RFX6

Chr 6

regulatory factor X6

Also known as: MTCHRS, MTFS, RFXDC1, dJ955L16.1

NCBI Gene: 222546 ENSG00000185002 UniProt: Q8HWS3

RFX6 encodes a transcription factor that directs islet cell differentiation during pancreatic development and is specifically required for insulin production and beta-cell maturation. Mutations cause Mitchell-Riley syndrome, an autosomal recessive disorder characterized by neonatal diabetes with pancreatic hypoplasia, duodenal and jejunal atresia, and gallbladder agenesis. The gene is highly constrained against loss-of-function variants (LOEUF 0.47), reflecting its critical role in pancreatic endocrine development.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMitchell-Riley syndrome

Clinical highlights

Gene-disease validity (ClinGen)

monogenic diabetes · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P

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GeneReview available — RFX6