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UniProtKB/Swiss-Prot P01133: Variant p.Pro1070Leu

Pro-epidermal growth factor
Gene: EGF
Variant information

Variant position:  1070
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 Proline (P) to Leucine (L) at position 1070 (P1070L, p.Pro1070Leu).
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:  Hypomagnesemia 4 (HOMG4) [MIM:611718]: A disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to moderate psychomotor retardation, and brisk tendon reflexes. {ECO:0000269|PubMed:17671655}. 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 HOMG4; affects basolateral sorting of pro-EGF preventing the hormone to stimulate EGFR; lack of TRPM6 activation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1070
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1207
The length of the canonical sequence.

Location on the sequence:   SLWGAHYYRTQKLLSKNPKN  P YEESSRDVRSRRPADTEDGM
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                         SLWGAHYYRTQKLLSKNPKNPYEESSRDVRSRRP-ADTEDGM

                              GLGGAHCYRTKKLSSKNLKNPYEEPSREGSSSRP-SDSEAR

Mouse                         GMWGTYYYRTRKQLSNPPKNPCDEPSGSVSSSGPNSSSGAA

Rat                           GMWGTYYYRTRKQLSESSKKPSEESSSNVSSNGP-DSSGAG

Pig                           GLWGAHYYRTQKLLSKNPKNPYEESGRDVSGIRP-ADGEAG

Cat                           GLWGAHCYRTKKLPSKNLKNPYEESSREVS--RP-TDSEAG

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 23 – 1207 Pro-epidermal growth factor
Topological domain 1054 – 1207 Cytoplasmic


Literature citations

Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia.
Groenestege W.M.T.; Thebault S.; van der Wijst J.; van den Berg D.; Janssen R.; Tejpar S.; van den Heuvel L.P.; van Cutsem E.; Hoenderop J.G.; Knoers N.V.; Bindels R.J.;
J. Clin. Invest. 117:2260-2267(2007)
Cited for: FUNCTION; TISSUE SPECIFICITY; VARIANT HOMG4 LEU-1070; CHARACTERIZATION OF VARIANT HOMG4 LEU-1070;

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.