Home  |  Contact

UniProtKB/Swiss-Prot P06213: Variant p.Lys487Glu

Insulin receptor
Gene: INSR
Chromosomal location: 19p13.2-p13.3
Variant information

Variant position:  487
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 Lysine (K) to Glutamate (E) at position 487 (K487E, p.Lys487Glu).
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 (K) to medium size and acidic (E)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  Leprechaunism (LEPRCH) [MIM:246200]: Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive. {ECO:0000269|PubMed:12023989, ECO:0000269|PubMed:12538626, ECO:0000269|PubMed:12970295, ECO:0000269|PubMed:1607067, ECO:0000269|PubMed:1730625, ECO:0000269|PubMed:22768670, ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:24498630, ECO:0000269|PubMed:2479553, ECO:0000269|PubMed:2834824, ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:7538143, ECO:0000269|PubMed:7815442, ECO:0000269|PubMed:8188715, ECO:0000269|PubMed:8326490, ECO:0000269|PubMed:8419945, ECO:0000269|PubMed:8636294, ECO:0000269|PubMed:9249867, ECO:0000269|PubMed:9299395, ECO:0000269|PubMed:9703342}. 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 LEPRCH; ARK-1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  487
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1382
The length of the canonical sequence.

Location on the sequence:   HKMEEVSGTKGRQERNDIAL  K TNGDQASCENELLKFSYIRT
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                         HKMEEVSGTKGRQ-ERNDIALKTNGDQASCENELLKFSYIRT

Mouse                         HKMEEVSGTKGRQ-ERNDIALKTNGDQASCENELLKFSFIR

Rat                           HKMEEVSGTKGRQ-ERNDIALKTNGDQASCENELLKFSFIR

Xenopus laevis                HQMEEVTGTKGRQ-DKNDIATKTNGDQASCEDNLLTFNFIK

Caenorhabditis elegans        KQLMSKLNIPLDPIDQSE---GTNGEKAICEDMAINVSITA

Drosophila                    NQLLPMLASKPKFFEKSDVGADSNGNRGSCGTAVLNVTLQS

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 28 – 758 Insulin receptor subunit alpha
Topological domain 28 – 758 Extracellular
Disulfide bond 462 – 495
Beta strand 486 – 490


Literature citations

Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance.
Kadowaki T.; Bevins C.; Cama A.; Ojamaa K.; Marcus-Samuels B.; Kadowaki H.; Beitz L.; McKeon C.; Taylor S.I.;
Science 240:787-790(1988)
Cited for: VARIANT LEPRCH GLU-487;

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.