RFX6

The nuclear protein encoded by this gene is a member of the regulatory factor X (RFX) family of transcription factors. Studies in mice suggest that this gene is specifically required for the differentiation of islet cells for the production of insulin, but not for the differentiation of pancreatic polypeptide-producing cells. It regulates the transcription factors involved in beta-cell maturation and function, thus, restricting the expression of the beta-cell differentiation and specification genes. Mutations in this gene are associated with Mitchell-Riley syndrome, which is characterized by neonatal diabetes with pancreatic hypoplasia, duodenal and jejunal atresia, and gall bladder agenesis. [provided by RefSeq, Sep 2010]

Full Name

RFX6

Function

Transcription factor required to direct islet cell differentiation during endocrine pancreas development. Specifically required for the differentiation of 4 of the 5 islet cell types and for the production of insulin (PubMed:20148032, PubMed:25497100).
Not required for pancreatic PP (polypeptide-producing) cells differentiation. Acts downstream of NEUROG3 and regulates the transcription factors involved in beta-cell maturation and function, thereby restricting the expression of the beta-cell differentiation and specification genes, and thus the beta-cell fate choice. Activates transcription by forming a heterodimer with RFX3 and binding to the X-box in the promoter of target genes (PubMed:20148032).
Involved in glucose-stimulated insulin secretion by promoting insulin and L-type calcium channel gene transcription (PubMed:25497100).

Biological Process

Biological Process endocrine pancreas developmentManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process glucose homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process pancreatic A cell differentiationISS:UniProtKB
Biological Process pancreatic D cell differentiationISS:UniProtKB
Biological Process pancreatic epsilon cell differentiationISS:UniProtKB
Biological Process positive regulation of insulin secretion involved in cellular response to glucose stimulusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:NTNU_SB
Biological Process positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of insulin secretionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process type B pancreatic cell differentiationISS:UniProtKB

Cellular Location

Nucleus

Involvement in disease

Mitchell-Riley syndrome (MTCHRS):
A disorder characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder. There is no dysmorphic features.