RFXANK

regulatory factor X associated ankyrin containing protein, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 19:19192229-19201869

Links

ENSG00000064490 ∙ NCBI:8625 ∙ OMIM:603200 ∙ HGNC:9987 ∙ Uniprot:O14593 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MHC class II deficiency (Strong), mode of inheritance: AR
• MHC class II deficiency (Strong), mode of inheritance: AR
• MHC class II deficiency (Supportive), 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
MHC class II deficiency	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	7951244; 9806546; 11313409; 12618906; 20414676; 21908431

ClinVar

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

• MHC_class_II_deficiency (253 variants)
• Inborn_genetic_diseases (36 variants)
• not_provided (15 variants)
• MHC_class_II_deficiency_2 (15 variants)
• RFXANK-related_disorder (5 variants)
• MHC_class_II_deficiency_1 (5 variants)
• not_specified (2 variants)
• MHC_class_II_deficiency_5 (1 variants)
• Inherited_Immunodeficiency_Diseases (1 variants)
• MHC_class_II_deficiency_3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFXANK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003721.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				70		70
missense		2	98	8	1	109
nonsense	4	4				8
start loss						0
frameshift	5	7				12
splice donor/acceptor (+/-2bp)	4	7				11
Total	13	20	98	78	1

Highest pathogenic variant AF is 0.000014921736

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RFXANK	protein_coding	protein_coding	ENST00000303088	8	9671

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000867	0.779	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.266	145	154	0.940	0.0000108	1658
Missense in Polyphen		48	54.582	0.8794		562
Synonymous	-0.794	79	70.5	1.12	0.00000572	555
Loss of Function	1.23	10	15.1	0.660	9.31e-7	148

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000293	0.000293
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000204	0.000202
Middle Eastern	0.000217	0.000217
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator/CIITA. May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters (PubMed:9806546, PubMed:10072068, PubMed:10725724). May also potentiate the activation of RAF1 (By similarity). {ECO:0000250|UniProtKB:Q9Z205, ECO:0000269|PubMed:10072068, ECO:0000269|PubMed:10725724, ECO:0000269|PubMed:9806546}.
• 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:10725724, ECO:0000269|PubMed:22649097, ECO:0000269|PubMed:9806546}. 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);Signaling events mediated by HDAC Class II (Consensus)

Recessive Scores

• pRec: 0.232

Intolerance Scores

• loftool: 0.845
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.38

Haploinsufficiency Scores

• pHI: 0.184
• hipred: Y
• hipred_score: 0.662
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.908

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rfxank

Gene ontology

• Biological process: Ras protein signal transduction;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;cytosol;intercellular bridge
• Molecular function: DNA binding;DNA-binding transcription factor activity;transcription coregulator activity;histone deacetylase binding