RFX6

regulatory factor X6, the group of Regulatory factor X family

Basic information

Region (hg38): 6:116877211-116932161

Previous symbols: [ "RFXDC1" ]

Links

ENSG00000185002 ∙ NCBI:222546 ∙ OMIM:612659 ∙ HGNC:21478 ∙ Uniprot:Q8HWS3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Martinez-Frias syndrome (Definitive), mode of inheritance: AR
• Mitchell-Riley syndrome (Strong), mode of inheritance: AR
• hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome (Supportive), mode of inheritance: AR
• hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia, with or without tracheoesophageal fistula; Martinez-Frias syndrome; Mitchell-Riley syndrome	AR	Endocrine; Gastrointestinal	While the condition may be recognizable, prompt treatment of gastrointestinal (including pancreatic) issues would be beneficical	Endocrine; Gastrointestinal	10528254; 15592663; 18512226; 19887127; 20148032; 21965172; 22662242; 23914949; 26264437

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RFX6 gene.

• not provided (174 variants)
• Inborn genetic diseases (22 variants)
• not specified (20 variants)
• Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome (19 variants)
• Monogenic diabetes (16 variants)
• RFX6-related condition (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFX6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	19	7	28
missense		4	76	12	1	93
nonsense	3	1	1			5
start loss						0
frameshift	3	2				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	5	4	10
non coding				23	45	68
Total	6	8	80	54	53

Variants in RFX6

This is a list of pathogenic ClinVar variants found in the RFX6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-116877325-C-A		not specified • Monogenic diabetes • Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome	Benign (Jan 23, 2024)
6-116877332-A-G		RFX6-related disorder	Likely benign (Jul 21, 2021)
6-116877337-C-A		Monogenic diabetes	Uncertain significance (Apr 03, 2023)
6-116877343-G-A		Inborn genetic diseases	Likely benign (Jan 04, 2022)
6-116877348-C-G		RFX6-related disorder	Uncertain significance (Oct 20, 2022)
6-116877377-C-G			Likely benign (Nov 27, 2021)
6-116877398-G-A			Likely benign (Jun 03, 2023)
6-116877398-G-C			Likely benign (Feb 15, 2023)
6-116877408-G-C		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
6-116877418-C-G		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
6-116877418-C-T		Monogenic diabetes	Likely benign (Nov 21, 2018)
6-116877436-G-A			Uncertain significance (May 25, 2022)
6-116877439-G-A		Inborn genetic diseases	Uncertain significance (May 25, 2022)
6-116877440-C-T		not specified • RFX6-related disorder	Benign (Dec 03, 2022)
6-116877441-G-T		Maturity onset diabetes mellitus in young	Likely pathogenic (Mar 03, 2022)
6-116877483-G-A		Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome	Uncertain significance (Sep 08, 2022)
6-116877485-G-A			Benign (Dec 11, 2023)
6-116877488-A-G			Likely benign (Oct 06, 2023)
6-116877498-G-C		RFX6-related disorder	Likely benign (Jan 22, 2024)
6-116877504-T-G		RFX6-related disorder	Benign (Dec 04, 2023)
6-116877506-C-G			Likely benign (Jan 13, 2024)
6-116877784-A-G		Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome • Diabetes mellitus	Pathogenic (Feb 11, 2010)
6-116877840-G-A		Monogenic diabetes	Conflicting classifications of pathogenicity (Jul 14, 2023)
6-116877842-C-T			Likely benign (Oct 03, 2023)
6-116877843-G-A			Uncertain significance (Aug 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RFX6	protein_coding	protein_coding	ENST00000332958	19	54952

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000409	1.00	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	419	494	0.848	0.0000249	6080
Missense in Polyphen		87	153.63	0.56628		1891
Synonymous	-0.322	191	185	1.03	0.00000978	1781
Loss of Function	4.56	16	51.2	0.312	0.00000279	587

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000214
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00190	0.00190
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: 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). {ECO:0000269|PubMed:20148032, ECO:0000269|PubMed:25497100}.
• Pathway: Maturity onset diabetes of the young - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.546
• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.43

Haploinsufficiency Scores

• pHI: 0.172
• hipred: Y
• hipred_score: 0.704

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.292

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rfx6
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: rfx6
• Affected structure: endocrine pancreas
• Phenotype tag: abnormal
• Phenotype quality: undifferentiated

Gene ontology

• Biological process: type B pancreatic cell differentiation;pancreatic A cell differentiation;pancreatic D cell differentiation;regulation of transcription by RNA polymerase II;endocrine pancreas development;positive regulation of insulin secretion involved in cellular response to glucose stimulus;glucose homeostasis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of insulin secretion;pancreatic epsilon cell differentiation
• Cellular component: nucleus;nucleolus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;transcription regulatory region DNA binding