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UniProtKB/Swiss-Prot Q08209: Variant p.His92Arg

Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
Gene: PPP3CA
Variant information

Variant position:  92
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 Arginine (R) at position 92 (H92R, p.His92Arg).
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 polar (H) to large size and basic (R)
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}. 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.

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



Sequence information

Variant position:  92
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:   LRQEKNLLDIDAPVTVCGDI  H GQFFDLMKLFEVGGSPANTR
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                         LRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFE--VGGSPANTR

Mouse                         LRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFE--VGGSPAN

Rat                           LRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFE--VGGSPAN

Bovine                        LRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFE--VGGSPAN

Slime mold                    LEKEPTLIQVEAPITVCGDTHGQFYDLIKIFENDIGGNPAN

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 – 521 Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
Region 56 – 340 Catalytic
Metal binding 90 – 90 Iron
Metal binding 92 – 92 Iron; via tele nitrogen
Alternative sequence 87 – 318 Missing. In isoform 4.


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;

Loss-of-function and gain-of-function mutations in PPP3CA cause two distinct disorders.
Mizuguchi T.; Nakashima M.; Kato M.; Okamoto N.; Kurahashi H.; Ekhilevitch N.; Shiina M.; Nishimura G.; Shibata T.; Matsuo M.; Ikeda T.; Ogata K.; Tsuchida N.; Mitsuhashi S.; Miyatake S.; Takata A.; Miyake N.; Hata K.; Kaname T.; Matsubara Y.; Saitsu H.; Matsumoto N.;
Hum. Mol. Genet. 27:1421-1433(2018)
Cited for: VARIANTS ACCIID LEU-470 AND THR-473; INVOLVEMENT IN ACCIID; VARIANTS IECEE1 ARG-92; ILE-150 AND GLU-234;

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.