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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P20823: Variant p.Pro447Leu

Hepatocyte nuclear factor 1-alpha
Gene: HNF1A
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Variant information Variant position: help 447 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Proline (P) to Leucine (L) at position 447 (P447L, p.Pro447Leu). 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: help 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: help -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
Variant description: help In MODY3. Any additional useful information about the variant.


Sequence information Variant position: help 447 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 631 The length of the canonical sequence.
Location on the sequence: help TNTGASTLVIGLASTQAQSV P VINSMGSSLTTLQPVQFSQP 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQP

Mouse                         TNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQP

Rat                           TNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQP

Chicken                       TNTGGSTLVIGLTSTQPQSVPVINSMGSSLTTLQPVQFSQQ
Sequence annotation in neighborhood: help 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 – 631 Hepatocyte nuclear factor 1-alpha
Alternative sequence 120 – 631 Missing. In isoform 8.
Alternative sequence 248 – 631 Missing. In isoform 5.
Alternative sequence 279 – 631 Missing. In isoform 4.
Alternative sequence 438 – 520 LASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPFMATMAQLQSPHALYSHKPEVAQYTHTGLLPQ -> KLVGMGGHLGGRLMGQPQNPGAGRATGTHSFIHTTCIYPVPTLDQSLCYISDTWVNQTDQNLSNSSREAGTKHNTSILWYLRR. In isoform 6.
Alternative sequence 438 – 494 LASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPFMATMA -> KLVGMGGHLGGRLMGQPQNPGAGRATGTHSFIHSFIQHVFIQCLLWTSHCATSVIPG. In isoform C.



Literature citations
Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3).
Yamagata K.; Oda N.; Kaisaki P.J.; Menzel S.; Furuta H.; Vaxillaire M.; Southam L.; Cox R.D.; Lathrop G.M.; Boriraj V.V.; Chen X.; Cox N.J.; Oda Y.; Yano H.; le Beau M.M.; Yamada S.; Nishigori H.; Takeda J.; Fajans S.S.; Hattersley A.T.; Iwasaki N.; Hansen T.; Pedersen O.; Polonsky K.S.; Turner R.C.; Velho G.; Chevre J.-C.; Froguel P.; Bell G.I.;
Nature 384:455-458(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT MODY3 LEU-447; VARIANT GLY-574; Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.
Hansen T.; Eiberg H.; Rouard M.; Vaxillaire M.; Moeller A.M.; Rasmussen S.K.; Fridberg M.; Urhammer S.A.; Holst J.J.; Almind K.; Echwald S.M.; Hansen L.; Bell G.I.; Pedersen O.;
Diabetes 46:726-730(1997)
Cited for: VARIANTS MODY3 ASN-128; TYR-143 AND LEU-447; Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.
Estalella I.; Rica I.; Perez de Nanclares G.; Bilbao J.R.; Vazquez J.A.; San Pedro J.I.; Busturia M.A.; Castano L.;
Clin. Endocrinol. (Oxf.) 67:538-546(2007)
Cited for: VARIANTS MODY3 ASP-31; MET-133; 171-ARG--GLN-631 DEL; GLY-271 AND LEU-447;
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.