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UniProtKB/Swiss-Prot O15357: Variant p.Pro659Ser

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Gene: INPPL1
Chromosomal location: 11q23
Variant information

Variant position:  659
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 Serine (S) at position 659 (P659S, p.Pro659Ser).
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 hydrophobic (P) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Opsismodysplasia (OPSMD) [MIM:258480]: A rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with very delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges. {ECO:0000269|PubMed:23273569}. 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 OPSMD.
Any additional useful information about the variant.

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



Sequence information

Variant position:  659
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1258
The length of the canonical sequence.

Location on the sequence:   LEREKHKVFLRFSEEEISFP  P TYRYERGSRDTYAWHKQKPT
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                         LEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPT

Mouse                         LEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPT

Rat                           LEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPT

Pig                           LEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPT

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 1 – 1258 Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2


Literature citations

Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia.
Huber C.; Faqeih E.A.; Bartholdi D.; Bole-Feysot C.; Borochowitz Z.; Cavalcanti D.P.; Frigo A.; Nitschke P.; Roume J.; Santos H.G.; Shalev S.A.; Superti-Furga A.; Delezoide A.L.; Le Merrer M.; Munnich A.; Cormier-Daire V.;
Am. J. Hum. Genet. 92:144-149(2013)
Cited for: FUNCTION; VARIANTS OPSMD TRP-401; SER-659; CYS-688 AND ILE-722;

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.