RFX6 (regulatory factor X6)

Gene

• Entrez ID: 222546
• Gene name: Regulatory factor X6
• Gene symbol: RFX6
• Synonyms (NCBI Gene): MTCHRS, MTFS, RFXDC1, dJ955L16.1
• Chromosome: 6
• Chromosome location: 6q22.1
• Summary: 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, bu

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs144648002	C>G,T	Uncertain-significance, pathogenic, benign	Coding sequence variant, stop gained, missense variant
rs267607012	T>C	Pathogenic	Coding sequence variant, missense variant
rs267607013	G>A	Pathogenic	Coding sequence variant, missense variant
rs587776514	T>C	Pathogenic	Genic upstream transcript variant, splice donor variant, upstream transcript variant
rs587776515	A>G	Pathogenic	Genic upstream transcript variant, intron variant, upstream transcript variant
rs587776516	T>G	Pathogenic	Splice donor variant
rs587776517	AGGTATCAATTACA>-	Pathogenic	Intron variant, splice donor variant, coding sequence variant
rs587780440	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs749827445	C>T	Pathogenic	Stop gained, coding sequence variant
rs781291978	C>A,T	Likely-pathogenic	Synonymous variant, stop gained, coding sequence variant
rs1445567359	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1562146029	TCTA>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT054825	hsa-miR-30c-5p	Luciferase reporter assay, qRT-PCR, Western blot	24623846
MIRT439148	hsa-let-7c-5p	3'LIFE	25074381
MIRT439148	hsa-let-7c-5p	3'LIFE	25074381

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	20148032
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	20148032
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	20148032
GO:0003309	Process	Type B pancreatic cell differentiation	IEA
GO:0003309	Process	Type B pancreatic cell differentiation	ISS
GO:0003310	Process	Pancreatic A cell differentiation	IEA
GO:0003310	Process	Pancreatic A cell differentiation	ISS
GO:0003311	Process	Pancreatic D cell differentiation	IEA
GO:0003311	Process	Pancreatic D cell differentiation	ISS
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	16189514, 20148032, 25416956, 26871637, 32296183
GO:0005634	Component	Nucleus	IDA	25497100
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0030154	Process	Cell differentiation	IEA
GO:0031018	Process	Endocrine pancreas development	IEA
GO:0031018	Process	Endocrine pancreas development	IMP	20148032
GO:0035774	Process	Positive regulation of insulin secretion involved in cellular response to glucose stimulus	IMP	25497100
GO:0042593	Process	Glucose homeostasis	IEA
GO:0042593	Process	Glucose homeostasis	IMP	20148032
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	20148032
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	20148032
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	25497100
GO:0050796	Process	Regulation of insulin secretion	IEA
GO:0050796	Process	Regulation of insulin secretion	IMP	20148032
GO:0090104	Process	Pancreatic epsilon cell differentiation	IEA
GO:0090104	Process	Pancreatic epsilon cell differentiation	ISS

Other IDs

• MIM: 612659
• HGNC: 21478
• e!Ensembl: ENSG00000185002

Protein

• UniProt ID: Q8HWS3
• Protein name: DNA-binding protein RFX6 (Regulatory factor X 6) (Regulatory factor X domain-containing protein 1)
• Protein 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:254
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02257	RFX_DNA_binding	121 → 199	RFX DNA-binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in pancreas (PubMed:25497100). Expressed in pancreatic beta-cells (insulin-positive cells) and alpha-cells (glucagon-positive cells) (at protein level). Specifically expressed in pancreas, small intestine and colon (PubMed:20
• Sequence:

  MAKVPELEDTFLQAQPAPQLSPGIQEDCCVQLLGKGLLVYPEETVYLAAEGQPGGEQGGG
  EKGEDPELPGAVKSEMHLNNGNFSSEEEDADNHDSKTKAADQYLSQKKTITQIVKDKKKQ
  TQLTLQWLEENYIVCEGVCLPRCILYAHYLDFCRKEKLEPACAATFGKTIRQKFPLLTTR
  RLGTRGHSKYHYYGIGIKESSAYYHSVYSGKGLTRFSGSKLKNEGGFTRKYSLSSKTGTL
  LPEFPSAQHLVYQGCISKDKVDTLIMMYKTHCQCILDNAINGNFEEIQHFLLHFWQGMPD
  HLLPLLENPVIIDIFCVCDSILYKVLTDVLIPATMQEMPESLLADIRNFAKNWEQWVVSS
  LENLPEALTDKKIPIVRRFVSSLKRQTSFLHLAQIARPALFDQHVVNSMVSDIERVDLNS
  IGSQALLTISGSTDTESGIYTEHDSITVFQELKDLLKKNATVEAFIEWLDTVVEQRVIKT
  SKQNGRSLKKRAQDFLLKWSFFGARVMHNLTLNNASSFGSFHLIRMLLDEYILLAMETQF
  NNDKEQELQNLLDKYMKNSDASKAAFTASPSSCFLANRNKGSMVSSDAVKNESHVETTYL
  PLPSSQPGGLGPALHQFPAGNTDNMPLTGQMELSQIAGHLMTPPISPAMASRGSVINQGP
  MAGRPPSVGPVLSAPSHCSTYPEPIYPTLPQANHDFYSTSSNYQTVFRAQPHSTSGLYPH
  HTEHGRCMAWTEQQLSRDFFSGSCAGSPYNSRPPSSYGPSLQAQDSHNMQFLNTGSFNFL
  SNTGAASCQGATLPPNSPNGYYGSNINYPESHRLGSMVNQHVSVISSIRSLPPYSDIHDP
  LNILDDSGRKQTSSFYTDTSSPVACRTPVLASSLQTPIPSSSSQCMYGTSNQYPAQETLD
  SHGTSSREMVSSLPPINTVFMGTAAGGT

• Sequence length: 928

Pathways

KEGG:

Maturity onset diabetes of the young

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Diabetes mellitus	Pathogenic	rs587776515	RCV001225303	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome	Likely pathogenic; Pathogenic	rs1775769921, rs587780440, rs587776514, rs587776515, rs587776516, rs267607012, rs267607013, rs587776517, rs144648002, rs1445567359, rs1562146029	RCV001333628 RCV000118186 RCV000000525 RCV000000526 RCV000000527 RCV000000528 RCV000000529 RCV000000530 RCV000208877 RCV000714518 RCV000714519	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Maturity-onset diabetes of the young	Likely pathogenic	rs1774484879	RCV003994672	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
RFX6-related disorder	Likely pathogenic	rs267607013, rs2481937153, rs2482492907, rs2481946427	RCV003415604 RCV003410529 RCV003404611 RCV003902192	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESTROGEN-RECEPTOR NEGATIVE BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MATURITY ONSET DIABETES MELLITUS IN YOUNG	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Monogenic diabetes	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN ENDOMETRIOID CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN SEROUS CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ULCERATIVE COLITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Annular pancreas	Annular pancreas	HPO_DG			★☆☆☆☆ Found in Text Mining only
Benign Prostatic Hyperplasia	Benign Prostatic Hyperplasia	BEFREE	23620269		★☆☆☆☆ Found in Text Mining only
Biliary Atresia	Biliary atresia	Pubtator	34715892	Associate	★☆☆☆☆ Found in Text Mining only
Biliary Atresia	Biliary Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	38093528	Stimulate	★☆☆☆☆ Found in Text Mining only
Cholestasis	Cholelithiasis	Pubtator	34715892	Associate	★☆☆☆☆ Found in Text Mining only
Congenital anomaly of gastrointestinal tract	Congenital anomaly of digestive tract	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of pancreas	Pancreatic hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital malrotation of intestine	Congenital malrotation of intestine	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	20148032, 25048417, 26264437, 26761945, 27523286, 29026101, 31001871		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	20148032, 25048417, 26264437, 26761945, 27523286, 29026101, 31001871		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Diabetes Mellitus	Diabetes mellitus	Pubtator	26264437, 26761945, 34715892, 36208030, 36418577, 38064570, 38408297	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Diabetes Mellitus Transient Neonatal 1	Diabetes mellitus transient neonatal	Pubtator	23914949, 25497100, 26264437, 34715892, 35813646	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	36418577	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	29439679, 33721395, 34019234, 34387403, 36208030, 36613572, 38049589	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	31001871		★☆☆☆☆ Found in Text Mining only
Diarrhea	Diarrhea	Pubtator	23914949, 35813646	Associate	★☆☆☆☆ Found in Text Mining only
Duodenal atresia	Duodenal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty liver	Pubtator	36895461	Associate	★☆☆☆☆ Found in Text Mining only
Gallbladder Agenesis Of	Gallbladder agenesis	Pubtator	23914949, 35813646	Associate	★☆☆☆☆ Found in Text Mining only
Gallbladder, Agenesis Of	Agenesis Of Gallbladder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperbilirubinemia	Hyperbilirubinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome	Hypoplastic Pancreas-Intestinal Atresia-Hypoplastic Gallbladder Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Intestinal Atresia	Intestinal Atresia	BEFREE	23914949		★☆☆☆☆ Found in Text Mining only
Intestinal Diseases	Intestinal disease	Pubtator	32410729	Associate	★☆☆☆☆ Found in Text Mining only
Jejunal Atresia	Jejunal Atresia	BEFREE	23914949		★☆☆☆☆ Found in Text Mining only
Jejunal Atresia	Jejunal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	36895461	Associate	★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	BEFREE	31668390		★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	20676098, 22662242, 23803082, 24390282, 24473320, 26537068		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	GWASDB_DG	20676098		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	24390282		★☆☆☆☆ Found in Text Mining only
Martinez-Frias Syndrome	Martinez-Frias Syndrome	GENOMICS_ENGLAND_DG	15592663, 26264437		★☆☆☆☆ Found in Text Mining only
Maturity onset diabetes mellitus in young	Mason type diabetes	BEFREE	29026101, 31001871		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
melanoma	Melanoma	CTD_human_DG	22535842		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	32462000	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitchell-Riley Syndrome	Mitchell-Riley Syndrome	UNIPROT_DG	20148032, 25497100		★☆☆☆☆ Found in Text Mining only
Mitchell-Riley Syndrome	Mitchell-Riley Syndrome	BEFREE	21215266, 26761945, 27523286, 31275908, 31668390		★☆☆☆☆ Found in Text Mining only
Mitchell-Riley Syndrome	Mitchell-Riley Syndrome	ORPHANET_DG	21965172		★☆☆☆☆ Found in Text Mining only
Mitchell-Riley Syndrome	Mitchell-Riley Syndrome	GENOMICS_ENGLAND_DG	25048417, 26264437, 27167055		★☆☆☆☆ Found in Text Mining only
Mitchell-Riley Syndrome	Mitchell-Riley Syndrome	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Mitchell-Riley Syndrome	Mitchell-Riley Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Neonatal diabetes mellitus	Diabetes Mellitus	BEFREE	21965172, 23914949, 25421130, 26264437		★☆☆☆☆ Found in Text Mining only
Neonatal diabetes mellitus	Diabetes Mellitus	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	Pubtator	23914949, 34715892, 35813646	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	20676098, 22662242, 23803082, 24390282, 24473320, 26537068		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate carcinoma	Prostate cancer	GWASCAT_DG	20676098, 26034056, 26443449, 31562322		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	22056501, 22114074, 22662242, 23803082, 26398868, 26537068, 26979803, 37550764, 38052806	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	24390282		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	24390282		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Stomach Diseases	Stomach disease	Pubtator	34715892	Associate	★☆☆☆☆ Found in Text Mining only
Trichohepatoenteric Syndrome	Trichohepatoenteric Syndrome	BEFREE	21965172		★☆☆☆☆ Found in Text Mining only
Ventricular Remodeling	Ventricular remodeling	Pubtator	36895461	Associate	★☆☆☆☆ Found in Text Mining only