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UniProtKB/Swiss-Prot P30153: Variant p.Pro179Leu

Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Gene: PPP2R1A
Chromosomal location: 19q13.4
Variant information

Variant position:  179
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 Proline (P) to Leucine (L) at position 179 (P179L, p.Pro179Leu).
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:  -3
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:  Mental retardation, autosomal dominant 36 (MRD36) [MIM:616362]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:26168268}. 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 MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; does not affect PPP2R3A binding; decreases phosphatase activity of PPP2CA.
Any additional useful information about the variant.

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



Sequence information

Variant position:  179
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  589
The length of the canonical sequence.

Location on the sequence:   SSAVKAELRQYFRNLCSDDT  P MVRRAAASKLGEFAKVLELD
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                         SSAVKAELRQYFRNLCSDDTPMVRRAAASKLGEFAKVLEL------D

Mouse                         SSAVKAELRQYFRNLCSDDTPMVRRAAASKLGEFAKVLEL-

Pig                           SSAVKAELRQYFRNLCSDDTPMVRRAAASKLGEFAKVLEL-

Bovine                        SSAVKAELRQYFRNLCSDDTPMVRRAAASKLGEFAKVLEL-

Caenorhabditis elegans        SPAIKSELKSMFRTLCRDDTPMVRRAAAAKLGEFAKVFEK-

Drosophila                    TQPVKAELRANFRKLCQDETPMVRRAAANKLGEFAKVVET-

Slime mold                    NAEMKKSLRKTFGGLCHDDTPMVKRAAATNLGSFAKQIEK-

Baker's yeast                 DDSLRKNILALYLQLAQDDTPMVKRAVGKNLPILIDLLTQN

Fission yeast                 NPAVKVSLRQSFSHLCHDEAPMVRRPAATNCAKFVFLVTK-

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 – 589 Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Repeat 162 – 200 HEAT 5
Region 8 – 399 PP2A subunit B binding
Region 47 – 321 Polyoma small and medium T antigens Binding
Region 85 – 239 SV40 small T antigen binding
Helix 179 – 194


Literature citations

B56delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.
Houge G.; Haesen D.; Vissers L.E.; Mehta S.; Parker M.J.; Wright M.; Vogt J.; McKee S.; Tolmie J.L.; Cordeiro N.; Kleefstra T.; Willemsen M.H.; Reijnders M.R.; Berland S.; Hayman E.; Lahat E.; Brilstra E.H.; van Gassen K.L.; Zonneveld-Huijssoon E.; de Bie C.I.; Hoischen A.; Eichler E.E.; Holdhus R.; Steen V.M.; Doeskeland S.O.; Hurles M.E.; FitzPatrick D.R.; Janssens V.;
J. Clin. Invest. 125:3051-3062(2015)
Cited for: VARIANTS MRD36 LEU-179; TRP-182 AND HIS-258; CHARACTERIZATION MRD36 OF VARIANTS LEU-179; TRP-182 AND HIS-258;

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.