Comparative

OMIA group 1990

Cancer, TP53-related

The chain reaches the human disease acute myeloid leukemia, which Mondo defines as: “Acute myeloid leukemia (AML) is a group of neoplasms arising from precursor cells committed to the myeloid cell-line differentiation. All of them are characterized by clonal expansion of myeloid blasts. AML manifests by fever, pallor, anemia, hemorrhages and recurrent infections.” It reaches 14 more human diseases, listed below.

The chain

From the animal disease to the drugs. The page shows what each step found and where the chain stopped. It does not say whether the animal is a model of a human disease.

  1. Animal disease

    Reached

    OMIA records it in 5 species entries marked as a defect.

  2. Human disease

    Reached

    15 Mondo diseases.

  3. Human gene

    Reached

    2 human genes.

  4. Target evidence

    Reached

    25 Open Targets associations, with a best score of 0.87.

  5. Drugs

    Reached

    13 ChEMBL drugs, 2 approved. At least one has been tested for this disease.

Natural-model score

How complete and how well supported the chain to each human disease is, out of 100, by stated rules. It does not say that the animal is a validated model of the human disease. How the score works.

hepatocellular carcinoma

84.9 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.80 27.9 of 35
Drugs A drug has reached approved for this disease 25.0 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
acute myeloid leukemia

83.3 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.75 26.3 of 35
Drugs A drug has reached approved for this disease 25.0 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
colorectal cancer

83.3 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.75 26.3 of 35
Drugs A drug has reached approved for this disease 25.0 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
lung cancer

79.6 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.65 22.6 of 35
Drugs A drug has reached approved for this disease 25.0 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
urinary bladder cancer

76.7 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.71 24.7 of 35
Drugs A drug has reached phase 3 for this disease 20.0 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
Li-Fraumeni syndrome

65.1 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.87 30.6 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
basal cell carcinoma, susceptibility to, 7

60.4 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.74 25.9 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
hereditary breast carcinoma

60.4 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.74 25.9 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
bone osteosarcoma

59.5 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.71 25.0 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
adrenocortical carcinoma, hereditary

59.4 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.71 24.9 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
autoimmune lymphoproliferative syndrome type 4

59.1 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.70 24.6 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
familial pancreatic carcinoma

58.9 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.70 24.4 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
glioma susceptibility 1

58.7 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.69 24.2 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
nasopharyngeal carcinoma, susceptibility to, 1

52.1 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.50 17.6 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10
CDH1-related diffuse gastric and lobular breast cancer syndrome

47.5 out of 100

Part Computed from Points
Target evidence Open Targets score of 0.37 13.0 of 35
Drugs Drugs act on its genes, but no drug has been tested for this disease 2.5 of 25
Ortholog One to one ortholog 20.0 of 20
Both routes One route found this disease 5.0 of 10
Species 2 naturally occurring species entries marked as a defect. 3 genetically engineered entries are not counted 7.0 of 10

Species

The chain follows only the species entries that OMIA marks as a defect.

Species Scientific name OMIA entry A defect
crab-eating macaque Genetically engineered, not naturally occurring. Not counted in the score. Macaca fascicularis OMIA:001990-9541 Yes
dog Canis lupus familiaris OMIA:001990-9615 Yes
golden hamster Genetically engineered, not naturally occurring. Not counted in the score. Mesocricetus auratus OMIA:001990-10036 Yes
northern tree shrew Tupaia belangeri OMIA:001990-37347 Yes
pig Genetically engineered, not naturally occurring. Not counted in the score. Sus scrofa OMIA:001990-9823 Yes

Genes

Each gene OMIA records for a species entry, and the human gene it reaches through Ensembl's orthologs.

Species Animal gene Human gene Ortholog
crab-eating macaque TP53 tumor protein p53 NCBI Gene 102135998 TP53 Ensembl one to one
dog TP53 tumor protein p53 NCBI Gene 403869 TP53 Ensembl one to one
golden hamster Tp53 tumor protein p53 NCBI Gene 101833915 TP53 Ensembl one to one
northern tree shrew No gene OMIA records no gene for this species entry.
pig KRAS Kirsten rat sarcoma viral oncogene homolog NCBI Gene 100518251 KRAS Ensembl one to one
pig TP53 tumor protein p53 NCBI Gene 397276 TP53 Ensembl one to one

Human diseases

Two routes lead from an OMIA group to a Mondo human disease: OMIA's own Mondo link, and the group's OMIM numbers through Mondo's cross-references.

Mondo disease Name Found by
MONDO:0018874 acute myeloid leukemia Acute myeloid leukemia (AML) is a group of neoplasms arising from precursor cells committed to the myeloid cell-line differentiation. All of them are characterized by clonal expansion of myeloid blasts. AML manifests by fever, pallor, anemia, hemorrhages and recurrent infections. OMIA's OMIM numbers
MONDO:0008734 adrenocortical carcinoma, hereditary An instance of adrenal cortex carcinoma that is caused by an inherited modification of the individual's genome. OMIA's OMIM numbers
MONDO:0013767 autoimmune lymphoproliferative syndrome type 4 RAS-associated autoimmune leukoproliferative disease (RALD) is a rare genetic disorder characterized by monocytosis, autoimmune cytopenias, lymphoproliferation, hepatosplenomegaly, and hypergammaglobulinemia. OMIA's OMIM numbers
MONDO:0013876 basal cell carcinoma, susceptibility to, 7 Any skin basal cell carcinoma in which the cause of the disease is a mutation in the TP53 gene. OMIA's OMIM numbers
MONDO:0002629 bone osteosarcoma A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It may arise de novo or from a pre-existing lesion of the bone. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs. OMIA's OMIM numbers
MONDO:0100488 CDH1-related diffuse gastric and lobular breast cancer syndrome Germline pathogenic or likely pathogenic variants in the CDH1 gene predispose to hereditary diffuse gastric cancer, a cancer susceptibility syndrome inherited in an autosomal dominant pattern, initially characterized by the increased risk for diffuse gastric cancer (DGC) but subsequently well documented to be associated with lobular breast cancer (LBC) in women. OMIA's OMIM numbers
MONDO:0005575 colorectal cancer A primary or metastatic malignant neoplasm that affects the colon or rectum. Representative examples include carcinoma, lymphoma, and sarcoma. OMIA's OMIM numbers
MONDO:0015278 familial pancreatic carcinoma Familial pancreatic carcinoma is defined by the presence of pancreatic cancer (PC) in two or more first-degree relatives. OMIA's OMIM numbers
MONDO:0024498 glioma susceptibility 1 OMIA's OMIM numbers
MONDO:0007256 hepatocellular carcinoma A malignant tumor that arises from hepatocytes. Hepatocellular carcinoma is relatively rare in the United States but very common in all African countries south of the Sahara and in Southeast Asia. Most cases are seen in patients over the age of 50 years, but this tumor can also occur in younger individuals and even in children. Hepatocellular carcinoma is more common in males than females and is associated with hepatitis B, hepatitis C, chronic alcohol abuse and cirrhosis. Serum elevation of alpha-fetoprotein occurs in a large percentage of patients with hepatocellular carcinoma. Grossly, hepatocellular carcinoma may present as a single mass, as multiple nodules, or as diffuse liver involvement. Microscopically, there is a wide range of differentiation from tumor to tumor (well differentiated to poorly differentiated tumors). Hepatocellular carcinomas quickly metastasize to regional lymph nodes and lung. The overall median survival of untreated liver cell carcinoma is about 4 months. The most effective treatment of hepatocellular carcinoma is complete resection of the tumor. Lately, an increasing number of tumors have been treated with liver transplantation. OMIA's OMIM numbers
MONDO:0016419 hereditary breast carcinoma Breast carcinoma that has developed in relatives of patients with history of breast carcinoma. OMIA's OMIM numbers
MONDO:0018875 Li-Fraumeni syndrome An autosomal dominant cancer predisposition disorder caused by pathogenic variants in the TP53 gene, characterized by an increased risk of a wide range of cancers, including but not limited to breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, adrenocortical carcinoma and leukemias. OMIA's OMIM numbers
MONDO:0008903 lung cancer A malignant neoplasm involving the lung. OMIA's OMIM numbers
MONDO:0011775 nasopharyngeal carcinoma, susceptibility to, 1 Any nasopharyngeal carcinoma in which the cause of the disease is a mutation in the TP53 gene. OMIA's OMIM numbers
MONDO:0001187 urinary bladder cancer A primary or metastatic malignant neoplasm involving the bladder. OMIA's OMIM numbers

Target evidence

Each Open Targets association between one of the group's human genes and one of its human diseases, with its overall score and the score for each kind of evidence.

Human gene Human disease Score Evidence Kinds of evidence
TP53 Li-Fraumeni syndrome 0.87 5,740 Genetic association 0.95 Genetic literature 0.85 Animal model 0.64 Somatic mutation 0.44 Literature 0.37
TP53 hepatocellular carcinoma 0.80 6,833 Literature 0.99 Genetic association 0.92 Somatic mutation 0.86 Animal model 0.61 Genetic literature 0.61
TP53 colorectal cancer 0.75 4,421 Literature 0.97 Genetic association 0.91 Somatic mutation 0.83 Genetic literature 0.83 Animal model 0.53 Known drug 0.11
KRAS acute myeloid leukemia 0.75 618 Literature 0.88 Genetic association 0.80 Somatic mutation 0.79 Animal model 0.61 Genetic literature 0.61 Affected pathway 0.57
TP53 basal cell carcinoma, susceptibility to, 7 0.74 91 Genetic association 0.92 Genetic literature 0.83 Animal model 0.75
TP53 hereditary breast carcinoma 0.74 197 Genetic association 0.92 Somatic mutation 0.87 Genetic literature 0.61 Animal model 0.29 Literature 0.16
TP53 acute myeloid leukemia 0.72 3,572 Literature 0.99 Somatic mutation 0.81 Affected pathway 0.76 Genetic association 0.68 Known drug 0.28
TP53 bone osteosarcoma 0.71 78 Genetic association 0.86 Animal model 0.78 Genetic literature 0.61 Somatic mutation 0.46 Literature 0.08
TP53 adrenocortical carcinoma, hereditary 0.71 227 Genetic association 0.94 Genetic literature 0.89 Animal model 0.40 Literature 0.06
TP53 urinary bladder cancer 0.71 1,547 Literature 0.96 Somatic mutation 0.91
KRAS urinary bladder cancer 0.70 153 Genetic association 0.83 Somatic mutation 0.79 Literature 0.61 Genetic literature 0.61 Animal model 0.57
KRAS autoimmune lymphoproliferative syndrome type 4 0.70 64 Genetic association 0.88 Genetic literature 0.83 Somatic mutation 0.56 Animal model 0.27 Literature 0.20
TP53 familial pancreatic carcinoma 0.70 2,186 Literature 0.96 Genetic association 0.92 Genetic literature 0.61 Somatic mutation 0.55 Animal model 0.27
TP53 glioma susceptibility 1 0.69 66 Genetic association 0.92 Genetic literature 0.83 Animal model 0.53
KRAS familial pancreatic carcinoma 0.67 3,974 Literature 0.98 Genetic association 0.86 Somatic mutation 0.68 Genetic literature 0.61
KRAS lung cancer 0.65 4,284 Literature 0.98 Genetic association 0.81 Animal model 0.75 Genetic literature 0.61 Somatic mutation 0.58 Known drug 0.48
KRAS hereditary breast carcinoma 0.60 29 Genetic association 0.83 Genetic literature 0.61 Animal model 0.35 Literature 0.07
KRAS colorectal cancer 0.53 5,006 Literature 0.97 Genetic association 0.70 Known drug 0.60
KRAS hepatocellular carcinoma 0.51 498 Literature 0.96 Affected pathway 0.87 Somatic mutation 0.62
TP53 nasopharyngeal carcinoma, susceptibility to, 1 0.50 3 Genetic literature 0.83
TP53 lung cancer 0.40 5,142 Literature 0.98 Genetic literature 0.61
KRAS CDH1-related diffuse gastric and lobular breast cancer syndrome 0.37 3 Genetic literature 0.61 Literature 0.02
TP53 autoimmune lymphoproliferative syndrome type 4 0.06 6 Animal model 0.50
TP53 CDH1-related diffuse gastric and lobular breast cancer syndrome 0.01 12 Literature 0.08
KRAS Li-Fraumeni syndrome 0.01 4 Literature 0.07

Drugs

A drug acts on KRAS and TP53 and has been tested for this disease.

Drug Acts on How Latest stage Tested for this disease
Adagrasib KRAS inhibitor Approved Phase 3 for colorectal cancer
Sotorasib KRAS inhibitor Approved Phase 3 for colorectal cancer
Idasanutlin TP53 inhibitor Phase 3 Phase 3 for acute myeloid leukemia
Eprenetapopt TP53 stabiliser Phase 3 Phase 2 for acute myeloid leukemia
Cenersen TP53 antisense inhibitor Phase 2 Phase 2 for acute myeloid leukemia
Cenersen Sodium TP53 antisense inhibitor Phase 2 Phase 2 for acute myeloid leukemia
Salirasib KRAS inhibitor Phase 2 Phase 2 for lung cancer
Navtemadlin TP53 inhibitor Phase 3 Phase 1/2 for acute myeloid leukemia
Alrizomadlin TP53 inhibitor Phase 2 Phase 1/2 for acute myeloid leukemia
Siremadlin TP53 inhibitor Phase 2 Phase 1/2 for acute myeloid leukemia
Contusugene Ladenovec TP53 exogenous gene Phase 3 No
Teprasiran TP53 rnai inhibitor Phase 3 No
Teprasiran Sodium TP53 rnai inhibitor Unknown No

The drug data is ChEMBL's, under CC BY-SA 3.0, and came through Open Targets release 26.09.