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UniProtKB/Swiss-Prot P12272: Variant p.Leu44Pro

Parathyroid hormone-related protein
Gene: PTHLH
Chromosomal location: 12p11.2-p12.1
Variant information

Variant position:  44
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 Leucine (L) to Proline (P) at position 44 (L44P, p.Leu44Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Brachydactyly E2 (BDE2) [MIM:613382]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. In brachydactyly type E2 variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges. {ECO:0000269|PubMed:20170896}. 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 BDE2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  44
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  177
The length of the canonical sequence.

Location on the sequence:   GRSVEGLSRRLKRAVSEHQL  L HDKGKSIQDLRRRFFLHHLI
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                         GRSVEGLSRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLI

                              GRSVEELGRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLI

Mouse                         GRSVEGLGRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLI

Rat                           GRSVEGLGRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLI

Bovine                        GRSVEELGRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLI

Rabbit                        GRSVEGPGRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLI

Chicken                       GRSVEGISRRLKRAVSEHQLLHDKGKSIQDLRRRIFLQNLI

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 37 – 177 Parathyroid hormone-related protein
Peptide 37 – 72 PTHrP[1-36]
Mutagenesis 57 – 57 R -> A. Strongly reduced affinity for PTH1R.
Mutagenesis 59 – 59 F -> A. Reduced affinity for PTH1R.
Mutagenesis 60 – 60 L -> AK. Strongly reduced affinity for PTH1R.
Mutagenesis 63 – 63 L -> A. Reduced affinity for PTH1R.
Mutagenesis 64 – 64 I -> A. Reduced affinity for PTH1R.
Helix 41 – 44


Literature citations

Deletion and point mutations of PTHLH cause brachydactyly type E.
Klopocki E.; Hennig B.P.; Dathe K.; Koll R.; de Ravel T.; Baten E.; Blom E.; Gillerot Y.; Weigel J.F.; Krueger G.; Hiort O.; Seemann P.; Mundlos S.;
Am. J. Hum. Genet. 86:434-439(2010)
Cited for: VARIANTS BDE2 PRO-44 AND PRO-60;

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.