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UniProtKB/Swiss-Prot P43026: Variant p.His440Leu

Growth/differentiation factor 5
Gene: GDF5
Chromosomal location: 20q11.2
Variant information

Variant position:  440
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 Histidine (H) to Leucine (L) at position 440 (H440L, p.His440Leu).
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 polar (H) to medium size and hydrophobic (L)
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:  Du Pan syndrome (DPS) [MIM:228900]: Rare autosomal recessive condition characterized by absence of the fibulae and severe acromesomelic limb shortening with small, non-functional toes. Although milder, the phenotype resembles the autosomal recessive Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia. {ECO:0000269|PubMed:12121354, ECO:0000269|PubMed:16222676, ECO:0000269|PubMed:18629880}. 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 DPS; located on the same allele as L-437 del and T-439.
Any additional useful information about the variant.

Sequence information

Variant position:  440
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  501
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 382 – 501 Growth/differentiation factor 5
Disulfide bond 400 – 466
Disulfide bond 429 – 498
Disulfide bond 433 – 500
Helix 439 – 441

Literature citations

Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene.
Szczaluba K.; Hilbert K.; Obersztyn E.; Zabel B.; Mazurczak T.; Kozlowski K.;
Am. J. Med. Genet. A 138:379-383(2005)
Cited for: VARIANTS DPS LEU-437 DEL; THR-439 AND LEU-440;

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.