Cancer, endocrine, neurological, and musculoskeletal disorders

Hyperinsulinemic hypoglycemia, familial, 5; Diabetes mellitus, insulin-resistant, with acanthosis nigricans; Donohue syndrome; Rabson-Mendenhall syndrome; Insulin resistance; Alzheimer's disease (AD); Myotonic dystrophy; Acanthosis nigricans; Ovarian disease; Hyperinsulinemic hypoglycemia; Diabetes mellitus, Type 2; Diabetes mellitus, noninsulin-dependent, late onset; Hypertension, Insulin resistance-related; Hemihypertrophy; Congenital fiber-type disproportion (CFTD); Myotonic dystrophy Type 2 (DM2); Acanthocytosis; Berardinelli-Seip congenital lipodystrophy (BSCL); Fetal macrosomia; Fasting hypoglycemia; Insulin autoimmune syndrome

Hyperinsulinemic Hypoglycemia, Familial, 5 is a rare disorder where insulin is overproduced because of insulin receptor deficiency. Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans is a rare disease with insulin-resistance that can affect bone and skin tissues. Donohue Syndrome is a rare syndrome where sufferers have greatly impaired insulin receptors and are characterized by elfin features, and smaller size (in stature). Rabson-Mendenhall Syndrome is a rare disorder with severe resistance to insulin resulting in impaired intrauterine and post-natal growth, increased volume of muscle and fat tissues, and physical abnormalities of the face, head, teeth, and nails. Alzheimer's disease (AD) is a rare neuro-degenerative disease that affects the thought, memory, and language portion of the brain. Myotonic Dystrophy is a rare disease that results in progressive muscle loss, typically in the face, neck, lower legs, and hands. Myotonic Dystrophy can affect skeletal muscle, brain, and heart. The rare skin disease, Acanthosis Nigricans, is characterized by making the folds and crevices of skin darker, thick, and velvety. Ovarian Disease is similar to the disorders insulin resistance and mccune albright syndrome. Sufferers of Type 2 Diabetes Mellitus have insulin resistance and excess blood glucose levels. Diabetes Mellitus, Noninsulin-Dependent, Late Onset is characterized by hyperglycemia (high blood glucose levels) induced by a reduced level of insulin production (but not fully abrogated, as would be the case in Type I diabetes). Diabetes Mellitus, Noninsulin-Dependent, Late Onset is similar to the familial hyperinsulinism and hyperinsulinemic hypoglycemia conditions. Hypertension, Insulin Resistance-Related is similar to the maturity-onset diabetes of the young and hyperandrogenism disorders. Diabetes Mellitus, Noninsulin-Dependent, Association with is related to the disorders maturity-onset diabetes of the young, and hyperinsulinism. Hemihypertrophy is a rare disease characterized by one side or part of the sufferer's body being larger than the other. Hemihypertrophy can be characterized by nephroblastoma (cancer of kidneys), asymmetrical rib cage, cognitive impairment, and other learning disabilities. The rare condition Congenital Fiber-Type Disproportion (CFTD) affects skeletal muscles required for movement, especially the hips, thighs, upper arms, shoulders, but also the eyelids, eye muscles (opthalmoplegia), breathing, and muscles for swallowing. Myotonic Dystrophy Type 2 (DM2) often correlates with sustained muscle tensing, and muscle weakness, pain, and stiffness. DM2 can also cause cataract opacification, and myotonia while affecting the eye, heart, and pancreatic tissues. The rare disease Acanthocytosis causes malformed red blood cells resulting in symptoms including chronic foul-smelling diarrhea, reduced growth, increased weight gain, and appetite loss. Berardinelli-Seip Congenital Lipodystrophy (BSCL) is noted for the lack of adipose (fatty) tissue in individuals with this disorder. Fetal Macrosomia is a rare disease similar to the gestational diabetes and diabetes mellitus disorders. Fetal Macrosomia can affect the testes and placenta. Fasting Hypoglycemia is related to the hypoglycemia and insulinoma disorders where there are high levels of insulin resulting in low blood glucose levels. Insulin Autoimmune Syndrome is characterized by the production of autoimmune antibodies targeting insulin.
 

Brain cancer; Hemihypertrophy

Hemihypertrophy can be characterized by nephroblastoma (cancer of kidneys), asymmetrical rib cage, cognitive impairment, and other learning disabilities.
 

The COSMIC website notes an up-regulated expression score for IRR in diverse human cancers of 322, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. Mutations that can inhibit IRR autophosphorylation are Y1145F with Y1146F.

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25455 diverse cancer specimens. This rate is only 13 % higher than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.54 % in 895 skin cancers tested; 0.33 % in 603 endometrium cancers tested; 0.25 % in 1270 large intestine cancers tested; 0.22 % in 589 stomach cancers tested; 0.15 % in 1956 lung cancers tested; 0.12 % in 65 Meninges cancers tested; 0.08 % in 548 urinary tract cancers tested; 0.08 % in 273 cervix cancers tested; 0.08 % in 1512 liver cancers tested; 0.07 % in 891 ovary cancers tested; 0.06 % in 1467 pancreas cancers tested; 0.06 % in 1364 kidney cancers tested; 0.06 % in 127 biliary tract cancers tested; 0.05 % in 710 oesophagus cancers tested; 0.05 % in 1490 breast cancers tested.

Most frequent mutations with the number of reports indicated in brackets: R1072* (5).

Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.