CDH1 - dismech genes

Normal function · from ai-gene-review (P12830, commit 79fe13b38970) · AI-generated, not KB evidence

CDH1 encodes E-cadherin (epithelial cadherin), the prototypical type-I classical cadherin and the principal calcium-dependent cell-cell adhesion molecule of epithelia. This single-pass transmembrane glycoprotein has five extracellular cadherin (EC) repeats that bind calcium and mediate homophilic trans-adhesion with E-cadherin on neighbouring cells, while its cytoplasmic tail nucleates the cadherin-catenin complex by binding p120-catenin, beta-catenin and gamma-catenin/plakoglobin; alpha-catenin in turn couples this complex to the cortical actin cytoskeleton. Through these interactions E-cadherin builds and maintains adherens junctions, establishes epithelial apicobasal polarity and tissue integrity, and facilitates early desmosome assembly. E-cadherin is a potent invasion and tumour suppressor: loss of function promotes epithelial-to-mesenchymal transition and is causative in hereditary diffuse gastric cancer and lobular breast carcinoma. E-cadherin is additionally exploited as a host cell-surface receptor by Listeria monocytogenes internalin A.

E-cadherin engages in calcium-dependent homophilic trans-interaction with E-cadherin molecules on adjacent epithelial cells through its five extracellular cadherin (EC) repeats. This homophilic binding is the molecular basis of E-cadherin-mediated cell-cell adhesion and the nucleation of adherens junctions.

molecular function: cadherin binding · directly involved in: homophilic cell-cell adhesion · locations: lateral plasma membrane; adherens junction

The C-terminal cytoplasmic domain of E-cadherin binds beta-catenin (and gamma-catenin/plakoglobin), forming the cadherin-catenin complex. This complex couples E-cadherin to the cortical actin cytoskeleton via alpha-catenin, mechanically linking cell-cell adhesion to the cytoskeleton and stabilizing adherens junctions.

molecular function: beta-catenin binding · directly involved in: adherens junction organization · locations: lateral plasma membrane; adherens junction

The juxtamembrane domain of E-cadherin's cytoplasmic tail binds p120-catenin (CTNND1/delta-catenin) at a site distinct from the C-terminal beta-catenin-binding domain. p120-catenin binding masks a dileucine endocytic motif and stabilizes E-cadherin at the plasma membrane, thereby controlling cadherin surface levels, turnover, and adhesion strength.

molecular function: delta-catenin binding · directly involved in: adherens junction organization · locations: lateral plasma membrane; adherens junction

Calcium ions bind at the linker regions between E-cadherin's extracellular cadherin repeats, rigidifying the ectodomain into the conformation required for homophilic trans-adhesion; cadherin-mediated cell-cell adhesion is strictly calcium-dependent.

molecular function: calcium ion binding · directly involved in: homophilic cell-cell adhesion · locations: lateral plasma membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
CDH1-Related Hereditary Diffuse Gastric Cancer	causative germline loss of function	mechanism: Germline CDH1 First-Hit Inactivation
Gastric Adenocarcinoma	causative germline	mechanism: CDH1 Inactivation and E-cadherin Loss subtype: Diffuse; HDGC scoped to subtype: HDGC
Gastric Cancer H. pylori Associated	untyped Somatic and Germline Mutations	mechanism: CDH1/E-cadherin Inactivation
Ulcerative Colitis	untyped Risk Factor	mechanism: Epithelial Barrier Dysfunction
Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome	no genetic record	mechanism: Loss of Apical-Basolateral Epithelial Polarity

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
CDH1-related diffuse gastric and lobular breast cancer syndrome MONDO:0100488	AD	Definitive 2024-03-22	CDH1-Related Hereditary Diffuse Gastric Cancer causative

Mechanism modules · computed from kb/

germline_two_hit_tumor_predisposition via CDH1-Related Hereditary Diffuse Gastric Cancer