UniProtKB/Swiss-Prot P15428: Variant p.Ala140Pro

15-hydroxyprostaglandin dehydrogenase [NAD(+)]
Gene: HPGD
Chromosomal location: 4q34-q35
Variant information

Variant position:  140
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 Proline (P) at position 140 (A140P, p.Ala140Pro).
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 (P)
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:  Cranioosteoarthropathy (COA) [MIM:259100]: A form of osteoarthropathy characterized by swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature. {ECO:0000269|PubMed:18500342}. 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 COA; inactive.
Any additional useful information about the variant.

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

Sequence information

Variant position:  140
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  266
The length of the canonical sequence.

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.





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.

Chain 1 – 266 15-hydroxyprostaglandin dehydrogenase [NAD(+)]
Active site 151 – 151 Proton acceptor
Binding site 138 – 138 Substrate
Binding site 148 – 148 Substrate
Alternative sequence 73 – 140 Missing. In isoform 5.
Alternative sequence 140 – 143 AGLM -> AAHH. In isoform 4.
Mutagenesis 148 – 148 Q -> A. Loss of activity.
Mutagenesis 148 – 148 Q -> EHN. Reduced affinity for NAD and prostaglandin E2.
Mutagenesis 151 – 151 Y -> A. Loss of activity.
Helix 139 – 141

Literature citations

Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy.
Uppal S.; Diggle C.P.; Carr I.M.; Fishwick C.W.G.; Ahmed M.; Ibrahim G.H.; Helliwell P.S.; Latos-Bielenska A.; Phillips S.E.V.; Markham A.F.; Bennett C.P.; Bonthron D.T.;
Nat. Genet. 40:789-793(2008)

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.