RFX6

Protein identityUniProt · HPA

UniProt accession

Q8HWS3

Gene

RFX6

Ensembl

ENSG00000185002

Chromosome

6

Canonical length

928 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

928 residues, UniProt reviewed canonical sequence.

>Q8HWS3|RFX6
     1  MAKVPELEDT FLQAQPAPQL SPGIQEDCCV QLLGKGLLVY PEETVYLAAE GQPGGEQGGG
    61  EKGEDPELPG AVKSEMHLNN GNFSSEEEDA DNHDSKTKAA DQYLSQKKTI TQIVKDKKKQ
   121  TQLTLQWLEE NYIVCEGVCL PRCILYAHYL DFCRKEKLEP ACAATFGKTI RQKFPLLTTR
   181  RLGTRGHSKY HYYGIGIKES SAYYHSVYSG KGLTRFSGSK LKNEGGFTRK YSLSSKTGTL
   241  LPEFPSAQHL VYQGCISKDK VDTLIMMYKT HCQCILDNAI NGNFEEIQHF LLHFWQGMPD
   301  HLLPLLENPV IIDIFCVCDS ILYKVLTDVL IPATMQEMPE SLLADIRNFA KNWEQWVVSS
   361  LENLPEALTD KKIPIVRRFV SSLKRQTSFL HLAQIARPAL FDQHVVNSMV SDIERVDLNS
   421  IGSQALLTIS GSTDTESGIY TEHDSITVFQ ELKDLLKKNA TVEAFIEWLD TVVEQRVIKT
   481  SKQNGRSLKK RAQDFLLKWS FFGARVMHNL TLNNASSFGS FHLIRMLLDE YILLAMETQF
   541  NNDKEQELQN LLDKYMKNSD ASKAAFTASP SSCFLANRNK GSMVSSDAVK NESHVETTYL
   601  PLPSSQPGGL GPALHQFPAG NTDNMPLTGQ MELSQIAGHL MTPPISPAMA SRGSVINQGP
   661  MAGRPPSVGP VLSAPSHCST YPEPIYPTLP QANHDFYSTS SNYQTVFRAQ PHSTSGLYPH
   721  HTEHGRCMAW TEQQLSRDFF SGSCAGSPYN SRPPSSYGPS LQAQDSHNMQ FLNTGSFNFL
   781  SNTGAASCQG ATLPPNSPNG YYGSNINYPE SHRLGSMVNQ HVSVISSIRS LPPYSDIHDP
   841  LNILDDSGRK QTSSFYTDTS SPVACRTPVL ASSLQTPIPS SSSQCMYGTS NQYPAQETLD
   901  SHGTSSREMV SSLPPINTVF MGTAAGGT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RFX6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.5

Highest tissue expression

6.1 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RFX6.

Disease | AllUniProt

Conditions RFX6 is implicated in, by any mechanism.

• Mitchell-Riley syndrome (MTCHRS) MIM:615710

Disease | GeneticClinVar

39 pathogenic / likely-pathogenic of 390 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome
• RFX6-related disorder
• Diabetes mellitus
• Maturity-onset diabetes of the young
• Monogenic diabetes

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.47

gnomAD pLI

0

gnomAD missense Z

1.2

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• endocrine pancreas development
• glucose homeostasis
• pancreatic A cell differentiation
• pancreatic D cell differentiation
• positive regulation of DNA-templated transcription
• positive regulation of insulin secretion involved in cellular response to glucose stimulus
• positive regulation of transcription by RNA polymerase II
• regulation of insulin secretion
• regulation of transcription by RNA polymerase II
• type B pancreatic cell differentiation
• pancreatic epsilon cell differentiation

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• transcription cis-regulatory region binding

Cellular components

• chromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• DNA-binding RFX-type winged-helix domain
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• RFX-like DNA-binding protein
• RFX1-4/6/8-like, BCD domain
• RFX DNA-binding domain
• RFX BCD domain

KeywordsUniProt

• Developmental protein
• Diabetes mellitus
• Differentiation
• DNA-binding
• Nucleus
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of RFX6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RFX3
• DTX2