UniProtKB/Swiss-Prot P19525: Variant p.Ser97Phe

Interferon-induced, double-stranded RNA-activated protein kinase
Gene: EIF2AK2
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Variant information Variant position:

97 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 Serine (S) to Phenylalanine (F) at position 97 (S97F, p.Ser97Phe). 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 small size and polar (S) to large size and aromatic (F) 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. Any additional useful information about the variant.

Sequence information Variant position:

97 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:

KEKKAVSPLLLTTTNSSEGL S MGNYIGLINRIAQKKRLTVN 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                         KEKKAVSPLLLTTTNSSEGLSMGNYIGLINRIAQKKRLTVN

Mouse                         NENKVDC----HTSASEQGLFVGNYIGLVNSFAQKKKLSVN

Rat                           NENKVDS----HTDASEQGLIEGNYIGLVNSFAQKENLPVN

Fission yeast                 TLQKI-------------GILEEEYIEELAAVRS------N

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
Chain	2 – 551	Interferon-induced, double-stranded RNA-activated protein kinase
Region	2 – 180	(Microbial infection) Interaction with HCV NS5A
Modified residue	83 – 83	Phosphoserine
Modified residue	88 – 88	Phosphothreonine; by autocatalysis
Modified residue	89 – 89	Phosphothreonine; by autocatalysis
Modified residue	90 – 90	Phosphothreonine; by autocatalysis
Modified residue	101 – 101	Phosphotyrosine; by autocatalysis
Mutagenesis	83 – 83	S -> A. No effect on enzymatic activity; when associated with A-88; A-89 and A-90.
Mutagenesis	88 – 88	T -> A. No effect on enzymatic activity; when associated with A-83; A-89 and A-90.
Mutagenesis	89 – 89	T -> A. No effect on enzymatic activity; when associated with A-83; A-88 and A-90.
Mutagenesis	90 – 90	T -> A. No effect on enzymatic activity; when associated with A-83; A-88 and A-89.

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.