Similarly, variations in the transcription factors GLIS3, NEUROD1, NEUROG3, NKX2-2, or MNX1 can result in malformed or absent β cells that do not secrete insulin. EIF2AK3 variants can exacerbate ER stress causing β-cell death, skeletal issues, and liver dysfunction. Some variations in immune gene FOXP3 can cause IPEX syndrome, a severe and multifaceted disease that includes neonatal diabetes among its symptoms.Two genes in this region that can be associated with TNDM:
ZAC and HYMAI Genes
ZAC is a zinc-finger protein that controls apoptosis (programmed cell death) and cell cycle arrest (cell division and duplication of DNA stops  when the cell detects cell damage or defects) in PLAG1
(pleomorphic adenoma gene-like 1). PLAG1  is a transcription regulator of the type 1 receptor for pituitary adenylated cyclase-activating polypeptide (is a polypeptide that activates adenylate cyclase and increases the cyclic adenosine monophosphate or cAMP. cAMP is a second messenger that is used for neighboring cells to perform  signal transduction in targeted cells), which is important for insulin secretion regulation. The function of the HYMAI (hydatiform mole-associated and imprinted transcript) is unknown.Second, chromosome 6q24-TNDM is caused by over-expression of imprinted genes at 6q24 (PLAGL1 [ZAC] and HYMAI). It was discovered that a differentially methylated region (DMR) is present within the shared promoter of these genes. Generally the expression of the mothers alleles of PLAGL1 and HYMAI are blocked or not expressed by DMR methylation and only the fathers alleles of PLAG1 and HYMA1 are expressed.
In Melmed S, Auchus RJ, Goldfine AB, Koeng RJ, Rosen CJ (eds.). Williams Textbook of Endocrinology (14 ed.). Elsevier. Lemelman MB, Letourneau L, Greeley SA (March 2018). "Neonatal Diabetes Mellitus: An Update on Diagnosis and Management". Clin Perinatol. 45 (1): 41–59. doi:10.1016/j.clp.2017.10.006. PMC 5928785. PMID 29406006. == External links ==