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UniProtKB/Swiss-Prot P06213: Variant p.Trp1220Leu

Insulin receptor
Gene: INSR
Variant information

Variant position:  1220
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Tryptophan (W) to Leucine (L) at position 1220 (W1220L, p.Trp1220Leu).
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 aromatic (W) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  In IRAN type A; accelerates degradation of the protein and impairs kinase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1220
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:   VRWMAPESLKDGVFTTSSDM  W SFGVVLWEITSLAEQPYQGL
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                         VRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGL

Mouse                         VRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGL

Rat                           VRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGL

Xenopus laevis                VRWMSPESLKDGVFTAFSDVWSFGVVLWEITSLAEQPYQGL

Caenorhabditis elegans        VRWMSPESLKDGKFDSKSDVWSFGVVLYEMVTLGAQPYIGL

Drosophila                    VRWMPPESLRDGVYSSASDVFSFGVVLWEMATLAAQPYQGL

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
Helix 1215 – 1230


Literature citations

A mutation (Trp1193-->Leu1193) in the tyrosine kinase domain of the insulin receptor associated with type A syndrome of insulin resistance.
Iwanishi M.; Haruta T.; Takata Y.; Ishibashi O.; Sasaoka T.; Egawa K.; Imamura T.; Naitou K.; Itazu T.; Kobayashi M.;
Diabetologia 36:414-422(1993)
Cited for: VARIANT INS RESISTANCE LEU-1220;

Two naturally occurring mutations in the kinase domain of insulin receptor accelerate degradation of the insulin receptor and impair the kinase activity.
Imamura T.; Takata Y.; Sasaoka T.; Takada Y.; Morioka H.; Haruta T.; Sawa T.; Iwanishi M.; Hu Y.G.; Suzuki Y.; Hamada J.; Kobayashi M.;
J. Biol. Chem. 269:31019-31027(1994)
Cited for: CHARACTERIZATION OF VARIANTS IRAN TYPE A ASP-1206 AND LEU-1220;

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.