Esophageal cancer: genes and variants

Genes linked to Esophageal cancer

• WWOX: WW domain-containing oxidoreductase

  It participates in cellular stress, metabolism, and transcriptional signaling and spans a common fragile site frequently altered in cancer. Biallelic loss-of-function variants cause severe developmental and epileptic encephalopathy or spinocerebellar ataxia, depending on residual function.

  2 ClinVar pathogenic / likely pathogenic and 8 uncertain variants in WWOX have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• TGFBR2: TGF-beta receptor type-2

  It binds TGF-beta ligands and activates TGFBR1 to initiate canonical and noncanonical signaling. Germline pathogenic variants cause Loeys-Dietz syndrome type 2, while somatic loss can remove growth-suppressive TGF-beta responses in cancer.

  1 ClinVar pathogenic / likely pathogenic and 28 uncertain variants in TGFBR2 have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• 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.

  0 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in TP53 have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• ARID1A: AT-rich interactive domain-containing protein 1A

  It helps BAF chromatin-remodeling complexes open or reposition nucleosomes at regulatory regions and thereby control lineage-specific transcription. Somatic loss is frequent in several cancers, while germline haploinsufficiency can cause Coffin-Siris syndrome.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ARID1A have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• CDKN2A: Tumor suppressor ARF

  The ARF product of CDKN2A is a tumor-suppressor protein that binds MDM2 and helps preserve p53 activity. By promoting cell-cycle arrest and apoptosis, it provides an important barrier to uncontrolled cell growth from within the nucleolus.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDKN2A have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• PDCD1: Programmed cell death protein 1

  PDCD1 is an inhibitory receptor on activated T cells that binds PD-L1 and PD-L2. Its signaling helps maintain immune tolerance by restraining T-cell activation, making the protein important in autoimmunity and cancer immunotherapy.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PDCD1 have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• SMAD4: SMAD family member 4

  It forms transcriptional complexes with activated receptor-regulated SMADs and is the central nuclear mediator shared by TGF-beta and BMP pathways. Germline loss-of-function variants cause juvenile polyposis or combined juvenile-polyposis-HHT, while specific gain-of-function variants cause Myhre syndrome.

  0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SMAD4 have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

• DCC: Netrin receptor DCC

  It guides developing axons in response to netrin signals and helps establish long-range neural connections across the midline. Heterozygous pathogenic variants can cause congenital mirror movements, while biallelic or severe variants can produce complex neurodevelopmental syndromes.

  1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in DCC have source records linked to Esophageal cancer. Association strength is not clinical gene validity.

Weakly linked (only a few uncertain records): CDKN1A.

ClinVar pathogenic and likely pathogenic variants linked to Esophageal cancer

Same protein, different disease

• Autosomal recessive spinocerebellar ataxia 12 also has ClinVar records linked to WWOX variants; they fall mostly in different places as the Esophageal cancer variants (5 pathogenic / likely pathogenic).
• Familial thoracic aortic aneurysm and aortic dissection also has ClinVar records linked to TGFBR2 variants; they fall mostly in different places as the Esophageal cancer variants (78 pathogenic / likely pathogenic).
• Marfan syndrome also has ClinVar records linked to TGFBR2 variants; they fall mostly in different places as the Esophageal cancer variants (52 pathogenic / likely pathogenic).
• Ehlers-Danlos syndrome also has ClinVar records linked to TGFBR2 variants; they fall mostly in different places as the Esophageal cancer variants (4 pathogenic / likely pathogenic).

Diseases related to Esophageal cancer

• Urinary bladder cancer, also linked to ARID1A, CDKN2A and TP53
• Lung adenocarcinoma, also linked to ARID1A, CDKN2A and TP53
• Hepatocellular carcinoma, also linked to ARID1A, CDKN2A and TP53
• Head and neck squamous cell carcinoma, also linked to CDKN2A, PDCD1 and TP53
• Familial thoracic aortic aneurysm and aortic dissection, also linked to SMAD4 and TGFBR2
• Colorectal cancer, also linked to ARID1A and TP53
• Gastric cancer, also linked to PDCD1 and TP53
• Non-small cell lung carcinoma, also linked to CDKN2A and PDCD1
• Parkinson disease, also linked to CDKN2A and TGFBR2
• Familial pancreatic carcinoma, also linked to SMAD4 and TP53
• Carcinoma of pancreas, also linked to SMAD4 and TP53
• Melanoma, also linked to CDKN2A and PDCD1

Frequently asked questions

Which genes have records linked to Esophageal cancer?

This view contains 8 analyzed proteins: WWOX, TGFBR2, TP53, ARID1A, CDKN2A and 3 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 4 pathogenic or likely pathogenic variants, 24 variants of uncertain significance and 13 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 51 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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