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UniProtKB/Swiss-Prot P06213: Variant p.Arg1201Gln

Insulin receptor
Gene: INSR
Variant information

Variant position:  1201
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 1201 (R1201Q, p.Arg1201Gln).
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.

Involvement in disease:  Familial hyperinsulinemic hypoglycemia 5 (HHF5) [MIM:609968]: Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. {ECO:0000269|PubMed:15161766}. 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 HHF5 and IRAN type A; interferes with kinase activation by insulin.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1201
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:   TRDIYETDYYRKGGKGLLPV  R WMAPESLKDGVFTTSSDMWS
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                         TRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWS

Mouse                         TRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWS

Rat                           TRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWS

Xenopus laevis                TRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTAFSDVWS

Caenorhabditis elegans        ARDLFYHDYYKPSGKRMMPVRWMSPESLKDGKFDSKSDVWS

Drosophila                    TRDIYETDYYRKGTKGLLPVRWMPPESLRDGVYSSASDVFS

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
Domain 1023 – 1298 Protein kinase
Modified residue 1185 – 1185 Phosphotyrosine; by autocatalysis
Modified residue 1189 – 1189 Phosphotyrosine; by autocatalysis
Modified residue 1190 – 1190 Phosphotyrosine; by autocatalysis
Mutagenesis 1189 – 1189 Y -> F. Reduced interaction with GRB7.
Mutagenesis 1190 – 1190 Y -> F. Strongly reduced interaction with GRB7.
Helix 1200 – 1202


Literature citations

Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance.
Moller D.E.; Cohen O.; Yamaguchi Y.; Assiz R.; Grigorescu F.; Eberle A.; Morrow L.A.; Moses A.C.; Flier J.S.;
Diabetes 43:247-255(1994)
Cited for: VARIANT IRAN TYPE A GLN-1201;

Functional properties of a heterozygous mutation (Arg1174-->Gln) in the tyrosine kinase domain of the insulin receptor from a type A insulin resistant patient.
Moritz W.; Froesch E.R.; Boeni-Schnetzler M.;
FEBS Lett. 351:276-280(1994)
Cited for: CHARACTERIZATION OF VARIANT IRAN TYPE A GLN-1201;

A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene.
Hoejlund K.; Hansen T.; Lajer M.; Henriksen J.E.; Levin K.; Lindholm J.; Pedersen O.; Bech-Nielsen H.;
Diabetes 53:1592-1598(2004)
Cited for: VARIANT HHF5 GLN-1201;

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.