Glioma susceptibility 1: genes and variants

Genes linked to Glioma susceptibility 1

• PTEN: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN

  A lipid and protein phosphatase that removes phosphate groups from signaling molecules, especially PIP3. By opposing the PI3K-AKT pathway, it limits cell growth and survival signals, and PTEN variants are associated with Cowden syndrome and multiple cancers.

  5 disease-causing and 29 uncertain variants in PTEN are linked to Glioma susceptibility 1.

• 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.

  5 disease-causing and 5 uncertain variants in TP53 are linked to Glioma susceptibility 1.

• 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 Glioma susceptibility 1.

• 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 28 uncertain variants in ERBB2 are linked to Glioma susceptibility 1.

Weakly linked (only a few uncertain records): IDH1.

Where Glioma susceptibility 1 variants cluster

• PTEN Phosphatase tensin-type (positions 14–185): 5 of 5 disease-causing changes, 2.3× more than its size predicts.

Known disease-causing variants in Glioma susceptibility 1

Which prediction tools work for Glioma susceptibility 1

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

• ESM1b (LLR): 99 out of 100
• AlphaMissense: 98 out of 100
• CATVariant: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 90 out of 100
• MetaLR: 78 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 mostly in different places as the Glioma susceptibility 1 variants (188 disease-causing).
• Adrenocortical carcinoma, hereditary is also caused by TP53 variants; they fall mostly in different places as the Glioma susceptibility 1 variants (23 disease-causing).
• Acute myeloid leukemia is also caused by TP53 variants; they fall mostly in different places as the Glioma susceptibility 1 variants (6 disease-causing).
• Familial cancer of breast is also caused by TP53 variants; they fall mostly in different places as the Glioma susceptibility 1 variants (5 disease-causing).
• Hereditary breast ovarian cancer syndrome is also caused by TP53 variants; they fall mostly in different places as the Glioma susceptibility 1 variants (5 disease-causing).
• PTEN hamartoma tumor syndrome is also caused by PTEN variants; they fall mostly in different places as the Glioma susceptibility 1 variants (147 disease-causing).
• Cowden syndrome is also caused by PTEN variants; they fall mostly in different places as the Glioma susceptibility 1 variants (41 disease-causing).
• Macrocephaly-autism syndrome is also caused by PTEN variants; they fall mostly in different places as the Glioma susceptibility 1 variants (13 disease-causing).
• Familial meningioma is also caused by PTEN variants; they fall mostly in different places as the Glioma susceptibility 1 variants (3 disease-causing).
• Malignant tumor of urinary bladder is also caused by ERBB2 variants; they fall mostly in different places as the Glioma susceptibility 1 variants (6 disease-causing).
• Lung adenocarcinoma is also caused by ERBB2 variants; they fall mostly in different places as the Glioma susceptibility 1 variants (3 disease-causing).

Diseases related to Glioma susceptibility 1

• Ovarian neoplasm, also linked to BRCA2, ERBB2 and TP53
• Ovarian cancer, also linked to BRCA2 and ERBB2
• Familial cancer of breast, also linked to PTEN and TP53
• Colorectal cancer, also linked to ERBB2 and TP53
• Gastric cancer, also linked to ERBB2 and TP53
• Breast-ovarian cancer, familial, susceptibility to, 1, also linked to BRCA2 and TP53
• Hereditary breast ovarian cancer syndrome, also linked to BRCA2 and TP53
• Lung adenocarcinoma, also linked to ERBB2 and TP53
• Prostate cancer, also linked to BRCA2 and PTEN
• Familial pancreatic carcinoma, also linked to BRCA2 and TP53
• Familial prostate cancer, also linked to BRCA2 and PTEN
• Li-Fraumeni syndrome, also linked to TP53

Frequently asked questions

Which genes are linked to Glioma susceptibility 1?

In CATVariant, Glioma susceptibility 1 is linked to 4 analyzed proteins: PTEN (Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN), TP53 (Cellular tumor antigen p53), BRCA2 (Breast cancer type 2 susceptibility protein) and ERBB2 (Receptor tyrosine-protein kinase erbB-2).

How many genetic variants are linked to Glioma susceptibility 1?

78 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 65 are of uncertain significance or have conflicting reports.

Which uncertain variants in Glioma susceptibility 1 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 Glioma susceptibility 1?

Among tools not trained on clinical labels, ESM1b (LLR) separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 8 disease-causing and 146 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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