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UniProtKB/Swiss-Prot P06213: Variant p.Arg1020Gln

Insulin receptor
Gene: INSR
Variant information

Variant position:  1020
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 Glutamine (Q) at position 1020 (R1020Q, p.Arg1020Gln).
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 (Q)
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:  Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]: Characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor. {ECO:0000269|PubMed:10733238, ECO:0000269|PubMed:11260230, ECO:0000269|PubMed:12107746, ECO:0000269|PubMed:12970295, ECO:0000269|PubMed:1563582, ECO:0000269|PubMed:1963473, ECO:0000269|PubMed:2002058, ECO:0000269|PubMed:2168397, ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:2544998, ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:3283938, ECO:0000269|PubMed:8243830, ECO:0000269|PubMed:8288049, ECO:0000269|PubMed:8314008, ECO:0000269|PubMed:8388389, ECO:0000269|PubMed:9175790}. 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 IRAN type A.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1020
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:   LSASDVFPCSVYVPDEWEVS  R EKITLLRELGQGSFGMVYEG
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                         LSASDVFPCSVYVPDEWEVSREKITLLRELGQGSFGMVYEG

Mouse                         LSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEG

Rat                           LSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEG

Xenopus laevis                LSASE-----VYIPDEWEVPRDKINLLRELGQGSFGMVYEG

Caenorhabditis elegans        CVDN------KYNADDWELRQDDVVLGQQCGEGSFGKVYLG

Drosophila                    ASM-------QYIPDDWEVLRENIIQLAPLGQGSFGMVYEG

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 763 – 1382 Insulin receptor subunit beta
Topological domain 980 – 1382 Cytoplasmic
Binding site 1033 – 1033 ATP
Modified residue 1011 – 1011 Phosphotyrosine; by autocatalysis
Mutagenesis 1000 – 1000 L -> AR. Severely reduces interaction with SHC1. Has no effect on interaction with IRS1.
Mutagenesis 1002 – 1002 A -> D. Reduces interaction with IRS1 but has no effect on interaction with SHC1.
Mutagenesis 1011 – 1011 Y -> A. Increases kinase activity.
Helix 1020 – 1022


Literature citations

Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles.
Kusari J.; Takata Y.; Hatada E.; Freidenberg G.; Kolterman O.; Olefsky J.M.;
J. Biol. Chem. 266:5260-5267(1991)
Cited for: VARIANT IRAN TYPE A GLN-1020;

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.