IgH enhancer region. In Non Hodgkin lymphoma, the ID4 promoter region is implicated in follicular lymphomas, diffuse B Cell lymphomas and lymphoid cell lines due to hypermethylation. In brain tumours, more specifically oligodendroglial tumours and glioblastomas, the ID4 gene has been shown to be expressed in the neoplastic astrocytes but not expressed in the neoplastic oligodendrocytes. The ID4 promoter region has been found to be hypermethylated and its mRNA suppressed in breast cancer cell lines including that of primary breast cancers. Patients with invasive carcinomas have shown ID4 expression in their breast cancer specimens. This has been identified as a significant risk factor in nodal metastasis. ID4 is constitutively expressed in normal human mammary epithelium but found to be suppressed in ER positive breast carcinomas and preneoplastic lesions. ER negative carcinomas also show ID4 expression. There is a hypothesis that ID4 acts as a tumour suppressor factory in human breast tissue where oestrogen is responsible for regulation of ID4 expression in the mammary ductal epithelium. It is unclear whether the ID4 gene plays a role in bladder cancer. ID4 is found on the 6p22.3 amplicon which is frequently associated with advance stage bladder cancer. ID4 has also been shown to be overexpressed in bladder cancer cell lines. This overexpression is equally seen in both normal urothelium which lines the urinary tract inclusive of the renal pelvis, ureters, bladder and parts of the urethra, but also seen in fresh cancer tissues. ID4 is closely associated with gastric cancer. The ID4 promoter region is hypermethylated and infrequently expressed in gastric adenocarcinomas and frequently expressed in gastric cancer cell lines. In contrast, ID4 is highly expressed in normal gastric mucosa. There is an undefined but significant association seen in ID4 promoter hypermethylation (which results in its down regulation) and microsatellite instability. ID4 is not found in normal epitheliums nor adenomas of colorectal cancer. Hypermethylation of ID4 causes silencing of the gene. This has been identified as a significant independent risk factor for poor prognosis of colorectal cancer. It is also frequently observed in liver metastases of colorectal cancer specimens. Developmental disorders Rett syndrome is an X linked neurodevelopment disorder. It is often identified after six to eight months of age in females. In human brain tissue specimens of Rett syndrome patients, the family of ID genes are seen to be significantly increased in expression. Society and culture Commonly used names The ID4 gene