Home  |  Contact

UniProtKB/Swiss-Prot Q08499: Variant p.Ala304Val

cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Gene: PDE4D
Variant information

Variant position:  304
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 Alanine (A) to Valine (V) at position 304 (A304V, p.Ala304Val).
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 hydrophobic (A) to medium size and hydrophobic (V)
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:  Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems. {ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252, ECO:0000269|PubMed:23033274, ECO:0000269|PubMed:23043190}. 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 ACRDYS2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  304
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  809
The length of the canonical sequence.

Location on the sequence:   LDWCLDQLETLQTRHSVSEM  A SNKFKRMLNRELTHLSEMSR
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                         LDWCLDQLETLQTRHSVSEMASNKFKRMLNRELTHLSEMSR

Mouse                         LDWCLDQLETLQTRHSVSEMASNKFKRMLNRELTHLSEMSR

Rat                           LDWCLDQLETLQTRHSVSEMASNKFKRMLNRELTHLSEMSR

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 – 809 cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Modified residue 299 – 299 Phosphoserine
Modified residue 301 – 301 Phosphoserine
Alternative sequence 280 – 809 Missing. In isoform N3.
Alternative sequence 284 – 809 Missing. In isoform 12.
Alternative sequence 292 – 306 ETLQTRHSVSEMASN -> MPEANYLLSVSWGYI. In isoform 6.


Literature citations

Identification of novel mutations confirms Pde4d as a major gene causing acrodysostosis.
Lynch D.C.; Dyment D.A.; Huang L.; Nikkel S.M.; Lacombe D.; Campeau P.M.; Lee B.; Bacino C.A.; Michaud J.L.; Bernier F.P.; Parboosingh J.S.; Innes A.M.;
Hum. Mutat. 34:97-102(2013)
Cited for: VARIANTS ACRDYS2 THR-225; THR-301; VAL-304; ALA-329 AND THR-678;

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.