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UniProtKB/Swiss-Prot Q9Y233: Variant p.Phe324Leu

cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Gene: PDE10A
Variant information

Variant position:  324
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 Phenylalanine (F) to Leucine (L) at position 324 (F324L, p.Phe324Leu).
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 large size and aromatic (F) to medium size and hydrophobic (L)
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:  Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269|PubMed:27058447}. 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 ADSD2; no effect on basal 3',5'-cyclic-nucleotide phosphodiesterase activity; the mutation severely disrupts the stimulatory effect on the enzyme activity mediated by cAMP binding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  324
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  779
The length of the canonical sequence.

Location on the sequence:   FDIGEEKEGKPVFKKTKEIR  F SIEKGIAGQVARTGEVLNIP
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                         FDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIP

Mouse                         FDIGEEKEGKPIFKKTKEIRFSIEKGIAGQVARTGEVLNIP

Rat                           FDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIP

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 – 779 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Domain 266 – 412 GAF 2
Beta strand 323 – 325


Literature citations

De novo mutations in PDE10A cause childhood-onset chorea with bilateral striatal lesions.
Mencacci N.E.; Kamsteeg E.J.; Nakashima K.; R'Bibo L.; Lynch D.S.; Balint B.; Willemsen M.A.; Adams M.E.; Wiethoff S.; Suzuki K.; Davies C.H.; Ng J.; Meyer E.; Veneziano L.; Giunti P.; Hughes D.; Raymond F.L.; Carecchio M.; Zorzi G.; Nardocci N.; Barzaghi C.; Garavaglia B.; Salpietro V.; Hardy J.; Pittman A.M.; Houlden H.; Kurian M.A.; Kimura H.; Vissers L.E.; Wood N.W.; Bhatia K.P.;
Am. J. Hum. Genet. 98:763-771(2016)
Cited for: TISSUE SPECIFICITY; INVOLVEMENT IN ADSD2; VARIANTS ADSD2 LEU-290 AND LEU-324; CHARACTERIZATION OF VARIANTS ADSD2 LEU-290 AND LEU-324;

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.