RFXAP

regulatory factor X associated protein

Basic information

Region (hg38): 13:36819221-36829104

Links

ENSG00000133111 ∙ NCBI:5994 ∙ OMIM:601861 ∙ HGNC:9988 ∙ Uniprot:O00287 ∙ 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	650344; 7021490; 9118943; 20197681

ClinVar

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

• MHC class II deficiency (153 variants)
• Inborn genetic diseases (11 variants)
• not provided (7 variants)
• not specified (1 variants)
• Bare Lymphocyte Syndrome, Type II, Complementation Group D (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFXAP 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			6	28	1	35
missense			72	2	1	75
nonsense	2	1	1			4
start loss			1			1
frameshift	5	1	2			8
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)						0
splice region			4	2		6
non coding			12	7	7	26
Total	7	2	96	38	9

Highest pathogenic variant AF is 0.000118

Variants in RFXAP

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

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

Position	Type	Phenotype	Significance	ClinVar
13-36819227-C-T		MHC class II deficiency	Uncertain significance (Feb 16, 2018)
13-36819242-C-G		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
13-36819253-C-A		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
13-36819257-T-G		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
13-36819276-G-C		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
13-36819359-T-C		MHC class II deficiency	Uncertain significance (Sep 29, 2019)
13-36819366-G-C		MHC class II deficiency	Likely benign (Mar 18, 2022)
13-36819366-G-T		MHC class II deficiency	Likely benign (Jun 04, 2020)
13-36819371-G-T		MHC class II deficiency • not specified	Uncertain significance (Dec 11, 2023)
13-36819372-T-C		MHC class II deficiency	Conflicting classifications of pathogenicity (Jul 25, 2023)
13-36819377-C-T		MHC class II deficiency	Uncertain significance (Jan 17, 2022)
13-36819381-G-A		MHC class II deficiency • RFXAP-related disorder	Benign/Likely benign (Feb 01, 2024)
13-36819384-C-T		MHC class II deficiency	Likely benign (Dec 17, 2023)
13-36819386-C-T		MHC class II deficiency	Uncertain significance (Apr 28, 2022)
13-36819393-G-T		MHC class II deficiency	Likely benign (Aug 22, 2022)
13-36819395-G-GCA		MHC class II deficiency	Likely pathogenic (Feb 18, 2022)
13-36819401-C-T		MHC class II deficiency	Uncertain significance (Oct 26, 2022)
13-36819408-C-T		MHC class II deficiency	Uncertain significance (Jun 16, 2020)
13-36819409-G-T		MHC class II deficiency	Uncertain significance (Aug 27, 2021)
13-36819411-G-T		MHC class II deficiency	Likely benign (May 05, 2023)
13-36819412-C-T		MHC class II deficiency	Uncertain significance (May 25, 2022)
13-36819415-C-T		MHC class II deficiency	Uncertain significance (Oct 28, 2022)
13-36819416-A-G		MHC class II deficiency	Uncertain significance (Dec 22, 2018)
13-36819427-C-G		not specified	Uncertain significance (Aug 22, 2023)
13-36819434-C-G		MHC class II deficiency	Conflicting classifications of pathogenicity (Jan 03, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RFXAP	protein_coding	protein_coding	ENST00000255476	3	9881

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0233	0.919	124965	0	2	124967	0.00000800

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	99	133	0.747	0.00000607	1730
Missense in Polyphen		41	54.681	0.7498		697
Synonymous	0.193	52	53.8	0.967	0.00000249	542
Loss of Function	1.62	4	9.36	0.427	3.97e-7	118

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000958	0.00000884
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the RFX complex that binds to the X-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:10072068, ECO:0000269|PubMed:9118943}. 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) (Consensus)

Recessive Scores

• pRec: 0.114

Haploinsufficiency Scores

• pHI: 0.0971
• hipred: N
• hipred_score: 0.403
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.463

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rfxap

Gene ontology

• Biological process: positive regulation of transcription, DNA-templated
• Cellular component: nucleus;nuclear speck
• Molecular function: DNA binding;DNA-binding transcription factor activity;transcription coactivator activity