UniProtKB/SwissProt variant VAR

Variant information

Variant position:

281

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 Histidine (H) to Glutamine (Q) at position 281 (H281Q, p.His281Gln).

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 polar.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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, infantile or early childhood, 1 (IECEE1) [MIM:617711]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood 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. IECEE1 is an autosomal dominant condition with onset of seizures between the first weeks and first years of life. {ECO:0000269|PubMed:28942967, ECO:0000269|PubMed:29432562}. 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 IECEE1.

Any additional useful information about the variant.

Sequence information

Variant position:

281

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

Protein sequence length:

521

The length of the canonical sequence.

Location on the sequence:

SYPAVCEFLQHNNLLSILRA H EAQDAGYRMYRKSQTTGFPS

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                         SYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPS

Mouse                         SYPAVCDFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPS

Rat                           SYPAVCDFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPS

Bovine                        SYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPS

Slime mold                    SYRAVCSFLQKNKLLSVIRAHEAQNAGYKMHLQNDATGFPS

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 – 521	Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
Region	56 – 340	Catalytic
Metal binding	281 – 281	Zinc; via pros nitrogen
Alternative sequence	87 – 318	Missing. In isoform 4.
Mutagenesis	288 – 288	Y -> F. Partial loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341.
Mutagenesis	288 – 288	Y -> NA. Loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341.

Literature citations

De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures.
Myers C.T.; Stong N.; Mountier E.I.; Helbig K.L.; Freytag S.; Sullivan J.E.; Ben Zeev B.; Nissenkorn A.; Tzadok M.; Heimer G.; Shinde D.N.; Rezazadeh A.; Regan B.M.; Oliver K.L.; Ernst M.E.; Lippa N.C.; Mulhern M.S.; Ren Z.; Poduri A.; Andrade D.M.; Bird L.M.; Bahlo M.; Berkovic S.F.; Lowenstein D.H.; Scheffer I.E.; Sadleir L.G.; Goldstein D.B.; Mefford H.C.; Heinzen E.L.;
Am. J. Hum. Genet. 101:516-524(2017)
Cited for: INVOLVEMENT IN IECEE1; VARIANTS IECEE1 ARG-92; GLN-281; LYS-282; 445-GLN--GLN-521 DEL AND THR-447;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q08209: Variant p.His281Gln