RFX3

regulatory factor X3, the group of Regulatory factor X family

Basic information

Region (hg38): 9:3218297-3526004

Links

ENSG00000080298 ∙ NCBI:5991 ∙ OMIM:601337 ∙ HGNC:9984 ∙ Uniprot:P48380 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RFX3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFX3 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				5	3	8
missense			27	1	1	29
nonsense		2	1			3
start loss						0
frameshift		3				3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region		1	1			2
non coding			1	3	1	5
Total	0	5	30	9	5

Variants in RFX3

This is a list of pathogenic ClinVar variants found in the RFX3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-3225088-G-C		Inborn genetic diseases	Uncertain significance (May 05, 2023)
9-3225104-C-T		RFX3-related disorder	Likely benign (Jan 08, 2024)
9-3225113-C-G			Uncertain significance (Jun 07, 2021)
9-3225133-A-C		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
9-3225200-C-G		Inborn genetic diseases	Uncertain significance (Aug 14, 2023)
9-3228838-G-A		RFX3-related disorder	Benign (Jun 06, 2018)
9-3247951-C-T		RFX3-related disorder	Benign (Nov 07, 2019)
9-3247972-G-C		RFX3-related disorder	Likely benign (May 08, 2024)
9-3248035-G-A			Likely benign (Jun 06, 2018)
9-3248078-C-T			Uncertain significance (Mar 01, 2024)
9-3248119-A-G		RFX3-related disorder	Likely benign (Mar 20, 2019)
9-3248121-G-C			Uncertain significance (Feb 26, 2024)
9-3248181-T-C			Uncertain significance (Dec 27, 2022)
9-3257004-A-G		Autism spectrum disorder	Uncertain significance (Apr 13, 2022)
9-3257026-G-A		RFX3-related disorder	Likely benign (May 28, 2019)
9-3257033-G-C		RFX3-related disorder	Uncertain significance (Apr 25, 2023)
9-3257053-A-G			Benign (Oct 19, 2017)
9-3257096-G-GC		Neurodevelopmental disorder	Likely pathogenic (Oct 06, 2020)
9-3257122-C-T		RFX3-related disorder	Benign/Likely benign (Jul 01, 2023)
9-3257130-T-A			Uncertain significance (Nov 22, 2022)
9-3257133-T-C		RFX3-related disorder	Uncertain significance (Sep 06, 2022)
9-3257152-T-A		Inborn genetic diseases	Uncertain significance (Jun 05, 2024)
9-3257159-A-T			Uncertain significance (Apr 27, 2022)
9-3257196-G-A			Uncertain significance (Oct 01, 2022)
9-3262994-T-C			Uncertain significance (Mar 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RFX3	protein_coding	protein_coding	ENST00000382004	16	307708

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.36e-7	125650	0	4	125654	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.47	223	424	0.526	0.0000227	4913
Missense in Polyphen		18	101.85	0.17673		1214
Synonymous	-2.11	193	159	1.21	0.00000956	1446
Loss of Function	6.14	1	45.8	0.0218	0.00000249	463

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development. Essential for the differentiation of nodal monocilia and left- right asymmetry specification during embryogenesis. Required for the biogenesis of motile cilia by governing growth and beating efficiency of motile cells. Also required for ciliated ependymal cell differentiation. Regulates the expression of genes involved in ciliary assembly (DYNC2LI1, FOXJ1 and BBS4) and genes involved in ciliary motility (DNAH11, DNAH9 and DNAH5) (By similarity). Together with RFX6, participates in the differentiation of 4 of the 5 islet cell types during endocrine pancreas development, with the exception of pancreatic PP (polypeptide-producing) cells. Regulates transcription by forming a heterodimer with another RFX protein and binding to the X-box in the promoter of target genes (PubMed:20148032). Represses transcription of MAP1A in non- neuronal cells but not in neuronal cells (PubMed:12411430). {ECO:0000250|UniProtKB:P48381, ECO:0000269|PubMed:12411430, ECO:0000269|PubMed:20148032}.

Recessive Scores

• pRec: 0.140

Intolerance Scores

• loftool: 0.294
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.46

Haploinsufficiency Scores

• pHI: 0.948
• hipred: Y
• hipred_score: 0.728
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rfx3
• Phenotype: embryo phenotype; normal 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; growth/size/body region phenotype; muscle phenotype; cellular phenotype

Gene ontology

• Biological process: transcription, DNA-templated;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;endocrine pancreas development;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell maturation;regulation of insulin secretion;cilium assembly;cilium-dependent cell motility;epithelial cilium movement involved in determination of left/right asymmetry;type B pancreatic cell maturation;positive regulation of type B pancreatic cell development
• Cellular component: nuclear chromatin;nucleus;transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;transcription regulatory region DNA binding