Adrenocortical carcinoma, hereditary: genes and variants

Genes linked to Adrenocortical carcinoma, hereditary

• TP53: Cellular tumor antigen p53

  It coordinates transcriptional responses to DNA damage and other cellular stresses, promoting cell-cycle arrest, senescence, DNA repair, or apoptosis when appropriate. Loss of this tumor-suppressive control is one of the most common events in cancer, while germline pathogenic variants cause Li-Fraumeni syndrome.

  23 disease-causing and 84 uncertain variants in TP53 are linked to Adrenocortical carcinoma, hereditary.

Where Adrenocortical carcinoma, hereditary variants cluster

• TP53 DNA binding (positions 102–292): 21 of 21 disease-causing changes, 2.1× more than its size predicts.

Known disease-causing variants in Adrenocortical carcinoma, hereditary

Which prediction tools work for Adrenocortical carcinoma, hereditary

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MutPred2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 96 out of 100
• AlphaGenome (regulatory): 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 94 out of 100
• phyloP: 94 out of 100
• REVEL: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 93 out of 100
• EVE: 91 out of 100
• SIFT: 91 out of 100
• DMS / MaveDB: 62 out of 100
• AlphaGenome (splicing): 53 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Li-Fraumeni syndrome is also caused by TP53 variants; they fall partly in the same places as the Adrenocortical carcinoma, hereditary variants (188 disease-causing).
• Acute myeloid leukemia is also caused by TP53 variants; they fall mostly in different places as the Adrenocortical carcinoma, hereditary variants (6 disease-causing).
• Hereditary breast ovarian cancer syndrome is also caused by TP53 variants; they fall in the same places as the Adrenocortical carcinoma, hereditary variants (5 disease-causing).
• Breast and/or ovarian cancer is also caused by TP53 variants; they fall in the same places as the Adrenocortical carcinoma, hereditary variants (3 disease-causing).

Diseases related to Adrenocortical carcinoma, hereditary

• Li-Fraumeni syndrome, also linked to TP53
• Acute myeloid leukemia, also linked to TP53
• Familial cancer of breast, also linked to TP53
• Colorectal cancer, also linked to TP53
• Gastric cancer, also linked to TP53
• Breast-ovarian cancer, familial, susceptibility to, 1, also linked to TP53
• Glioma susceptibility 1, also linked to TP53
• Hereditary breast ovarian cancer syndrome, also linked to TP53
• Ovarian neoplasm, also linked to TP53
• Multiple myeloma, also linked to TP53
• Lung adenocarcinoma, also linked to TP53
• Hepatocellular carcinoma, also linked to TP53

Frequently asked questions

Which genes are linked to Adrenocortical carcinoma, hereditary?

In CATVariant, Adrenocortical carcinoma, hereditary is linked to 1 analyzed protein: TP53 (Cellular tumor antigen p53).

How many genetic variants are linked to Adrenocortical carcinoma, hereditary?

109 variants: 23 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 84 are of uncertain significance or have conflicting reports.

Which uncertain variants in Adrenocortical carcinoma, hereditary look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Adrenocortical carcinoma, hereditary?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 21 disease-causing and 138 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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