UniProtKB/Swiss-Prot P20823: Variant p.Arg272His

Hepatocyte nuclear factor 1-alpha
Gene: HNF1A
Chromosomal location: 12q24.3
Variant information

Variant position:  272
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 Arginine (R) to Histidine (H) at position 272 (R272H, p.Arg272His).
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 large size and basic (R) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10078571, ECO:0000269|PubMed:10102714, ECO:0000269|PubMed:10482964, ECO:0000269|PubMed:10588527, ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:12453420, ECO:0000269|PubMed:8945470, ECO:0000269|PubMed:9032114, ECO:0000269|PubMed:9075818, ECO:0000269|PubMed:9075819, ECO:0000269|PubMed:9097962, ECO:0000269|PubMed:9166684, ECO:0000269|PubMed:9287053, ECO:0000269|PubMed:9392505, ECO:0000269|PubMed:9626139, ECO:0000269|PubMed:9754819}. 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.

Involvement in disease:  Diabetes mellitus, insulin-dependent, 20 (IDDM20) [MIM:612520]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10333057, ECO:0000269|PubMed:9313763, ECO:0000269|PubMed:9867222}. Note=Disease susceptibility is associated with variations 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 IDDM20 and MODY3.
Any additional useful information about the variant.



Sequence information

Variant position:  272
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  631
The length of the canonical sequence.

Location on the sequence:   QGLGSNLVTEVRVYNWFANR  R KEEAFRHKLAMDTYSGPPPG
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                         QGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYSGPPPG

Mouse                         QGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYNGPPPG

Rat                           QGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYNGPPPG

Chicken                       QGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDNFSGPQPT

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 1 – 631 Hepatocyte nuclear factor 1-alpha
DNA binding 199 – 279 Homeobox; HNF1-type
Region 270 – 273 Interaction with DNA
Alternative sequence 120 – 631 Missing. In isoform 8.
Alternative sequence 176 – 278 QFTHAGQGGLIEEPTGDELPTKKGRRNRFKWGPASQQILFQAYERQKNPSKEERETLVEECNRAECIQRGVSPSQAQGLGSNLVTEVRVYNWFANRRKEEAFR -> RRNASREGCPHHRHRGWAPTSSRRCVSTTGLPTGAKKKPSGTSWPWTRTAGPPQGQARDLRCPLTAPLACLHLPSPPVRSTVCAMDSLRPVRLQKYPQAAAVP. In isoform 4.
Alternative sequence 248 – 631 Missing. In isoform 5.
Mutagenesis 257 – 257 N -> W. Reduces transcription activation by 70%.
Helix 261 – 274


Literature citations

Novel mutations and a mutational hotspot in the MODY3 gene.
Glucksmann M.A.; Lehto M.; Tayber O.; Scotti S.; Berkemeier L.; Pulido J.C.; Wu Y.; Nir W.-J.; Fang L.; Markel P.; Munnelly K.D.; Goranson J.; Orho M.; Young B.M.; Whitacre J.L.; McMenimen C.; Wantman M.; Tuomi T.; Warram J.; Forsblom C.M.; Carlsson M.; Rosenzweig J.; Kennedy G.; Duyk G.M.; Krolewski A.S.; Groop L.C.; Thomas J.D.;
Diabetes 46:1081-1086(1997)
Cited for: VARIANTS MODY3 ARG-107; TRP-131; MET-260 AND HIS-272;

Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.
Yamada S.; Nishigori H.; Onda H.; Utsugi T.; Yanagawa T.; Maruyama T.; Onigata K.; Nagashima K.; Nagai R.; Morikawa A.; Takeuchi T.; Takeda J.;
Diabetes 46:1643-1647(1997)
Cited for: VARIANTS IDDM20 HIS-272 AND GLY-583;

Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.
Kaisaki P.J.; Menzel S.; Lindner T.; Oda N.; Rjasanowski I.; Sahm J.; Meincke G.; Schulze J.; Schmechel H.; Petzold C.; Ledermann H.M.; Sachse G.; Boriraj V.V.; Menzel R.; Kerner W.; Turner R.C.; Yamagata K.; Bell G.I.;
Diabetes 46:528-535(1997)
Cited for: VARIANTS MODY3 GLN-131; GLN-229; GLY-241 AND HIS-272;

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.