP 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                         MAGDLSAGFFMEELNTYRQKQGVVLKYQELP

Mouse                         MASD-TPGFYMDKLNKYRQMHGVAITYKELS

Rat                           MASD-TPGFYVDKLNKYSQIHKVKIIYKEIS

Fission yeast                 HKSA-EDGNYSETTNAISLKNERQSRDLSVN

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.

Type	Positions	Description
Initiator methionine	1 – 1	Removed
Chain	2 – 551	Interferon-induced, double-stranded RNA-activated protein kinase
Domain	9 – 77	DRBM 1
Region	2 – 180	(Microbial infection) Interaction with HCV NS5A
Modified residue	2 – 2	N-acetylalanine
Helix	10 – 21

Literature citations
De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation.
Mao D.; Reuter C.M.; Ruzhnikov M.R.Z.; Beck A.E.; Farrow E.G.; Emrick L.T.; Rosenfeld J.A.; Mackenzie K.M.; Robak L.; Wheeler M.T.; Burrage L.C.; Jain M.; Liu P.; Calame D.; Kuery S.; Sillesen M.; Schmitz-Abe K.; Tonduti D.; Spaccini L.; Iascone M.; Genetti C.A.; Koenig M.K.; Graf M.; Tran A.; Alejandro M.; Lee B.H.; Thiffault I.; Agrawal P.B.; Bernstein J.A.; Bellen H.J.; Chao H.T.;
Am. J. Hum. Genet. 106:570-583(2020)
Cited for: INVOLVEMENT IN LEUDEN; FUNCTION; VARIANTS LEUDEN LEU-11; SER-32; PHE-97; SER-109; VAL-109; PHE-133; SER-325 AND CYS-461; CHARACTERIZATION OF VARIANTS LEUDEN LEU-11; PHE-133 AND CYS-461; VARIANT GLN-114;

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.