Ovarian neoplasm: genes and variants

Genes linked to Ovarian neoplasm

• PIK3CA: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

  Its p110-alpha catalytic activity generates PIP3 and activates AKT-dependent growth, survival, and metabolic signaling downstream of many receptors. Activating variants are frequent cancer drivers and, when present mosaically during development, can cause PIK3CA-related overgrowth spectrum.

  5 disease-causing and 0 uncertain variants in PIK3CA are linked to Ovarian neoplasm.

• 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.

  1 disease-causing and 0 uncertain variants in TP53 are linked to Ovarian neoplasm.

• BRCA1: Breast cancer type 1 susceptibility protein

  It coordinates DNA-damage signaling and homologous-recombination repair while helping protect stalled replication forks and chromosome integrity. Germline loss-of-function variants strongly predispose to breast and ovarian cancer and increase risk for several other malignancies.

  0 disease-causing and 0 uncertain variants in BRCA1 are linked to Ovarian neoplasm.

• BRCA2: Breast cancer type 2 susceptibility protein

  It loads RAD51 onto damaged DNA to enable homologous recombination and also protects stressed replication forks from degradation. Germline loss-of-function variants strongly predispose to breast, ovarian, prostate, pancreatic, and other cancers.

  0 disease-causing and 0 uncertain variants in BRCA2 are linked to Ovarian neoplasm.

• PARP2: Poly [ADP-ribose] polymerase 2

  It cooperates with PARP1 in sensing DNA damage and promoting poly(ADP-ribose)-dependent repair, particularly at single-strand breaks. Its activity contributes to the response to PARP inhibitors and to DNA-repair redundancy in cancer cells.

  0 disease-causing and 0 uncertain variants in PARP2 are linked to Ovarian neoplasm.

• TOP1: DNA topoisomerase 1

  It relieves torsional strain in DNA by creating and resealing transient single-strand breaks during replication and transcription. Trapping of the cleavage intermediate is the mechanism exploited by topoisomerase I inhibitors such as irinotecan and topotecan in cancer therapy.

  0 disease-causing and 0 uncertain variants in TOP1 are linked to Ovarian neoplasm.

• TOP2A: DNA topoisomerase 2-alpha

  It resolves DNA tangles and supercoils by passing one double helix through a transient double-strand break in another, a process essential during replication and chromosome segregation. It is the target of widely used anticancer drugs including anthracyclines and etoposide.

  0 disease-causing and 0 uncertain variants in TOP2A are linked to Ovarian neoplasm.

• ERBB2: Receptor tyrosine-protein kinase erbB-2

  ERBB2, also called HER2, is a cell-surface receptor tyrosine kinase that works with other ERBB receptors to transmit growth signals. It helps organize signaling and cytoskeletal responses, and abnormal ERBB2 activity is a major feature of several cancers.

  2 disease-causing and 0 uncertain variants in ERBB2 are linked to Ovarian neoplasm.

• CTNNB1: Catenin beta-1

  It links cadherins to the cytoskeleton at adherens junctions and, when stabilized by Wnt signaling, enters the nucleus to regulate transcription. Activating somatic variants drive many cancers, while germline loss-of-function variants cause CTNNB1 neurodevelopmental disorder.

  1 disease-causing and 1 uncertain variants in CTNNB1 are linked to Ovarian neoplasm.

• BRIP1: Fanconi anemia group J protein

  It unwinds DNA structures and works with BRCA1 and the Fanconi-anemia pathway to repair damaged replication intermediates and interstrand crosslinks. Biallelic loss causes Fanconi anemia group J, while heterozygous loss-of-function variants increase ovarian-cancer risk.

  1 disease-causing and 0 uncertain variants in BRIP1 are linked to Ovarian neoplasm.

• PRKN: E3 ubiquitin-protein ligase parkin

  Its parkin ubiquitin-ligase activity marks damaged mitochondrial proteins after PINK1 activation and helps eliminate dysfunctional mitochondria through mitophagy. Biallelic loss-of-function variants are a major cause of autosomal recessive juvenile or early-onset Parkinson disease.

  0 disease-causing and 5 uncertain variants in PRKN are linked to Ovarian neoplasm.

Weakly linked (only a few uncertain records): FGFR3, MSH2, PTEN and RB1.

Where Ovarian neoplasm variants cluster

• PIK3CA PIK helical (positions 517–694): 3 of 5 disease-causing changes, 3.6× more than its size predicts.

Known disease-causing variants in Ovarian neoplasm

Which prediction tools work for Ovarian neoplasm

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

• PolyPhen-2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 82 out of 100
• CATVariant: 61 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• PIK3CA related overgrowth syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Ovarian neoplasm variants (30 disease-causing).
• Cowden syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Ovarian neoplasm variants (23 disease-causing).
• Megalencephaly-capillary malformation-polymicrogyria syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Ovarian neoplasm variants (22 disease-causing).
• PIK3CA constitutional syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Ovarian neoplasm variants (4 disease-causing).
• Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes is also caused by PIK3CA variants; they fall mostly in different places as the Ovarian neoplasm variants (4 disease-causing).
• Malignant tumor of urinary bladder is also caused by ERBB2 variants; they fall mostly in different places as the Ovarian neoplasm variants (6 disease-causing).
• Lung adenocarcinoma is also caused by ERBB2 variants; they fall mostly in different places as the Ovarian neoplasm variants (3 disease-causing).
• Pilomatrixoma is also caused by CTNNB1 variants; they fall partly in the same places as the Ovarian neoplasm variants (8 disease-causing).
• Severe intellectual disability-progressive spastic diplegia syndrome is also caused by CTNNB1 variants; they fall mostly in different places as the Ovarian neoplasm variants (5 disease-causing).
• Medulloblastoma is also caused by CTNNB1 variants; they fall mostly in different places as the Ovarian neoplasm variants (4 disease-causing).
• Li-Fraumeni syndrome is also caused by TP53 variants; they fall mostly in different places as the Ovarian neoplasm variants (188 disease-causing).
• Adrenocortical carcinoma, hereditary is also caused by TP53 variants; they fall mostly in different places as the Ovarian neoplasm variants (23 disease-causing).
• Acute myeloid leukemia is also caused by TP53 variants; they fall mostly in different places as the Ovarian neoplasm variants (6 disease-causing).
• Familial cancer of breast is also caused by TP53 variants; they fall mostly in different places as the Ovarian neoplasm variants (5 disease-causing).
• Glioma susceptibility 1 is also caused by TP53 variants; they fall mostly in different places as the Ovarian neoplasm variants (5 disease-causing).

Diseases related to Ovarian neoplasm

• Ovarian cancer, also linked to BRCA1, BRCA2, BRIP1, CTNNB1 and 6 more
• Colorectal cancer, also linked to CTNNB1, ERBB2, PIK3CA, TOP1 and 1 more
• Gastric cancer, also linked to BRIP1, ERBB2, PIK3CA and TP53
• Breast-ovarian cancer, familial, susceptibility to, 1, also linked to BRCA1, BRCA2, BRIP1 and TP53
• Hereditary breast ovarian cancer syndrome, also linked to BRCA1, BRCA2, BRIP1 and TP53
• Familial cancer of breast, also linked to BRIP1, PIK3CA and TP53
• Malignant tumor of urinary bladder, also linked to CTNNB1, ERBB2 and PIK3CA
• Non-small cell lung carcinoma, also linked to ERBB2, PIK3CA and TOP1
• Glioma susceptibility 1, also linked to BRCA2, ERBB2 and TP53
• Lung cancer, also linked to ERBB2, PIK3CA and PRKN
• Hepatocellular carcinoma, also linked to CTNNB1, PIK3CA and TP53
• Prostate cancer, also linked to BRCA2, PARP2 and TOP2A

Frequently asked questions

Which genes are linked to Ovarian neoplasm?

In CATVariant, Ovarian neoplasm is linked to 11 analyzed proteins: PIK3CA (Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform), TP53 (Cellular tumor antigen p53), BRCA1 (Breast cancer type 1 susceptibility protein), BRCA2 (Breast cancer type 2 susceptibility protein), PARP2 (Poly [ADP-ribose] polymerase 2), TOP1 (DNA topoisomerase 1) and 5 more.

How many genetic variants are linked to Ovarian neoplasm?

25 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 9 are of uncertain significance or have conflicting reports.

Which uncertain variants in Ovarian neoplasm 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 Ovarian neoplasm?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.82, based on 8 disease-causing and 536 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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