Endometrial carcinoma: genes and variants

Genes linked to Endometrial carcinoma

• MSH6: DNA mismatch repair protein Msh6

  Together with MSH2, it recognizes single-base mismatches and small insertion-deletion loops during DNA replication and initiates mismatch repair. Germline loss-of-function variants cause Lynch syndrome, while biallelic variants can cause constitutional mismatch-repair deficiency.

  1 disease-causing and 123 uncertain variants in MSH6 are linked to Endometrial carcinoma.

• CDH1: Cadherin-1

  Its E-cadherin-mediated adhesion preserves epithelial architecture and suppresses inappropriate cell detachment and invasion. Germline loss-of-function variants cause hereditary diffuse gastric cancer syndrome and substantially increase diffuse gastric and lobular breast-cancer risk.

  1 disease-causing and 20 uncertain variants in CDH1 are linked to Endometrial carcinoma.

• PMS2: Mismatch repair endonuclease PMS2

  Together with MLH1, it provides endonuclease activity needed to complete DNA mismatch repair after replication errors are recognized. Germline loss-of-function variants cause Lynch syndrome, while biallelic variants cause constitutional mismatch-repair deficiency.

  1 disease-causing and 0 uncertain variants in PMS2 are linked to Endometrial carcinoma.

• MSH3: DNA mismatch repair protein Msh3

  Together with MSH2, it recognizes larger insertion-deletion loops and certain DNA secondary structures during mismatch repair. Variation can modify the behavior of repeat-expansion disorders, while biallelic loss has been associated with a recessive adenomatous-polyposis phenotype.

  0 disease-causing and 365 uncertain variants in MSH3 are linked to Endometrial carcinoma.

• MLH3: DNA mismatch repair protein Mlh3

  It partners with other mismatch-repair proteins and also participates in meiotic crossover formation. Biallelic or monoallelic variants have been investigated in cancer predisposition, but the clinical significance of many MLH3 variants remains less firmly established than for core Lynch-syndrome genes.

  0 disease-causing and 1 uncertain variants in MLH3 are linked to Endometrial carcinoma.

• MLH1: DNA mismatch repair protein Mlh1

  The protein partners with PMS2 to form MutL alpha, a core complex in post-replicative DNA mismatch repair. By helping correct copying errors in DNA, MLH1 protects genome stability, and inherited MLH1 variants are a major cause of Lynch syndrome.

  0 disease-causing and 0 uncertain variants in MLH1 are linked to Endometrial carcinoma.

• MSH2: DNA mismatch repair protein Msh2

  The protein forms mismatch-recognition complexes with MSH6 or MSH3 that detect base mismatches and insertion-deletion loops in DNA. This first step of mismatch repair helps preserve genome integrity, and inherited MSH2 variants are associated with Lynch syndrome.

  0 disease-causing and 0 uncertain variants in MSH2 are linked to Endometrial carcinoma.

• 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.

  0 disease-causing and 0 uncertain variants in PTEN are linked to Endometrial carcinoma.

• 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.

  1 disease-causing and 0 uncertain variants in PIK3CA are linked to Endometrial carcinoma.

Known disease-causing variants in Endometrial carcinoma

Same protein, different disease

• Hereditary nonpolyposis colorectal neoplasms is also caused by MSH6 variants; they fall mostly in different places as the Endometrial carcinoma variants (14 disease-causing).
• Lynch syndrome is also caused by MSH6 variants; they fall mostly in different places as the Endometrial carcinoma variants (12 disease-causing).
• Hereditary nonpolyposis colon cancer is also caused by MSH6 variants; they fall mostly in different places as the Endometrial carcinoma variants (3 disease-causing).
• Hereditary nonpolyposis colorectal neoplasms is also caused by PMS2 variants; they fall mostly in different places as the Endometrial carcinoma variants (12 disease-causing).
• Lynch syndrome is also caused by PMS2 variants; they fall mostly in different places as the Endometrial carcinoma variants (11 disease-causing).
• Hereditary nonpolyposis colon cancer is also caused by PMS2 variants; they fall mostly in different places as the Endometrial carcinoma variants (4 disease-causing).
• CDH1-related diffuse gastric and lobular breast cancer syndrome is also caused by CDH1 variants; they fall mostly in different places as the Endometrial carcinoma variants (11 disease-causing).
• Hereditary diffuse gastric adenocarcinoma is also caused by CDH1 variants; they fall mostly in different places as the Endometrial carcinoma variants (4 disease-causing).
• PIK3CA related overgrowth syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Endometrial carcinoma variants (30 disease-causing).
• Cowden syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Endometrial carcinoma variants (23 disease-causing).
• Megalencephaly-capillary malformation-polymicrogyria syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Endometrial carcinoma variants (22 disease-causing).
• Ovarian neoplasm is also caused by PIK3CA variants; they fall mostly in different places as the Endometrial carcinoma variants (5 disease-causing).
• PIK3CA constitutional syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Endometrial carcinoma variants (4 disease-causing).

Diseases related to Endometrial carcinoma

• Lynch syndrome, also linked to MLH1, MLH3, MSH2, MSH6 and 1 more
• Ovarian cancer, also linked to CDH1, MLH1, MSH2, MSH6 and 1 more
• Colorectal cancer, also linked to MLH1, MLH3, MSH2, MSH6 and 1 more
• Breast and/or ovarian cancer, also linked to CDH1, MLH1, MSH2, MSH6 and 1 more
• Hereditary nonpolyposis colorectal neoplasms, also linked to MLH1, MSH2, MSH6 and PMS2
• Gastric cancer, also linked to MLH1, MSH6, PIK3CA and PMS2
• Hereditary nonpolyposis colon cancer, also linked to MLH1, MSH2, MSH6 and PMS2
• Mismatch repair cancer syndrome, also linked to MLH1, MSH2, MSH6 and PMS2
• Familial cancer of breast, also linked to CDH1, PIK3CA and PTEN
• Cowden syndrome, also linked to PIK3CA and PTEN
• Colorectal cancer, hereditary nonpolyposis, type 6, also linked to MLH1 and MLH3
• Hereditary breast ovarian cancer syndrome, also linked to CDH1 and MLH1

Frequently asked questions

Which genes are linked to Endometrial carcinoma?

In CATVariant, Endometrial carcinoma is linked to 9 analyzed proteins: MSH6 (DNA mismatch repair protein Msh6), CDH1 (Cadherin-1), PMS2 (Mismatch repair endonuclease PMS2), MSH3 (DNA mismatch repair protein Msh3), MLH3 (DNA mismatch repair protein Mlh3), MLH1 (DNA mismatch repair protein Mlh1) and 3 more.

How many genetic variants are linked to Endometrial carcinoma?

544 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 509 are of uncertain significance or have conflicting reports.

Which uncertain variants in Endometrial carcinoma look disease-causing?

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

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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