RFX5

regulatory factor X5, the group of Regulatory factor X family

Basic information

Region (hg38): 1:151340639-151347326

Links

ENSG00000143390 ∙ NCBI:5993 ∙ OMIM:601863 ∙ HGNC:9986 ∙ Uniprot:P48382 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MHC class II deficiency (Supportive), mode of inheritance: AR
• MHC class II deficiency (Strong), mode of inheritance: AR
• MHC class II deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bare lymphocyte syndrome, type II	AR	Allergy/Immunology/Infectious	Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II	Allergy/Immunology/Infectious; Gastrointestinal	7744245; 9401005; 10079298; 12368908

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RFX5 gene.

• MHC class II deficiency (324 variants)
• Inborn genetic diseases (20 variants)
• not provided (14 variants)
• not specified (10 variants)
• RFX5-related condition (5 variants)
• Bare lymphocyte syndrome, type II, complementation group c (2 variants)
• Bare lymphocyte syndrome type 2, complementation group E (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFX5 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	40	5	47
missense		1	172	1	4	178
nonsense	6	1	2			9
start loss						0
frameshift	8	3	6			17
inframe indel			4			4
splice donor/acceptor (+/-2bp)	2	9				11
splice region			7	6		13
non coding			22	21	7	50
Total	16	14	208	62	16

Highest pathogenic variant AF is 0.000151

Variants in RFX5

This is a list of pathogenic ClinVar variants found in the RFX5 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-151340665-A-AAAT		MHC class II deficiency	Uncertain significance (Jun 14, 2016)
1-151340760-T-C		MHC class II deficiency	Uncertain significance (Feb 02, 2018)
1-151340773-T-G		MHC class II deficiency	Likely benign (Jan 13, 2018)
1-151340856-G-A		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151340934-G-C		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341009-G-A		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341020-T-C		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
1-151341028-C-T		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
1-151341068-T-C		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341102-T-G		MHC class II deficiency	Benign (Jan 13, 2018)
1-151341108-G-A		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341200-GA-G		MHC class II deficiency	Uncertain significance (Jun 14, 2016)
1-151341298-A-G		MHC class II deficiency	Benign (Jan 13, 2018)
1-151341305-G-A		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
1-151341348-T-C		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341425-T-A		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
1-151341465-C-A		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341491-TC-T		MHC class II deficiency	Uncertain significance (Jun 14, 2016)
1-151341525-A-G		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341813-C-A		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
1-151341822-T-G		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
1-151341903-T-C		MHC class II deficiency	Benign (Jan 13, 2018)
1-151341942-T-C		MHC class II deficiency	Benign (Jan 13, 2018)
1-151341962-A-G		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
1-151342157-A-C		MHC class II deficiency	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RFX5	protein_coding	protein_coding	ENST00000290524	9	6718

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.96e-11	0.391	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.476	314	339	0.927	0.0000198	3915
Missense in Polyphen		92	111.4	0.82589		1248
Synonymous	2.23	95	127	0.748	0.00000661	1348
Loss of Function	1.14	20	26.3	0.760	0.00000183	299

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000669	0.000662
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00111	0.00111
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000218	0.000217
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters.
• Disease: DISEASE: Bare lymphocyte syndrome 2 (BLS2) [MIM:209920]: A severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon- gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections. {ECO:0000269|PubMed:10825209}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Prion disease pathway (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.506
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.41

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.377
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rfx5
• Phenotype: endocrine/exocrine gland phenotype; immune system phenotype; hematopoietic system phenotype; 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); liver/biliary system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: 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;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding